Next Article in Journal
Prospection of Psychrotrophic Filamentous Fungi Isolated from the High Andean Paramo Region of Northern Ecuador: Enzymatic Activity and Molecular Identification
Next Article in Special Issue
A Study and Modeling of Bifidobacterium and Bacillus Coculture Continuous Fermentation under Distal Intestine Simulated Conditions
Previous Article in Journal
Neofunctionalization of Glycolytic Enzymes: An Evolutionary Route to Plant Parasitism in the Oomycete Phytophthora nicotianae
Previous Article in Special Issue
Phylogenetic, Functional and Safety Features of 1950s B. infantis Strains
 
 
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Review

Why Are Bifidobacteria Important for Infants?

1
Centre for Human Microbiome and Probiotic Research, Lawson Health Research Institute, London, ON N6A4V2, Canada
2
Departments of Microbiology and Immunology and Surgery, Western University, London, ON N6A 3K7, Canada
3
Seed Health Inc., Venice, CA 90291, USA
*
Author to whom correspondence should be addressed.
Microorganisms 2022, 10(2), 278; https://doi.org/10.3390/microorganisms10020278
Submission received: 10 December 2021 / Revised: 14 January 2022 / Accepted: 20 January 2022 / Published: 25 January 2022
(This article belongs to the Special Issue The Gut Microbiota in Infants: Focus on Bifidobacterium)

Abstract

:
The presence of Bifidobacterium species in the maternal vaginal and fecal microbiota is arguably an evolutionary trait that allows these organisms to be primary colonizers of the newborn intestinal tract. Their ability to utilize human milk oligosaccharides fosters their establishment as core health-promoting organisms throughout life. A reduction in their abundance in infants has been shown to increase the prevalence of obesity, diabetes, metabolic disorder, and all-cause mortality later in life. Probiotic strains have been developed as supplements for premature babies and to counter some of these ailments as well as to confer a range of health benefits. The ability to modulate the immune response and produce short-chain fatty acids, particularly acetate and butyrate, that strengthen the gut barrier and regulate the gut microbiome, makes Bifidobacterium a core component of a healthy infant through adulthood.

1. Introduction

As has been elegantly described, human milk has evolved to deliver all the nutrients, hormones, and bioactive compounds to give a newborn the best chance of surviving and thriving [1]. Within its complex composition lie oligosaccharides known to be utilized by the first organisms that colonize the gastrointestinal tract. Whether these compounds evolved to feed organisms, particularly bifidobacteria, or the organisms colonized to take advantage of them as nutrients, remains to be determined. Nevertheless, bifidobacteria are important bacteria for infants, and this mini review will explore their beneficial properties for early human life.

2. From Whence They Came

Acquisition of a healthy gut microbiota during the developmental stages of early human life plays a significant role in the health of that individual later in life. It has been proposed [2], though not universally accepted [3,4], that microbes begin to colonize the newborn while in the uterus. Then, at least during the natural birthing process, the organisms that live in the female genital tract have access to and interact with the baby. Gram-positive, polymorphic rod-shaped Bifidobacterium species are part of this maternal vaginal and fecal microbiota [5,6,7]. In the gut, B. adolescentis, B. longum, B. angulatum, B. bifidum, B. pseudocatenulatum, B. breve, B. catenulatum, B. dentium, and B. pseudolongum are commonly found [8]. To date, the role of each bacterial species acquired from those habitats in the infant’s development remains poorly understood, except for their decreased abundance in patients with atopic disease and intestinal ailments [9],. Apart from pathogens harming the infant, and organisms that are beneficial to infants early in development (for example, Bacteroides thetaiotamicron potentially aiding in intestinal cellular differentiation [10]) the bulk of research has been performed on Lactobacillus and Bifidobacterium species.

3. Why a Focus on Bifidobacterium?

The composition of the human gut microbiome is not static throughout development and undergoes dramatic changes as an individual grows older [11]. Highlighting this, the most dominant phyla in the adult gut microbiota include Actinobacteria, Proteobacteria, Firmicutes, and Bacteroidetes, with the latter two representing ~90% of the total; Actinobacteria (including bifidobacteria) are significantly less abundant [12,13,14]. This is in stark contrast to the microbial compositions observed throughout infancy, where Bifidobacterium spp. are drastically more abundant than in adults. In fact, the genus Bifidobacterium represents the most prominent microbial members in the gut of healthy, breast-fed infants [15,16,17]. This overrepresentation in the early gut environment suggests an important role in infantile development. As such, the origins, role, and potential therapeutic application of Bifidobacterium spp. in early human development, across multiple avenues, are discussed below.
That a strict and relatively fastidious anaerobe reaches the newborn gut and plays a key role in host health supports its co-evolution with humans [18]. In terms of overall abundance in the infant gut, bifidobacteria vary in terms of time, species, and strains. Part of the reason appears to be varied gene sets [19]; Bifidobacterium spp. demonstrate both inter- and intra-strain variance in metabolic and fermentative functions [20]. For example, genomic analysis has shown that individual strains of B. longum and B. breve vary in the number of human milk oligosaccharide (HMO) utilization genes, which alters their ability to use these compounds as a source of nutrients [21,22]. As such, the strains that can use HMOs efficiently are suspected to dominate the gut of a breast-fed infant. Changes in the diet and lifestyle of mothers in different parts of the world can affect the HMOs and bifidobacteria that colonize the infant’s gut. In a study performed on Bangladeshi infants, bifidobacterial dominance correlated with reduced colonization by organisms with antimicrobial resistance genes, thereby suggesting an important function for fighting infection [23]. A study on Malawian children showed higher proportions of bifidobacteria than in Finnish children, suggesting perhaps that diet impacts abundance [24], though this is difficult to pin down without a study examining confounding factors and dietary recall. As with any cause-and-effect study, large numbers of subjects would have to be included to ascertain direct correlations and interrogate mechanisms. Thus, the importance of one Bifidobacterium species over another, their abundance and metabolic activity, cannot easily be deciphered, though studies have shown different abilities to use fucosyllactose or sialyllactose [25]. Certainly, the use of antibiotics as well as the milk’s glycan composition are factors of importance [16].
A case has been made for a critical role of B. longum subsp. infantis due to its diverse genomic capacity and ability to digest and utilize HMOs [26]. If this is the case, it would make sense to supplement this species as a probiotic in infant formula. However, to date, single probiotic strains have been added to infant formula without any transparent reason. For example, formulas contain Lacticaseibacillus (formerly Lactobacillus) rhamnosus GG or Bifidobacterium lactis BB-12. The literature indicates these strains have very different attributes, yet the assumption of the parent and pediatrician is that they should confer the same health-promoting benefits. This puts into question which of these strains, if any, would lead to the best health outcomes for infants. Since few comparative studies have been done on two or more probiotic infant formulas, the question is difficult to answer. One clinical trial did show that a strain of B. infantis in either formula or human milk increased the fecal bifidobacterial numbers more so than B. lactis [27]. This study was not designed to establish a health benefit, but there was an assumption that an overall increase in Bifidobacterium species is desirable for infants. Further to other studies, this strain was commercialized and is now advertised as “the most infant-appropriate B. infantis strain”.
It is not the intent of this commentary to analyze the data supporting this statement, but it is worth asking the question of what evidence is required to select probiotic strains for universal usage in infants and in gauging one over another.
The desired health outcome of a probiotic is specific to the target disease and the strain(s) used. By ignoring differences that exist in function and metabolic capacity between bacterial strains, the unique effect of a probiotic on the host is ignored. Unfortunately, too little emphasis has been placed on strain properties for the desired application to humans. Many companies combine strains in an impromptu manner without considering the between-strain interference that could alter the desired outcome observed in clinical trials employing an individual strain [28,29]. With ethical issues surrounding the supplementation of live microorganisms to infants, such an intervention would require proof of the strain’s necessity in addition to rigorous safety testing. We have recently shown for Lactobacillus crispatus that metabolomic analysis can identify strains appropriate or not for probiotic applications to improve vaginal health [30]. It might not seem to be a relevant topic for a female infant but debilitating urinary tract infections can occur at that age [31]. Considering this is the stage where bacteria colonize the gut, implanting beneficial ones and reducing pathogens is important. Thus, the early-life application of probiotic strains, whether lactobacilli or bifidobacteria, requires an investigation of the properties and a rationale for their use, including their safety, not simply because they belong to those genera [28,29].
As an example, we recently examined four Bifidobacterium strains for their ability to counter the toxic effects of p-cresol, a compound detrimental to chronic kidney and cardiovascular health. It turned out there were some differences between B. breve HRVD521-US, B. animalis HRVD574-US, B. longum SD-BB536-JP and B. longum SD-CECT7347-SP (Unpublished data), though each appeared to have beneficial attributes. These experiments were performed in vitro and in a Drosophila model, which raises the question of how do you select strains and predict efficacy in humans? The answer is that models and genomic analysis can provide insight into the strain, but human studies alone can prove efficacy. Arguably, a strain can only perform tasks for which it has the genes. Whilst true, the environment within which it resides, in this case the gut, can alter gene expression and compound availability, and present molecules that the strain can then utilize. This is the case with Clostridium and Enterobacteriaceae spp. residing in the gut, which produce phenolic compounds including p-cresol from the metabolization of tyrosine and phenylalanine.
So, which properties are desirable for bifidobacteria in the infant gut and how can these influence the probiotic formulation that is being developed? We propose there are three important activities bifidobacteria carry out in the infant gut: they establish themselves as primary colonizers, allowing their health benefits to be ingrained; modulating immunological development; and producing metabolites that confer other physiological benefits.

