Immunometabolism of obesity and diabetes: microbiota link compartmentalized immunity in the gut to metabolic tissue inflammation

Abstract

The bacteria that inhabit us have emerged as factors linking immunity and metabolism. Changes in our microbiota can modify obesity and the immune underpinnings of metabolic diseases such as Type 2 diabetes. Obesity coincides with a low-level systemic inflammation, which also manifests within metabolic tissues such as adipose tissue and liver. This metabolic inflammation can promote insulin resistance and dysglycaemia. However, the obesity and metabolic disease-related immune responses that are compartmentalized in the intestinal environment do not necessarily parallel the inflammatory status of metabolic tissues that control blood glucose. In fact, a permissive immune environment in the gut can exacerbate metabolic tissue inflammation. Unravelling these discordant immune responses in different parts of the body and establishing a connection between nutrients, immunity and the microbiota in the gut is a complex challenge. Recent evidence positions the relationship between host gut barrier function, intestinal T cell responses and specific microbes at the crossroads of obesity and inflammation in metabolic disease. A key problem to be addressed is understanding how metabolite, immune or bacterial signals from the gut are relayed and transferred into systemic or metabolic tissue inflammation that can impair insulin action preceding Type 2 diabetes.

The Therapeutic Potential of T Cell Metabolism

“…While there is much research dedicated to the study of the interface of immunology and metabolism in the context of how metabolic diseases such as obesity and dyslipidemia promote inflammation and impact host defense, this area of immunometabolism is beyond the scope of this mini-review. Therefore, we direct readers to other excellent discussions of these topics (1)(2)(3)(4).…”

Immunologic impact of the intestine in metabolic disease

“…The intestinal immune system has recently emerged as a site that is altered by diet-induced obesity. The specific influence of the gut microbiota on the development of metabolic disorders, and how bacterial signals compartmentalized in the gut directly shape immune responses linked to systemic and metabolic tissue inflammation, are active areas of interest and have been previously reviewed (12)(13)(14). In addition to microbial signals, dietary cues also help shape the composition of the intestinal immune system, and these effects collectively contribute to its role as a novel regulator of metabolic disease.…”

The Gut Bacteria-Driven Obesity Development

“…Obesity is now recognized as a complex process involving genetic and environmental factors and associated with pathways that bi-directionally connect metabolism with the immune system [4]. …”