Abstract
Bile is a biological fluid synthesized in the liver, mainly constituted by bile acids and cholesterol, which functions as a biological detergent that emulsifies and solubilizes lipids, thereby playing an essential role in fat digestion. Besides, bile acids are important signaling molecules that regulate key functions at intestinal and systemic levels in the human body, affecting glucose and lipid metabolism, and immune homeostasis. Apart from this, due to their amphipathic nature, bile acids are toxic for bacterial cells and, thus, exert a strong selective pressure on the microbial populations inhabiting the human gut, decisively shaping the microbial profiles of our gut microbiota, which has been recognized as a metabolic organ playing a pivotal role in host health. Remarkably, bacteria in our gut also display a range of enzymatic activities capable of acting on bile acids and, to a lesser extent, cholesterol. These activities can have a direct impact on host physiology as they influence the composition of the intestinal and circulating bile acid pool in the host, affecting bile homeostasis. Given that bile acids are important signaling molecules in the human body, changes in the microbiota-residing bile biotransformation ability can significantly impact host physiology and health status. Elucidating ways to fine-tune microbiota-bile acids-host interplay are promising strategies to act on bile and cholesterol-related disorders. This manuscript summarizes the current knowledge on bile and cholesterol metabolism by intestinal bacteria, as well as its influence on host physiology, identifying knowledge gaps and opportunities to guide further advances in the field.
Highlights
The human gastrointestinal tract (GIT) is colonized by a vast array of microbes which dynamically interact with dietary and host-derived molecules in the intestinal lumen, significantly contributing to host physiology
The interaction of cholesterol and bile acids (BAs) with gut bacteria has been known for decades, the role of these interactions in host health, and the possibility to modulate them through targeting the gut microbiota composition to improve human health, have only started to be recently explored
In light of the recently unearthed gut microbiota-BA-host signaling interactions, microbiota-based approaches, from probiotics to dietary interventions, may become novel strategies to manage specific diseases linked to BAs metabolism dysregulation, as suggested by some in vivo studies (Devkota and Chang, 2015; Fukui, 2017)
Summary
The human gastrointestinal tract (GIT) is colonized by a vast array of microbes which dynamically interact with dietary and host-derived molecules in the intestinal lumen, significantly contributing to host physiology. The composition of the BAs pool in humans is determined by the enterohepatic cycle and the microbial metabolism of intestinal BAs. Briefly, the liver synthesizes two primary BAs from cholesterol, cholic acid and chenodeoxycholic acid, which are conjugated to either taurine or glycine before being poured into the bile flow.
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