Human gut bacteria produce ΤΗ17-modulating bile acid metabolites

Paik, Donggi; Yao, Lina; Zhang, Yancong; Bae, Sena; D’Agostino, Gabriel D.; Zhang, Minghao; Kim, Eunha; Franzosa, Eric A.; Ávila-Pacheco, Julián; Bisanz, Jordan E.; Rakowski, Christopher K.; Vlamakis, Hera; Xavier, Ramnik J.; Turnbaugh, Peter J.; Longman, Randy S.; Krout, Michael R.; Clish, Clary B.; Rastinejad, Fraydoon; Huttenhower, Curtis; Huh, Jun R.; Devlin, A. Sloan

doi:10.1038/s41586-022-04480-z

Cited by 320 publications

(205 citation statements)

References 54 publications

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“…Eggerthella lenta also possesses 3α- and one 3β-HSDH for converting DCA to isoDCA to reduce gut bacteria toxicity [ 56 ]. These HSDHs also convert LCA to 3-exoLCA and isoLCA, both of which modulate Th17 populations in mice [ 57 , 58 ].…”

Section: Ba Biosynthesismentioning

confidence: 99%

Molecular Basis of Bile Acid-FXR-FGF15/19 Signaling Axis

Katafuchi,

Makishima

2022

IJMS

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Bile acids (BAs) are a group of amphiphilic molecules consisting of a rigid steroid core attached to a hydroxyl group with a varying number, position, and orientation, and a hydrophilic side chain. While BAs act as detergents to solubilize lipophilic nutrients in the small intestine during digestion and absorption, they also act as hormones. Farnesoid X receptor (FXR) is a nuclear receptor that forms a heterodimer with retinoid X receptor α (RXRα), is activated by BAs in the enterohepatic circulation reabsorbed via transporters in the ileum and the colon, and plays a critical role in regulating gene expression involved in cholesterol, BA, and lipid metabolism in the liver. The FXR/RXRα heterodimer also exists in the distal ileum and regulates production of fibroblast growth factor (FGF) 15/FGF19, a hormone traveling via the enterohepatic circulation that activates hepatic FGF receptor 4 (FGFR4)-β-klotho receptor complex and regulates gene expression involved in cholesterol, BA, and lipid metabolism, as well as those regulating cell proliferation. Agonists for FXR and analogs for FGF15/19 are currently recognized as a promising therapeutic target for metabolic syndrome and cholestatic diseases.

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Section: Ba Biosynthesismentioning

confidence: 99%

Molecular Basis of Bile Acid-FXR-FGF15/19 Signaling Axis

Katafuchi,

Makishima

2022

IJMS

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“…Paik et al identified 12 human gut bacterial genera and their corresponding enzymes required to convert LCA to 3-oxoLCA and isoLCA: Adlercreutzia, Bifidobacterium, Enterocloster, Clostridium, Collinsella, Eggerthella, Gordonibacter, Monoglobus, Peptoniphilus, Phocea, Raoultibacter, and Mediterraneibacter [53].…”

Section: Other Barsmentioning

confidence: 99%

Bile Acid-Related Regulation of Mucosal Inflammation and Intestinal Motility: From Pathogenesis to Therapeutic Application in IBD and Microscopic Colitis

et al. 2022

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Inflammatory bowel diseases (IBD) and microscopic colitis are chronic immune-mediated inflammatory disorders that affect the gastroenterological tract and arise from a complex interaction between the host’s genetic risk factors, environmental factors, and gut microbiota dysbiosis. The precise mechanistic pathways interlinking the intestinal mucosa homeostasis, the immunological tolerance, and the gut microbiota are still crucial topics for research. We decided to deeply analyze the role of bile acids in these complex interactions and their metabolism in the modulation of gut microbiota, and thus intestinal mucosa inflammation. Recent metabolomics studies revealed a significant defect in bile acid metabolism in IBD patients, with an increase in primary bile acids and a reduction in secondary bile acids. In this review, we explore the evidence linking bile acid metabolites with the immunological pathways involved in IBD pathogenesis, including apoptosis and inflammasome activation. Furthermore, we summarize the principal etiopathogenetic mechanisms of different types of bile acid-induced diarrhea (BAD) and its main novel diagnostic approaches. Finally, we discuss the role of bile acid in current and possible future state-of-the-art therapeutic strategies for both IBD and BAD.

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“…Microbial metabolites, such as bile acids, short-chain fatty acids (SCFA), and the tryptophan metabolites quinolinic and kynurenic acids are involved in the control of important metabolic, immune, and neuronal functions of the host. Recent results suggest that bile acids produced by gut bacteria inhibit T H 17 cell function, potentially contributing to inflammatory disorders, including IBD ( Paik et al, 2022 ). While bile acids are known as digestive agents for lipids, they also affect brain function during normal physiological and pathological conditions.…”

Section: Metabolic Pathwaysmentioning

confidence: 99%

Chronic Effects of Dietary Pesticides on the Gut Microbiome and Neurodevelopment

2022

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Many agricultural pesticides include substances that are known to be harmful to human health and while some have been banned from developed countries, they are still being used in developing countries such as Brazil. Recent studies have shown that low-level chronic dietary exposure to pesticides can affect the human gut microbiota. This possible hazardous effect of pesticides on human health has not been specifically recognized by government regulatory agencies. In Brazil, for instance, of the 10 best-selling active ingredients in pesticides in 2019, two are considered extremely toxic, Paraquat and Chlorpyrifos. Even though Paraquat has been banned in Brazil since 2020, the values of maximum residue limits (MRLs) of toxic pesticides allowed in the country are still higher than in other countries. Unfortunately, many developing countries still lack the resources and expertise needed to monitor adequately and systematically the presence of pesticide residues on food. In this work, we raise awareness to the danger the chronic exposure to high dietary levels of pesticides can pose to the public, especially considering their prolonged effects on the gut microbiome.

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Human gut bacteria produce ΤΗ17-modulating bile acid metabolites

Cited by 320 publications

References 54 publications

Molecular Basis of Bile Acid-FXR-FGF15/19 Signaling Axis

Molecular Basis of Bile Acid-FXR-FGF15/19 Signaling Axis

Bile Acid-Related Regulation of Mucosal Inflammation and Intestinal Motility: From Pathogenesis to Therapeutic Application in IBD and Microscopic Colitis

Chronic Effects of Dietary Pesticides on the Gut Microbiome and Neurodevelopment

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