Bile Acid Metabolism and the Microbiome
Summary:
Bile metabolism and absorption are gut microbiome-mediated processes. Bile and bile metabolism can have major impacts on the gut microbiome and host health.
The liver produces cholesterol, which is then converted into bile acids—metabolites that get secreted into the intestine to help digest fat during eating. In the gut, certain microbiota then convert these bile acid metabolites into microbial bile acids.
Norovirus is not the only virus influenced by metabolites like bile acids. Influenza, chikungunya, and herpes viruses, for example, are inhibited by the same types of microbial bile acids that are not present in newborns. Meanwhile, host bile acids also promote human coronavirus infection.
Reviews:
Review, 2023: Gut microbiota derived bile acid metabolites maintain the homeostasis of gut and systemic immunity https://www.frontiersin.org/articles/10.3389/fimmu.2023.1127743/full
Review, 2022: Bile acid coordinates microbiota homeostasis and systemic immunometabolism in cardiometabolic diseases https://www.sciencedirect.com/science/article/pii/S2211383521004834
Review, 2019: Bile salt hydrolases: Gatekeepers of bile acid metabolism and host-microbiome crosstalk in the gastrointestinal tract https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1007581
Review, 2018: Microbial impact on cholesterol and bile acid metabolism: current status and future prospects http://www.jlr.org/content/early/2018/11/28/jlr.R088989.full.pdf+html
Review, 2018: Nutritional Modulation of Innate Immunity: The Fat–Bile–Gut Connection https://doi.org/10.1016/j.tem.2018.08.002
Review, 2018: Bile acids in glucose metabolism in health and disease: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5789421/
Review, 2017: Bile acid control of metabolism and inflammation in obesity, type 2 diabetes, dyslipidemia and non-alcoholic fatty liver disease. A review showing how important & multifaceted bile is.
Review, 2017: Bile acids at the cross-roads of gut microbiome–host cardiometabolic interactions https://dmsjournal.biomedcentral.com/articles/10.1186/s13098-017-0299-9
Review, 2017: A similar review that includes FXR - Targeting the Gut Microbiota–FXR Signaling Axis for Glycemic Control: Does a Dietary Supplement Work Magic?
Review, 2016: Interaction of gut microbiota with bile acid metabolism and its influence on disease states.
Review, 2017: Bile Acids and the Gut Liver Axis. Disease-Associated Changes in Bile Acid Profiles and Links to Altered Gut Microbiota.
Review, 2017: Bile Acids and Intestinal Microbiota in Autoimmune Cholestatic Liver Diseases. "Dysbiosis of the intestinal microbiome can exert profound influence on the bile acid pool and significantly alters the immunological balance of the gut-liver axis in cholestatic liver diseases."
Review, 2017: Interactions between Bacteria and Bile Salts in the Gastrointestinal and Hepatobiliary Tracts: https://www.frontiersin.org/articles/10.3389/fmed.2017.00163/full
FMT:
Microbial bile salt hydrolases mediate the efficacy of faecal microbiota transplant in the treatment of recurrent Clostridioides difficile infection (Feb 2019): https://gut.bmj.com/content/early/2019/02/11/gutjnl-2018-317842 - Video abstract. Other previous studies pointing to fecal transplant success depending on changing bile acid metabolism: [1][2][3][4].
Fecal microbiota from children with vitamin A deficiency impair colonic barrier function in germ-free mice: The possible role of alterative bile acid metabolites (Apr 2021) https://www.sciencedirect.com/science/article/abs/pii/S0899900721001362
IBS:
Up to 50% of cases of chronic diarrhea/IBS-D may be due to Bile Acid Malabsorption [1][2][3].
A Clostridia-rich microbiota enhances bile acid excretion in diarrhea-predominant irritable bowel syndrome (Dec 2019, n=345) https://www.jci.org/articles/view/130976
Faecal bile acids and colonic bile acid membrane receptor correlate with symptom severity of diarrhoea-predominant irritable bowel syndrome: A pilot study (May 2021) https://www.dldjournalonline.com/article/S1590-8658(21)00207-3/fulltext
Microbiome-encoded bile acid metabolism modulates colonic transit times (May 2021, mice) https://www.cell.com/iscience/fulltext/S2589-0042(21)00476-4
Cancer:
Bile-mediated dysbiosis as a cause of carcinogenesis: Secondary bile acid‐induced dysbiosis promotes intestinal carcinogenesis (2017): http://onlinelibrary.wiley.com/doi/10.1002/ijc.30643/abstract - It's not directly caused by the bile, but by the dysbiosis the bile (secondary bile acids) causes.
