Are gut dysbiosis, barrier disruption, and endotoxemia related to adipose tissue dysfunction in metabolic disorders? Overview of the mechanisms involved

Recently, compelling evidence points to dysbiosis and disruption of the epithelial intestinal barrier as major players in the pathophysiology of metabolic disorders, such as obesity. Upon the intestinal barrier disruption, components from bacterial metabolism and bacteria itself can reach peripheral tissues through circulation. This has been associated with the low-grade inflammation that characterizes obesity and other metabolic diseases. While circulating bacterial DNA has been postulated as a common feature of obesity and even type 2 diabetes, almost no focus has been given to the existence and effects of bacteria in peripheral tissues, namely the adipose tissue. As a symbiont population, it is expected that gut microbiota modulate the immunometabolism of the host, thus influencing energy balance mechanisms and inflammation. Gut inflammatory signals cause direct deleterious inflammatory responses in adipose tissue and may also affect key gut neuroendocrine mechanisms governing nutrient sensing and energy balance, like incretins and ghrelin, which play a role in the gut-brain-adipose tissue axis. Thus, it is of major importance to disclose how gut microbiota and derived signals modulate neuroendocrine and inflammatory pathways, which contribute to the dysfunction of adipose tissue and to the metabolic sequelae of obesity and related disorders. This review summarizes the current knowledge regarding these topics and identifies new perspectives in this field of research, highlighting new pathways toward the reduction of the inflammatory burden of metabolic diseases.

Automated summary

Recently, dysbiosis and disruption of the intestinal barrier have emerged as major contributors to the pathophysiology of metabolic disorders, including obesity. The breakdown of the intestinal barrier allows bacterial components to reach peripheral tissues, causing low-grade inflammation. However, the focus on the existence and effects of bacteria in peripheral tissues, particularly adipose tissue, has been limited. Understanding how gut microbiota and derived signals modulate neuroendocrine and inflammatory pathways is crucial in addressing the dysfunction of adipose tissue and the metabolic consequences of obesity.