Emerging role of intestinal microbiota and microbial metabolites in metabolic control

Abstract

The role of the intestinal microbiota and microbial metabolites in the maintenance of host health and development of metabolic disease has gained significant attention over the past decade. Mechanistic insight revealing causality, however, is scarce. Work by Ussar and co-workers demonstrates that a complex interaction between microbiota, host genetics and environmental factors is involved in metabolic disease development in mice. In addition, Perry and coworkers show that the microbial metabolite acetate augments insulin resistance in rats. These studies underscore an important role of the microbiota in the development of obesity and symptoms of type 2 diabetes in rodents. If causality can be demonstrated in humans, development of novel diagnostic and therapeutic tools that target the gut microbiota will have high potential.Keywords Gut microbiota . Insulin resistance . Obesity . Short-chain fatty acids . Type 2 diabetes Abbreviations BBB Blood-brain barrier FMT Faecal microbiota transfer GSIS Glucose-stimulated insulin secretion HFD High-fat diet ICV Intracerebroventricular SCFA Short-chain fatty acidThe symbiotic relationship with our intestinal microbiota is exemplified by a broad range of beneficial effects for the host metabolism, including digestion of complex carbohydrates and maturation of the immune response. In addition, the intestinal microbiota serves an endocrine role by producing a vast amount of metabolites with the potential to modulate host metabolism [1]. The intestinal microbiota has, as such, also been implicated in the development of obesity and type 2 diabetes in human and rodent models [2]. This adds another layer of complexity to studying the origin of these multifactorial metabolic pathologies that arise from a complicated interplay between genetic risk factors and external factors, including dietary intake and physical activity. This commentary discusses two recent rodent studies on the potential importance of the intestinal microbiota in metabolic disease. Ussar and co-workers [3] studied the complex interaction between environmental and genetic factors in microbiota-related metabolic disease development in mice, while Perry and co-workers [4] investigated a potential mechanism underlying microbiota-driven disease development using a rat model.Colonisation of the gastrointestinal tract starts as early as in utero [5], and a core microbiome composed mainly of Bacteroidetes, Firmicutes, Actinobacteria, Proteobacteria and Verrucomicrobia is established around the third year of life. Extrinsic factors, including host genetic makeup [6], cohousing/family members [7], oral antibiotic use early in life [8] and diet [9] are dominating factors in shaping the intestinal microbiota. Whether these early life events are determinants of microbiota-related disease in later life remains to be

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