FXR Signaling-Mediated Bile Acid Metabolism Is Critical for Alleviation of Cholesterol Gallstones by
            <i>Lactobacillus</i>
            Strains

Ye, Xin; Huang, Dan; Dong, Zhiya; Wang, Xiaoxin; Ning, Min; Xia, Jie; Shen, Shuang; Wu, Shan; Shi, Yan; Wang, Jingjing; Wan, Xinjian

doi:10.1128/spectrum.00518-22

Cited by 26 publications

(19 citation statements)

References 69 publications

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“…Previous studies have demonstrated that Lactobacillales can effectively suppress the expression of farnesoid X receptor (FXR) antagonists, such as tauro-α-muricholic acid and tauro-β-muricholic acid. 42 This suppression leads to an increase in FXR activity, resulting in reduced bile acid and cholesterol production in the liver and circulation. Moreover, alterations in gut microbiology have been found to contribute to pancreatic diseases.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, we identified the risk factor posed by the genus‐level Peptococcus , which is consistent with previous research in this area. Previous studies have demonstrated that Lactobacillales can effectively suppress the expression of farnesoid X receptor (FXR) antagonists, such as tauro‐α‐muricholic acid and tauro‐β‐muricholic acid 42 . This suppression leads to an increase in FXR activity, resulting in reduced bile acid and cholesterol production in the liver and circulation.…”

Section: Discussionmentioning

confidence: 99%

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Association between gut microbiota and seven gastrointestinal diseases: A Mendelian randomized study

Zhu,

Ding

2023

The Journal of Gene Medicine

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BackgroundObservational research has shed light on the ability of gut microbes to influence the onset and progression of gastrointestinal diseases. The causal relationships between specific gut microbiomes and various gastrointestinal conditions, however, remain unknown.MethodsWe investigated the relationship between gut microbiota and seven specific gastrointestinal disorders using a robust two‐sample Mendelian randomization (MR) approach. The inverse variance‐weighted (IVW) method was used as the primary analysis tool in our study. Furthermore, we conducted multiple sensitivity analyses to strengthen the robustness of our findings and ensure the reliability of the IVW method.ResultsOur research has discovered significant links between the composition of gut microbiota and a variety of gastrointestinal ailments. We found compelling links between 13 gut microbiota and fatty liver, four gut microbiota and cirrhosis, eight gut microbiota and hepatocellular carcinoma, four gut microbiota and cholelithiasis, 12 gut microbiota and acute pancreatitis, eight gut microbiota and chronic pancreatitis, and 11 gut microbiota and pancreatic cancer. These findings shed light on the intricate relationship between gut microbes and the emergence of these specific gastrointestinal conditions.ConclusionsThe findings of this extensive study not only validate the potential role of specific gut microbiota in gastrointestinal diseases, but also fill a critical gap in previous research. The discovery of these specific gut microbiota is a significant step forward because they may serve as novel and promising biomarkers for both the prevention and treatment of gastrointestinal conditions.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Association between gut microbiota and seven gastrointestinal diseases: A Mendelian randomized study

Zhu,

Ding

2023

The Journal of Gene Medicine

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“…It governs the synthesis of BAs mainly by downregulating the expression of cholesterol 7α-hydroxylase via both the intrahepatic FXR-small heterodimer partner and the extrahepatic FXR-fibroblast growth factor 19 (FGF19)fibroblast growth factor receptor pathways. 21 FXR activation promotes BAs secretion by upregulating the bile salt export pump and multiple related proteins (e.g., multidrug resistance-associated protein 2/3 and ATPbinding cassette subfamily G member 5/8) [22][23][24] and inhibits their reabsorption by downregulating sodiumdependent bile acid transporter 25 and sodium/taurocholate cotransporting polypeptide. 26 In addition, this NR plays an essential role in the metabolism of lipids and glucose.…”

