Gut microbiota and sirtuins in obesity-related inflammation and bowel dysfunction

Abstract

Obesity is a chronic disease characterized by persistent low-grade inflammation with alterations in gut motility. Motor abnormalities suggest that obesity has effects on the enteric nervous system (ENS), which controls virtually all gut functions. Recent studies have revealed that the gut microbiota can affect obesity and increase inflammatory tone by modulating mucosal barrier function. Furthermore, the observation that inflammatory conditions influence the excitability of enteric neurons may add to the gut dysfunction in obesity. In this article, we discuss recent advances in understanding the role of gut microbiota and inflammation in the pathogenesis of obesity and obesity-related gastrointestinal dysfunction. The potential contribution of sirtuins in protecting or regulating the circuitry of the ENS under inflamed states is also considered.

Weight Loss Mediated Reduction in Xanthine Oxidase Activity and Uric Acid Clearance in Adolescents with Severe Obesity

“…10 For example, a high-fat diet or high consumption of dietary fats, which are common in subjects with extreme obesity, may also increase LPS levels by altering the gut microbiota to express more gram-negative bacteria. 16,17 Meal replacement therapy may be partially responsible for changes in XO activity by altering the gut microbiota to decrease LPS production, since the diet included less fat than an average diet (approximately 19% fat in current diet regimen vs. 33% in an average US diet), and meal replacement therapy has been shown in previous studies to lower LPS levels in obese adolescents. 18 Uric acid has been shown to be important in regulating blood pressure in children with hypertension.…”

Health impact of the Anthropocene: the complex relationship between gut microbiota, epigenetics, and human health, using obesity as an example

“…A lack of diversity in the microbiota has been associated with dysbiosis in the gut and low-grade chronic inflammation that promotes metabolic disorders, such as obesity and type-2 diabetes in both humans and animals [34,64,[94][95][96]. Importantly, the ecosystem of the microbiota continues to change throughout a life course and is likely to be affected by epigenetics [97].…”

High-Fat Diet Promotes Neuronal Loss in the Myenteric Plexus of the Large Intestine in Mice

“…Such diets can change the patterns of colonic motility [12], alter the secretion of the mucosal barrier [8], and increase the permeability of the epithelial barrier [7]. These intestinal functions are regulated and coordinated by the enteric nervous system, the segment of the autonomic nervous system that innervates the gastrointestinal tract and has a high degree of functional autonomy.…”

“…Studies that used animal models of genetic and highfat-induced obesity reported an increase in the production of tumor necrosis factor a and interleukin-6 by adipose tissue [5,6] and the intestine [7], and an increase in the activation of Toll-like receptor (TLR) and nuclear factor jB signaling pathways [8]. Experimental and clinical evidence indicates that these molecules and the signaling pathways integrated by them are directly related to inflammation and the development of metabolic diseases and their complications, activating the endoplasmic reticulum stress response and production of reactive oxygen species (ROS) [2].…”