4. Primary Colonization and Shaping Microbial Composition in the Gut

In the infantile gut environment, bifidobacteria engage in advantageous interactions with the host and other members of the microbiota that benefit intestinal and body-wide physiology. On the surface of bifidobacterial cells exist a myriad of proteins that facilitate their adhesion to intestinal epithelium [17,32,33]. This adherence is important as it can limit the colonization of pathogenic microbes by mitigating space and nutrient availability at the intestinal lining [17,32]. This process is enhanced by the presence of HMOs, which bifidobacteria use as growth promoters. The sequential establishment of a microbiota has been well characterized in the oral cavity, with primary then secondary colonizers taking on important roles [34]. Studies are required to gain this same insight into intestinal colonization [35].
To understand how the gut microbiota is established, a tremendous effort has been made to decipher the compositional shifts that occur throughout the first year of development. As the infant grows, the gut microbiota both increases and decreases in α-diversity and β-diversity, respectively, which is indicative of the increasing complexity of the community [15,36]. However, this is a non-random process driven by both environmental factors as well as the birthing method (i.e., vaginal vs. C-section) [15,37,38]. The first bacteria to colonize the gut are derived from vertical, mother–infant transmission [15]. Vaginally derived infants acquire bacterial communities from the vaginal and intestinal microbes of the mother, dominated by Bifidobacterium, Lactobacillus, and Prevotella [15,39], whereas C-section infants are more likely to be colonized by skin surface bacteria such as Staphylococcus and Corynebacterium [15,39]. Postnatal factors, the most important being breastfeeding, help shape the microbiota of children throughout the first year of life [15,40]. Notably, the gut microbiota develops more slowly than once thought, as evidenced by the functional and taxonomic difference between adult and child microbiotas [41]. Indeed, the gut microbiota composition of a 1-year-old is more similar to that of its mother than a newborn [15]. However, even after 12 months of life, Bifidobacterium and Lactobacillus dominate the intestinal environment of breast-fed infants; the overall abundance of Bifidobacterium is expected to decline, slowly but continuously, as one progresses through to adulthood [15,40,41,42]. While breast milk selects for these infant-associated genera, it is also breast-feeding, rather than the shift to solid foods, that is required for a successful transition to an adult-like microbiota, dominated by Bacteroides [12,13,14,15,40,42]. While the reason for this is not yet clear, the effect of breast feeding on the gut microbiota seems to extend into later stages of life and is tightly linked with bifidobacterial abundance in the intestinal environment.
A loss of bifidobacteria at an early age can cause a wide range of disorders. Specifically, a reduction in the abundance of the genus Bifidobacterium in infants has been shown to increase the prevalence of obesity, diabetes, metabolic disorder, and all-cause mortality later in life [17,43,44]. This might be because bifidobacteria are needed to increase the presence of other microbes associated with health. As a result of cross-feeding interactions, metabolites produced by bifidobacteria [45,46], including those formed from HMO utilization [47], select for the butyrogenic bacteria such as Faecalibacterium prausnitzi, Anaerostipes, and Eubacterium [48]. Butyrate is the main source of energy for colonocytes and is important for the maintenance of the epithelial barrier. The compound has also been shown to improve outcomes in colorectal cancers and metabolic diseases [49]. This offers a reasonable explanation for the reduced incidence of metabolic disease in individuals who were sufficiently colonized by bifidobacteria in early life. Furthermore, a loss of these important butyrate-producing microbes has been associated with conditions such as kidney stone disease and chronic kidney disease [48]; two conditions that are increasing in prevalence in children [50,51]. However, the list of important cross-feeding interactions, mediated by bifidobacteria, does not end here.
Other cross-feeding networks established between bifidobacteria and other commensals rely on the degradation of nutrients such as oligosaccharides, xylan, starch, arabinogalactan, mucin and more [52,53,54,55,56,57,58,59]. Importantly, the degradation of arabinogalactan establishes a network of Bifidobacterium and Bacteroides (a key member of the adult microbiota) that support one another by sharing catabolites [59]. These and other syntrophic interactions highlight the co-evolution of gut microbes and the human host. Many of these interactions seem to be mediated by bifidobacteria, which exemplifies their ecological role in obtaining and sharing substrates to and from other organisms [52,53,54,55,56,57,58,59]. Thus, bifidobacteria help establish and modulate microbiota composition and facilitate metabolic interaction to promote a healthy microbial community. Furthermore, the main fermentation metabolites of bifidobacteria, acetic and lactic acid, antagonize pathogens such as Salmonella and Listeria and can limit infection [15]. Taken together, these observations emphasize the importance of integrating bifidobacteria into the intestinal microbiota early in life.
Given the clear role that bifidobacteria play in establishing a healthy infant gut microbiota, and the transition to an “adult-like” composition, there is the potential to utilize certain strains to drive microbiome diversity. The most obvious group to benefit from probiotic supplementation are those delivered via C-section because they have much lower proportions of beneficial bacteria and take a longer time to develop a “normal” microbiota, compositionally speaking [60]. To date, some evidence exists to show that probiotic supplementation is sufficient to normalize the gut microbiota of C-section babies [61,62]. If this is true, then the early intervention of well-selected probiotic strains in these infants may provide a healthier start to development and prevent some of the chronic illnesses associated with microbial dysbiosis later in life [15,17,30,31,39,60]. However, investigations to elucidate which strain(s) are most effective remain to be conducted.

