The therapeutic potential of manipulating gut microbiota in obesity and type 2 diabetes mellitus.

Obesity and type 2 diabetes mellitus (T2DM) are attributed to a combination of genetic susceptibility and lifestyle factors. Their increasing prevalence necessitates further studies on modifiable causative factors and novel treatment options. The gut microbiota has emerged as an important contributor to the obesity--and T2DM--epidemic proposed to act by increasing energy harvest from the diet. Although obesity is associated with substantial changes in the composition and metabolic function of the gut microbiota, the pathophysiological processes remain only partly understood. In this review we will describe the development of the adult human microbiome and discuss how the composition of the gut microbiota changes in response to modulating factors. The influence of short-chain fatty acids, bile acids, prebiotics, probiotics, antibiotics and microbial transplantation is discussed from studies using animal and human models. Ultimately, we aim to translate these findings into therapeutic pathways for obesity and T2DM in humans.

Kootte RS ，Vrieze A ，Holleman F ，Dallinga-Thie GM ，Zoetendal EG ，de Vos WM ，Groen AK ，Hoekstra JB ，Stroes ES ，Nieuwdorp M ... -  《-》

Gut microbiota interactions with obesity, insulin resistance and type 2 diabetes: did gut microbiote co-evolve with insulin resistance?

Esteve E ，Ricart W ，Fernández-Real JM 《-》

Probiotics, prebiotics, energy balance, and obesity: mechanistic insights and therapeutic implications.

Obesity-related disorders derive from a combination of genetic susceptibility and environmental factors. Recent evidence supports the role of gut microbiota in the pathogenesis of obesity, type 2 diabetes mellitus, and insulin resistance by increasing energy harvest from diet and by inducing chronic, low-grade inflammation. Several studies describe characteristic differences between composition and activity of gut microbiota of lean individuals and those with obesity. Despite this evidence, some pathophysiological mechanisms remain to be clarified. This article discusses mechanisms connecting gut microbiota to obesity and fat storage and the potential therapeutic role of probiotics and prebiotics.

Molinaro F ，Paschetta E ，Cassader M ，Gambino R ，Musso G ... -  《-》

Do nutrient-gut-microbiota interactions play a role in human obesity, insulin resistance and type 2 diabetes?

The current obesity and type 2 diabetes pandemics have causes beyond changes in eating and exercise habits against a susceptible genetic background. Gut bacteria seem to additionally contribute to the differences in body weight, fat distribution, insulin sensitivity and glucose- and lipid-metabolism. Data, mostly derived from preclinical studies, suggest that gut microbiota play an important role in conditions such as obesity, diabetes, metabolic syndrome and non-alcoholic fatty liver disease. Regulation of energy uptake from the gut, by digesting otherwise indigestible common polysaccharides in our diet, production or activation of signalling molecules involved in host metabolism, modification of gut permeability, the release of gut hormones and inflammation, are among the mechanisms by which gut microbiota may influence the host cardiometabolic phenotype. Recent evidence suggests that quantitative and qualitative differences in gut microbiota exist between lean and obese, and between diabetic and non-diabetic individuals. Modification of the gut microbiota composition and/or its biochemical capacity by specific dietary or pharmacological interventions may favourably affect host metabolism. Large-scale intervention trials, investigating the potential benefit of prebiotics and probiotics in improving cardiometabolic health in high-risk populations, are eagerly awaited.

Diamant M ，Blaak EE ，de Vos WM 《-》

Gut microbiota, intestinal permeability, obesity-induced inflammation, and liver injury.

Frazier TH ，DiBaise JK ，McClain CJ 《-》