Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10−/− mice

Abstract

The composite human microbiome of Western populations has likely changed over the past century, brought on by new environmental triggers that often have a negative impact on human health 1 . Here we show that consumption of a diet high in saturated (milk derived)-fat (MF), but not polyunsaturated (safflower oil)-fat (PUFA), changes the conditions for microbial assemblage and promotes expansion of a low abundance, sulfite-reducing pathobiont, Bilophila wadsworthia 2 . This was associated with a pro-inflammatory T H 1 immune response and increased incidence of colitis in genetically susceptible IL-10 −/− , but not wild type mice. These effects are mediated by MF-promoted taurine-conjugation of hepatic bile acids, which increases the availability of organic sulfur used by sulfite-reducing microbes like B. wadsworthia . When mice were fed a low-fat (LF) diet supplemented with taurocholic, but not with glycocholic acid, for example, a bloom of B. wadsworthia and development of colitis were observed in IL10 −/− mice. Together these data show that dietary fats, by promoting changes in host bile acid composition, can dramatically alter conditions for gut microbial assemblage, resulting in dysbiosis that can perturb immune homeostasis. The data provide a plausible mechanistic basis by which Western type diets high in certain saturated fats might increase the prevalence of complex immune-mediated diseases like inflammatory bowel diseases in genetically susceptible hosts.

Consequences of bile salt biotransformations by intestinal bacteria

“…49 Consumption of taurine and TCA has been shown recently to cause a bloom in the sulfidogenic bacterium, Bilophila wadsworthia, resulting in colitis in the IL10-/-mouse model. 50 Consequences of bile salt hydrolysis for the mammalian host Cardiovascular disease is responsible for 16.7 million deaths worldwide and is the leading cause of mortality and morbidity worldwide. 51 There is a clear link between serum cholesterol and cardiovascular disease, particularly coronary artery disease (CAD).…”

Early-Life Sugar Consumption Affects the Rat Microbiome Independently of Obesity

“…Early-life gut microbial populations play a critical role in the development of the nervous system and the immune response and have been shown to affect behaviors such as anxiety and motor control into adulthood (3)(4)(5)(6). Current findings also identified a role for the gut microbiome in the development of gastrointestinal diseases, such as ulcerative colitis and irritable bowel syndrome (7,8), in metabolic pathologies such as insulin resistance (9) and obesity (10,11) and in neurological disorders such as autism (12), Parkinson disease (13), and Alzheimer disease (14). Due to evidence linking the gut microbiome with human health and disease, it has been suggested that nurturing the development of a healthy patient/microbial ''superorganism'' is a cornerstone in the future of medicine (15,16).…”

Taurocholic acid metabolism by gut microbes and colon cancer

“…Dextran sodium sulfate (DSS) treatment of MF-fed SPF C57BL/6 mice induced more severe colitis than in their LF and PUFA fed counterparts, as well as consistent observations of B. wadsworthia. 52 In mono-associated germ-free Il10 ¡/¡ mice, colonization of B. wadsworthia could only be obtained in MF fed mice, and abundance was greater mainly in the mucosa. B. wadsworthia grown in culture medium was selectively stimulated by gallbladder bile from MF-fed mice.…”