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Review

Maternal Supplementation of Probiotics, Prebiotics or Postbiotics to Prevent Offspring Metabolic Syndrome: The Gap between Preclinical Results and Clinical Translation

by
Ying-Hua Huang
1,†,
You-Lin Tain
1,2,† and
Chien-Ning Hsu
3,4,*
1
Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
2
College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
3
Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
4
School of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Int. J. Mol. Sci. 2022, 23(17), 10173; https://doi.org/10.3390/ijms231710173
Submission received: 27 July 2022 / Revised: 1 September 2022 / Accepted: 2 September 2022 / Published: 5 September 2022
(This article belongs to the Special Issue New Approaches for the Management of Metabolic Syndrome and Related Health Alterations: A Focus in Probiotics, Parabiotics and Postbiotics)
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Abstract

:
Metabolic syndrome (MetS) is an extremely prevalent complex trait and it can originate in early life. This concept is now being termed the developmental origins of health and disease (DOHaD). Increasing evidence supports that disturbance of gut microbiota influences various risk factors of MetS. The DOHaD theory provides an innovative strategy to prevent MetS through early intervention (i.e., reprogramming). In this review, we summarize the existing literature that supports how environmental cues induced MetS of developmental origins and the interplay between gut microbiota and other fundamental underlying mechanisms. We also present an overview of experimental animal models addressing implementation of gut microbiota-targeted reprogramming interventions to avert the programming of MetS. Even with growing evidence from animal studies supporting the uses of gut microbiota-targeted therapies start before birth to protect against MetS of developmental origins, their effects on pregnant women are still unknown and these results require further clinical translation.

1. Introduction

Metabolic syndrome (MetS) is a group of concurrent medical conditions that raise risk of cardiovascular disease (CVD). The major components of MetS are obesity, hypertension, dyslipidemia and insulin resistance [1]. It is estimated that around one-quarter of the world population (one billion) is affected by MetS [2]. Of note is that MetS and associated disorders constitute two thirds of the non-communicable diseases (NCDs), the leading causes of death globally [3]. Without specific therapeutic regimens for diverse phenotypes of MetS, its prevalence is rising worldwide [2]. Hence, a strategic approach to avert the spread of MetS should be switched from disease treatment to prevention.
Recent epidemiological and experimental studies suggest that metabolic syndrome can originate in early life [4,5,6,7]. Exposure to various environmental cues in early life can alter organ structure and function that may raise the risk for developing MetS in later life [4,5,6,7]. This notion is now being termed the developmental origins of health and disease (DOHaD) [8].
Notably, different environmental insults in early life can program similar features of MetS, proposing a commonality of mechanistic pathways behind MetS of developmental origins. Despite these pathogenic mechanisms underlying developmental programming are still inconclusive, several common mechanisms have been reported, including nitric oxide (NO) deficiency, oxidative stress, aberrant activation of the renin-angiotensin-aldosterone system (RAAS), dysfunctional nutrient sensing signals, epigenetic regulation and gut microbiota dysbiosis [4,5,6,7,9,10,11,12].
Recent research has highlighted the influence of the gut microbiota in MetS and associated disorders [13]. Gut microbiota derived metabolites can work as signaling compounds through systemic circulation involving in human disease, including MetS [13]. Fetal exposure to environmental insults has been connected with negative impact on offspring gut microbiota maturation, which precede later onset of disease in adult life [14]. Nevertheless, relatively little information exists regarding whether and how various maternal insults could shape gut microbiota, leading to MetS and associated disorders in adult offspring.
Conversely, unfavorable programming processes can be averted by intervention in early life to stop or delay the development of chronic diseases throughout life, which is referred to as reprogramming [15]. Considering gut microbiota dysbiosis is closely connected with the developmental of MetS, interventions gut microbiota and relevant metabolites may serve as a potential target for therapeutics [16,17,18,19].
Probiotics (i.e., beneficial microorganisms), prebiotics (i.e., compounds in food can assist the growth of probiotics) and postbiotics (i.e., metabolites of probiotics providing physiological benefits) are commonly used gut microbiota-targeted therapies. Our review aims to map the fundamental concepts in how the uses of probiotics, prebiotics and postbiotics in early life prevent the developmental programming of MetS.
We searched the MEDLINE/PubMed and Embase databases for studies written in English between January 1980 and July 2022 using the following list of keywords: “gut microbiota”, “probiotics”, “prebiotics”, “synbiotics”, “postbiotics”, “parabiotics”, “cardiovascular disease”, “cardiometabolic disorder”, “developmental programming”, “DOHaD”, “reprogramming”, “dyslipidemia”, “hyperlipidemia”, “obesity”, “diabetes”, “insulin resistance”, “hyperglycemia”, “hypertension”, “mother”, “father”, “gestation”, “pregnancy”, “progeny”, “offspring” and “metabolic syndrome”. Additional studies were selected and evaluated based on references in eligible literature. The search was ended by 10 July 2022.

2. Current Evidence Supports MetS of Developmental Origins

2.1. Epidemiological Evidence

There is tremendously epidemiological evidence suggesting that negative early-life conditions are associated with the risk of MetS later in life. First, available data indicate that famines increase risk of developing MetS [20,21,22,23]. The Dutch Famine Birth Cohort Study revealed that pregnant women under famine had children who developed obesity, hypertension, dyslipidemia and insulin resistance [20,22]. Studies in other famines show similar effects [21,23]. Another line of evidence supports MetS of developmental origins coming from many observational studies of risk factors. Risk factors reported in these studies relating to MetS and associated disorders include environmental chemicals exposure [24], maternal obesity [25,26], gestational diabetes [26,27] and excessive postnatal weight gain [28]. Third, data from twin pregnancy revealed that there was an association between low birth weight (LBW) and certain features of MetS [29,30]. Lastly, a systematic review recruiting 39 studies demonstrated that rapid weight gain in infant with LBW had an around 80% great risk for CVDs [31]. From these observations, there might be a relationship between early-life environmental exposure, fetal programming and the development of MetS later in life.
Notably, these observational studies are not able to offer molecular mechanisms underlying programming processes of MetS for the creation of reprogramming interventions. Accordingly, the biological plausibility of the associations, proof of causality and development of reprogramming strategies have long been reliant on evidence whereby animal models stand.

2.2. Experimental Evidence

Considering the difficulties in building animal models that exhibit all the components of MetS, studying MetS of developmental origins are performed using models that manifest certain, but not all, characteristics of MetS in most investigations [4,5,6,7]. According to the experimental approach, several species such as rats [32], mice [33], rabbits [34], sheep [35], pigs [36] and non-human primate [37] have been used to evaluate developmental programming of MetS. Among them, rats are most commonly used animals for comparisons of major features of MetS develop throughout the lifetime [7]. Several environmental insults in early life have been reported to program certain features of MetS in adult offspring, containing maternal imbalanced nutrition, maternal illness, environmental chemical exposure, medication use, etc. [4,5,6,7,27,28,29,30].

2.2.1. Maternal Nutrition Imbalance

The array of maternal imbalanced nutrition that have been established to induce different features of MetS is categorized into models that aim to restrict calorie intake, restrict certain nutrients or increase consumption of specific nutrients. Several maternal nutrient restriction models have been created to mimic the malnutrition experienced by pregnant women exposed to famine.
Caloric restriction is a dietary regimen that reduces energy intake without incurring specific nutrient. Restriction of calories ranging from 30% to 70% in dams has been stated to cause offspring hypertension, a key characteristic of MetS [38]. In addition to hypertension, severe 70% maternal caloric restriction resulted in obesity, hyperleptinemia and insulin resistance in adult offspring [39]. The severity of deleterious consequence seems related to the degree of caloric restriction and the timing of exposure [38,40].
The protein restriction model is the same as the caloric restriction model that mimics the challenge faced in developing countries. In rats, protein restriction with a range from 6–9% to pregnant dams resulted in offspring hypertension [38]. Rodent studies of maternal protein restriction also result in intrauterine growth retardation (IUGR) with subsequent insulin resistance, obesity, hyperglycemia, glucose intolerance and adipocyte hypertrophy [41].
There is also evidence to endorse that deficiencies in certain nutrients in pregnant mothers resulting in MetS in adult progeny. In rodent models, when deficiencies in iron [42], zinc [43], sodium [44], calcium [45], vitamin D [46] or methyl donor nutrients (folic acid; methionine; choline; vitamins B2, B6 and B12) [47], in dams, their adult offspring were likely to have elevated BP [38]. In addition, offspring of pregnant mothers with low levels of trace elements and vitamins are at risk for developing MetS-related phenotypes, such as insulin resistance [48,49], impaired glucose tolerance [50], increased visceral adiposity and altered lipid metabolism [51].
On the other hand, the excessive consumption of specific nutrients can also program MetS and associated disorders in adult offspring [25]. The Western diet is characterized for being rich in saturated fats, salt and refined sugars. Animal models of maternal diets containing key components of the human Western diet, synergistic effects of fat, salt and refined sugars on the elevation of BP in adult offspring were noticed [52,53,54]. Rodent models of high-fat diet-induced obesity have been used widely to study human obesity-related disorders [55,56]. Numerous animal studies reveal that maternal high-fat diet can program MetS traits in adult rat progeny, such as hypertension [57], obesity [58], dyslipidemia [59] and insulin resistance [59].
Much of the increase in sugar consumption is from high-fructose corn syrup and refined sugars [60]. Prior work indicates that intake of high-fructose alone or as a part of diet by rodent mothers induces multiple characteristics of MetS in adult progeny, such as hypertension, obesity, insulin resistance, dyslipidemia and hepatic steatosis [61,62,63].

2.2.2. Maternal Illness

Maternal illness and/or complications during pregnancy impact fetal programming, which can be marked by IUGR [64]. IUGR offspring displayed dyslipidemia, hypertension and insulin resistance in a rat model of uteroplacental insufficiency [65,66]. So far, several animal models have been built resembling various maternal illnesses to evaluate MetS of developmental origins, including polycystic ovary syndrome (PCOS) [67,68], hypoxia [69], inflammation [70,71], diabetes [72,73,74] and chronodisruption [75,76].
In the PCOS model, adult offspring manifested dyslipidemia and hypertension at 16–17 weeks of age [67,68]. Maternal hypoxia and inflammation are also able to induce MetS-related phenotypes in adult rat progeny, including hypertension [69,70], obesity [69] and insulin resistance [71]. Additionally, rodent studies of maternal diabetes induced by streptozotocin (STZ) cause various features of MetS in offspring, such as insulin resistance, obesity, dyslipidemia, hypertension and CVDs [72,73,74].
Since the circadian system is the principal regulator of metabolism, circadian rhythm sleep disorders have been linked to MetS [77]. Data from animal studies indicated that maternal constant light exposure or dams received pinealectomy can program offspring’s hypertension [75] and insulin resistance [76].

2.2.3. Exposures to Chemicals or Drugs

Prior review showed adult rats exposed to several chemicals during early life developed hypertension, a major feature of MetS [78]. These chemicals, while only bisphenol A and di-(2-ethylhexyl) phthalate (DEHP), have shown their programming effects resulting in insulin resistance in adult progeny [79,80].
Additionally, maternal substance abuse is also involved in the development of offspring MetS. In rodent models, gestational exposure to alcohol or nicotine can induce hypertension [81,82], insulin resistance [83,84] and obesity [84] in adult offspring.
The uses of drugs in pregnancy have also been connected with developmentally programmed hypertension in adult offspring, such as glucocorticoid [85], cyclosporine [86] or minocycline [87]. In addition to hypertension, early-life glucocorticoid exposure can also induce offspring’s insulin resistance [88,89,90].
In view of the fact that animal models are in line with the epidemiological observations revealing different maternal insults induce similar feature of MetS in offspring, perhaps various early-life environmental cues may mediate common mechanisms culminating in the developmental programming of MetS.

3. Gut Microbiota and MetS of Developmental Origins

Although the exact mechanisms underlying MetS of developmental origins have not yet been completely understood, animal studies have provided insights on potential mechanisms, including oxidative stress [90,91], dysfunctional nutrient-sensing signals [91], epigenetic regulation [92], aberrant activation of the renin–angiotensin-aldosterone system (RAAS) [92,93] and gut microbiota dysbiosis [94,95]. Notably, gut microbiota dysbiosis is interrelated to most of the above-mentioned mechanisms.
Although growing evidence supports the pathogenic interconnection between the dysbiotic gut microbiota and MetS [90,91,92], there is paucity of data about the impact of early-life disturbance of gut microbiota on offspring MetS in later life. Hence, this section primarily document evidence addressing the influence of gut microbiota on various components of MetS, with an emphasis on animal models.

3.1. Early-Life Gut Microbiome

Microbiota is usually defined as all the microorganisms living in a given environment, while the microbiome is a term used to describe the collection of genomes from all microorganisms in a specific environment. Though microbes will colonize the neonatal gut soon after birth [93], microbial colonization keep evolving and modulate in species abundance to attain an adult-like structure at the age of 2–3 years [94]. An important underlying contributor of offspring gut microbial structure and composition if mother microbiome [95]. Importantly, many factors can impact offspring gut microbiome, such as maternal conditions, gestational age, model of delivery, feeding type, antibiotic exposure and ecological factors [95]. Several above-mentioned risk factors connected with MetS of developmental origins have also been associated with disturbed gut microbiota, including maternal malnutrition [96], maternal obesity [97], gestational diabetes [98], LBW [99] and prematurity [100]. In addition, the establishment of the microbiome has a strong connection with developing immune system, which closely ties inflammation to MetS [61]. All of these studies indicate that adverse environmental insults induce microbial alterations may contribute to the development of MetS later in life.