5. Impact of the Strains on the Host’s Immunity

The binding interaction between bifidobacteria and enterocytes plays a role in educating the immature immune system through the triggering of proinflammatory responses [33,63]. As mentioned, because C-section babies are exposed to fewer routes for the vertical transmission of microbes, the likelihood that they acquire microbes from the external environment instead of common anaerobes coming from the mother’s vagina or feces is increased [17,64]. Not surprisingly, the colonization of bifidobacteria in C-section babies occurs at a much slower rate compared to those born vaginally [65,66,67]. This delay could improve the adherence of potentially pathogenic microbes such as E. coli to the intestinal epithelium and could result in high titers of bacterial toxins in circulation or infection [68]. Depending on the bacteria present, this could increase the risk of disease in these individuals as they transition into adulthood [69].
Variations in the adherence ability between Bifidobacterium strains can cause immunological aberrations. For example, B. adolescentis is better at adhering to the intestinal lining than B. bifidum, and hence at utilizing nutrients found at this site and limiting pathogen burden [32,70]. Infants predominately colonized with B. bifidum rather than B. adolescentis are at greater risk of allergy [32,70]. Furthermore, the reduced colonization of Bifidobacterium is associated with a higher risk of other atopic diseases, including dermatitis and eczema. Considering that these are characterized by an overactive IgE immune response, it is likely that Bifidobacterium play a role in modulating the host’s response to common allergens. Unfortunately, the mechanisms behind how Bifidobacterium can regulate the immune system are not well known. Despite this, work is being done to elucidate the underlying causes for these observations, and one study showed that a reduction in Bifidobacterium longum prevents the maturation of circulating T-regulatory cells and increases the risk of allergy [71].
Multiple in vitro and animal studies have used a range of experimental protocols to predict how a strain will manipulate innate and adaptive immunity with limited success. Some successes have occurred when transferring the findings to humans, such as reducing allergic responses and inflammatory processes, including in infants [72,73]. Given that hosts may respond to certain strains and not others [74], and because Bifidobacterium strain propagation depends on which prebiotic it can assimilate [75], accurate predictions are difficult to achieve. Nevertheless, clinical studies have shown, for example, that bifidobacterial strains can improve plasma lipid profiles in children [76], and some can reduce the incidence of necrotizing enterocolitis in premature infants [77], although the extent to which immune modulation plays a role has not been defined.

6. Bifidobacterial Metabolites

Beyond the surface-bound features that are beneficial to humans, bifidobacteria are also able to secrete factors that improve host health. Short-chain fatty acids (SCFAs) are the primary waste product of the microbiota that results from the fermentation of indigestible polysaccharides, including HMOs [78]. The most relevant SCFAs to human health are formate, acetate, butyrate, and propionate, because they account for the vast majority present in the colon [79]. These compounds are multi-functional in human health and play a significant role in gut barrier integrity, intestinal pH, and the inhibition of pathogens, but are of particular relevance to childhood development because they act as food for colonocytes [32]. By doing so, there is a reduction in the translocation of deleterious compounds such as lipopolysaccharides (LPS) and other bacterial toxins from the intestine into circulation, thereby protecting the infant [80]. Considering that LPS is present in baby formula and can increase the permeability of the infant’s intestinal epithelium, improving the gut integrity of infants not breastfeeding takes on even more significance [81]. The release of a broad range of SCFAs by bifidobacteria and their extrapolysaccharides utilized by other bacteria [82] also leads to a drop in pH, associated with enterocyte generation and improved colonic surface area, allowing more mineral absorption, which supports infantile development [83]. For example, negatively charged SCFAs conjugate with Ca2+ ions to improve passive diffusion through the lipid membrane of enterocytes. The significance of SCFAs is corroborated by the fact that a reduction in these compounds in the body is associated with many chronic diseases, including in the kidney [79,84,85]. However, it is not yet clear if these chronic conditions have origins in childhood.
As reviewed by Daisley et al. [86], acetate is emerging as a molecule that drives many important processes, including waste management, energy generation and the regulation of microbial communities. Recently, our group showed that acetate selects for beneficial Akkermansia in the colon [87]. This suggests that acetate is fundamental in the cross-feeding interactions between Bifidobacterium and butyrogenic bacteria. This is further supported by the fact that bifidobacterial-synthesized acetate is used to make butyrate directly [46,88,89]. Interestingly, although lactate can be used by some anaerobes to produce butyrate, it seems that acetate is still required in this process, further highlighting its importance.
While the focus of this review is not the role of acetate as a master regulator in the gut, the molecule has other beneficial properties relevant to infant well-being. Acetate can be formed from H2S and CO2, and H2 by dissimilatory sulfate-reducing bacteria and acetogens, respectively [86,90,91]. While this represents a hyper-simplification of the complex underlying mechanisms of acetogenesis from intestinal gas, these processes have been described elsewhere [90,92]. Bloating caused by the over-production of gas in the colon can cause significant discomfort to an infant [93]. Therefore, acetate production might help provide relief.
Ultimately, the introduction of acetate-producing Bifidobacterium could select for a microbiota associated with good health. The fact that these organisms produce higher yields of acetate than other SCFAs further suggests an evolutionary contribution to infant health [94].

7. Further Potential

Two interesting areas of future potential applications of bifidobacteria are for brain and kidney health. Although heavily debated, there is growing evidence to suggest that microbes play a role in neurodevelopmental disorders such as autism. While work in animal models is not translatable to humans, a recent rodent model of autism indicated the resulting changes in social behavior correlated with alterations in bile acid and tryptophan metabolism [95]. One of the most significant findings from this study was a reduction in bifidobacterial colonization. As mentioned above, Clostridium and Enterobacteriaceae spp. residing in the gut produce p-cresol from the metabolism of tryptophan and the other aromatic amino acids tyrosine and phenylalanine. Increased levels of p-cresol exacerbate the autism-like behaviors of these rats, which has been corroborated in autistic children who have a higher burden of p-cresol in the urine, indicating greater systemic loads [96,97,98]. However, at the current time, it is not known whether the accumulation of p-cresol is the cause or result of autism spectrum disorder.
Chronic kidney disease management of children has improved but remains a major cause of reduced longevity [99]. Elevated p-cresol levels are also associated with chronic kidney and cardiovascular disease in adults. Of interest would be to examine the levels of these toxins in children, particularly those with kidney diseases, or indeed their mothers, since acute renal injury can arise in neonates and premature infants born with less than half the normal numbers of nephrons [100]. Recent work from our group has identified that four strains of bifidobacteria can sequester p-cresol from the extracellular environment and offer protection from the toxin in vivo (Unpublished data). As applications of p-cresol-sequestering probiotic bifidobacterial strains are safe for adults and children, it would be possible to see if this influences the incidence and management of children with autism spectrum disorder and kidney disease.