Treating mice with antibiotics changes antitumor immune function in the liver due to changes in bile acid metabolism (2018): https://web.archive.org/web/20230610131805/https://old.reddit.com/r/HumanMicrobiome/comments/8m4fh4/study_finds_gut_microbiome_can_control_antitumor/ - "one bacterial species, Clostridium scindens, controls metabolism of bile acids in the mouse gut—and ultimately CXCL16 expression, NKT cell accumulation, and tumor growth in the liver"
Gut microbiota bile acid metabolism controls cancer immunosurveillance (2018): https://www.nature.com/articles/s41579-018-0053-9
The study led by EMBL scientists focuses on a process in which certain gut bacteria turn bile acids that are part of our digestive juices into metabolites that can be carcinogenic (April 2019): https://medicalxpress.com/news/2019-04-global-microbial-signatures-colorectal-cancer.html - https://www.nature.com/articles/s41591-019-0406-6.
Bile Acids, the Microbiome, Immunity, and Liver Tumors (2018): https://www.nejm.org/doi/10.1056/NEJMcibr1807106 Bile acids affect the expression of a chemokine ligand by liver sinusoidal endothelial cells, which in turn affects the extent to which a type of natural killer cell is present in and diminishes the burden of hepatocellular carcinomas in a mouse model of the disease.
Misc:
Thousands of Previously Unknown Bile Acids Discovered. Researchers have uncovered thousands of bile acids that the gut microbiome uses to communicate with the rest of the body. (Mar 2024) https://www.technologynetworks.com/applied-sciences/news/thousands-of-previously-unknown-bile-acids-discovered-384686 The underappreciated diversity of bile acid modifications.
The bile acid tauroursodeoxycholic acid (TUDCA) can increase mucus secretion rates. TUDCA treatment reversed the mucus secretion defect caused by vancomycin treatment, restoring a proper mucus barrier (2024) https://forum.humanmicrobiome.info/threads/antibiotics-damage-the-colonic-mucus-barrier-in-a-microbiota-independe.580/
Gallbladder-derived surfactant protein D (delivered to the intestine via bile) regulates gut commensal bacteria for maintaining intestinal homeostasis: http://www.pnas.org/content/early/2017/09/05/1712837114.abstract
Novel bile acid biosynthetic pathways are enriched in the microbiome of centenarians (Jul 2021) https://www.nature.com/articles/s41586-021-03832-5
Depletion of key gut bacteria predicts disrupted bile acid metabolism in inflammatory bowel disease (Dec 2024) https://journals.asm.org/doi/10.1128/spectrum.01999-24
Altered bile acid profile associates with cognitive impairment in Alzheimer's disease—An emerging role for gut microbiome (Oct 2018): https://doi.org/10.1016/j.jalz.2018.07.217
Gut Microbiota Dysbiosis Is Associated with Elevated Bile Acids in Parkinson’s Disease (Jan 2021, n=28) https://www.mdpi.com/2218-1989/11/1/29/htm
First evidence that patients with fibromyalgia show different amounts and species of bile-metabolizing gut bacteria, as well as different concentrations of bile acids in the blood (May 2022) https://medicalxpress.com/news/2022-07-secret-fibromyalgia-microbiome.html "Our findings show a strong relationship between patient microbiome composition, bile acids and the severity of fibromyalgia symptoms"
Interpersonal Gut Microbiome Variation Drives Susceptibility and Resistance to Cholera Infection. Colonization resistance is mediated through the bile salt hydrolase enzyme activity. Microbiome-dependent infection resistance can be restored through co-transplantation (Jun 2020) https://news.ucr.edu/articles/2020/06/29/microbiome-confers-resistance-cholera
Bile acid is a significant host factor shaping the gut microbiome of diet-induced obese mice (2017): https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-017-0462-7
The gut microbiota drives the impact of bile acids and fat source in diet on mouse metabolism (2018): https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-018-0510-8
Pharmacological Activation of PXR and CAR Down-regulates Distinct Bile Acid-metabolizing Intestinal Bacteria and Alters Bile Acid Homeostasis (2018): https://doi.org/10.1093/toxsci/kfy271