3.2. Dysbiotic Gut Microbiota and MetS of Developmental Origins

Disruption of gut microbiota participates in the development of several MetS phenotypes, such as hypertension [101], obesity [102], dyslipidemia [103] and insulin resistance [104]. Additionally, decreased gut microbial diversity and richness are linked to a high risk for CVD [11,105].
The absence of microbiota in germ-free rats gave rise to relative hypotension in comparison with their conventional counterparts, indicating a vital role of gut microbiota in the regulation of BP [106]. In several hypertensive rat models [107,108,109], gut microbiome is disturbed and significantly different from the microbiota of normotensive control rats.
Gut microbiota metabolites are also involved in MetS of developmental origins. Short chain fatty acids (SCFAs) are products of fermentation of polysaccharides by gut microbiota. SCFAs are commonly accepted to control BP through activating their SCFA receptors [110]. Moreover, SCFAs modulate glucose homeostasis, appetite regulation and obesity [111]. Another example is trimethylamine-N-oxide (TMAO), a molecule generated from choline and carnitine via gut microbial metabolism [112]. TMAO is transformed from trimethylamine (TMA) by flavin-containing monooxygenase (FMO). High TMAO and TMO link to CVD mortality [113,114]. TMAO also contributes to MetS and associated disorders, such as type II diabetes, insulin resistance, non-alcoholic fatty liver disease and chronic kidney disease [112].
A maternal high-fat diet has been generally used to evaluate the mechanisms of MetS of developmental origins, as this model induces all features of MetS in adult rat offspring [7]. Prior work revealed that maternal high-fat diet caused offspring hypertension coincided with alterations of gut microbiota composition, reduced fecal SCFA level, dysregulated SCFA receptor expression and increased TMA levels and decreases of TMAO-to-TMA ratio in adult rat offspring [101,115]. Moreover, several indole derivatives generated from tryptophan by microbial metabolism may participate in MetS pathogenesis via activating AhR signaling [116,117]. Dysbiotic gut microbiota can mediate AhR signaling resulting in metabolic impairments, particularly liver steatosis and glucose dysmetabolism [118].
Moreover, other gut-microbiota metabolites such as lipopolysaccharide (LPS), long-chain fatty acid and bile acids (BAs) have also been linked to the MetS traits. LPS could induce low-grade inflammation, which features obesity and insulin resistance [119]. Another report showed that long chain fatty acids derived by gut microbes could be one of the mechanisms implicated in the anti-inflammatory properties of probiotics [120]. Gut microbiota-derived long chain fatty acids also play a vital role in host metabolism and adipocyte thermogenesis, which mediate anti-obesity effects [121,122,123]. Additionally, gut microbiota can convert primary BAs to secondary BAs to balance the BA pool and regulate lipid metabolism. High-fat diet-induced hyperlipidemia is related to impaired BA metabolism [124]. Figure 1 is a graphic illustration of environmental cues in early life mediate gut microbiota dysbiosis and program different organ systems, leading to MetS of developmental origins later in life.

3.3. Common Mechanisms behind MetS Linking to Gut Microbiota

The pathogenic interconnections between the gut microbiota and certain mechanisms are implicated in MetS of developmental origins. These core mechanisms include aberrant activation of the RAAS, oxidative stress, NO deficiency and dysregulated nutrient sensing signals [4,5,6,7,9,10,11,12].
First, activation of the RAAS can induce various phenotypes of MetS, including insulin resistance, hypertension, obesity and hyperglycemia [125]. The most common studied phenotype of MetS connected with the RAAS is hypertension [126]. There is a bidirectional interaction between the gut microbiota and RAAS; gut microbiota-derived metabolites can moderate the gut RAAS, whereas alterations in RAAS shift microbial structure and composition [127]. Angiotensin-converting enzyme 2 (ACE2), a homologue of ACE, converts angiotensin (ANG) II to ANG-(1–7) that adversely regulates the RAAS [128]. Previous studies showed that ACE2 not only can modulate gut microbiota but also alleviate hypertension and cardiovascular dysfunction in adult rat offspring [126,129,130]. Importantly, ACE2 activation has shown benefits of anti-obesity and improvement of metabolic parameters, such as blood glucose and lipids [131,132,133].
Second, data from several animal models supports a connection between gut microbiota dysbiosis and oxidative stress in the pathogenesis of developmental programming [57,134,135,136]. Enteric microbial communities govern redox signaling to maintain host–microbiota homeostasis [137]. Conversely, an imbalanced redox state induces gut microbiota dysbiosis. A maternal high-fructose diet has been reported to motivate many characteristics of MetS in adult offspring [134]. In particular, oxidative stress is close lined to dyslipidemia [138], insulin resistance [139] and hypertension [140]. Conversely, early interventions targeting gut microbiota have shown beneficial effects against oxidative stress as well as many adverse offspring outcomes in the maternal high-fructose diet rat model [141,142]. Likewise, perinatal gut microbiota-targeted therapy using resveratrol prevented the rise of BP programmed by maternal CKD in adult offspring, which coincided with altering the gut microbiota and reducing oxidative stress concurrently [132].
Third, increasing evidence suggests that NO deficiency is involved in developmental programming and has a key role in the pathogeneses of MetS [143,144]. NO deficiency can be induced by enhancing asymmetric dimethylarginine (ADMA) production, a NO synthase inhibitor [145]. A high ADMA level is connected with MetS-related disorders, such as hypertension, hypercholesterolemia, diabetes mellitus, obesity and coronary artery disease [145]. Decreased NO bioavailability and increased plasma ADMA levels have been shown to participate in several models of developmental programming [144]. As dietary nitrate (a precursor of NO) and NO metabolism can be mediated by microbiome [146], NO deficiency may work with the dysbiotic gut microbiota under the developmental programming of MetS. Resveratrol is a commonly used nutritional supplement with prebiotics and antioxidant properties [147,148]. The positive actions of resveratrol against developmental programming of hypertension are likely related to its ability to restore the ADMA/NO pathway as well alter gut microbiota in a maternal CKD model [149] and a maternal NO deficiency model [150].
Last, nutrient-sensing signals govern metabolic homeostasis in response to maternal insults during fetal development [151,152]. Hence, dysregulated nutrient-sensing signals have a crucial influence in the pathogenesis of MetS of developmental origins [7]. Gut microbiota-diet interactions interfere in nutrient-sensing signals from the gut to the brain, where the information is processed to govern whole-body metabolic and energy homeostasis [153]. It has long been known that cyclic adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a key nutrient-sensing signal. Dysfunctional AMPK signal is related to developmental programming of hypertension, while AMPK activation in early life could prevent offspring hypertension [154]. Additionally, resveratrol, an AMPK activator, can regulate nutrient-sensing signals to increase expression of PPARs target genes and thereby reverse MetS-related programmed processes [9,147].
With regard to the multifaceted role of gut microbiota in human health, other possible pathways might be interconnected and all work together to program MetS, for example, hydrogen sulfide signaling [155] or nuclear factor erythroid 2-related factor 2 (NRF2) [156]. Although the exact mechanism behind MetS of developmental origins remains inconclusive, animal studies provide a possibility regarding gut microbiota as a possible reprogramming target.

4. Reprogramming Strategy: Probiotics, Prebiotics and Postbiotics

The DOHaD theory generates opportunities to stop or delay the programming process by an early reprogramming strategy aiming to prevent adult disease later in life [15]. With a deeper understanding on MetS programming, the development of mechanism-targeted strategies provides potential for reprogramming. Emerging evidence from animal studies in DOHaD research supports that gut microbiota-targeted therapy might act as a reprogramming strategy to avert adult disease of developmental origins [11].

4.1. Gut-Microbiota Targeted Therapy

Several gut microbiota-targeted therapies have proven to manipulate the gut microbiome in various disorders. Probiotics and prebiotics are the most frequently used gut microbiota-targeted options in clinical work [16,17,18]. Probiotics refers to live microorganisms that, when administered in adequate amounts, confer a health benefit on the host [157]. The international scientific association of prebiotics and probiotics (ISAPP) defined prebiotics as substrates that are selectively utilized by host microorganisms conferring a health benefit [158]. Synbiotics, a probiotic-prebiotic combination, also confers a health benefit [16].
Postbiotics and parabiotics and the emerging concepts in the functional foods field, which have shown to promote health, too [159]. The postbiotics are the complex mixture of metabolic bioproducts generated by probiotics in cell-free supernatants such as vitamins, enzymes, organic acids, secreted proteins, amino acids, SCFAs, peptides and secreted biosurfactants. While the parabiotics are the inactivated microbial cells of probiotics or crude cell extracts [159]. Another way to modify the gut microbiome is by transplanting fecal matter. Emerging evidence suggests efficacy of fecal microbiota transplant (FMT) for the therapy of obesity associated disorders [160].
Here, we illustrate Table 1 that summarizes studies reporting microbiota-targeted reprogramming interventions in animal models for studying MetS of developmental origins, restricting those therapeutic duration is starting before birth to cover the periods of organogenesis [57,101,141,142,149,150,161,162,163,164,165,166,167,168,169,170,171,172,173,174,175,176,177,178].
The most widely used species are rats. A number of MetS programming models have been used to examine gut microbiota-targeted interventions, such as maternal high-fructose diet [141,142], perinatal high-fat diet [57,101,167,169], maternal high-fat/sucrose diet [162], maternal high-fat diet [161,163,171,176], maternal ADMA and TMAO exposure [164], perinatal TCDD exposure [165,177], maternal adenine-induced CKD [149], maternal protein restriction [165], maternal L-NAME and high-fat diet exposure [150], maternal bisphenol A exposure and high-fat diet [162], maternal hypertension [170], maternal bisphenol A exposure [172,173], maternal minocycline exposure [174], maternal tryptophan-free diet [175] and combined maternal high-fructose diet and TCDD exposure. [173].
Reported gut microbiota-targeted strategies include probiotics, prebiotics and postbiotics. A schematic summary of gut microbiota-targeted reprogramming interventions for MetS of developmental origins is illustrated in Figure 2.
In view of the fact that the difficulties in developing animal models exhibiting all characteristics of MetS, gut microbiota-targeted interventions into developmental programming of MetS have been evaluated for their protective effects against some but not all characteristics of MetS. Table 1 illustrates maternal high-fat diet induces almost all characteristics of MetS in adult offspring at 3–24 weeks of age, such as obesity [54,57,60,62,63], hypertension [57,101,141,142,149,150,161,162,163,164,165,166,167,168,169,170,171,172,173,174,175,176,177,178], dyslipidemia [60,62,63], hepatic steatosis [162,169,173], insulin resistance [161,162,166] and CVD [176]. Hypertension is the most commonly studied phenotype of MetS.

4.2. Probiotics

The major probiotics consist of one or mor strains coming from the genera Lactobacillus spp. and Bifidobacterium spp. [16,17,18]. A recent systematic review reported that probiotics supplementation in patients with MetS improved obesity, hypertension, glucose metabolism and dyslipidemia [179]. In spite of probiotics demonstrating benefits in MetS [179], there was scant evidence with respect to their impact on MetS of developmental origins. Using the perinatal high-fat diet [101] or high-fructose diet [141] rat model, the use of Lactobacillus casei during gestation and lactation periods has shown to benefits on hypertension in adult progeny. Another study showed that maternal multi-strain probiotics supplementation (Bifidobacterium breve, Lactobacillus acidophilus, Lactobacillus casei and Staphylococcus thermophilus) improved glucose and insulin levels in female mice offspring programmed by maternal high-fat diets [161].

4.3. Prebiotics

Dietary fibers, such as inulin or oligosaccharides, are the best-known prebiotics [18]. Inulin supplementation during gestation and lactation has been reported to protect adult rat offspring against hypertension induced by maternal high-fructose or high-fat diet [101,141]. Another study tested the maternal high-fat/sucrose diet model and revealed that modulation of gut microbiota by oligofructose can avert insulin sensitivity, hepatic steatosis and glucose tolerance in adult progeny [162].
In addition to fibers, a large proportion of foods remains unabsorbed and are metabolized by the gut microbiota. These dietary contents, such as garlic and polyphenols, have shown prebiotic-like effects [180,181]. Although there are many prebiotic foods, Table 1 shows that only garlic and resveratrol have shown benefits on protection of MetS in adult offspring. The protective effects of maternal garlic oil treatment against high-fat diet-induced offspring hypertension accompanying by enhanced α-diversity; increased plasma levels of acetate, butyrate and propionate; and augmented abundance of beneficial microbes Bifidobacterium and Lactobacillus [57].