8. Conclusions

In summary, Bifidobacterium species are important primary colonizers of the infant intestinal tract, and their abundance, especially following ingestion of HMOs, correlates with health (Figure 1). For premature babies, those delivered by C-section and those not gaining access to human milk, supplementation with probiotic strains is worthy of consideration, although more studies are required to select strains with appropriate properties. Much still needs to be done to correlate abundance, species, and function in healthy infants before selecting probiotic strains for infant formula. Ultimately, the risks associated with low bifidobacterial loads and potentially low levels of certain species could translate into diseases later in infancy through to adulthood.

Author Contributions

Conceptualization, G.R.; formal analysis, G.R., G.A.S. and P.A.B.; investigation, G.R., G.A.S., J.P.B. and P.A.B.; resources, G.R. and P.A.B.; writing—original draft preparation, G.R.; writing—review and editing, G.R., G.A.S., J.P.B. and P.A.B.; supervision, G.R.; project administration, G.R.; funding acquisition, P.A.B. All authors have read and agreed to the published version of the manuscript.

Funding

This work was in part funded by the Government of Canada Natural Sciences and Engineering Research Council of Canada (NSERC).

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Conflicts of Interest

P.A.B. is an employee of SEED, a producer of a synbiotic product. G.R. consults for SEED and KGK Science.

