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. 2024 Aug 24;16(17):2838. doi: 10.3390/nu16172838

Figure 4.

Figure 4

The impact of BPs on metabolic disease treatment via gut microbiota modulation. BPs, upon ingestion, play a pivotal role in regulating gut microbiota. This can shift the microbial imbalance seen in patients with metabolic diseases toward a state of equilibrium. They also promote the production of beneficial metabolic byproducts in the gut, like short-chain fatty acids (SCFAs) and bile acids (BAs). The synergetic action of the gut microbiota and its metabolites strengthens the intestinal barrier in metabolic disease patients. This enhancement leads to a reduction in lipopolysaccharides (LPS) entering the circulatory system and subsequently decreases inflammation in adipose tissue, liver, and cardiovascular system—actions that are vital in mitigating metabolic diseases. Moreover, microbial metabolites such as SCFAs trigger the secretion of glucagon-like peptide-1 (GLP-1) from enteroendocrine L cells in the intestines. This secretion influences pancreatic islets by reducing islet cell apoptosis and boosting insulin production, consequently diminishing insulin resistance (IR), which is instrumental in treating Type 2 diabetes mellitus (T2DM). SCFAs also impact the body’s white adipose tissue, enhancing fatty acid β-oxidation and hindering fat accumulation, which is crucial in obesity treatment. Additionally, in the liver, SCFAs elevate lipid β-oxidation and inhibit lipid synthesis, thereby aiding in non-alcoholic fatty liver disease (NAFLD) management. Specific BAs, like GUDCA and HCA, activate GLP-1 secretion from enteroendocrine L cells by engaging the Takeda G protein-coupled receptor 5 (TGR5). This action can spur insulin release and improve insulin sensitivity through its circulatory effect on pancreatic islets, aiding in the body’s glucose metabolism regulation. In an alternate pathway, BAs interact with the brain via the GLP-1 receptor (GLP-1R), modulating energy and glucose metabolism to enhance satiety and reduce food intake. Furthermore, through the FXR/FGF19 pathway, BAs can regulate glucose and energy metabolism within the brain. These mechanisms support the overall alleviation of metabolic diseases. Additionally, BAs can enhance cardiac function by activating TGR5/FXR receptors, thereby achieving the mitigation or treatment of CVD. The red downward arrow in the figure indicates a decrease or downregulate, while the blue upward arrow signifies an increase or upregulate.