4.4. Resveratrol

Polyphenols are the greatest group of phytochemicals. The use of polyphenols as a reprogramming intervention has been examined in animal models of developmental hypertension [182]. One of the most extensively studied groups of polyphenols is resveratrol [182]. Importantly, resveratrol has been proposed as a reprogramming strategy for preventing MetS programming [183].
Table 1 shows that the use of resveratrol before birth has beneficial effects against adverse offspring outcomes, including obesity [163,166,169,171], hypertension [149,164,165,167,168,170], insulin resistance [166], hepatic steatosis [169] and hyperlipidemia [169,171] in various MetS programming models.
Resveratrol prevented maternal FCDD exposure-induced offspring hypertension was related to alterations of the gut microbiota by enhancing microbes that can inhibit T helper 17 cell (TH17) responses and diminishing the Firmicutes to Bacteroidetes (F/B) ratio [165]. Additionally, perinatal resveratrol therapy prevented adult offspring from maternal CKD-induced hypertension, which was associated with restoration of microbial richness and diversity and an increase in beneficial microbes, Bifidobacterium and Lactobacillus [149].
However, the low bioavailability of resveratrol restricts its clinical translation [184]. On this matter, resveratrol was esterified to resveratrol butyrate esters (RBE), to enhance the efficacy and facilitate broad applications [185]. Our recent study demonstrated that low-dose RBE (30 mg/L) is able to protect against maternal bisphenol A exposure-induced obesity and hyperlipidemia [172] in female progeny and hepatic steatosis in male progeny [173] in a sex-specific manner.
Although some prebiotics have shown benefits in offspring MetS-related disorders, much remains unclear regarding the interplay between gut microbiota and prebiotics and the impact of prebiotic foods as a reprogramming strategy for MetS of developmental origins.

4.5. Postbiotics

SCFAs are the main microbial metabolites and can serve as postbiotics. One previous study reported that acetate supplementation during pregnancy and lactation periods was able to prevent offspring against hypertension programmed by maternal high-fructose diet [142] or maternal minocycline exposure [174]. Another study examined the maternal tryptophan-free diet model and found that modulation of gut microbiota by maternal butyrate supplementation can protect the development of hypertension in adult progeny [175]. Conjugated linoleic acid is a gut microbiota-derived metabolite from dietary polyunsaturated fatty acids. As a postbiotic, maternal conjugated linoleic acid supplementation reversed maternal high-fat diet-induced offspring hypertension [176]. Since postbiotics cover a wide range of bioactive compounds produced by microorganisms, the reprogramming effects of other postbiotics on various characteristics of MetS are awaiting further clarification.

4.6. Others

Another way to manipulate the gut microbiome is to regulate microbial metabolites. For example, microbe-dependent TMA and TMAO formation can be inhibited by a structural analog of choline, 3,3-dimethyl-1-butanol (DMB) [186]. In a maternal high-fructose diet model, maternal DMB treatment protected adult rat offspring against hypertension, which was coincided with the reduction of TMA and TMAO levels [142]. Similarly, the use of DMB in pregnancy and lactation as a reprogramming intervention to prevent offspring hypertension has been proven in a maternal TCDD exposure model [177] and a combined TCDD and high-fructose exposure model [178].

5. Translating Animal Models to Clinical Practice

Animal studies support that early use of certain probiotics, prebiotics or postbiotics may prevent MetS of developmental origins, while this growing body of evidence awaits translating into clinical practice.
In clinical work, the most generally used treatment options to manipulate gut microbiota are probiotics and prebiotics. When discussing the therapeutic benefits of probiotics and prebiotics in clinical practice, special consideration should be paid to their safety. So far, probiotic or prebiotics supplementation during pregnancy are limited in human studies [187]. Limited information that currently exists suggests that probiotic supplementation for pregnant women is mostly safe and may have a beneficial role in gestational diabetes [188], preeclampsia [189], vaginal infections [190], obesity, [191] and spontaneous preterm delivery [192]. However, little reliable information is available about the uses of various prebiotic-like components or prebiotic-rich food, either individually or in combination, in pregnant women [193]. More importantly, currently no information exists regarding their effectiveness in protecting adult disease or long-term safety in offspring.
In the context of safety, postbiotics and parabiotics are safer as compared to probiotics. Unlike definitions were provided by the ISAPP and the Food and Agriculture Organization of the United Nations-WHO (FAO-WHO) for probiotics and prebiotics, currently there remains a lack of a clear definition for postbiotics and parabiotics. Considering the complex nature of postbiotics and parabiotics, there is urgent need to define both terms clearly from a regulatory perspective.
Currently, no information regarding the impact of probiotic or prebiotics supplementation during pregnancy on long-term offspring outcome related to MetS is available in human studies. As review elsewhere [194,195], prior studies investigating the impact of maternal probiotics or prebiotics supplementation on offspring outcome have mainly focused on allergic or metabolic diseases as main outcomes. Nevertheless, the offspring outcome in almost all studies are only determined in neonatal or infantile period.
Recently, several clinical trials were completed in overweight women and women diagnosed with gestational diabetes [191,196,197,198,199]. Mid- or late-pregnancy supplementation with several mixtures of Lactobacillus, Bifidobacterium and Streptococcus species had no impact on anthropometric measures at birth. Nevertheless, their long-term effects on metabolic outcomes are still unknown. Although there are more than 10 ongoing trials working on probiotic or prebiotics supplementation during pregnancy [200], none of them focus primarily on offspring outcome related to MetS and associated disorders. To briefly sum up, maternal prebiotic and probiotic interventions in animals show promising results; however, transferability to the human trial is yet to be confirmed. Accordingly, future work in large prospective trials is required to better identify probiotic species and improve formulation of prebiotics for MetS of developmental origins.

6. Conclusions and Future Perspectives

Previous research has indicated the impact of the gut microbiota in MetS and associated disorders. This review sought to highlight disturbance of gut microbiota during fetal development linking to MetS in later life. Our review also, reflecting current knowledge, opens a new window for preventing MetS of developmental origins via gut microbiota-targeted reprogramming strategies.
No matter recent advances in building appropriate animal models for studying developmental programming of MetS, only few models exhibit the full characteristics of MetS. Even though several gut microbiota-targeted interventions have brought about a significant progress in certain components of MetS in one model, attention should be given to clarify whether their reprogramming effects are also advantageous for other MetS phenotypes. After all this tremendous growth in gut microbiota-targeted interventions and deeper understanding of MetS programming, we expect that microbiota-based reprogramming therapies will be employed in clinics to reduce the global burden of MetS and associated disorders.

Author Contributions

Conceptualization, Y.-H.H., C.-N.H. and Y.-L.T.; data curation, Y.-L.T.; project administration, C.-N.H. and Y.-L.T.; Y.-L.T., funding acquisition; writing—original draft, Y.-H.H., C.-N.H. and Y.-L.T.; writing—review and editing, Y.-H.H., C.-N.H. and Y.-L.T. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by Chang Gung Memorial Hospital, Kaohsiung, Taiwan, grants CORPG8M0151, CORPG8M0081, CMRPG8L1221, CORPG8L0301, CMRPG8L0961, and CMRPG8M0751.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