Section: Beneficial Effects Of Fxr Activationmentioning

confidence: 99%

FXR agonists for MASH therapy: Lessons and perspectives from obeticholic acid

Wang,

Zhang,

Wang

et al. 2023

Medicinal Research Reviews

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Nonalcoholic fatty liver disease, also called metabolic dysfunction‐associated steatotic liver disease, is the most common liver disease worldwide and has no approved pharmacotherapy. Due to its beneficial effects on metabolic regulation, inflammation suppression, cell death prevention, and fibrogenesis inhibition, farnesoid X receptor (FXR) is widely accepted as a promising therapeutic target for nonalcoholic steatosis (NASH) or called metabolic dysfunction‐associated steatohepatitis (MASH). Many FXR agonists have been developed for NASH/MASH therapy. Obeticholic acid (OCA) is the pioneering frontrunner FXR agonist and the first demonstrating success in clinical trials. Unfortunately, OCA did not receive regulatory approval as a NASH pharmacotherapy because its moderate benefits did not outweigh its safety risks, which may cast a shadow over FXR‐based drug development for NASH/MASH. This review summarizes the milestones in the development of OCA for NASH/MASH and discuss its limitations, including moderate hepatoprotection and the undesirable side effects of dyslipidemia, pruritus, cholelithiasis, and liver toxicity risk, in depth. More importantly, we provide perspectives on FXR‐based therapy for NASH/MASH, hoping to support a successful bench‐to‐clinic transition.

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“…Intervention of lithogenic-diet (LD)-fed mice with Lactobacillus reuteri and Lactobacillus plantarum regulated the gut microbiota, which increased the relative abundance of Muribaculaceae and Akkermansia in the former and latter, respectively. These strains may alleviate gallstones and hepatic steatosis by activating FXR and inhibiting the activities of hepatic sterol 7α-hydroxylase (CYP7A1) and hepatic sterol 7α-hydroxylase (CYP7B1) ( 114 ). The probiotic Prevotella copri can significantly increase the intestinal microbiota diversity and activate the FXR-Cyp7a1 signaling pathway to inhibit BA synthesis to improve the progression of cholestasis and liver fibrosis in PSC mouse models ( 115 ).…”

Section: Biotherapiesmentioning

confidence: 99%

The gut microbiota: A new perspective for tertiary prevention of hepatobiliary and gallbladder diseases

Huang

Yang²,

Li³

et al. 2023

Front. Nutr.

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The gut microbiota is a complex ecosystem that has coevolved with the human body for hundreds of millions of years. In the past 30 years, with the progress of gene sequencing and omics technology, the research related to gut microbiota has developed rapidly especially in the field of digestive system diseases and systemic metabolic diseases. Mechanical, biological, immune, and other factors make the intestinal flora form a close bidirectional connection with the liver and gallbladder, which can be called the “gut–liver–biliary axis.” Liver and gallbladder, as internal organs of the peritoneum, suffer from insidious onset, which are not easy to detect. The diagnosis is often made through laboratory chemical tests and imaging methods, and intervention measures are usually taken only when organic lesions have occurred. At this time, some people may have entered the irreversible stage of disease development. We reviewed the literature describing the role of intestinal flora in the pathogenesis and biotherapy of hepatobiliary diseases in the past 3–5 years, including the dynamic changes of intestinal flora at different stages of the disease, as well as the signaling pathways involved in intestinal flora and its metabolites, etc. After summarizing the above contents, we hope to highlight the potential of intestinal flora as a new clinical target for early prevention, early diagnosis, timely treatment and prognosis of hepatobiliary diseases.

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FXR Signaling-Mediated Bile Acid Metabolism Is Critical for Alleviation of Cholesterol Gallstones by Lactobacillus Strains

Abstract: Cholesterol gallstone (CGS) disease is prevalent worldwide. None of the medical options for prevention and treatment of CGS disease are recommended, and surgical management has a high rate of recurrence.

Cited by 26 publications

References 69 publications

Association between gut microbiota and seven gastrointestinal diseases: A Mendelian randomized study

Association between gut microbiota and seven gastrointestinal diseases: A Mendelian randomized study

FXR agonists for MASH therapy: Lessons and perspectives from obeticholic acid

The gut microbiota: A new perspective for tertiary prevention of hepatobiliary and gallbladder diseases

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