Abstract
The gut microbiota plays a crucial role in regulating many physiological systems of the host, including the metabolic and immune system. Disturbances in microbiota composition are increasingly correlated with disease; however, the underlying mechanisms are not well understood. Recent evidence suggests that changes in microbiota composition directly affect the metabolism of bile salts. Next to their role in digestion of dietary fats, bile salts function as signaling molecules for bile salt receptors such as Farnesoid X receptor (FXR) and G protein-coupled bile acid receptor (TGR5). Complementary to their role in metabolism, FXR and TGR5 are shown to play a role in intestinal homeostasis and immune regulation. This review presents an overview of evidence showing that changes in bile salt pool and composition due to changes in gut microbial composition contribute to the pathogenesis of inflammatory bowel disease and metabolic disease, possibly through altered activation of TGR5 and FXR. We further discuss how dietary interventions, such as pro- and synbiotics, may be used to treat metabolic disease and inflammatory bowel disease (IBD) through normalization of bile acid dysregulation directly or indirectly through normalization of the intestinal microbiota.
Highlights
The gut microbiota plays a crucial role in regulating many physiological systems of the host, including the metabolic and immune system
Accumulating evidence suggests a link between dysbiosis and pathological changes in the metabolism of bile acids (BA) in patients suffering from obesity and type 2 diabetes [21], cardiovascular disease [22] and inflammatory bowel disease [23]
The composition of the microbiota is causatively related to BA pool size and BA species diversity and perturbations of the microbiota leads to BA dysregulation as observed in inflammatory bowel disease (IBD) and metabolic disease
Summary
The human microbiota is established soon after birth and starts out as a dynamic ecosystem, subjected to large compositional shifts, that stabilizes and converges to a more “adult”-type of microbiota at 2–3 years of life [1,2]. Defining a healthy human gut microbiome requires studies that address “who is there” and “what are they doing” to link microbial composition with function in health and disease [6,7]. Infants receive their first bacterial inoculum via vertical transmission of components of the mother’s microbiome at birth, which is further reinforced by breastfeeding [8]. We discuss how the gut microbiota regulates BA homeostasis and how this impacts metabolic function and intestinal immune homeostasis through activation of FXR and TGR5. We discuss how dietary interventions, such as pro- and synbiotics, could be used to restore BA dysregulation and alleviate IBD and metabolic disease
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