All data are contained within the article.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Weihe, P.; Weihrauch-Blüher, S. Metabolic Syndrome in Children and Adolescents: Diagnostic Criteria, Therapeutic Options and Perspectives. Curr. Obes. Rep. 2019, 8, 472–479. [Google Scholar] [CrossRef] [PubMed]
  2. Saklayen, M.G. The Global Epidemic of the Metabolic Syndrome. Curr. Hypertens. Rep. 2018, 20, 125. [Google Scholar] [CrossRef]
  3. Zarocostas, J. Need to increase focus on non-communicable diseases in global health, says WHO. Br. Med. J. 2010, 341, c7065. [Google Scholar] [CrossRef]
  4. Armitage, J.A.; Khan, I.Y.; Taylor, P.D.; Nathanielsz, P.W.; Poston, L. Developmental programming of the metabolic syndrome by maternal nutritional imbalance: How strong is the evidence from experimental models in mammals? J. Physiol. 2004, 561, 355–377. [Google Scholar] [CrossRef]
  5. McMillen, I.C.; Robinson, J.S. Developmental origins of the metabolic syndrome: Prediction, plasticity, and programming. Physiol. Rev. 2005, 85, 571–633. [Google Scholar] [CrossRef]
  6. de Gusmão Correia, M.L.; Volpato, A.M.; Águila, M.B.; Mandarim-de-Lacerda, C.A. Developmental origins of health and disease: Experimental and human evidence of fetal programming for metabolic syndrome. J. Hum. Hypertens. 2012, 26, 405–419. [Google Scholar] [CrossRef]
  7. Hsu, C.N.; Hou, C.Y.; Hsu, W.H.; Tain, Y.L. Early-Life Origins of Metabolic Syndrome: Mechanisms and Preventive Aspects. Int. J. Mol. Sci. 2021, 22, 11872. [Google Scholar] [CrossRef]
  8. Haugen, A.C.; Schug, T.T.; Collman, G.; Heindel, J.J. Evolution of DOHaD: The impact of environmental health sciences. J. Dev. Orig. Health Dis. 2015, 6, 55–64. [Google Scholar] [CrossRef]
  9. Tain, Y.L.; Hsu, C.N.; Chan, J.Y. PPARs Link Early Life Nutritional Insults to Later Programmed Hypertension and Metabolic Syndrome. Int. J. Mol. Sci. 2015, 17, 20. [Google Scholar] [CrossRef]
  10. Ma, N.; Hardy, D.B. The Fetal Origins of the Metabolic Syndrome: Can We Intervene? J. Pregnancy 2012, 2012, 482690. [Google Scholar] [CrossRef] [Green Version]
  11. Hsu, C.N.; Hou, C.Y.; Hsu, W.H.; Tain, Y.L. Cardiovascular Diseases of Developmental Origins: Preventive Aspects of Gut Microbiota-Targeted Therapy. Nutrients 2021, 13, 2290. [Google Scholar] [CrossRef] [PubMed]
  12. Picó, C.; Reis, F.; Egas, C.; Mathias, P.; Matafome, P. Lactation as a programming window for metabolic syndrome. Eur. J. Clin. Investig. 2021, 51, e13482. [Google Scholar] [CrossRef] [PubMed]
  13. Dabke, K.; Hendrick, G.; Devkota, S. The gut microbiome and metabolic syndrome. J. Clin. Investig. 2019, 129, 4050–4057. [Google Scholar] [CrossRef]
  14. Vandenplas, Y.; Carnielli, V.P.; Ksiazyk, J.; Luna, M.S.; Migacheva, N.; Mosselmans, J.M.; Picaud, J.C.; Possner, M.; Singhal, A.; Wabitsch, M. Factors affecting early-life intestinal microbiota development. Nutrition 2020, 78, 110812. [Google Scholar] [CrossRef]
  15. Tain, Y.L.; Joles, J.A. Reprogramming: A preventive strategy in hypertension focusing on the kidney. Int. J. Mol. Sci. 2016, 17, 23. [Google Scholar] [CrossRef]
  16. Pandey, K.R.; Naik, S.R.; Vakil, B.V. Probiotics, prebiotics and synbiotics-A review. J. Food Sci. Technol. 2015, 52, 7577–7587. [Google Scholar] [CrossRef]
  17. Thushara, R.M.; Gangadaran, S.; Solati, Z.; Moghadasian, M.H. Cardiovascular benefits of probiotics: A review of experimental and clinical studies. Food Funct. 2016, 7, 632–642. [Google Scholar] [CrossRef]
  18. Barengolts, E. Gut microbiota, prebiotics, probiotics, and synbiotics in management of obesity and prediabetes: Review of randomized controlled trials. Endocr. Pract. 2016, 22, 1224–1234. [Google Scholar] [CrossRef]
  19. Żółkiewicz, J.; Marzec, A.; Ruszczy ´nski, M.; Feleszko, W. Postbiotics-A step beyond pre- and probiotics. Nutrients 2020, 12, 2189. [Google Scholar] [CrossRef]
  20. Lumey, L.H. Reproductive outcomes in women prenatally exposed to undernutrition: A review of findings from the Dutch famine birth cohort. Proc. Nutr. Soc. 1998, 57, 129–135. [Google Scholar] [CrossRef] [Green Version]
  21. Stanner, S.A.; Yudkin, J.S. Fetal programming and the Leningrad Siege study. Twin Res. 2001, 4, 287–292. [Google Scholar] [CrossRef] [PubMed]
  22. Schulz, L.C. The Dutch Hunger Winter and the Developmental Origins of Health and Disease. Proc. Natl. Acad. Sci. USA 2010, 107, 16757–16758. [Google Scholar] [CrossRef]
  23. Hult, M.; Tornhammar, P.; Ueda, P.; Chima, C.; Bonamy, A.K.; Ozumba, B.; Norman, M. Hypertension, diabetes and overweight: Looming legacies of the Biafran famine. PLoS ONE 2010, 5, e13582. [Google Scholar] [CrossRef]
  24. Wang, G.; Chen, Z.; Bartell, T.; Wang, X. Early Life Origins of Metabolic Syndrome: The Role of Environmental Toxicants. Curr. Environ. Health Rep. 2014, 1, 78–89. [Google Scholar] [CrossRef]
  25. Hrudey, E.J.; Reynolds, R.M.; Oostvogels, A.J.; Brouwer, I.A.; Vrijkotte, T.G. The association between maternal 25-hydroxyvitamin D concentration during gestation and early childhood cardio-metabolic outcomes: Is there interaction with pre-pregnancy BMI? PLoS ONE 2015, 10, e0133313. [Google Scholar]
  26. Boney, C.M.; Verma, A.; Tucker, R.; Vohr, B.R. Metabolic syndrome in childhood: Association with birth weight, maternal obesity, and gestational diabetes mellitus. Pediatrics 2005, 115, e290–e296. [Google Scholar] [CrossRef]
  27. Tam, W.H.; Ma, R.C.W.; Ozaki, R.; Li, A.M.; Chan, M.H.M.; Yuen, L.Y.; Lao, T.T.H.; Yang, X.; Ho, C.S.; Tutino, G.E.; et al. In utero exposure to maternal hyperglycemia increases childhood cardiometabolic risk in offspring. Diabetes Care 2017, 40, 679–686. [Google Scholar] [CrossRef]
  28. Fraser, A.; Tilling, K.; Macdonald-Wallis, C.; Sattar, N.; Brion, M.J.; Benfield, L.; Ness, A.; Deanfield, J.; Hingorani, A.; Nelson, S.M.; et al. Association of maternal weight gain in pregnancy with offspring obesity and metabolic and vascular traits in childhood. Circulation 2010, 121, 2557–2564. [Google Scholar] [CrossRef]
  29. Vaag, A.; Poulsen, P. Twins in metabolic and diabetes research: What do they tell us? Curr. Opin. Clin. Nutr. Metab. Care 2007, 10, 591–596. [Google Scholar] [CrossRef]
  30. Bo, S.; Cavallo-Perin, P.; Ciccone, G.; Scaglione, L.; Pagano, G. The metabolic syndrome in twins: A consequence of low birth weight or of being a twin? Exp. Clin. Endocrinol. Diabetes 2001, 109, 135–140. [Google Scholar] [CrossRef]
  31. Kelishadi, R.; Haghdoost, A.A.; Jamshidi, F.; Aliramezany, M.; Moosazadeh, M. Low birthweight or rapid catch-up growth: Which is more associated with cardiovascular disease and its risk factors in later life? A systematic review and cryptanalysis. Paediatr. Int. Child Health 2015, 35, 110–123. [Google Scholar] [CrossRef]
  32. Sheen, J.M.; Yu, H.R.; Tain, Y.L.; Tsai, W.L.; Tiao, M.M.; Lin, I.C.; Tsai, C.C.; Lin, Y.J.; Huang, L.T. Combined maternal and postnatal high-fat diet leads to metabolic syndrome and is effectively reversed by resveratrol: A multiple-organ study. Sci. Rep. 2018, 8, 5607. [Google Scholar] [CrossRef] [PubMed]
  33. Ito, J.; Nakagawa, K.; Kato, S.; Miyazawa, T.; Kimura, F.; Miyazawa, T. The combination of maternal and offspring high-fat diets causes marked oxidative stress and development of metabolic syndrome in mouse offspring. Life Sci. 2016, 151, 70–75. [Google Scholar] [CrossRef] [PubMed]
  34. Rousseau-Ralliard, D.; Richard, C.; Hoarau, P.; Lallemand, M.S.; Morillon, L.; Aubrière, M.C.; Valentino, S.A.; Dahirel, M.; Guinot, M.; Fournier, N.; et al. Prenatal air pollution exposure to diesel exhaust induces cardiometabolic disorders in adulthood in a sex-specific manner. Environ. Res. 2021, 200, 111690. [Google Scholar] [CrossRef]
  35. Pankey, C.L.; Walton, M.W.; Odhiambo, J.F.; Smith, A.M.; Ghnenis, A.B.; Nathanielsz, P.W.; Ford, S.P. Intergenerational impact of maternal overnutrition and obesity throughout pregnancy in sheep on metabolic syndrome in grandsons and granddaughters. Domest. Anim. Endocrinol. 2017, 60, 67–74. [Google Scholar] [CrossRef]
  36. Arentson-Lantz, E.J.; Buhman, K.K.; Ajuwon, K.; Donkin, S.S. Excess pregnancy weight gain leads to early indications of metabolic syndrome in a swine model of fetal programming. Nutr. Res. 2014, 34, 241–249. [Google Scholar] [CrossRef]
  37. Puppala, S.; Li, C.; Glenn, J.P.; Saxena, R.; Gawrieh, S.; Quinn, A.; Palarczyk, J.; Dick, E.J., Jr.; Nathanielsz, P.W.; Cox, L.A. Primate fetal hepatic responses to maternal obesity: Epigenetic signalling pathways and lipid accumulation. J. Physiol. 2018, 596, 5823–5837. [Google Scholar] [CrossRef]
  38. Hsu, C.N.; Tain, Y.L. Animal Models for DOHaD Research: Focus on Hypertension of Developmental Origins. Biomedicines 2021, 9, 623. [Google Scholar] [CrossRef]
  39. Vickers, M.H.; Reddy, S.; Ikenasio, B.A.; Breier, B.H. Dysregulation of the adipoinsular axis—A mechanism for the pathogenesis of hyperleptinemia and adipogenic diabetes induced by fetal programming. J. Endocrinol. 2001, 170, 323–332. [Google Scholar] [CrossRef]
  40. Gardner, D.S.; Tingey, K.; Van Bon, B.W.; Ozanne, S.E.; Wilson, V.; Dandrea, J.; Keisler, D.H.; Stephenson, T.; Symonds, M.E. Programming of glucose-insulin metabolism in adult sheep after maternal undernutrition. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2005, 289, R947–R954. [Google Scholar] [CrossRef]
  41. Remacle, C.; Bieswal, F.; Bol, V.; Reusens, B. Developmental programming of adult obesity and cardiovascular disease in rodents by maternal nutrition imbalance. Am. J. Clin. Nutr. 2011, 94, 1846S–1852S. [Google Scholar]
  42. Gambling, L.; Dunford, S.; Wallace, D.I.; Zuur, G.; Solanky, N.; Srai, K.S.; McArdle, H.J. Iron deficiency during pregnancy affects post-natal blood pressure in the rat. J. Physiol. 2003, 552, 603–610. [Google Scholar] [PubMed]
  43. Tomat, A.; Elesgaray, R.; Zago, V.; Fasoli, H.; Fellet, A.; Balaszczuk, A.M.; Schreier, L.; Costa, M.A.; Arranz, C. Exposure to zinc deficiency in fetal and postnatal life determines nitric oxide system activity and arterial blood pressure levels in adult rats. Br. J. Nutr. 2010, 104, 382–389. [Google Scholar] [PubMed]
  44. Koleganova, N.; Piecha, G.; Ritz, E.; Becker, L.E.; Müller, A.; Weckbach, M.; Nyengaard, J.R.; Schirmacher, P.; Gross-Weissmann, M.L. Both high and low maternal salt intake in pregnancy alter kidney development in the offspring. Am. J. Physiol. Renal Physiol. 2011, 301, F344–F354. [Google Scholar]
  45. Bergel, E.; Belizán, J.M. A deficient maternal calcium intake during pregnancy increases blood pressure of the offspring in adult rats. BJOG 2002, 109, 540–545. [Google Scholar]
  46. Tare, M.; Emmett, S.J.; Coleman, H.A.; Skordilis, C.; Eyles, D.W.; Morley, R.; Parkington, H.C. Vitamin D insufficiency is associated with impaired vascular endothelial and smooth muscle function and hypertension in young rats. J. Physiol. 2011, 589, 4777–4786. [Google Scholar]
  47. Tain, Y.L.; Chan, J.Y.H.; Lee, C.T.; Hsu, C.N. Maternal melatonin therapy attenuates methyl-donor diet-induced programmed hypertension in male adult rat offspring. Nutrients 2018, 10, 1407. [Google Scholar]
  48. Takaya, J.; Yamanouchi, S.; Kino, J.; Tanabe, Y.; Kaneko, K. A Calcium-Deficient Diet in Dams during Gestation Increases Insulin Resistance in Male Offspring. Nutrients 2018, 10, 1745. [Google Scholar]
  49. Zhang, H.; Chu, X.; Huang, Y.; Li, G.; Wang, Y.; Li, Y.; Sun, C. Maternal vitamin D deficiency during pregnancy results in insulin resistance in rat offspring, which is associated with inflammation and Iκbα methylation. Diabetologia 2014, 57, 2165–2172. [Google Scholar]