References

  1. Hinde, K.; German, J.B. Food in an evolutionary context: Insights from mother’s milk. J. Sci. Food Agric. 2012, 92, 2219–2223. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  2. Aagaard, K.; Ma, J.; Antony, K.M.; Ganu, R.; Petrosino, J.; Versalovic, J. The Placenta Harbors a Unique Microbiome. Sci. Transl. Med. 2014, 6, 237ra65. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  3. Dudley, D.J. The placental microbiome: Yea, nay or maybe? Brit. J. Obstet. Gynecol. 2020, 127, 170. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  4. Fricke, W.F.; Ravel, J. Microbiome or no microbiome: Are we looking at the prenatal environment through the right lens? Microbiome 2021, 9, 9. [Google Scholar] [CrossRef] [PubMed]
  5. Burton, J.; Dixon, J.; Reid, G. Detection of Bifidobacterium species and Gardnerella vaginalis in the vagina using PCR and denaturing gradient gel electrophoresis (DGGE). Int. J. Gynecol. Obstet. 2003, 81, 61–63. [Google Scholar] [CrossRef]
  6. Sirilun, S.; Takahashi, H.; Boonyaritichaikij, S.; Chaiyasut, C.; Lertruangpanya, P.; Koga, Y.; Mikami, K. Impact of maternal bifidobacteria and the mode of delivery on Bifidobacterium microbiota in infants. Benef. Microbes 2015, 6, 767–774. [Google Scholar] [CrossRef]
  7. Freitas, A.C.; Hill, J.E. Bifidobacteria isolated from vaginal and gut microbiomes are indistinguishable by comparative genomics. PLoS One 2018, 13, e0196290. [Google Scholar] [CrossRef] [Green Version]
  8. Turroni, F.; Marchesi, J.R.; Foroni, E.; Gueimonde, M.; Shanahan, F.; Margolles, A.; Van Sinderen, D.; Ventura, M. Microbiomic analysis of the bifidobacterial population in the human distal gut. ISME J. 2009, 3, 745–751. [Google Scholar] [CrossRef] [Green Version]
  9. Tojo, R.; Suárez, A.; Clemente, M.G.; de los Reyes-Gavilán, C.G.; Margolles, A.; Gueimonde, M.; Ruas-Madiedo, P. Intestinal microbiota in health and disease: Role of bifidobacteria in gut homeostasis. World J. Gastroenterol. 2014, 20, 15163–15176. [Google Scholar] [CrossRef]
  10. Stappenbeck, T.S.; Hooper, L.V.; Gordon, J.I. Nonlinear partial differential equations and applications: Developmental regulation of intestinal angiogenesis by indigenous microbes via Paneth cells. Proc. Natl. Acad. Sci. USA 2002, 99, 15451–15455. [Google Scholar] [CrossRef] [Green Version]
  11. Wilmanski, T.; Diener, C.; Rappaport, N.; Patwardhan, S.; Wiedrick, J.; Lapidus, J.; Earls, J.C.; Zimmer, A.; Glusman, G.; Robinson, M.; et al. Gut microbiome pattern reflects healthy ageing and predicts survival in humans. Nat. Metab. 2021, 3, 274–286. [Google Scholar] [CrossRef] [PubMed]
  12. Rinninella, E.; Raoul, P.; Cintoni, M.; Franceschi, F.; Miggiano, G.A.; Gasbarrini, A.; Mele, M.C. What is the healthy gut microbiota composition? A changing ecosystem across age, environment, diet, and diseases. Microorganisms 2019, 7, 14. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  13. Laterza, L.; Rizzatti, G.; Gaetani, E.; Chiusolo, P.; Gasbarrini, A. The gut microbiota and immune system relationship in human graft-versus-host disease. Mediterr. J. Hematol. Infect. Dis. 2016, 8, 2016025. [Google Scholar] [CrossRef] [Green Version]
  14. Arumugam, M.; Raes, J.; Pelletier, E.; Le Paslier, D.; Yamada, T.; Mende, D.R.; Fernandes, G.D.R.; Tap, J.; Bruls, T.; Batto, J.M.; et al. Enterotypes of the human gut microbiome. Nature 2011, 473, 174–180. [Google Scholar] [CrossRef] [PubMed]
  15. Bäckhed, F.; Roswall, J.; Peng, Y.; Feng, Q.; Jia, H.; Kovatcheva-Datchary, P.; Li, Y.; Xia, Y.; Xie, H.; Zhong, H.; et al. Dynamics and stabilization of the human gut microbiome during the first year of life. Cell Host Microbe 2015, 17, 690–703. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  16. Lewis, Z.T.; Mills, D.A. Differential establishment of bifidobacteria in the breastfed infant gut. In Global Landscape of Nutrition Challenges in Infants and Children; Karger Medical and Scientific Publishers: Basel, Switzerland, 2017; Volume 88, pp. 149–159. [Google Scholar]
  17. 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] [CrossRef] [PubMed] [Green Version]
  18. Turroni, F.; Milani, C.; Duranti, S.; Ferrario, C.; Lugli, G.A.; Mancabelli, L.; Van Sinderen, D.; Ventura, M. Bifidobacteria and the infant gut: An example of co-evolution and natural selection. Cell. Mol. Life Sci. 2018, 75, 103–118. [Google Scholar] [CrossRef]
  19. Sakanaka, M.; Gotoh, A.; Yoshida, K.; Odamaki, T.; Koguchi, H.; Xiao, J.-Z.; Kitaoka, M.; Katayama, T. Varied pathways of infant gut-associated Bifidobacterium to assimilate human milk oligosaccharides: Prevalence of the gene set and its correlation with bifidobacteria-rich microbiota formation. Nutrients 2019, 12, 71. [Google Scholar] [CrossRef] [Green Version]
  20. Devika, N.T.; Raman, K. Deciphering the metabolic capabilities of bifidobacteria using genome-scale metabolic models. Sci. Rep. 2019, 9, 18222. [Google Scholar] [CrossRef] [Green Version]
  21. Duar, R.M.; Casaburi, G.; Mitchell, R.D.; Scofield, L.N.; Ramirez, C.A.O.; Barile, D.; Henrick, B.M.; Frese, S.A. Comparative genome analysis of Bifidobacterium longum subsp. infantis strains reveals variation in human milk oligosaccharide utilization genes among commercial probiotics. Nutrients 2020, 12, 3247. [Google Scholar] [CrossRef]
  22. Lawson, M.A.E.; O’neill, I.J.; Kujawska, M.; Javvadi, S.G.; Wijeyesekera, A.; Flegg, Z.; Chalklen, L.; Hall, L.J. Breast milk-derived human milk oligosaccharides promote Bifidobacterium interactions within a single ecosystem. ISME J. 2019, 14, 635–648. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  23. Taft, D.H.; Liu, J.; Maldonado-Gomez, M.X.; Akre, S.; Huda, M.N.; Ahmad, S.M.; Stephensen, C.B.; Mills, D.A. Bifidobacterial dominance of the gut in early life and acquisition of antimicrobial resistance. mSphere 2018, 3, e00441-18. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  24. Grzeskowiak, L.; Collado, M.C.; Mangani, C.; Maleta, K.; Laitinen, K.; Ashorn, P.; Isolauri, E.; Salminen, S. Distinct gut microbiota in southeastern African and northern European infants. J. Pediatr. Gastroenterol. Nutr. 2012, 54, 812–816. [Google Scholar] [CrossRef] [PubMed]
  25. Garrido, D.; Ruiz-Moyano, S.; Lemay, D.; Sela, D.A.; German, J.B.; Mills, D.A. Comparative transcriptomics reveals key differences in the response to milk oligosaccharides of infant gut-associated bifidobacteria. Sci. Rep. 2015, 5, 13517. [Google Scholar] [CrossRef]
  26. Underwood, M.A.; German, J.B.; Lebrilla, C.B.; Mills, D.A. Bifidobacterium longum subspecies infantis: Champion colonizer of the infant gut. Pediatr. Res. 2015, 77, 229–235. [Google Scholar] [CrossRef] [Green Version]
  27. Underwood, M.A.; Kalanetra, K.M.; Bokulich, N.A.; Lewis, Z.T.; Mirmiran, M.; Tancredi, D.; Mills, D.A. A comparison of two probiotic strains of bifidobacteria in premature infants. J. Pediatr. 2013, 163, 1585–1591.e9. [Google Scholar] [CrossRef] [Green Version]
