Branched-chain and obese patients [66]. Additionally, changes in

Branched-chain amino acids (BCAAs) were associated with insulin resistance. Pedersen et al. (2016) revealed that serum BCAAs levels, synthesized by intestinal bacteria like Prevotella copri and Bacteroides vulgatus, were increased in insulin-resistant patients 55. Furthermore, this study showed that Prevotella copri CB7 was able to induce insulin resistance and impair glucose tolerance in mice. In line with this, in obese and T2D patients, levels of BCAAs were negatively correlated with insulin resistance 56, 57. However, more studies are needed to investigate how BCAAs modulate insulin resistance in detail.Choline metabolism by intestinal microbiota was shown to modulate the development of NAFLD. Feeding of HFD to a susceptible mouse strain (129S6) revealed that choline is excessively metabolized by the intestinal microbiota which then induced the development of NAFLD 58. This is in line with the observations that the occurrence of this disease is also observed in mice fed a choline-deficient diet 59, 60. Moreover, NASH patients had a higher abundance of alcohol-producing bacteria like Escherichia coli which resulted in higher serum ethanol levels 38. In line with this, obese ob/ob mice fed a standard laboratory diet, exhibited a higher endogenous ethanol production compared to wild type mice 61. This might be a hint how obesity and the accompanied changes in gut microbiota composition could induce the development of NAFLD and it progression to NASH.Changes in bile acid composition as well as an increased bile acid pool were also observed in obesity and T2D 62–65. Surprisingly, serum glycine- and taurine-conjugated forms of chenodeoxy and deoxycholic acid (CDCA and DCA, respectively), glycocholic acid (GCA) and total bile acid concentrations were increased after Roux-en-Y gastric bypass compared to overweight and obese patients 66. Additionally, changes in fecal bile acid composition in NAFLD and NASH patients were accompanied with changes in the gut microbiota 67.More and more clinical studies evaluate the effects of modulating the bile acid metabolism via the two key regulators farnesoid X receptor (FXR; also referred to as FXR-? and Nr1H4) and the G protein-coupled bile acid receptor TGR5 (also referred to as GPBAR1) using semisynthetic agonists and antagonists as well as bile acid sequestrants 68, 69. Only some will be introduced in the next section. Treatment with FXR agonists like GW4064, WAY-362450 and obeticholic acid (OCA, INT-747) protected