  50. Lewis, R.M.; Petry, C.J.; Ozanne, S.E.; Hales, C.N. Effects of maternal iron restriction in the rat on blood pressure, glucose tolerance, and serum lipids in the 3-month-old offspring. Metabolism 2001, 50, 562–567. [Google Scholar]
  51. Kumar, K.A.; Lalitha, A.; Pavithra, D.; Padmavathi, I.J.; Ganeshan, M.; Rao, K.R.; Venu, L.; Balakrishna, N.; Shanker, N.H.; Reddy, S.U.; et al. Maternal dietary folate and/or vitamin B12 restrictions alter body composition (adiposity) and lipid metabolism in Wistar rat offspring. J. Nutr. Biochem. 2013, 24, 25–31. [Google Scholar] [PubMed]
  52. Tain, Y.L.; Lee, W.C.; Leu, S.; Wu, K.; Chan, J. High salt exacerbates programmed hypertension in maternal fructose-fed male offspring. Nutr. Metab. Cardiovasc. Dis. 2015, 25, 1146–1151. [Google Scholar]
  53. Yamada-Obara, N.; Yamagishi, S.I.; Taguchi, K.; Kaida, Y.; Yokoro, M.; Nakayama, Y.; Ando, R.; Asanuma, K.; Matsui, T.; Ueda, S.; et al. Maternal exposure to high-fat and high-fructose diet evokes hypoadiponectinemia and kidney injury in rat offspring. Clin. Exp. Nephrol. 2016, 20, 853–886. [Google Scholar]
  54. Tain, Y.L.; Wu, K.L.H.; Lee, W.C.; Leu, S.; Chan, J.Y.H. Prenatal Metformin Therapy Attenuates Hypertension of Developmental Origin in Male Adult Offspring Exposed to Maternal High-Fructose and Post-Weaning High-Fat Diets. Int. J. Mol. Sci. 2018, 19, 1066. [Google Scholar]
  55. Buettner, R.; Schölmerich, J.; Bollheimer, L.C. High-fat diets: Modeling the metabolic disorders of human obesity in rodents. Obesity 2007, 15, 798–808. [Google Scholar]
  56. Williams, L.; Seki, Y.; Vuguin, P.M.; Charron, M.J. Animal models of in utero exposure to a high fat diet: A review. Biochim. Biophys. Acta 2014, 1842, 507–519. [Google Scholar]
  57. Hsu, C.N.; Hou, C.Y.; Chang-Chien, G.P.; Lin, S.; Tain, Y.L. Maternal Garlic Oil Supplementation Prevents High-Fat Diet-Induced Hypertension in Adult Rat Offspring: Implications of H2S-Generating Pathway in the Gut and Kidneys. Mol. Nutr. Food Res. 2021, 65, e2001116. [Google Scholar]
  58. Tsai, T.A.; Tsai, C.K.; Huang, L.T.; Sheen, J.M.; Tiao, M.M.; Tain, Y.L.; Chen, C.C.; Lin, I.C.; Lai, Y.J.; Tsai, C.C.; et al. Maternal Resveratrol Treatment Re-Programs and Maternal High-Fat Diet-Induced Retroperitoneal Adiposity in Male Offspring. Int. J. Environ. Res. Public Health 2020, 17, 2780. [Google Scholar]
  59. Wu, Z.; Zhao, J.; Xu, H.; Lyv, Y.; Feng, X.; Fang, Y.; Xu, Y. Maternal quercetin administration during gestation and lactation decrease endoplasmic reticulum stress and related inflammation in the adult offspring of obese female rats. Eur. J. Nutr. 2014, 53, 1669–1683. [Google Scholar]
  60. Havel, P.J. Dietary fructose: Implications for dysregulation of energy homeostasis and lipid/carbohydrate metabolism. Nutr. Rev. 2005, 63, 133–157. [Google Scholar]
  61. Chao, Y.M.; Tain, Y.L.; Leu, S.; Wu, K.L.; Lee, W.C.; Chan, J.Y. Developmental programming of the metabolic syndrome: Next-generation sequencing analysis of transcriptome expression in a rat model of maternal high fructose intake. Sheng Li Xue Bao 2016, 68, 557–567. [Google Scholar]
  62. Saad, A.F.; Dickerson, J.; Kechichian, T.B.; Yin, H.; Gamble, P.; Salazar, A.; Patrikeev, I.; Motamedi, M.; Saade, G.R.; Costantine, M.M. High-fructose diet in pregnancy leads to fetal programming of hypertension, insulin resistance, and obesity in adult offspring. Am. J. Obstet. Gynecol. 2016, 215, e1–e6. [Google Scholar] [CrossRef]
  63. Lee, W.C.; Wu, K.L.H.; Leu, S.; Tain, Y.L. Translational insights on developmental origins of metabolic syndrome: Focus on fructose consumption. Biomed. J. 2018, 41, 96–101. [Google Scholar] [CrossRef]
  64. Sharma, D.; Sharma, P.; Shastri, S. Genetic, metabolic and endocrine aspect of intrauterine growth restriction: An update. J. Matern. Fetal Neonatal Med. 2017, 30, 2263–2275. [Google Scholar] [CrossRef]
  65. Wlodek, M.E.; Westcott, K.; Siebel, A.L.; Owens, J.A.; Moritz, K.M. Growth restriction before or after birth reduces nephron number and increases blood pressure in male rats. Kidney Int. 2008, 74, 187–195. [Google Scholar] [CrossRef]
  66. Nüsken, K.D.; Dötsch, J.; Rauh, M.; Rascher, W.; Schneider, H. Uteroplacental insufficiency after bilateral uterine artery ligation in the rat: Impact on postnatal glucose and lipid metabolism and evidence for metabolic programming of the offspring by sham operation. Endocrinology 2008, 149, 1056–1063. [Google Scholar] [CrossRef]
  67. Zuchowski, Y.; Dalmasso, C.; Shawky, N.M.; Reckelhoff, J.F. Cardiometabolic consequences of maternal hyperandrogenemia in male offspring. Physiol. Rep. 2021, 9, e14941. [Google Scholar] [CrossRef]
  68. Sherman, S.B.; Sarsour, N.; Salehi, M.; Schroering, A.; Mell, B.; Joe, B.; Hill, J.W. Prenatal androgen exposure causes hypertension and gut microbiota dysbiosis. Gut Microbes 2018, 9, 400–421. [Google Scholar] [CrossRef]
  69. Iqbal, W.; Ciriello, J. Effect of maternal chronic intermittent hypoxia during gestation on offspring growth in the rat. Am. J. Obstet. Gynecol. 2013, 209, 564.e1–564.e9. [Google Scholar] [CrossRef]
  70. Wang, J.; Yin, N.; Deng, Y.; Wei, Y.; Huang, Y.; Pu, X.; Li, L.; Zheng, Y.; Guo, J.; Yu, J.; et al. Ascorbic Acid Protects against Hypertension through Downregulation of ACE1 Gene Expression Mediated by Histone Deacetylation in Prenatal Inflammation-Induced Offspring. Sci. Rep. 2016, 6, 39469. [Google Scholar] [CrossRef]
  71. Tsosura, T.V.S.; Chiba, F.Y.; Mattera, M.S.L.C.; Pereira, R.F.; Cintra, L.T.A.; Conti, L.C.; Santos, R.M.D.; Mateus, J.H.P.; Garbin, C.A.S.; Sumida, D.H. Maternal apical periodontitis is associated with insulin resistance in adult offspring. Int. Endod. J. 2019, 52, 1040–1050. [Google Scholar] [CrossRef]
  72. Tain, Y.L.; Lee, W.C.; Hsu, C.N.; Lee, W.C.; Huang, L.T.; Lee, C.T.; Lin, C.Y. Asymmetric dimethylarginine is associated with developmental programming of adult kidney disease and hypertension in offspring of streptozotocin-treated mothers. PLoS ONE 2013, 8, e55420. [Google Scholar] [CrossRef]
  73. Oliveira, A.C.; Andreotti, S.; Chimin, P.; Sertié, R.A.; Farias Tda, S.; Torres-Leal, F.L.; de Proença, A.R.; Campaña, A.B.; D’Avila, L.S.; Oliveira, K.A.; et al. Neonatal streptozotocin-induced diabetes in mothers promotes metabolic programming of adipose tissue in male rat offspring. Life Sci. 2015, 136, 151–156. [Google Scholar] [CrossRef]
  74. Thaeomor, A.; Teangphuck, P.; Chaisakul, J.; Seanthaweesuk, S.; Somparn, N.; Roysommuti, S. Perinatal Taurine Supplementation Prevents Metabolic and Cardiovascular Effects of Maternal Diabetes in Adult Rat Offspring. Adv. Exp. Med. Biol. 2017, 975, 295–305. [Google Scholar] [PubMed]
  75. Tain, Y.L.; Lin, Y.J.; Chan, J.Y.H.; Lee, C.T.; Hsu, C.N. Maternal melatonin or agomelatine therapy prevents programmed hypertension in male offspring of mother exposed to continuous light. Biol. Reprod. 2017, 97, 636–643. [Google Scholar] [CrossRef] [PubMed]
  76. Ferreira, D.S.; Amaral, F.G.; Mesquita, C.C.; Barbosa, A.P.; Lellis-Santos, C.; Turati, A.O.; Santos, L.R.; Sollon, C.S.; Gomes, P.R.; Faria, J.A.; et al. Maternal melatonin programs the daily pattern of energy metabolism in adult offspring. PLoS ONE 2012, 7, e38795. [Google Scholar] [CrossRef]
  77. Lian, Y.; Yuan, Q.; Wang, G.; Tang, F. Association between sleep quality and metabolic syndrome: A systematic review and meta-analysis. Psychiatry Res. 2019, 274, 66–74. [Google Scholar] [CrossRef]
  78. Hsu, C.N.; Tain, Y.L. Adverse Impact of Environmental Chemicals on Developmental Origins of Kidney Disease and Hypertension. Front. Endocrinol. 2021, 12, 745716. [Google Scholar] [CrossRef]
  79. Rajagopal, G.; Bhaskaran, R.S.; Karundevi, B. Maternal di-(2-ethylhexyl) phthalate exposure alters hepatic insulin signal transduction and glucoregulatory events in rat F1 male offspring. J. Appl. Toxicol. 2019, 39, 751–763. [Google Scholar] [CrossRef]
  80. Galyon, K.D.; Farshidi, F.; Han, G.; Ross, M.G.; Desai, M.; Jellyman, J.K. Maternal bisphenol A exposure alters rat offspring hepatic and skeletal muscle insulin signaling protein abundance. Am. J. Obstet. Gynecol. 2017, 216, 290.e1–290.e9. [Google Scholar] [CrossRef]
  81. Gray, S.P.; Denton, K.M.; Cullen-McEwen, L.; Bertram, J.F.; Moritz, K.M. Prenatal exposure to alcohol reduces nephron number and raises blood pressure in progeny. J. Am. Soc. Nephrol. 2010, 21, 1891–1902. [Google Scholar]
  82. Xiao, D.; Huang, X.; Li, Y.; Dasgupta, C.; Wang, L.; Zhang, L. Antenatal Antioxidant Prevents Nicotine-Mediated Hypertensive Response in Rat Adult Offspring. Biol. Reprod. 2015, 93, 66. [Google Scholar]
  83. Nguyen, T.M.T.; Steane, S.E.; Moritz, K.M.; Akison, L.K. Prenatal alcohol exposure programmes offspring disease: Insulin resistance in adult males in a rat model of acute exposure. J. Physiol. 2019, 597, 5619–5637. [Google Scholar]
  84. Holloway, A.C.; Lim, G.E.; Petrik, J.J.; Foster, W.G.; Morrison, K.M.; Gerstein, H.C. Fetal and neonatal exposure to nicotine in Wistar rats results in increased beta cell apoptosis at birth and postnatal endocrine and metabolic changes associated with type 2 diabetes. Diabetologia 2005, 48, 2661–2666. [Google Scholar]
  85. Tain, Y.L.; Sheen, J.M.; Chen, C.C.; Yu, H.R.; Tiao, M.M.; Kuo, H.C.; Huang, L.T. Maternal citrulline supplementation prevents prenatal dexamethasone-induced programmed hypertension. Free Radic. Res. 2014, 48, 580–586. [Google Scholar]
  86. Slabiak-Blaz, N.; Adamczak, M.; Gut, N.; Grajoszek, A.; Nyengaard, J.R.; Ritz, E.; Wiecek, A. Administration of cyclosporine a in pregnant rats—The effect on blood pressure and on the glomerular number in their offspring. Kidney Blood Press. Res. 2015, 40, 413–423. [Google Scholar]
  87. Hsu, C.N.; Chan, J.Y.H.; Wu, K.L.H.; Yu, H.R.; Lee, W.C.; Hou, C.Y.; Tain, Y.L. Altered Gut Microbiota and Its Metabolites in Hypertension of Developmental Origins: Exploring Differences between Fructose and Antibiotics Exposure. Int. J. Mol. Sci. 2021, 22, 2674. [Google Scholar]
  88. Chang, H.Y.; Tain, Y.L. Postnatal dexamethasone-induced programmed hypertension is related to the regulation of melatonin and its receptors. Steroids 2016, 108, 1–6. [Google Scholar]
  89. Cottrell, E.C.; Seckl, J.R. Prenatal stress, glucocorticoids and the programming of adult disease. Front. Behav. Neurosci. 2009, 3, 19. [Google Scholar]
  90. Pascale, A.; Marchesi, N.; Marelli, C.; Coppola, A.; Luzi, L.; Govoni, S.; Giustina, A.; Gazzaruso, C. Microbiota and metabolic diseases. Endocrine 2018, 61, 357–371. [Google Scholar]
  91. Tain, Y.L.; Hsu, C.N. Interplay between Oxidative Stress and Nutrient Sensing Signaling in the Developmental Origins of Cardiovascular Disease. Int. J. Mol. Sci. 2017, 18, 841. [Google Scholar]
  92. Croci, S.; D’Apolito, L.I.; Gasperi, V.; Catani, M.V.; Savini, I. Dietary Strategies for Management of Metabolic Syndrome: Role of Gut Microbiota Metabolites. Nutrients 2021, 13, 1389. [Google Scholar] [PubMed]
  93. Milani, C.; Duranti, S.; Bottacini, F.; Casey, E.; Turroni, F.; Mahony, J.; Belzer, C.; Delgado Palacio, S.; Arboleya Montes, S.; Mancabelli, L.; et al. The First Microbial Colonizers of the Human Gut: Composition, Activities, and Health Implications of the Infant Gut Microbiota. Microbiol. Mol. Biol. Rev. 2017, 81, e00036-17. [Google Scholar]
  94. Matamoros, S.; Gras-Leguen, C.; Le Vacon, F.; Potel, G.; De La Cochetiere, M.-F. Development of intestinal microbiota in infants and its impact on health. Trends Microbiol. 2013, 21, 167–173. [Google Scholar] [PubMed]
