Search Results (228)

The pathogenesis of primary biliary cholangitis (PBC) is not fully understood. Despite recent progress, many aspects require further clarification. Thus, PBC is regarded as an autoimmune disease, but immunosuppressive treatment, which is effective in other autoimmune diseases, is not working in the case of PBC. Moreover, there are controversies over the pathogenetic role of anti-mitochondrial antibodies as mitochondria are present in all cells but only cholangiocytes are damaged. In this review, all the proposed models and factors that have been involved in the pathogenesis of PBC are presented. They include mechanisms such as dysregulated autophagy, senescence, apoptosis, impairment of the protective bicarbonate umbrella, immunological abnormalities, the dysbiosis of gut microbiota, and the role of bile acids. Genetics of PBC and epigenetic transcriptional modifications are also presented. Data supporting molecular mimicry and the viral etiology of PBC are analyzed. Finally, an integrated model is proposed based on interactions of the factors that may participate in PBC pathogenesis. Therefore, the purpose of this review is to provide a unifying presentation of the various aspects of PBC pathophysiology, which will allow for a better understanding of this multifaceted disease. New treatment targets may also be identified in such a holistic model. Full article

Background/Objectives: Eggshell quality is a critical factor influencing consumer preference and the economic benefits of poultry enterprises, and the uterus is the key site for eggshell synthesis. Yaoshan chicken (YS), an indigenous chicken breed in China, is renowned for its flavorful meat and high-quality eggs. However, its egg production is lower compared to specialized strains. Therefore, the GYR crossbreed was developed by three-line hybridization for YS chicken, which can produce green-shelled eggs with better eggshell thickness and strength than YS chicken (p < 0.01). To explore the molecular mechanisms underlying the differences in eggshell quality between GYR and YS chickens, we conducted an integrated transcriptomic and metabolomic analysis. Methods: Twelve uterus samples (six from GYR and six from YS chickens) were collected during the period of eggshell calcification at 260 days of age. RNA sequencing (RNA-seq) and liquid chromatography–mass spectrometry (LC-MS/MS) were performed to identify differentially expressed genes (DEGs) and differential metabolites (DMs), respectively. Results: A total of 877 DEGs were identified in the GYR group, including 196 upregulated and 681 downregulated genes (|log₂ (fold change)| > 1, p-value < 0.05). Additionally, 79 DMs were detected, comprising 50 upregulated and 29 downregulated metabolites (|log₂ (fold change)| > 1, VIP > 1). Notably, the key DEGs (SLCO1B3, SLCO1B1, PTGR1, LGR6, MELTF, CRISP2, GVINP1, and OVSTL), important DMs (prostaglandin-related DMs and biliverdin) and signaling pathways (calcium signaling, neuroactive ligand–receptor interaction, arachidonic acid metabolism, bile secretion, and primary bile acid biosynthesis) were major regulators of the eggshell quality. Furthermore, an integrated transcriptomic and metabolomic analysis revealed two significant gene–metabolite pairs associated with eggshell quality: PTGDS–prostaglandin E2 and PTGS1–prostaglandin E2. Conclusions: This study provides a theoretical foundation for the improved eggshell quality of Yaoshan chicken. Full article

Background/Objectives: Severe fever with thrombocytopenia syndrome (SFTS) is a viral infection primarily found in Asia, with a case fatality rate of about 10%. Despite its increasing prevalence, the underlying pathogenic mechanisms remain poorly understood, limiting the development of effective therapeutic interventions. Methods: We employed an untargeted metabolomics approach using liquid chromatography–mass spectrometry (LC-MS) to analyze serum samples from 78 SFTS patients during the acute phase of their illness. Differential metabolic features between survival and fatal cases were identified through multivariate statistical analysis. Furthermore, we constructed a metabolic prognostic model based on these biomarkers to predict disease severity. Results: Significant alterations were observed in four key metabolic pathways: sphingolipid metabolism, biosynthesis of phenylalanine, tyrosine, and tryptophan, primary bile acid biosynthesis, and phenylalanine metabolism. Elevated levels of phenyllactic acid and isocitric acid were strongly associated with adverse outcomes and demonstrated high discriminatory power in distinguishing fatal cases from survivors. The metabolic prognostic model incorporating these biomarkers achieved a sensitivity of 75% and a specificity of 90% in predicting disease severity. Conclusions: Our findings highlight the pivotal role of metabolic dysregulation in the pathogenesis of SFTS and suggest that targeting specific metabolic pathways could open new avenues for therapeutic development. The identification of prognostic biomarkers provides a valuable tool for early risk stratification and timely clinical intervention, potentially improving patient outcomes. Full article