  28. De Simone, C. The unregulated probiotic market. Clin. Gastroenterol. Hepatol. 2019, 17, 809–817. [Google Scholar] [CrossRef] [Green Version]
  29. Stuivenberg, G.; Daisley, B.; Akouris, P.; Reid, G. In vitro assessment of histamine and lactate production by a multi-strain synbiotic. J. Food Sci. Technol. 2021, 1–9. [Google Scholar] [CrossRef]
  30. Puebla-Barragan, S.; Watson, E.; van der Veer, C.; Chmiel, J.; Carr, C.; Burton, J.; Sumarah, M.; Kort, R.; Reid, G. Interstrain variability of human vaginal Lactobacillus crispatus for metabolism of biogenic amines and antimicrobial activity against urogenital pathogens. Molecules 2021, 26, 4538. [Google Scholar] [CrossRef]
  31. E Silva, A.C.S.; Oliveira, E.A.; Mak, R.H. Urinary tract infection in pediatrics: An overview. J. Pediatr. 2020, 96 (Suppl. S1), 65–79. [Google Scholar] [CrossRef]
  32. Ewaschuk, J.B.; Diaz, H.; Meddings, L.; Diederichs, B.; Dmytrash, A.; Backer, J.; Looijer-van Langen, M.; Madsen, K.L. Secreted bioactive factors from Bifidobacterium infantis enhance epithelial cell barrier function. Am. J. Physiol. Liver Physiol. 2008, 295, G1025–G1034. [Google Scholar]
  33. Alessandri, G.; Ossiprandi, M.C.; Mac Sharry, J.; Van Sinderen, D.; Ventura, M. Bifidobacterial dialogue with its human host and consequent modulation of the immune system. Front. Immunol. 2019, 10, 2348. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  34. Deo, P.N.; Deshmukh, R. Oral microbiome: Unveiling the fundamentals. J. Oral Maxillofac. Pathol. 2019, 23, 122–128. [Google Scholar] [CrossRef]
  35. Reid, G.; Gadir, A.A.; Barragan, S.P.; Dhir, R. Deconstructing then priming gut microbiota resilience. OBM Hepatol. Gastroenterol. 2021, 5, 9. [Google Scholar] [CrossRef]
  36. Yatsunenko, T.; Rey, F.E.; Manary, M.J.; Trehan, I.; Dominguez-Bello, M.G.; Contreras, M.; Magris, M.; Hidalgo, G.; Baldassano, R.N.; Anokhin, A.P.; et al. Human gut microbiome viewed across age and geography. Nature 2012, 486, 222–227. [Google Scholar] [CrossRef]
  37. La Rosa, P.S.; Warner, B.B.; Zhou, Y.; Weinstock, G.M.; Sodergren, E.; Hall-Moore, C.M.; Stevens, H.J.; Bennett, W.E.; Shaikh, N.; Linneman, L.A.; et al. Patterned progression of bacterial populations in the premature infant gut. Proc. Natl. Acad. Sci. USA 2014, 111, 12522–12527. [Google Scholar] [CrossRef] [Green Version]
  38. Eggesbø, M.; Moen, B.; Peddada, S.; Baird, D.; Rugtveit, J.; Midtvedt, T.; Bushel, P.R.; Sekelja, M.; Rudi, K. Development of gut microbiota in infants not exposed to medical interventions. Apmis 2010, 119, 17–35. [Google Scholar] [CrossRef]
  39. Dominguez-Bello, M.G.; Costello, E.K.; Contreras, M.; Magris, M.; Hidalgo, G.; Fierer, N.; Knight, R. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc. Natl. Acad. Sci. USA 2010, 107, 11971–11975. [Google Scholar] [CrossRef] [Green Version]
  40. Ding, T.; Schloss, P.D. Dynamics and associations of microbial community types across the human body. Nature 2014, 509, 357–360. [Google Scholar] [CrossRef]
  41. Derrien, M.; Alvarez, A.-S.; de Vos, W.M. The gut microbiota in the first decade of life. Trends Microbiol. 2019, 27, 997–1010. [Google Scholar] [CrossRef] [Green Version]
  42. Avershina, E.; Lundgård, K.; Sekelja, M.; Dotterud, C.; Storrø, O.; Øien, T.; Johnsen, R.; Rudi, K. Transition from infant- to adult-like gut microbiota. Environ. Microbiol. 2016, 18, 2226–2236. [Google Scholar] [CrossRef] [PubMed]
  43. Sutharsan, R.; Mannan, M.; Doi, S.A.; Al Mamun, A. Caesarean delivery and the risk of offspring overweight and obesity over the life course: A systematic review and bias-adjusted meta-analysis. Clin. Obes. 2015, 5, 293–301. [Google Scholar] [CrossRef]
  44. Korpela, K.; Zijlmans, M.A.C.; Kuitunen, M.; Kukkonen, K.; Savilahti, E.; Salonen, A.; De Weerth, C.; De Vos, W.M. Childhood BMI in relation to microbiota in infancy and lifetime antibiotic use. Microbiome 2017, 5, 26. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  45. Moens, F.; Verce, M.; De Vuyst, L. Lactate- and acetate-based cross-feeding interactions between selected strains of lactobacilli, bifidobacteria and colon bacteria in the presence of inulin-type fructans. Int. J. Food Microbiol. 2017, 241, 225–236. [Google Scholar] [CrossRef] [PubMed]
  46. Rivière, A.; Selak, M.; Lantin, D.; Leroy, F.; De Vuyst, L. Bifidobacteria and butyrate-producing colon bacteria: Importance and strategies for their stimulation in the human gut. Front. Microbiol. 2016, 7, 979. [Google Scholar] [CrossRef] [Green Version]
  47. Özcan, E.; Sela, D.A. Inefficient metabolism of the human milk oligosaccharides Lacto-N-tetraose and Lacto-N-neotetraose shifts Bifidobacterium longum subsp. infantis physiology. Front. Nutr. 2018, 5, 46. [Google Scholar] [CrossRef]
  48. Stanford, J.; Charlton, K.; Stefoska-Needham, A.; Ibrahim, R.; Lambert, K. The gut microbiota profile of adults with kidney disease and kidney stones: A systematic review of the literature. BMC Nephrol. 2020, 21, 215. [Google Scholar] [CrossRef]
  49. Canani, R.B.; Di Costanzo, M.; Leone, L.; Pedata, M.; Meli, R.; Calignano, A. Potential beneficial effects of butyrate in intestinal and extraintestinal diseases. World J. Gastroenterol. 2011, 17, 1519–1528. [Google Scholar] [CrossRef]
  50. Clayton, D.B.; Pope, J.C. The increasing pediatric stone disease problem. Ther. Adv. Urol. 2011, 3, 3–12. [Google Scholar] [CrossRef] [Green Version]
  51. Bikbov, B.; Purcell, C.A.; Levey, A.S.; Smith, M.; Abdoli, A.; Abebe, M.; Adebayo, O.M.; Afarideh, M.; Agarwal, S.K.; Agudelo-Botero, M.; et al. Global, regional, and national burden of chronic kidney disease, 1990–2017: A systematic analysis for the Global Burden of Disease Study 2017. Lancet 2020, 395, 709–733. [Google Scholar] [CrossRef] [Green Version]
  52. Kelly, S.M.; Munoz-Munoz, J.; van Sinderen, D. Plant glycan metabolism by bifidobacteria. Front. Microbiol. 2021, 12, 25. [Google Scholar] [CrossRef] [PubMed]
  53. Turroni, F.; Özcan, E.; Milani, C.; Mancabelli, L.; Viappiani, A.; van Sinderen, D.; Sela, D.; Ventura, M. Glycan cross-feeding activities between bifidobacteria under in vitro conditions. Front. Microbiol. 2015, 6, 1030. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  54. Egan, M.; Motherway, M.O.; Kilcoyne, M.; Kane, M.; Joshi, L.; Ventura, M.; Van Sinderen, D. Cross-feeding by Bifidobacterium breve UCC2003 during co-cultivation with Bifidobacterium bifidum PRL2010 in a mucin-based medium. BMC Microbiol. 2014, 14, 282. [Google Scholar] [CrossRef] [Green Version]
  55. Bunesova, V.; Lacroix, C.; Schwab, C. Mucin cross-feeding of infant bifidobacteria and Eubacterium hallii. Microb. Ecol. 2018, 75, 228–238. [Google Scholar] [CrossRef] [PubMed]
