Pharmacological modulation of the gut microbiota and endotoxemia: A next-generation approach to treating metabolic syndrome

Central obesity, atherogenic dyslipidemia, insulin resistance, and hypertension are among the metabolic dysregulations associated with metabolic syndrome (MetS). Insulin resistance and chronic low-grade inflammation are 2 of the many acquired and genetic components that make up the pathophysiology of MetS. MetS is strongly linked to a greater risk of diabetes and cardiovascular disease in the absence of effective treatment. To create effective intervention strategies and preventative techniques, the MetS process needs to be thoroughly examined. Recent research has emphasized the critical roles that metabolic endotoxemia and the gut microbiota play in the pathophysiology of MetS. The manipulation of gut microbiota‒host metabolism interactions has been linked to several factors, including bile acid metabolism, short-chain fatty acid metabolism, and inflammation caused by malfunction of the gut barrier. Pharmacological treatments for the gut microbiota are becoming increasingly popular as treatment alternatives. This brief message highlights some of the most recent developments in pharmaceutical strategies for preventing both gut dysbiosis and systemic low-grade inflammation caused by endotoxemia. Antibiotics, prebiotics, probiotics, synbiotics, postbiotics, and metabolite modulators produced from the microbiota are all used in these tactics. Particular focus is placed on next-generation treatments such as small chemical inhibitors of microbial‒host interactions, bacteriophage therapy, and tailored probiotics. Significance Statement: Pharmacologic alteration of the gut microbiota to target endotoxemia, a major cause of systemic inflammation, is a viable next-generation treatment for metabolic syndrome. These treatments help stop lipopolysaccharide translocation, restore metabolic balance, and improve insulin sensitivity by strengthening the gut barrier and changing the makeup of microbes. This method improves lipid metabolism, decreases chronic inflammation, and targets the underlying causes of disease. As a result, to improve results, treatment is moving from just managing symptoms to changing the disease itself.