Background: Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by bile duct destruction, cholestasis, and fibrosis. Acylcarnitines are esters of carnitine responsible for the transport of long-chain fatty acids into mitochondria for β-oxidation, playing a crucial role in energy metabolism and lipid homeostasis. This study aimed to assess acylcarnitine and free fatty acid (FFA) profiles in PBC patients and their associations with fibrosis severity and inflammation. Methods: This cross-sectional study included 46 PBC patients and 32 healthy controls. Acylcarnitines and FFAs were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and enzymatic assays, respectively. Liver stiffness was measured by point shear wave elastography (ElastPQ), and fibrosis was assessed using APRI and FIB-4 scores. Inflammatory markers (IL-6, IL-1β) were also analyzed. Results: PBC patients had significantly higher levels of C18:1-acylcarnitine (median: 165.1 ng/mL) compared with the controls (152.4 ng/mL, p = 0.0036). Similarly, the FFA levels were markedly elevated in the PBC patients (median: 0.46 mM/L) compared with the controls (0.26 mM/L, p < 0.0001). Patients with higher liver stiffness (ElastPQ > 5.56 kPa) had significantly elevated C18:1-acylcarnitine (p = 0.0008) and FFA levels (p = 0.00098). Additionally, FFAs were significantly increased in patients with higher APRI and FIB-4 scores and were associated with elevated inflammatory markers (IL-6, IL-1β) and liver injury markers. Multivariate regression analysis confirmed C18:1-acylcarnitine (OR = 1.031, 95% CI: 1.007–1.057, p = 0.013) and FFAs (OR = 2.25 per 0.1 mM/L increase, 95% CI: 1.20–4.22, p = 0.012) as independent predictors of fibrosis severity in PBC. Conclusions: C18:1-acylcarnitine and FFAs are significantly elevated in PBC and are strongly associated with fibrosis severity and inflammation. These findings suggest a link between lipid metabolism disturbances and PBC. Both metabolites may potentially serve as non-invasive biomarkers of fibrosis progression in PBC, warranting further investigation. Full article

Background/Objectives: This article presents the case of a 31-year-old primigravida who experienced acute liver failure in the 23rd week of pregnancy, along with a review of the literature on this rare condition during pregnancy. The purpose of this publication is to highlight the diagnostic and therapeutic challenges associated with acute liver failure in pregnant women. Methods: The patient presented with jaundice, pruritus, and dark-colored urine. Laboratory tests revealed a significant increase in aminotransferase, bilirubin, and bile acid levels, suggesting liver problems; however, due to the patient’s rapidly deteriorating condition and test results, autoimmune hepatitis was considered. Viral infections and other causes of liver damage were excluded. No clear diagnosis was established. The patient was administered ursodeoxycholic acid and due to her worsening condition, a cesarean section was performed at 23 weeks of gestation. After delivery, the patient’s condition improved, although she did experience cardiac arrest during hospitalization. The patient was discharged with a diagnosis of acute liver failure in the course of an overlap syndrome of autoimmune hepatitis and primary cholangitis or intrahepatic cholestasis of pregnancy. No abnormalities were noted during a follow-up visit 6 weeks after delivery. Despite a detailed case analysis, a final diagnosis was not established, which complicates planning for future pregnancies. Discussion: Several liver conditions can occur during pregnancy, including intrahepatic cholestasis of pregnancy, primary biliary cholangitis, and autoimmune hepatitis. Diagnosing these conditions can be challenging due to overlapping symptoms and metabolic and immunological adaptations during pregnancy that can affect the course of liver diseases. Rapid intervention is crucial to protect the health of both the mother and the fetus. Conclusions: In summary, this article aims to increase awareness of the complexities surrounding acute liver failure during pregnancy, highlighting the diagnostic challenges and importance of prompt medical intervention for the well-being of both the mother and the child. This paper aims to provide a comprehensive overview of the complexities surrounding acute liver failure during pregnancy, aiming to improve the understanding, diagnosis, and management of this condition. Full article