  56. Rios-Covian, D.; Gueimonde, M.; Duncan, S.H.; Flint, H.J.; de Los Reyes-Gavilan, C. Enhanced butyrate formation by cross-feeding between Faecalibacterium prausnitzii and Bifidobacterium adolescentis. FEMS Microbiol. Lett. 2015, 362, fnv176. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  57. Boger, M.C.L.; van Bueren, A.L.; Dijkhuizen, L. Cross-feeding among probiotic bacterial strains on prebiotic inulin involves the extracellular exo-inulinase of Lactobacillus paracasei strain W20. Appl. Environ. Microbiol. 2018, 84, e01539-18. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  58. Cheng, C.C.; Duar, R.M.; Lin, X.; Perez-Munoz, M.E.; Tollenaar, S.; Oh, J.-H.; van Pijkeren, J.-P.; Li, F.; van Sinderen, D.; Gänzle, M.G.; et al. Ecological importance of cross-feeding of the intermediate metabolite 1,2-propanediol between bacterial gut symbionts. Appl. Environ. Microbiol. 2020, 86, e00190-20. [Google Scholar] [CrossRef]
  59. Munoz, J.; James, K.; Bottacini, F.; Van Sinderen, D. Biochemical analysis of cross-feeding behaviour between two common gut commensals when cultivated on plant-derived arabinogalactan. Microb. Biotechnol. 2020, 13, 1733–1747. [Google Scholar] [CrossRef]
  60. Neu, J.; Rushing, J. Cesarean versus vaginal delivery: Long-term infant outcomes and the hygiene hypothesis. Clin. Perinatol. 2011, 38, 321–331. [Google Scholar] [CrossRef] [Green Version]
  61. Yang, W.; Tian, L.; Luo, J.; Yu, J. Ongoing supplementation of probiotics to caesarean-born neonates during the first month of life may impact the gut microbial. Am. J. Perinatol. 2021, 38, 1181–1191. [Google Scholar] [CrossRef]
  62. Korpela, K.; Salonen, A.; Vepsäläinen, O.; Suomalainen, M.; Kolmeder, C.; Varjosalo, M.; Miettinen, S.; Kukkonen, K.; Savilahti, E.; Kuitunen, M.; et al. Probiotic supplementation restores normal microbiota composition and function in antibiotic-treated and in caesarean-born infants. Microbiome 2018, 6, 182. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  63. Motherway, M.O.; Houston, A.; O’Callaghan, G.; Reunanen, J.; O’brien, F.; O’driscoll, T.; Casey, P.G.; De Vos, W.M.; Van Sinderen, D.; Shanahan, F. A bifidobacterial pilus-associated protein promotes colonic epithelial proliferation. Mol. Microbiol. 2019, 111, 287–301. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  64. Penders, J.; Thijs, C.; Vink, C.; Stelma, F.F.; Snijders, B.; Kummeling, I.; Van den Brandt, P.A.; Stobberingh, E.E. Factors influencing the composition of the intestinal microbiota in early infancy. Pediatrics 2006, 118, 511–521. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  65. Rutayisire, E.; Huang, K.; Liu, Y.; Tao, F. The mode of delivery affects the diversity and colonization pattern of the gut microbiota during the first year of infants’ life: A systematic review. BMC Gastroenterol. 2016, 16, 86. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  66. Werlang, I.C.R.; Mueller, N.T.; Pizoni, A.; Wisintainer, H.; Matte, U.; de Almeida Martins Costa, S.H.; Ramos, J.G.L.; Goldani, M.Z.; Dominguez-Bello, M.G.; Goldani, H.A.S. Associations of birth mode with cord blood cytokines, white blood cells, and newborn intestinal bifidobacteria. PLoS One 2018, 13, e0205962. [Google Scholar] [CrossRef]
  67. Morais, L.H.; Golubeva, A.V.; Moloney, G.M.; Moya-Pérez, A.; Ventura-Silva, A.P.; Arboleya, S.; Bastiaanssen, T.F.; O’sullivan, O.; Rea, K.; Borre, Y.; et al. Enduring behavioral effects induced by birth by caesarean section in the mouse. Curr. Biol. 2020, 30, 3761–3774.e6. [Google Scholar] [CrossRef]
  68. Fukuda, S.; Toh, H.; Hase, K.; Oshima, K.; Nakanishi, Y.; Yoshimura, K.; Tobe, T.; Clarke, J.M.; Topping, D.L.; Suzuki, T.; et al. Bifidobacteria can protect from enteropathogenic infection through production of acetate. Nature 2011, 469, 543–547. [Google Scholar] [CrossRef]
  69. Henrick, B.M.; Rodriguez, L.; Lakshmikanth, T.; Pou, C.; Henckel, E.; Arzoomand, A.; Olin, A.; Wang, J.; Mikes, J.; Tan, Z.; et al. Bifidobacteria-mediated immune system imprinting early in life. Cell 2021, 184, 3884–3898.e11. [Google Scholar] [CrossRef]
  70. He, F.; Ouwehand, A.C.; Isolauri, E.; Hashimoto, H.; Benno, Y.; Salminen, S. Comparison of mucosal adhesion and species identification of bifidobacteria isolated from healthy and allergic infants. FEMS Immunol. Med. Microbiol. 2001, 30, 43–47. [Google Scholar] [CrossRef]
  71. Sun, S.; Luo, L.; Liang, W.; Yin, Q.; Guo, J.; Rush, A.M.; Lv, Z.; Liang, Q.; Fischbach, M.A.; Sonnenburg, J.L.; et al. Bifidobacterium alters the gut microbiota and modulates the functional metabolism of T regulatory cells in the context of immune checkpoint blockade. Proc. Natl. Acad. Sci. USA 2020, 177, 27509–27515. [Google Scholar] [CrossRef]
  72. Mansfield, J.A.; Bergin, S.W.; Cooper, J.R.; Olsen, C.H. Comparative probiotic strain efficacy in the prevention of eczema in infants and children: A systematic review and meta-analysis. Mil. Med. 2014, 179, 580–592. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  73. Xiao, J.Z.; Kondo, S.; Yanagisawa, N.; Takahashi, N.; Odamaki, T.; Iwabuchi, N.; Iwatsuki, K.; Kokubo, S.; Togashi, H.; Enomoto, K.; et al. Effect of probiotic Bifidobacterium longum BB536 [corrected] in relieving clinical symptoms and modulating plasma cytokine levels of Japanese cedar pollinosis during the pollen season. A randomized double-blind, placebo-controlled trial. J. Investig. Allergol. Clin. Immunol. 2006, 16, 86–93. [Google Scholar] [PubMed]
  74. Reid, G.; Gaudier, E.; Guarner, F.; Huffnagle, G.B.; Macklaim, J.M.; Munoz, A.M.; Martini, M.; Ringel-Kulka, T.; Sartor, B.R.; Unal, R.R.; et al. Responders and non-responders to probiotic interventions: How can we improve the odds? Gut Microbes 2010, 1, 200–204. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  75. Ojima, M.N.; Gotoh, A.; Takada, H.; Odamaki, T.; Xiao, J.-Z.; Katoh, T.; Katayama, T. Bifidobacterium bifidum suppresses gut inflammation caused by repeated antibiotic disturbance without recovering gut microbiome diversity in mice. Front. Microbiol. 2020, 11, 1349. [Google Scholar] [CrossRef] [PubMed]
  76. Guardamagna, O.; Amaretti, A.; Puddu, P.E.; Raimondi, S.; Abello, F.; Cagliero, P.; Rossi, M. Bifidobacteria supplementation: Effects on plasma lipid profiles in dyslipidemic children. Nutrition 2014, 30, 831–836. [Google Scholar] [CrossRef]
  77. Van den Akker, C.H.; van Goudoever, J.B.; Shamir, R.; Domellöf, M.; Embleton, N.D.; Hojsak, I.; Lapillonne, A.; Mihatsch, W.A.; Canani, R.B.; Bronsky, J.; et al. Probiotics and preterm infants: A position paper by the European Society for Paediatric Gastroenterology Hepatology and Nutrition Committee on Nutrition and the European Society for Paediatric Gastroenterology Hepatology and Nutrition Working Group for Probiotics and Prebiotics. J. Pediatr. Gastroenterol. Nutr. 2020, 70, 664–680. [Google Scholar]