  95. Arrieta, M.C.; Stiemsma, L.T.; Amenyogbe, N.; Brown, E.M.; Finlay, B. The intestinal microbiome in early life: Health and disease. Front. Immunol. 2014, 5, 427. [Google Scholar] [PubMed]
  96. Mischke, M.; Plösch, T. More than just a gut instinct–the potential interplay between a baby’s nutrition, its gut microbiome, and the epigenome. Am. J. Physiol. Integr. Comp. Physiol. 2013, 304, R1065–R1069. [Google Scholar]
  97. Zhou, L.; Xiao, X. The role of gut microbiota in the effects of maternal obesity during pregnancy on offspring metabolism. Biosci. Rep. 2018, 38, BSR20171234. [Google Scholar]
  98. Mehta, S.H.; Kruger, M.; Sokol, R.J. Is maternal diabetes a risk factor for childhood obesity? J. Matern. Neonatal Med. 2012, 25, 41–44. [Google Scholar]
  99. Unger, S.; Stintzi, A.; Shah, P.; Mack, D.; O’Connor, D.L. Gut microbiota of the very- low-birth-weight infant. Pediatr. Res. 2015, 77, 205–213. [Google Scholar]
  100. Groer, M.; Luciano, A.A.; Dishaw, L.J.; Ashmeade, T.L.; Miller, E.M.; Gilbert, J.A. Development of the preterm infant gut microbiome: A research priority. Microbiome 2014, 2, 38. [Google Scholar]
  101. Hsu, C.N.; Hou, C.Y.; Chan, J.Y.H.; Lee, C.T.; Tain, Y.L. Hypertension Programmed by Perinatal High-Fat Diet: Effect of Maternal Gut Microbiota-Targeted Therapy. Nutrients 2019, 11, 2908. [Google Scholar] [CrossRef]
  102. Wankhade, U.D.; Zhong, Y.; Kang, P.; Alfaro, M.; Chintapalli, S.V.; Thakali, K.M.; Shankar, K. Enhanced offspring predisposition to steatohepatitis with maternal high-fat diet is associated with epigenetic and microbiome alterations. PLoS ONE 2017, 12, e0175675. [Google Scholar]
  103. De Oliveira, Y.; Cavalcante, R.G.S.; Cavalcanti Neto, M.P.; Magnani, M.; Braga, V.A.; de Souza, E.L.; de Brito Alves, J.L. Oral administration of Lactobacillus fermentum post-weaning improves the lipid profile and autonomic dysfunction in rat offspring exposed to maternal dyslipidemia. Food Funct. 2020, 11, 5581–5594. [Google Scholar] [CrossRef] [PubMed]
  104. Guimarães, K.S.L.; Braga, V.A.; Noronha, S.I.S.R.; Costa, W.K.A.D.; Makki, K.; Cruz, J.C.; Brandão, L.R.; Chianca Junior, D.A.; Meugnier, E.; Leulier, F.; et al. Lactiplantibacillus plantarum WJL administration during pregnancy and lactation improves lipid profile, insulin sensitivity and gut microbiota diversity in dyslipidemic dams and protects male offspring against cardiovascular dysfunction in later life. Food Funct. 2020, 11, 8939–8950. [Google Scholar] [CrossRef] [PubMed]
  105. Wang, Z.; Zhao, Y. Gut microbiota derived metabolites in cardiovascular health and disease. Protein Cell 2018, 9, 416–431. [Google Scholar] [CrossRef] [PubMed]
  106. Joe, B.; McCarthy, C.G.; Edwards, J.M.; Cheng, X.; Chakraborty, S.; Yang, T.; Golonka, R.M.; Mell, B.; Yeo, J.Y.; Bearss, N.R.; et al. Microbiota Introduced to Germ-Free Rats Restores Vascular Contractility and Blood Pressure. Hypertension 2020, 76, 1847–1855. [Google Scholar] [CrossRef]
  107. Wilck, N.; Matus, M.G.; Kearney, S.M.; Olesen, S.W.; Forslund, K.; Bartolomaeus, H.; Haase, S.; Mähler, A.; Balogh, A.; Markó, L.; et al. Salt-responsive gut commensal modulates TH17 axis and disease. Nature 2017, 551, 585–589. [Google Scholar] [CrossRef]
  108. Robles-Vera, I.; de la Visitación, N.; Toral, M.; Sánchez, M.; Romero, M.; Gómez-Guzmán, M.; Yang, T.; Izquierdo-García, J.L.; Guerra-Hernández, E.; Ruiz-Cabello, J.; et al. Probiotic Bifidobacterium breve prevents DOCA-salt hypertension. FASEB J. 2020, 34, 13626–13640. [Google Scholar] [CrossRef]
  109. Marques, F.Z.; Nelson, E.; Chu, P.Y.; Horlock, D.; Fiedler, A.; Ziemann, M.; Tan, J.K.; Kuruppu, S.; Rajapakse, N.W.; El-Osta, A.; et al. High-fiber diet and acetate supplementation change the gut microbiota and prevent the development of hypertension and heart failure in hypertensive mice. Circulation 2017, 135, 964–977. [Google Scholar] [CrossRef] [PubMed]
  110. Pluznick, J.L. Microbial short-chain fatty acids and blood pressure regulation. Curr. Hypertens. Rep. 2017, 19, 25. [Google Scholar] [CrossRef]
  111. Canfora, E.E.; Jocken, J.W.; Blaak, E.E. Short-chain fatty acids in control of body weight and insulin sensitivity. Nat. Rev. Endocrinol. 2015, 11, 577–591. [Google Scholar]
  112. Velasquez, M.T.; Ramezani, A.; Manal, A.; Raj, D.S. Trimethylamine N-Oxide: The good, the bad and the unknown. Toxins 2016, 8, 326. [Google Scholar] [CrossRef]
  113. Schiattarella, G.G.; Sannino, A.; Toscano, E.; Giugliano, G.; Gargiulo, G.; Franzone, A.; Trimarco, B.; Esposito, G.; Perrino, C. Gut microbe-generated metabolite trimethylamine-N-oxide as cardiovascular risk biomarker: A systematic review and doseresponse meta-analysis. Eur. Heart J. 2017, 38, 2948–2956. [Google Scholar] [CrossRef]
  114. Jaworska, K.; Hering, D.; Mosieniak, G.; Bielak-Zmijewska, A.; Pilz, M.; Konwerski, M.; Gasecka, A.; Kapłon-Cie´slicka, A.; Filipiak, K.; Sikora, E.; et al. TMA, A Forgotten Uremic Toxin, but Not TMAO, Is Involved in Cardiovascular Pathology. Toxins 2019, 11, 490. [Google Scholar] [CrossRef]
  115. Hsu, C.N.; Hou, C.Y.; Lee, C.T.; Chan, J.Y.H.; Tain, Y.L. The Interplay between Maternal and Post-Weaning High-Fat Diet and Gut Microbiota in the Developmental Programming of Hypertension. Nutrients 2019, 11, 1982. [Google Scholar] [CrossRef] [PubMed]
  116. Hsu, C.N.; Tain, Y.L. Developmental programming and reprogramming of hypertension and kidney disease: Impact of tryptophan metabolism. Int. J. Mol. Sci. 2020, 21, 8705. [Google Scholar] [CrossRef]
  117. Agus, A.; Planchais, J.; Sokol, H. Gut Microbiota Regulation of Tryptophan Metabolism in Health and Disease. Cell Host Microbe 2018, 23, 716–724. [Google Scholar] [CrossRef]
  118. Natividad, J.M.; Agus, A.; Planchais, J.; Lamas, B.; Jarry, A.C.; Martin, R.; Michel, M.L.; Chong-Nguyen, C.; Roussel, R.; Straube, M.; et al. Impaired Aryl Hydrocarbon Receptor Ligand Production by the Gut Microbiota Is a Key Factor in Metabolic Syndrome. Cell Metab. 2018, 28, 737–749.e4. [Google Scholar] [CrossRef] [Green Version]
  119. Jia, X.; Xu, W.; Zhang, L.; Li, X.; Wang, R.; Wu, S. Impact of Gut Microbiota and Microbiota-Related Metabolites on Hyperlipidemia. Front. Cell Infect. Microbiol. 2021, 11, 634780. [Google Scholar] [CrossRef]
  120. Pujo, J.; Petitfils, C.; Le Faouder, P.; Eeckhaut, V.; Payros, G.; Maurel, S.; Perez-Berezo, T.; Van Hul, M.; Barreau, F.; Blanpied, C.; et al. Bacteria-derived long chain fatty acid exhibits anti-inflammatory properties in colitis. Gut 2021, 70, 1088–1097. [Google Scholar] [CrossRef]
  121. Gao, Z.; Daquinag, A.C.; Yu, Y.; Kolonin, M.G. Endothelial Prohibitin Mediates Bidirectional Long-Chain Fatty Acid Transport in White and Brown Adipose Tissues. Diabetes 2022, 71, 1400–1409. [Google Scholar] [CrossRef] [PubMed]
  122. Quan, L.H.; Zhang, C.; Dong, M.; Jiang, J.; Xu, H.; Yan, C.; Liu, X.; Zhou, H.; Zhang, H.; Chen, L.; et al. Myristoleic acid produced by enterococci reduces obesity through brown adipose tissue activation. Gut 2020, 69, 1239–1247. [Google Scholar] [CrossRef]
  123. Buckley, J.D.; Howe, P.R. Long-chain omega-3 polyunsaturated fatty acids may be beneficial for reducing obesity-a review. Nutrients 2010, 2, 1212–1230. [Google Scholar] [CrossRef]
  124. Duan, R.; Guan, X.; Huang, K.; Zhang, Y.; Li, S.; Xia, J.; Shen, M. Flavonoids from Whole-Grain Oat Alleviated High-Fat Diet-Induced Hyperlipidemia via Regulating Bile Acid Metabolism and Gut Microbiota in Mice. J. Agric. Food Chem. 2021, 69, 7629–7640. [Google Scholar] [CrossRef]
  125. Putnam, K.; Shoemaker, R.; Yiannikouris, F.; Cassis, L.A. The renin-angiotensin system: A target of and contributor to dyslipidemias, altered glucose homeostasis, and hypertension of the metabolic syndrome. Am. J. Physiol. Heart Circ. Physiol. 2012, 302, H1219–H1230. [Google Scholar] [CrossRef]
  126. Hsu, C.N.; Tain, Y.L. Targeting the Renin-Angiotensin-Aldosterone System to Prevent Hypertension and Kidney Disease of Developmental Origins. Int. J. Mol. Sci. 2021, 22, 2298. [Google Scholar] [CrossRef]
  127. Jaworska, K.; Koper, M.; Ufnal, M. Gut microbiota and renin-angiotensin system: A complex interplay at local and systemic levels. Am. J. Physiol. Liver Physiol. 2021, 321, G355–G366. [Google Scholar] [CrossRef]
  128. Oliveira Andrade, J.M.; de Farias Lelis, D.; Mafra, V.; Cota, J. The angiotensin converting enzyme 2 (ACE2), gut microbiota, and cardiovascular health. Protein Pept. Lett. 2017, 24, 827–832. [Google Scholar] [CrossRef]
  129. Bessa, A.S.M.; Jesus, É.F.; Nunes, A.D.C.; Pontes, C.N.R.; Lacerda, I.S.; Costa, J.M.; Souza, E.J.; Lino-Júnior, R.S.; Biancardi, M.F.; Dos Santos, F.C.A.; et al. Stimulation of the ACE2/Ang-(1-7)/Mas axis in hypertensive pregnant rats attenuates cardiovascular dysfunction in adult male offspring. Hypertens. Res. 2019, 42, 1883–1893. [Google Scholar] [CrossRef]
  130. Rubak, Y.T.; Nuraida, L.; Iswantini, D.; Prangdimurti, E. Angiotensin-I-converting enzyme inhibitory peptides in milk fermented by indigenous lactic acid bacteria. Vet. World 2020, 13, 345–353. [Google Scholar] [CrossRef] [PubMed]
  131. Kawabe, Y.; Mori, J.; Morimoto, H.; Yamaguchi, M.; Miyagaki, S.; Ota, T.; Tsuma, Y.; Fukuhara, S.; Nakajima, H.; Oudit, G.Y.; et al. ACE2 exerts anti-obesity effect via stimulating brown adipose tissue and induction of browning in white adipose tissue. Am. J. Physiol. Endocrinol. Metab. 2019, 317, E1140–E1149. [Google Scholar] [CrossRef] [PubMed]
  132. Bruce, E.B.; Sakarya, Y.; Kirichenko, N.; Toklu, H.Z.; Sumners, C.; Morgan, D.; Tümer, N.; Scarpace, P.J.; Carter, C.S. ACE2 activator diminazene aceturate reduces adiposity but preserves lean mass in young and old rats. Exp. Gerontol. 2018, 111, 133–140. [Google Scholar] [CrossRef] [PubMed]
  133. Cao, X.; Shi, T.T.; Zhang, C.H.; Jin, W.Z.; Song, L.N.; Zhang, Y.C.; Liu, J.Y.; Yang, F.Y.; Rotimi, C.N.; Xu, A.; et al. ACE2 pathway regulates thermogenesis and energy metabolism. eLife 2022, 11, e72266. [Google Scholar] [CrossRef] [PubMed]
  134. Hsu, C.N.; Yang, H.W.; Hou, C.Y.; Chang-Chien, G.P.; Lin, S.; Tain, Y.L. Maternal Adenine-Induced Chronic Kidney Disease Programs Hypertension in Adult Male Rat Offspring: Implications of Nitric Oxide and Gut Microbiome Derived Metabolites. Int. J. Mol. Sci. 2020, 21, 7237. [Google Scholar] [CrossRef]
  135. Hsu, C.N.; Yu, H.R.; Chan, J.Y.H.; Wu, K.L.H.; Lee, W.C.; Tain, Y.L. The Impact of Gut Microbiome on Maternal Fructose Intake-Induced Developmental Programming of Adult Disease. Nutrients 2022, 14, 1031. [Google Scholar] [CrossRef]
  136. Tain, Y.L.; Lee, W.C.; Wu, K.L.H.; Leu, S.; Chan, J.Y.H. Resveratrol Prevents the Development of Hypertension Programmed by Maternal Plus Post-Weaning High-Fructose Consumption Through Modulation of Oxidative Stress, Nutrient-Sensing Signals, and Gut Microbiota. Mol. Nutr. Food Res. 2018, 62, e1800066. [Google Scholar] [CrossRef]
  137. Campbell, E.L.; Colgan, S.P. Control and dysregulation of redox signalling in the gastrointestinal tract. Nat. Rev. Gastroenterol. Hepatol. 2019, 16, 106–120. [Google Scholar] [CrossRef]
  138. Ching, R.H.H.; Yeung, L.O.Y.; Tse, I.M.Y.; Sit, W.-H.; Li, E.T.S. Supplementation of Bitter Melon to Rats Fed a High-Fructose Diet During Gestation and Lactation Ameliorates Fructose-Induced Dyslipidemia and Hepatic Oxidative Stress in Male Offspring. J. Nutr. 2011, 141, 1664–1672. [Google Scholar] [CrossRef] [Green Version]
