Endotoxins and Metabolic Endotoxemia in Obesity and Associated Noncommunicable Diseases: A Focus on Sex Differences

Metabolic endotoxemia has been proposed as a possible mechanism to explain the strong link between inflammation, obesity, and obesity-associated disorders. Gut dysbiosis is a hallmark of obesity, and diet has been reported to regulate both inflammation and disease risk by affecting the composition of gut microbiota and gut barrier function. In the condition of microbial imbalance and impaired intestinal mucosa, bacterial endotoxins, specifically lipopolysaccharides, translocate from the gut into the bloodstream, where they can sustain a prolonged, sterile, low-grade inflammation, raising the risk of several non-communicable diseases. Increasing evidence indicates that the risk and incidence of obesity and several obesity-associated disorders are sex-specific, although the underlying mechanisms are only just emerging. Notably, most of the factors influencing metabolic endotoxemia exhibit sexual dimorphism. This review aims to summarize the human studies investigating the role of metabolic endotoxemia in obesity and associated diseases, with a focus on those highlighting sex differences. We also discuss the clinical relevance of circulating endotoxins in metabolic derangements and their potential role as sex-related and modifiable risk factors to consider in future prevention strategies.