Type 2 diabetes (T2D) is a chronic disease prevalent in the world, accompanied by a variety of diseases, endangering human health and safety. Bile acids (BAs) play an important role in the regulation of host glucose and lipid metabolism homeostasis, and are strictly regulated by gut microbiota. However, the relationship between key BAs, BAs transporters and signaling, as well as gut microbiota, and host metabolism in T2D remains elusive. In this study, 9-week-old db/db mice were used as diabetes model (db/db group, n = 10), and their wild-type (wt) littermates of same age were used as the healthy control (CON group, n = 10). After 8 weeks of feeding, the BA profiles and microbial composition in the colon, and gene expression level of BA regulatory factors were analyzed in the db/db and CON groups to explore the underlying mechanisms of T2D. Compared with healthy mice, the body weight, blood glucose and lipid levels of db/db mice were significantly increased. The concentrations of total BAs, primary BAs, conjugated BAs and non-12α–hydroxylated BAs (non-12–OH BAs) were significantly decreased, while Deoxycholic acid (DCA) in secondary BAs was increased in db/db group. Compared with wt mice, the synthesis of BAs in the liver was transformed from the alternative pathway to the classical pathway, and hepatic BAs transporters (NTCP, BSEP, MRP2, OATP–1 and OSTβ) and receptors (FXR and TGR5) were significantly down-regulated in the db/db mice. In the colon, the mRNA level of FXR was up-regulated, while TGR5 was down-regulated. The diabetic (db/db) mice presented a changed gut microbiota composition, including an increased abundance of secondary BAs-producing bacteria, Escherichia–Shigella, and a decreased the abundance of Akkermansia, which are involved in the synthesis of non-12–OH BAs. We further found that the reduced BA types in db/db mice were negatively correlated with metabolic-disorder-related indicators, while an increased DCA level had the opposite correlation. Our results shed light into how the imbalance of BAs’ metabolism mediated by intestinal flora may be potential mechanisms of T2D. Full article

Patients with chronic cholestatic liver diseases often experience itch and struggle with this symptom. We discuss the mechanism of itch in patients with chronic cholestatic liver diseases, such as primary biliary cholangitis (PBC) and others, and their therapies, including ileal bile acid transporter (IBAT) inhibitors. In patients with PBC, there are high serum/plasma concentrations of multiple factors, including bile salts, bilirubin, endogenous opioids, lysophosphatidic acid (LPA), autotaxin, and histamine. Bile salts, bilirubin, LPA, and autotaxin affect itch mediators in the skin and sensory nerves, while the endogenous opioid balance affects mediators in the spinal cord. Itch is sensitized by both the peripheral and central nervous systems. Both mechanisms are involved in itch in patients with chronic cholestatic liver disease. Although IBAT inhibitors have been approved for use in pediatric cholestatic conditions, such as progressive familial intrahepatic cholestasis and Alagille syndrome, IBAT inhibition seems to be a promising treatment for chronic refractory itch in patients with PBC. A traditional non-systematic review results in this narrative review. Multidisciplinary cooperation, involving hepatologists, dermatologists, and pharmacists, could provide better treatment for PBC patients suffering from refractory itch. In conclusion, we summarized the existing knowledge on itch caused by chronic cholestatic liver diseases, especially in PBC with a focus on the mechanisms and therapies. This narrative review provides the mechanisms and therapeutic options for itch in patients with chronic cholestatic liver diseases. Full article