  139. Rodríguez, L.; Otero, P.; Panadero, M.I.; Rodrigo, S.; Álvarez-Millán, J.J.; Bocos, C. Maternal Fructose Intake Induces Insulin Resistance and Oxidative Stress in Male, but Not Female, Offspring. J. Nutr. Metab. 2015, 2015, 158091. [Google Scholar] [CrossRef]
  140. Tain, Y.-L.; Wu, K.L.; Lee, W.-C.; Leu, S.; Chan, J.Y. Maternal fructose-intake-induced renal programming in adult male offspring. J. Nutr. Biochem. 2015, 26, 642–650. [Google Scholar] [CrossRef]
  141. Hsu, C.N.; Lin, Y.J.; Hou, C.Y.; Tain, Y.L. Maternal administration of probiotic or prebiotic prevents male adult rat offspring against developmental programming of hypertension induced by high fructose consumption in pregnancy and lactation. Nutrients 2018, 10, 1229. [Google Scholar]
  142. Hsu, C.N.; Chang-Chien, G.P.; Lin, S.; Hou, C.Y.; Tain, Y.L. Targeting on gut microbial metabolite trimethylamine-N-Oxide and short-chain fatty acid to prevent maternal high-fructose-diet-induced developmental programming of hypertension in adult male offspring. Mol. Nutr. Food Res. 2019, 63, e1900073. [Google Scholar] [CrossRef]
  143. Litvinova, L.; Atochin, D.N.; Fattakhov, N.; Vasilenko, M.; Zatolokin, P.; Kirienkova, E. Nitric oxide and mitochondria in metabolic syndrome. Front. Physiol. 2015, 6, 20. [Google Scholar]
  144. Huang, L.T.; Hsieh, C.S.; Chang, K.A.; Tain, Y.L. Roles of nitric oxide and asymmetric dimethylarginine in pregnancy and fetal programming. Int. J. Mol. Sci. 2012, 13, 14606–14622. [Google Scholar]
  145. Tain, Y.L.; Hsu, C.N. Toxic Dimethylarginines: Asymmetric Dimethylarginine (ADMA) and Symmetric Dimethylarginine (SDMA). Toxins 2017, 9, 92. [Google Scholar] [CrossRef]
  146. Jones, A.M.; Vanhatalo, A.; Seals, D.R.; Rossman, M.J.; Piknova, B.; Jonvik, K.L. Dietary Nitrate and Nitric Oxide Metabolism: Mouth, Circulation, Skeletal Muscle, and Exercise Performance. Med. Sci. Sports Exerc. 2021, 53, 280–294. [Google Scholar]
  147. Kulkarni, S.S.; Cantó, C. The molecular targets of resveratrol. Biochim. Biophys. Acta 2015, 1852, 1114–1123. [Google Scholar]
  148. Hsu, C.N.; Tain, Y.L. Preventive Aspects of Early Resveratrol Supplementation in Cardiovascular and Kidney Disease of Developmental Origins. Int. J. Mol. Sci. 2021, 22, 4210. [Google Scholar] [CrossRef]
  149. Hsu, C.N.; Hou, C.Y.; Chang-Chien, G.P.; Lin, S.; Yang, H.W.; Tain, Y.L. Perinatal Resveratrol Therapy Prevents Hypertension Programmed by Maternal Chronic Kidney Disease in Adult Male Offspring: Implications of the Gut Microbiome and Their Metabolites. Biomedicines 2020, 8, 567. [Google Scholar] [CrossRef]
  150. Chen, H.E.; Lin, Y.J.; Lin, I.C.; Yu, H.R.; Sheen, J.M.; Tsai, C.C.; Huang, L.T.; Tain, Y.L. Resveratrol prevents combined prenatal NG-nitro-L-arginine-methyl ester (L-NAME) treatment plus postnatal high-fat diet induced programmed hypertension in adult rat offspring: Interplay between nutrient-sensing signals, oxidative stress and gut microbiota. J. Nutr. Biochem. 2019, 70, 28–37. [Google Scholar] [CrossRef]
  151. Efeyan, A.; Comb, W.C.; Sabatini, D.M. Nutrient-sensing mechanisms and pathways. Nature 2015, 517, 302–310. [Google Scholar] [CrossRef] [PubMed]
  152. Jansson, T.; Powell, T.L. Role of placental nutrient sensing in developmental programming. Clin. Obstet. Gynecol. 2013, 56, 591–601. [Google Scholar] [PubMed]
  153. Romaní-Pérez, M.; Bullich-Vilarrubias, C.; López-Almela, I.; Liébana-García, R.; Olivares, M.; Sanz, Y. The Microbiota and the Gut-Brain Axis in Controlling Food Intake and Energy Homeostasis. Int. J. Mol. Sci. 2021, 22, 5830. [Google Scholar] [CrossRef]
  154. Tain, Y.L.; Hsu, C.N. AMP-Activated protein kinase as a reprogramming strategy for hypertension and kidney disease of developmental origin. Int. J. Mol. Sci. 2018, 19, 1744. [Google Scholar] [CrossRef] [PubMed]
  155. Hsu, C.N.; Tain, Y.L. Preventing developmental origins of cardiovascular disease: Hydrogen sulfide as a potential target? Antioxidants 2021, 10, 247. [Google Scholar] [CrossRef]
  156. Robledinos-Antón, N.; Fernández-Ginés, R.; Manda, G.; Cuadrado, A. Activators and inhibitors of NRF2: A review of their potential for clinical development. Oxid. Med. Cell. Longev. 2019, 2019, 9372182. [Google Scholar]
  157. Food and Agriculture Organization of the United Nations/World Health Organization (FAO/WHO). Guidelines for the Evaluation of Probiotics in Food. In Joint FAO/WHO Working Group on Drafting Guidelines for the Evaluation of Probiotics in Food; WHO: London, ON, Canada, 2002. [Google Scholar]
  158. Gibson, G.R.; Hutkins, R.; Sanders, M.E.; Prescott, S.L.; Reimer, R.A.; Salminen, S.J.; Scott, K.; Stanton, C.; Swanson, K.S.; Cani, P.D.; et al. Expert consensus document: The international scientific association for probiotics and prebiotics (isapp) consensus statement on the definition and scope of prebiotics. Nat. Rev. Gastroenterol. Amp. Hepatol. 2017, 14, 491. [Google Scholar]
  159. Nataraj, B.H.; Ali, S.A.; Behare, P.V.; Yadav, H. Postbiotics-parabiotics: The new horizons in microbial biotherapy and functional foods. Microb. Cell Fact. 2020, 19, 168. [Google Scholar]
  160. Marotz, C.A.; Zarrinpar, A. Treating Obesity and Metabolic Syndrome with Fecal Microbiota Transplantation. Yale J. Biol. Med. 2016, 89, 383–388. [Google Scholar]
  161. Guo, Y.; Wang, Z.; Chen, L.; Tang, L.; Wen, S.; Liu, Y.; Yuan, J. Diet induced maternal obesity affects offspring gut microbiota and persists into young adulthood. Food Funct. 2018, 9, 4317–4327. [Google Scholar] [CrossRef]
  162. Paul, H.A.; Collins, K.H.; Nicolucci, A.C.; Urbanski, S.J.; Hart, D.A.; Vogel, H.J.; Reimer, R.A. Maternal prebiotic supplementation reduces fatty liver development in offspring through altered microbial and metabolomic profiles in rats. FASEB J. 2019, 33, 5153–5167. [Google Scholar] [CrossRef] [PubMed]
  163. Ros, P.; Díaz, F.; Freire-Regatillo, A.; Argente-Arizón, P.; Barrios, V.; Argente, J.; Chowen, J.A. Resveratrol Intake during Pregnancy and Lactation Modulates the Early Metabolic Effects of Maternal Nutrition Differently in Male and Female Offspring. Endocrinology 2018, 159, 810–825. [Google Scholar] [CrossRef]
  164. Hsu, C.N.; Hou, C.Y.; Chang-Chien, G.P.; Lin, S.; Chan, J.Y.H.; Lee, C.T.; Tain, Y.L. Maternal resveratrol therapy protected adult rat offspring against hypertension programmed by combined exposures to asymmetric dimethylarginine and trimethylamine-N-oxide. J. Nutr. Biochem. 2021, 93, 1086. [Google Scholar] [CrossRef]
  165. Hsu, C.N.; Hung, C.H.; Hou, C.Y.; Chang, C.I.; Tain, Y.L. Perinatal Resveratrol Therapy to Dioxin-Exposed Dams Prevents the Programming of Hypertension in Adult Rat Offspring. Antioxidants 2021, 10, 1393. [Google Scholar] [CrossRef] [PubMed]
  166. Vega, C.C.; Reyes-Castro, L.A.; Rodríguez-González, G.L.; Bautista, C.J.; Vázquez-Martínez, M.; Larrea, F.; Chamorro-Cevallos, G.A.; Nathanielsz, P.W.; Zambrano, E. Resveratrol partially prevents oxidative stress and metabolic dysfunction in pregnant rats fed a low protein diet and their offspring. J. Physiol. 2016, 594, 1483–1499. [Google Scholar] [CrossRef] [PubMed]
  167. Hsu, M.H.; Sheen, J.M.; Lin, I.C.; Yu, H.R.; Tiao, M.M.; Tain, Y.L.; Huang, L.T. Effects of Maternal Resveratrol on Maternal High-Fat Diet/Obesity with or without Postnatal High-Fat Diet. Int. J. Mol. Sci. 2020, 21, 3428. [Google Scholar] [CrossRef]
  168. Hsu, C.N.; Lin, Y.J.; Tain, Y.L. Maternal Exposure to Bisphenol A Combined with High-Fat Diet-Induced Programmed Hypertension in Adult Male Rat Offspring: Effects of Resveratrol. Int. J. Mol. Sci. 2019, 20, 4382. [Google Scholar] [CrossRef] [Green Version]
  169. Liu, T.Y.; Yu, H.R.; Tsai, C.C.; Huang, L.T.; Chen, C.C.; Sheen, J.M.; Tiao, M.M.; Tain, Y.L.; Lin, I.C.; Lai, Y.J.; et al. Resveratrol intake during pregnancy and lactation re-programs adiposity and ameliorates leptin resistance in male progeny induced by maternal high-fat/high sucrose plus postnatal high-fat/high sucrose diets via fat metabolism regulation. Lipids Health Dis. 2020, 19, 174. [Google Scholar] [CrossRef]
  170. Care, A.S.; Sung, M.M.; Panahi, S.; Gragasin, F.S.; Dyck, J.R.; Davidge, S.T.; Bourque, S.L. Perinatal Resveratrol Supplementation to Spontaneously Hypertensive Rat Dams Mitigates the Development of Hypertension in Adult Offspring. Hypertension 2016, 67, 1038–1044. [Google Scholar] [CrossRef]
  171. Zou, T.; Chen, D.; Yang, Q.; Wang, B.; Zhu, M.J.; Nathanielsz, P.W.; Du, M. Resveratrol supplementation of high-fat diet-fed pregnant mice promotes brown and beige adipocyte development and prevents obesity in male offspring. J. Physiol. 2017, 595, 1547–1562. [Google Scholar] [CrossRef]
  172. Shih, M.K.; Tain, Y.L.; Chen, Y.W.; Hsu, W.H.; Yeh, Y.T.; Chang, S.K.C.; Liao, J.X.; Hou, C.Y. Resveratrol Butyrate Esters Inhibit Obesity Caused by Perinatal Exposure to Bisphenol A in Female Offspring Rats. Molecules 2021, 26, 4010. [Google Scholar] [CrossRef] [PubMed]
  173. Liao, J.X.; Chen, Y.W.; Shih, M.K.; Tain, Y.L.; Yeh, Y.T.; Chiu, M.H.; Chang, S.K.C.; Hou, C.Y. Resveratrol Butyrate Esters Inhibit BPA-Induced Liver Damage in Male Offspring Rats by Modulating Antioxidant Capacity and Gut Microbiota. Int. J. Mol. Sci. 2021, 22, 5273. [Google Scholar] [CrossRef] [PubMed]
  174. Hsu, C.N.; Yu, H.R.; Chan, J.Y.H.; Lee, W.C.; Lin, I.C.; Wu, K.L.H.; Hou, C.Y.; Chang-Chien, G.P.; Lin, S.; Tain, Y.L. Maternal Acetate Supplementation Reverses Blood Pressure Increase in Male Offspring Induced by Exposure to Minocycline during Pregnancy and Lactation. Int. J. Mol. Sci. 2022, 23, 7924. [Google Scholar] [CrossRef]
  175. Hsu, C.N.; Yu, H.R.; Lin, I.C.; Tiao, M.M.; Huang, L.T.; Hou, C.Y.; Chang-Chien, G.P.; Lin, S.; Tain, Y.L. Sodium butyrate modulates blood pressure and gut microbiota in maternal tryptophan-free diet-induced hypertension rat offspring. J. Nutr. Biochem. 2022, 108, 109090. [Google Scholar] [CrossRef] [PubMed]
  176. Gray, C.; Vickers, M.H.; Segovia, S.A.; Zhang, X.D.; Reynolds, C.M. A maternal high fat diet programmes endothelial function and cardiovascular status in adult male offspring independent of body weight, which is reversed by maternal conjugated linoleic acid (CLA) supplementation. PLoS ONE 2015, 10, e0115994. [Google Scholar]
  177. Hsu, C.N.; Hou, C.Y.; Lee, C.T.; Chang-Chien, G.P.; Lin, S.; Tain, Y.L. Maternal 3,3-Dimethyl-1-Butanol Therapy Protects Adult Male Rat Offspring against Hypertension Programmed by Perinatal TCDD Exposure. Nutrients 2021, 13, 3041. [Google Scholar] [CrossRef]
  178. Hsu, C.N.; Chan, J.Y.H.; Yu, H.R.; Lee, W.C.; Wu, K.L.H.; Chang-Chien, G.P.; Lin, S.; Hou, C.Y.; Tain, Y.L. Targeting on Gut Microbiota-Derived Metabolite Trimethylamine to Protect Adult Male Rat Offspring against Hypertension Programmed by Combined Maternal High-Fructose Intake and Dioxin Exposure. Int. J. Mol. Sci. 2020, 21, 5488. [Google Scholar] [CrossRef]
  179. Tenorio-Jiménez, C.; Martínez-Ramírez, M.J.; Gil, Á.; Gómez-Llorente, C. Effects of Probiotics on Metabolic Syndrome: A Systematic Review of Randomized Clinical Trials. Nutrients 2020, 12, 124. [Google Scholar] [CrossRef] [Green Version]
  180. Sunu, P.; Sunartim, D.; Mahfudz, L.D.; Yunianto, V.D. Prebiotic activity of garlic Allium sativum extract on Lactobacillus acidophilus. Vet. World 2019, 12, 2046–2051. [Google Scholar] [CrossRef]
  181. Garcia-Alonso, A.; Sánchez-Paniagua López, M.; Manzanares-Palenzuela, C.L.; Redondo-Cuenca, A.; López-Ruíz, B. Edible plant by-products as source of polyphenols: Prebiotic effect and analytical methods. Crit. Rev. Food Sci. Nutr. 2022, 6, 1–22. [Google Scholar] [CrossRef]
