Linking Gut Microbiota and Inflammation to Obesity and Insulin Resistance

Abstract

Obesity and insulin resistance are the major predisposing factors to comorbidities, such as Type 2 diabetes, nonalcoholic fatty liver disease, cardiovascular and neurodegenerative diseases, and several types of cancer. The prevalence of obesity is still increasing worldwide and now affects a large number of individuals. Here, we review the role of the gut microbiota in the pathophysiology of insulin resistance/obesity. The human intestine is colonized by ∼100 trillion bacteria, which constitute the gut microbiota. Studies have shown that lean and overweight rodents and humans may present differences in the composition of their intestinal flora. Over the past 10 years, data from different sources have established a causal link between the intestinal microbiota and obesity/insulin resistance. It is important to emphasize that diet-induced obesity promotes insulin resistance by mechanisms independent and dependent on gut microbiota. In this review, we present several mechanisms that contribute to explaining the link between intestinal flora and insulin resistance/obesity. The LPS from intestinal flora bacteria can induce a chronic subclinical inflammatory process and obesity, leading to insulin resistance through activation of TLR4. The reduction in circulating SCFA may also have an essential role in the installation of reduced insulin sensitivity and obesity. Other mechanisms include effects of bile acids, branched-chain amino acids (BCAA), and some other lesser-known factors. In the near future, this area should open new therapeutic avenues for obesity/insulin resistance and its comorbidities.

Gut‐Derived Serum Lipopolysaccharide is Associated With Enhanced Risk of Major Adverse Cardiovascular Events in Atrial Fibrillation: Effect of Adherence to Mediterranean Diet

“…LPS is a potentially interesting molecule that, once it crosses the gut mucosa and enters into the systemic circulation, may lead to atherosclerosis, possibly via chronic inflammation and thrombosis 7. About 100 trillion gut bacteria contribute to an enteric reservoir of >1 g LPS, which travels in the circulation of healthy subjects in a range of ≈10 to 200 pg/mL 8. LPS is translocated to human circulation with chylomicrons and, therefore, increases after a meal, particularly in the case of a fatty meal, suggesting a prominent role of diet in modulating circulating LPS 9, 10.…”

“…Experimental studies have showed that LPS is proatherogenic in vivo as its injection in mice and rabbits accelerates the formation of plaque 13. In humans, a relationship between LPS levels and carotid atherosclerosis has been documented,14 and circulating LPS has been found to be increased in several conditions associated with atherosclerosis, such as type 2 diabetes mellitus and obesity 8, 15. However, so far, no data regarding LPS and clinical outcomes have been reported.…”

Gut Microbiota and Diabetes Mellitus - An Interlinkage

“…Breastfeeding children develop B. bacterium in their early life which produces a high amount of acetate and lactate; these metabolic by-products have suggested to restrict the growth of pathogenic bacteria in their gut [24].…”

MECHANISMS IN ENDOCRINOLOGY: Aging and anti-aging: a Combo-Endocrinology overview

“…It has been demonstrated that altered intestinal microbiota leads to increased intestinal permeability and deregulated mucosal immune response and has an important role to play in both inflammatory and allergic diseases (195). Aging per se also has a major impact on chronic diseases as the natural changes occurring during aging, such as decreased gastric motility and secretion, changes in dietary intake and frequent use of several medications may all promote chronic inflammation due to a deregulation and lack of richness of gut microbiota, promoting the presentation of chronic inflammatory diseases, including obesity, insulin resistance, diabetes and other metabolic disturbances (196).…”