Background and Aims: Primary biliary cholangitis (PBC) leads to the slow, progressive destruction of the small bile ducts with consecutive cholestasis and intrahepatic cholangitis. If this disease remains untreated, liver parenchyma will be damaged resulting in fibrosis and end-stage liver disease with the need for transplantation. The approval of the Farnesoid X receptor agonist obeticholic acid (Ocaliva; OCA) in early 2017 expanded the drug therapy options of PBC, which previously consisted primarily of the administration of ursodeoxycholic acid (UDCA). Patients and Methods: Included in our prospective pilot study were 16 patients with a confirmed diagnosis of PBC who were treated with an add-on therapy with OCA (5 mg/d). None of the patients had an overlap to autoimmune hepatitis. Patients were investigated between 09/2022 and 09/2023. Results: The majority of patients was female (15/16, 93.75%), and the mean age was 57.63 ± 9.59 (43–77) years. OCA treatment led to a statistically significant decrease in aspartate aminotransferase (AST; AST baseline: 38.50 [26.25; 50.00] IU/L vs. AST 6-month follow-up: 23.50 [21.50; 44.25] IU/L, p = 0.0012), alanine aminotransferase (ALT; ALT baseline: 55.50 [28.75; 97.00] IU/L vs. ALT 6-month follow-up: 36.50 [28.00; 57.25] IU/L, p = 0.0035), and gamma-glutamyl transferase (GGT; GGT baseline: 168.00 [100.30; 328.50] IU/L vs. GGT 6-month follow-up: 88.00 [44.50; 259.80] IU/L, p = 0.0063), while the decrease in alkaline phosphatase (AP) was not statistically significant (AP baseline: 197.00 [170.00; 253.30] IU/L vs. AP 6-month follow-up: 196.00 [134.00; 227.00] IU/L, p = 0.0915). In addition, liver stiffness measurement (LSM) showed a statistically significant decrease after six months of treatment with OCA (LSM baseline: 7.85 [5.55; 10.13] kPa vs. LSM 6-month follow-up: 5.95 [4.55; 8.225] kPa, p = 0.0001). However, the increase in enzymatic liver function measured by LiMAx failed to reach statistical significance, but showed a positive trend (LiMAx baseline: 402.50 [341.50; 469.80] μg/kg/h vs. LiMAx 6-month follow-up: 452.50 [412.50; 562.00] μg/kg/h, p = 0.0625). In none of our patients did therapy with obeticholic acid have to be stopped due to pruritus or poor tolerability. Conclusions: In patients with PBC without adequate response to UDCA, OCA is a promising alternative, which in our group of 16 patients led to a significant improvement of liver enzymes, the amelioration of liver fibrosis, and an increase in liver function capacity in a short-term clinical course. Full article

Bile salt hydrolase (BSH; EC 3.5.1.24) is the microbial enzyme that catalyzes the conversion of primary bile acids (BAs) into secondary ones, promoting microbial adaptation and modulating several host’s biological functions. Probiotics with BSH activity are supposed to survive harsh intestinal conditions and exert a cholesterol-lowering effect. Here, Lacticaseibacillus rhamnosus strains (VB4 and VB1), isolated from the vaginal ecosystem, were submitted to a genomic survey, in vitro BSH activity, and BAs tolerance assay to unravel their probiotic potential as BAs modulators. The draft genomes of Lcb. rhamnosus VB4 and VB1 strains comprised 2769 and 2704 CDSs, respectively. Gene annotation revealed numerous strain-specific genes involved in metabolism and transport, as well as in DNA recombination. Each strain harbors a single bsh gene, encoding a C-N amide hydrolase, which conserved the essential residues required in the BSH core site. According to the results, compared to VB1, the VB4 strain tolerated better BAs stress and was more active in deconjugating BAs. However, BAs stress increased the bsh gene transcription in the VB1 strain but not in the VB4 strain, suggesting a partially nonlinear relationship between BSH activity and gene expression. In conclusion, despite the complexity of the BSH transcriptional system, the results support the VB4 strain as a promising BAs-deconjugating probiotic candidate. Full article

Fatty liver hemorrhagic syndrome (FLHS) in laying hens is a nutritional and metabolic disease involving liver enlargement, hepatic steatosis, and hepatic hemorrhage as the primary symptoms. The syndrome is prone to occur during the peak laying period of laying hens, which has resulted in significant economic losses in the laying hen breeding industry; however, the specific pathogenesis of FLHS remains unclear. Our group and previous studies have shown that bile acid levels are significantly decreased during the development of fatty liver and that targeted activation of bile acid–related signaling pathways is beneficial for preventing and treating fatty liver. In this study, we generated a FLHS laying hen model by feeding hens a high-energy, low-protein diet, with goose deoxycholic acid (CDCA) given as an intervention. HE staining, fluorescence quantitative PCR, and ELISA were used to evaluate the effects of CDCA on pathological changes and inflammatory responses in the liver. The results showed that hepatic hemorrhage in FLHS laying hens was reduced after CDCA treatment. Furthermore, fat vacuoles and transaminase levels decreased significantly. In addition, expression levels of M1-type macrophage markers and polarization products were significantly reduced, and the expression of pro-inflammatory regulatory factors related to the JAK-STAT signaling pathway, LPS-TLR4-Myd88–NF-kB signaling pathway, and NLRP3 inflammasomes decreased significantly as well. Expression levels of M2-type macrophage markers and polarization products increased significantly, as did the expression of anti-inflammatory regulators related to the JAK-STAT signaling pathway. These results suggest that CDCA ameliorates liver injury in laying hens with FLHS by inhibiting macrophage M1-type polarization and the resulting pro-inflammatory response, thereby promoting M2-type macrophage polarization and an anti-inflammatory response. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major contributor to liver-related morbidity, cardiovascular disease, and metabolic complications. Lifestyle interventions, including diet and exercise, are first line in treating MASLD. Dietary approaches such as the low-glycemic-index Mediterranean diet, the ketogenic diet, intermittent fasting, and high fiber diets have demonstrated potential in addressing the metabolic dysfunction underlying this condition. The development and progression of MASLD are closely associated with taxonomic shifts in gut microbial communities, a relationship well-documented in the literature. Given the importance of diet as a primary treatment for MASLD, it is important to understand how gut microbiota and their metabolic byproducts mediate favorable outcomes induced by healthy dietary patterns. Conversely, microbiota changes conferred by unhealthy dietary patterns such as the Western diet may induce dysbiosis and influence steatotic liver disease through promoting hepatic inflammation, up-regulating lipogenesis, dysregulating bile acid metabolism, increasing insulin resistance, and causing oxidative damage in hepatocytes. Although emerging evidence has identified links between diet, microbiota, and development of MASLD, significant gaps remain in understanding specific microbial roles, metabolite pathways, host interactions, and causal relationships. Therefore, this review aims to provide mechanistic insights into the role of microbiota-mediated processes through the analysis of both healthy and unhealthy dietary patterns and their contribution to MASLD pathophysiology. By better elucidating the interplay between dietary nutrients, microbiota-mediated processes, and the onset and progression of steatotic liver disease, this work aims to identify new opportunities for targeted dietary interventions to treat MASLD efficiently. Full article

The presence of bile acids in the cystic fibrosis patient’s lungs contributes to an increase in the inflammatory response, in the dominance of pathogens, as well as in the decline in lung function, increasing morbidity. The aim of this study is to determine the effects of exposure of Pseudomonas aeruginosa to primary and secondary bile acids on the production of several virulence factors which are involved in its pathogenic power. The presence of bile acids in the bacterial culture medium had no effect on growth up to a concentration of 1 mM. However, a slight decrease in the adhesion index as well as a reduction in the virulence of the bacteria on the HT29 cell line could be observed. In this model, exposure of P. aeruginosa to bile acids showed a significant decrease in the production of LasB and AprA proteases due to the reduction in the expression of their genes. A decrease in pyocyanin production was also observed in relation to the effects of bile acids on the quorum sensing regulators. In order to have an effect on gene expression, it is necessary for bile acids to enter the bacteria. P. aeruginosa harbors two potential homologs of the eukaryotic genes encoding the bile acid transporters NTCP1 and NTCP2 that are expressed in hepatocytes and enterocytes, respectively. By carrying out a comparative BLAST-P between the amino acid sequences of the PAO1 proteins and those of NTCP1 and NTCP2, we identified the products of the PA1650 and PA3264 genes as the unique homologs of the two eukaryotic genes. Exposure of the mutant in the PA1650 gene to chenodeoxycholic acid (CDCA) and lithocholic acid (LCA) showed a less significant effect on pyocyanin production than with the isogenic PAO1 strain. Also, no effect of CDCA on the PA3264 gene mutant was observed. This result indicated that CDCA should enter the bacteria by the transporter produced by this gene. The entry of LCA into bacteria seemed more complex and rather responded to a multifactorial system involving the product of the PA1650 gene but also the products of other genes encoding potential transporters. Full article

Micelles formed by bile salts in aqueous solution are important for the solubilization of hydrophobic molecules in the gastrointestinal tract. The molecular level information about the mechanism and driving forces for primary-to-secondary micelle transition is still missing. In the current study, the micelle formation of 50 mM solutions of taurodeoxycholate (TDC) is studied by atomistic molecular dynamics simulations. It is shown that primary micelles with an aggregation number of 8–10 emerge and persist within the first 50 ns. Then, they coalesce to form secondary micelles with an aggregation number of 19 molecules. This transition is governed by hydrophobic interactions, which significantly decrease the solvent-accessible surface area per molecule in the secondary micelles. The addition of monomers of the sodium salt of fatty acids (FAs), as agents aiding hydrophobic drug delivery, to secondary TDC micelles results in the co-existence of mixed FA-TDC and pure FA micelles. The studied saturated FAs, with chain lengths of C14:0 and C18:0, are incorporated into the micelle core, whereas TDC molecules position themselves around the FAs, forming a shell on the micelle surface. In contrast, the tails of the C18:1 unsaturated fatty acid mix homogeneously with TDC molecules throughout the entire micelle volume. The latter creates a very suitable medium for hosting hydrophobic molecules in the micelles containing unsaturated fatty acids. Full article

Background/Objectives: Milk is one of the main sources of nutrition in people’s daily diet, but the fat in milk raises health concerns in consumers. Here, we aimed to elucidate the impact of Buffalo milk and Holstein cow milk consumption on blood lipid health through metabolomics analysis. Methods: Golden hamsters were administered Murrah Buffalo milk (BM) or Holstein cow milk (HM), and the body weight and serum lipid indicators were tested and recorded. The hamsters receiving equal amounts of physiological saline were used as the negative control (NC). Serum and fecal samples were collected, and LC-MS was used to identify the metabolites in the samples. Results: The results showed that both the BM and HM groups exhibited a significant reduction in body weight compared to that of the NC group from day 9, and the serum TG, TC, and LDL-C levels were significantly lower than those of the NC group. Further analysis identified 564 and 567 metabolites in the serum and fecal samples shared in the BM and HM groups and significantly different from those in the NC group, which were mainly enriched in the pathways related to lipid metabolism, such as fatty acid biosynthesis, arachidonic acid metabolism, and primary bile acid biosynthesis. Correlation analysis further suggested that milk intake can increase the levels of Muramic Acid, Oleoyl Ethanolamide, Seratrodast, Chenodeoxycholic Acid, Docosahexaenoic Acid Ethyl Ester, and Deoxycholic Acid in the serum and gut microbiota, which may affect TG, TC, HDL-C, and LDL-C in the serum, and thereby benefit the body’s lipid health. Conclusions: The results further confirmed that milk intake has a beneficial effect on blood lipid health by altering multiple metabolites in the serum and the gut. This study provides novel evidence that milk consumption is beneficial to health and is a reference for guiding people to a healthy diet. Full article

Non-communicable diseases (NCDs) are the leading cause of morbidity and mortality worldwide. These conditions have numerous health consequences and significantly impact patients’ lifestyles. Effective long-term treatment is essential since NCDs are irreversible. Therefore, primary healthcare must be both exclusive and of the highest quality, ensuring comprehensive care. The primary goal should be to improve quality of life with a focus on patients, families, and communities, as most of these diseases can be prevented and controlled, although not cured. Several factors have been linked to individual health, including social, cultural, and economic aspects, lifestyle, and certain environmental factors, including work, that can have positive or negative effects. More of these variables may contribute to the onset of NCDs, which are defined by their chronic nature, propensity for prolongation, and generally slow rate of progression. Examples of NCDs include hypertension, type 2 diabetes (T2D), dyslipidemia, and fatty liver disease linked to metabolic dysfunction. The onset of these diseases has been associated with an imbalance in certain microbial niches, such as the gut, which hosts billions of microorganisms performing multiple metabolic functions, such as the production of metabolites like bile acids (BAs), short-chain fatty acids (SCFAs), and trimethylamine N-oxide (TMAO). Therefore, lifestyle changes and personal habits can significantly impact the gut microbiota (GM), potentially preventing chronic diseases associated with metabolism. NCDs are highly prevalent worldwide, prompting increased attention to strategies for modifying the intestinal microbiota (IM). Approaches such as probiotics, prebiotics, synbiotics, and fecal transplantation (FMT) have demonstrated improvements in the quality of life for individuals with these conditions. Additionally, lifestyle changes and the adoption of healthy habits can significantly impact IM and may help prevent chronic diseases related to metabolism. Therefore, the main aim of this review is to analyze and understand the importance of microbiota intervention in the prevention of non-communicable diseases. R3:A1 Full article