  182. Tain, Y.L.; Hsu, C.N. Novel Insights on Dietary Polyphenols for Prevention in Early-Life Origins of Hypertension: A Review Focusing on Preclinical Animal Models. Int. J. Mol. Sci. 2022, 33, 6620. [Google Scholar] [CrossRef] [PubMed]
  183. Tain, Y.L.; Hsu, C.N. Developmental Programming of the Metabolic Syndrome: Can We Reprogram with Resveratrol? Int. J. Mol. Sci. 2018, 19, 2584. [Google Scholar] [CrossRef] [PubMed]
  184. Walle, T.; Hsieh, F.; DeLegge, M.H.; Oatis, J.E., Jr.; Walle, U.K. High absorption but very low bioavailability of oral resveratrol in humans. Drug Metab. Dispos. 2004, 32, 1377–1382. [Google Scholar] [CrossRef] [PubMed]
  185. Tain, Y.L.; Chang, S.K.C.; Liao, J.X.; Chen, Y.W.; Huang, H.T.; Li, Y.L.; Hou, C.Y. Synthesis of Short-Chain-Fatty-Acid Resveratrol Esters and Their Antioxidant Properties. Antioxidants 2021, 10, 420. [Google Scholar] [CrossRef] [PubMed]
  186. Wang, Z.; Roberts, A.B.; Buffa, J.A.; Levison, B.S.; Zhu, W.; Org, E.; Gu, X.; Huang, Y.; Zamanian-Daryoush, M.; Culley, M.K.; et al. Non-lethal Inhibition of Gut Microbial Trimethylamine Production for the Treatment of Atherosclerosis. Cell 2015, 163, 1585–1595. [Google Scholar] [CrossRef]
  187. Gomez Arango, L.F.; Barrett, H.L.; Callaway, L.K.; Nitert, M.D. Probiotics and pregnancy. Curr. Diabet. Rep. 2015, 15, 567. [Google Scholar] [CrossRef] [PubMed]
  188. Luoto, R.; Laitinen, K.; Nermes, M.; Isolauri, E. Impact of maternal probiotic-supplemented dietary counselling on pregnancy outcome and prenatal and postnatal growth: A double-blind, placebo controlled study. Br. J. Nutr. 2010, 103, 1792–1799. [Google Scholar]
  189. Brantsaeter, A.L.; Myhre, R.; Haugen, M.; Myking, S.; Sengpiel, V.; Magnus, P.; Jacobsson, B.; Meltzer, H.M. Intake of probiotic food and risk of preeclampsia in primiparous women: The norwegian mother and child cohort study. Am. J. Epidemiol. 2011, 174, 807–815. [Google Scholar]
  190. Vitali, B.; Cruciani, F.; Baldassarre, M.E.; Capursi, T.; Spisni, E.; Valerii, M.C.; Candela, M.; Turroni, S.; Brigidi, P. Dietary supplementation with probiotics during late pregnancy: Outcome on vaginal microbiota and cytokine secretion. BMC Microbiol. 2012, 12, 236. [Google Scholar]
  191. Wiedmer, E.B.; Herter-Aeberli, I. The Potential of Prebiotic and Probiotic Supplementation During Obese Pregnancy to Improve Maternal and Offspring’s Metabolic Health and Reduce Obesity Risk-A Narrative Review. Front. Nutr. 2022, 9, 819882. [Google Scholar]
  192. Othman, M.; Neilson, J.P.; Alfirevic, Z. Probiotics for preventing preterm labour. Cochrane Database Syst. Rev. 2007, 1, CD005941. [Google Scholar]
  193. Jinno, S.; Toshimitsu, T.; Nakamura, Y.; Kubota, T.; Igoshi, Y.; Ozawa, N.; Suzuki, S.; Nakano, T.; Morita, Y.; Arima, T.; et al. Maternal prebiotic ingestion increased the number of fecal bifidobacteria in pregnant women but not in their neonates aged one month. Nutrients 2017, 9, 196. [Google Scholar]
  194. Okesene-Gafa, K.A.M.; Li, M.; McKinlay, C.J.D.; Taylor, R.S.; Rush, E.C.; Wall, C.R.; Wilson, J.; Murphy, R.; Taylor, R.; Thompson, J.M.D.; et al. Effect of antenatal dietary interventions in maternal obesity on pregnancy weight-gain and birthweight: Healthy Mums and Babies (HUMBA) randomized trial. Am. J. Obstet. Gynecol. 2019, 221, 152.e1–152.e13. [Google Scholar] [PubMed]
  195. Kijmanawat, A.; Panburana, P.; Reutrakul, S.; Tangshewinsirikul, C. Effects of probiotic supplements on insulin resistance in gestational diabetes mellitus: A double-blind randomized controlled trial. J. Diabetes Investig. 2019, 10, 163–170. [Google Scholar]
  196. Halkjær, S.I.; de Knegt, V.E.; Lo, B.; Nilas, L.; Cortes, D.; Pedersen, A.E.; Mirsepasi-Lauridsen, H.C.; Andersen, L.O.B.; Nielsen, H.V.; Stensvold, C.R.; et al. Multistrain probiotic increases the gut microbiota diversity in obese pregnant women: Results from a randomized, double-blind placebo-controlled study. Curr. Dev. Nutr. 2020, 4, nzaa095. [Google Scholar]
  197. Asgharian, H.; Homayouni-Rad, A.; Mirghafourvand, M.; Mohammad-Alizadeh-Charandabi, S. Effect of probiotic yoghurt on plasma glucose in overweight and obese pregnant women: A randomized controlled clinical trial. Eur. J. Nutr. 2020, 59, 205–215. [Google Scholar] [CrossRef]
  198. Shahriari, A.; Karimi, E.; Shahriari, M.; Aslani, N.; Khooshideh, M.; Arab, A. The effect of probiotic supplementation on the risk of gestational diabetes mellitus among high-risk pregnant women: A parallel double-blind, randomized, placebo-controlled clinical trial. Biomed. Pharmacother. 2021, 141, 111915. [Google Scholar]
  199. Cuinat, C.; Stinson, S.E.; Ward, W.E.; Comelli, E.M. Maternal Intake of Probiotics to Program Offspring Health. Curr. Nutr. Rep. 2022. [Google Scholar] [CrossRef]
  200. ClinicalTrials.gov. 2022. Available online: https://clinicaltrials.gov/ (accessed on 27 August 2022).
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Figure 1. A schematic depiction delineating early-life environmental cues that may cause the developmental programming in different organ systems leading to MetS and associated disorders in adult life.
Figure 1. A schematic depiction delineating early-life environmental cues that may cause the developmental programming in different organ systems leading to MetS and associated disorders in adult life.
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Figure 2. A summary of the currently available reprogramming interventions for metabolic syndrome of developmental origins.
Figure 2. A summary of the currently available reprogramming interventions for metabolic syndrome of developmental origins.
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Table
Table 1. Summary of animal models reporting gut microbiota-targeted therapies for MetS of developmental origins.
Table 1. Summary of animal models reporting gut microbiota-targeted therapies for MetS of developmental origins.
Gut Microbiota-Targeted TherapiesAnimal ModelsSpecies/GenderAge at EvaluationReprogramming EffectsRef.
Probiotics
Daily oral gavage of Lactobacillus casei during gestation and lactationMaternal high-fructose dietSD rat/M12 weeksPrevented hypertension[141]
Daily oral gavage of Lactobacillus casei during gestation and lactationPerinatal high-fat dietSD rat/M16 weeksPrevented hypertension[101]
Daily oral gavage of multi-strain probiotics (Bifidobacterium breve, Lactobacillus acidophilus, Lactobacillus casei and Staphylococcus thermophilus) during gestation and lactationMaternal high-fat dietC57BL/6 J mice/F20 weeksImproved glucose and insulin levels[161]
Prebiotics
5% w/w long chain inulin during gestation and lactationMaternal high-fructose dietSD rat/M12 weeksPrevented hypertension[141]
5% w/w long chain inulin during gestation and lactationPerinatal high-fat dietSD rat/M16 weeksPrevented hypertension[101]
10% w/w oligofructose during gestation and lactationMaternal high-fat/sucrose dietSD rat/M24 weeksImproved glucose tolerance, insulin sensitivity and hepatic steatosis[162]
Daily oral gavage of garlic oil (100 mg/kg/day) during gestation and lactationPerinatal high-fat dietSD rat/M16 weeksPrevented hypertension[57]
Resveratrol (50 mg/L) in drinking water during gestation and lactationMaternal high-fat dietWistar rat/M and F3 weeksImproved obesity[163]
Resveratrol (50 mg/L) in drinking water during gestation and lactationMaternal ADMA and TMAO exposureSD rat/M12 weeksPrevented hypertension[164]
Resveratrol (50 mg/L) in drinking water during gestation and lactationPerinatal TCDD exposureSD rat/M12 weeksPrevented hypertension[165]
Resveratrol (50 mg/L) in drinking water during gestation and lactationMaternal adenine-induced CKDSD rat/M12 weeksPrevented hypertension[149]
Daily oral gavage of resveratrol (20 mg/kg/day) during gestationMaternal protein restrictionWistar rat/M and F110 daysImproved obesity and insulin resistance[166]
Resveratrol (50 mg/L) in drinking water during gestation and lactationMaternal L-NAME administration and high-fat dietSD rat/M16 weeksPrevented hypertension[150]
Resveratrol (50 mg/L) in drinking water during gestation and lactationMaternal and post-weaning high-fat dietSD rat/M16 weeksPrevented hypertension[167]
Resveratrol (50 mg/L) in drinking water during gestation and lactationMaternal bisphenol A exposure and high-fat dietSD rat/M16 weeksPrevented hypertension[168]
Resveratrol (50 mg/L) in drinking water during gestation and lactationMaternal and post-weaning high-fat dietSD rat/M16 weeksImproved obesity, hyperlipidemia and hepatic steatosis [169]
Resveratrol (4 g/kg of diet) during gestation and lactationMaternal hypertension SHR/M and F 20 weeksPrevented hypertension[170]
Resveratrol (0.2% w/w) during gestation and lactationMaternal high-fat dietC57BL/6 J mice/M14 weeksImproved obesity and hyperlipidemia[171]
Daily oral gavage of resveratrol butyrate ester (30 or 50 mg/kg/day) during gestation and lactationMaternal bisphenol A exposureSD rat/F50 daysImproved obesity and hyperlipidemia[172]
Daily oral gavage of resveratrol butyrate ester (30 mg/kg/day) during gestation and lactationMaternal bisphenol A exposureSD rat/M50 daysImproved hepatic steatosis[173]
Postbiotics
Magnesium acetate (200 mmol/L) in drinking water during gestation and lactationMaternal high-fructose dietSD rat/M12 weeksPrevented hypertension[142]
Magnesium acetate (200 mmol/L) in drinking water during gestation and lactationMaternal minocycline exposureSD rat/M12 weeksPrevented hypertension[174]
Sodium butyrate (400 mg/kg/day) in drinking water during gestation and lactationMaternal tryptophan-free dietSD rat/M12 weeksPrevented hypertension[175]
1% conjugated linoleic acid in chow during gestation and lactationMaternal high-fat dietSD rat/M150 daysImproved cardiometabolic dysfunction[176]
Others
1% DMB in drinking water during gestation and lactationMaternal high-fructose dietSD rat/M12 weeksPrevented hypertension[142]
1% DMB in drinking water during gestation and lactationPerinatal TCDD exposureSD rat/M12 weeksPrevented hypertension[177]
1% DMB in drinking water during gestation and lactationMaternal high-fructose diet and TCDD exposureSD rat/M12 weeksPrevented hypertension[178]
Studies tabulated based on types of intervention, animal models and age at evaluation. CKD = chronic kidney disease; TCDD = 2,3,7,8-tetrachlorodibenzo-p-dioxin; ADMA = asymmetric dimethylarginine; TMAO = trimethylamine-N-oxide; SD = Sprague-Dawley rat; DMB = 3,3-maternal dimethyl-1-butanol.
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Huang, Y.-H.; Tain, Y.-L.; Hsu, C.-N. Maternal Supplementation of Probiotics, Prebiotics or Postbiotics to Prevent Offspring Metabolic Syndrome: The Gap between Preclinical Results and Clinical Translation. Int. J. Mol. Sci. 2022, 23, 10173. https://doi.org/10.3390/ijms231710173

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Huang Y-H, Tain Y-L, Hsu C-N. Maternal Supplementation of Probiotics, Prebiotics or Postbiotics to Prevent Offspring Metabolic Syndrome: The Gap between Preclinical Results and Clinical Translation. International Journal of Molecular Sciences. 2022; 23(17):10173. https://doi.org/10.3390/ijms231710173

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Huang, Ying-Hua, You-Lin Tain, and Chien-Ning Hsu. 2022. "Maternal Supplementation of Probiotics, Prebiotics or Postbiotics to Prevent Offspring Metabolic Syndrome: The Gap between Preclinical Results and Clinical Translation" International Journal of Molecular Sciences 23, no. 17: 10173. https://doi.org/10.3390/ijms231710173

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