  78. Cheng, L.; Kiewiet, M.B.G.; Logtenberg, M.J.; Groeneveld, A.; Nauta, A.; Schols, H.A.; Walvoort, M.T.C.; Harmsen, H.J.M.; De Vos, P. Effects of different human milk oligosaccharides on growth of bifidobacteria in monoculture and co-culture with Faecalibacterium prausnitzii. Front. Microbiol. 2020, 11, 569700. [Google Scholar] [CrossRef]
  79. Silva, Y.P.; Bernardi, A.; Frozza, R.L. The role of short-chain fatty acids from gut microbiota in gut-brain communication. Front. Endocrinol. 2020, 11, 25. [Google Scholar] [CrossRef] [Green Version]
  80. Dalile, B.; Van Oudenhove, L.; Vervliet, B.; Verbeke, K. The role of short-chain fatty acids in microbiota-gut-brain communication. Nat. Rev. Gastroenterol. Hepatol. 2019, 160, 461–478. [Google Scholar] [CrossRef]
  81. Townsend, S.; Caubillabarron, J.; Loc-Carrillo, C.; Forsythe, S. The presence of endotoxin in powdered infant formula milk and the influence of endotoxin and Enterobacter sakazakii on bacterial translocation in the infant rat. Food Microbiol. 2007, 24, 67–74. [Google Scholar] [CrossRef]
  82. Liu, G.; Chen, H.; Chen, J.; Wang, X.; Gu, Q.; Yin, Y. Effects of bifidobacteria-produced exopolysaccharides on human gut microbiota in vitro. Appl. Microbiol. Biotechnol. 2019, 103, 1693–1702. [Google Scholar] [CrossRef] [PubMed]
  83. Collins, S.; Reid, G. Distant site effects of ingested prebiotics. Nutrition 2016, 8, 523. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  84. Li, L.-Z.; Tao, S.-B.; Ma, L.; Fu, P. Roles of short-chain fatty acids in kidney diseases. Chin. Med. J. 2019, 132, 1228–1232. [Google Scholar] [CrossRef] [PubMed]
  85. Wang, S.; Lv, D.; Jiang, S.; Jiang, J.; Liang, M.; Hou, F.; Chen, Y. Quantitative reduction in short-chain fatty acids, especially butyrate, contributes to the progression of chronic kidney disease. Clin. Sci. 2019, 133, 1857–1870. [Google Scholar] [CrossRef] [PubMed]
  86. Daisley, B.A.; Koenig, D.; Engelbrecht, K.; Doney, L.; Hards, K.; Al, K.F.; Reid, G.; Burton, J.P. Emerging connections between gut microbiome bioenergetics and chronic metabolic diseases. Cell Rep. 2021, 37, 1–19. [Google Scholar] [CrossRef] [PubMed]
  87. Daisley, B.A.; Chanyi, R.M.; Abdur-Rashid, K.; Al, K.F.; Gibbons, S.; Chmiel, J.A.; Wilcox, H.; Reid, G.; Anderson, A.; Dewar, M.; et al. Abiraterone acetate preferentially enriches for the gut commensal Akkermansia muciniphila in castrate-resistant prostate cancer patients. Nat. Commun. 2020, 11, 4822. [Google Scholar] [CrossRef] [PubMed]
  88. Duncan, S.H.; Hold, G.L.; Barcenilla, A.; Stewart, C.S.; Flint, H.J. Roseburia intestinalis sp. nov., a novel saccharolytic, butyrate-producing bacterium from human faeces. Int. J. Syst. Evol. Microbiol. 2002, 52, 1615–1620. [Google Scholar] [CrossRef] [Green Version]
  89. Shetty, S.A.; Boeren, S.; Bui, T.P.N.; Smidt, H.; De Vos, W.M. Unravelling lactate-acetate and sugar conversion into butyrate by intestinal Anaerobutyricum and Anaerostipes species by comparative proteogenomics. Environ. Microbiol. 2020, 22, 4863–4875. [Google Scholar] [CrossRef] [PubMed]
  90. Dordević, D.; Jančíková, S.; Vítězová, M.; Kushkevych, I. Hydrogen sulfide toxicity in the gut environment: Meta-analysis of sulfate-reducing and lactic acid bacteria in inflammatory processes. J. Adv. Res. 2021, 27, 55–69. [Google Scholar] [CrossRef]
  91. Wang, G.; Wang, D.; Huang, L.; Song, Y.; Chen, Z.; Du, M. Enhanced production of volatile fatty acids by adding a kind of sulfate reducing bacteria under alkaline pH. Colloids Surf. B Biointerfaces 2020, 195, 111249. [Google Scholar] [CrossRef]
  92. Sagheddu, V.; Patrone, V.; Miragoli, F.; Morelli, L. Abundance and diversity of hydrogenotrophic microorganisms in the infant gut before the weaning period assessed by denaturing gradient gel electrophoresis and quantitative PCR. Front. Nutr. 2017, 4, 29. [Google Scholar] [CrossRef] [PubMed]
  93. Infante, D.; Segarra, O.; Le Luyer, B. Dietary treatment of colic caused by excess gas in infants: Biochemical evidence. World J. Gastroenterol. 2011, 17, 2104–2108. [Google Scholar] [CrossRef] [PubMed]
  94. Fukuda, S.; Toh, H.; Taylor, T.; Ohno, H.; Hattori, M. Acetate-producing bifidobacteria protect the host from enteropathogenic infection via carbohydrate transporters. Gut Microbes 2012, 3, 449–454. [Google Scholar] [CrossRef] [Green Version]
  95. Golubeva, A.V.; Joyce, S.A.; Moloney, G.; Burokas, A.; Sherwin, E.; Arboleya, S.; Flynn, I.; Khochanskiy, D.; Moya-Pérez, A.; Peterson, V.; et al. Microbiota-related changes in bileaAcid & tryptophan metabolism are associated with gastrointestinal dysfunction in a mouse model of autism. EBioMedicine 2017, 24, 166–178. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  96. Persico, A.M.; Napolioni, V. Urinary p-cresol in autism spectrum disorder. Neurotoxicol. Teratol. 2013, 36, 82–90. [Google Scholar] [CrossRef] [PubMed]
  97. Gabriele, S.; Sacco, R.; Altieri, L.; Neri, C.; Urbani, A.; Bravaccio, C.; Riccio, M.P.; Iovene, M.R.; Bombace, F.; De Magistris, L.; et al. Slow intestinal transit contributes to elevate urinary p-cresol level in Italian autistic children. Autism Res. 2016, 9, 752–759. [Google Scholar] [CrossRef]
  98. Pascucci, T.; Colamartino, M.; Fiori, E.; Sacco, R.; Coviello, A.; Ventura, R.; Puglisi-Allegra, S.; Turriziani, L.; Persico, A.M. p-cresol alters brain dopamine metabolism and exacerbates autism-like behaviors in the BTBR mouse. Brain Sci. 2020, 10, 233. [Google Scholar] [CrossRef]
  99. Harambat, J.; Van Stralen, K.J.; Kim, J.J.; Tizard, E.J. Epidemiology of chronic kidney disease in children. Pediatr. Nephrol. 2012, 27, 363–373. [Google Scholar] [CrossRef] [Green Version]
  100. Nada, A.; Bonachea, E.M.; Askenazi, D.J. Acute kidney injury in the fetus and neonate. Semin. Fetal Neonatal Med. 2017, 22, 90–97. [Google Scholar] [CrossRef] [Green Version]
Figure 1. Influence of bifidobacteria on promoting a healthy gut microbiota and factors that affect their colonization.
Figure 1. Influence of bifidobacteria on promoting a healthy gut microbiota and factors that affect their colonization.
Microorganisms 10 00278 g001
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Share and Cite

MDPI and ACS Style

Stuivenberg, G.A.; Burton, J.P.; Bron, P.A.; Reid, G. Why Are Bifidobacteria Important for Infants? Microorganisms 2022, 10, 278. https://doi.org/10.3390/microorganisms10020278

AMA Style

Stuivenberg GA, Burton JP, Bron PA, Reid G. Why Are Bifidobacteria Important for Infants? Microorganisms. 2022; 10(2):278. https://doi.org/10.3390/microorganisms10020278

Chicago/Turabian Style

Stuivenberg, Gerrit A., Jeremy P. Burton, Peter A. Bron, and Gregor Reid. 2022. "Why Are Bifidobacteria Important for Infants?" Microorganisms 10, no. 2: 278. https://doi.org/10.3390/microorganisms10020278

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop