The gut microbiome as therapeutic target.

Obesity, type-2 diabetes and low-grade inflammation are becoming worldwide epidemics. In this regard, the literature provides a novel concept that we call "MicrObesity" (Microbes and Obesity), which is devoted to deciphering the specific role of dysbiosis and its impact on host metabolism and energy storage. In the present review, we discuss novel findings that may partly explain how the microbial community participates in the development of the fat mass development, insulin resistance and low-grade inflammation that characterise obesity. In recent years, numerous mechanisms have been proposed and several proteins identified. Amongst the key players involved in the control of fat mass development, Fasting induced adipose factor, AMP-activated protein kinase, G-protein coupled receptor 41 and G-protein coupled receptor 43 have been linked to gut microbiota. In addition, the discovery that low-grade inflammation might be directly linked to the gut microbiota through metabolic endotoxaemia (elevated plasma lipopolysaccharide levels) has led to the identification of novel mechanisms involved in the control of the gut barrier. Amongst these, the impacts of glucagon-like peptide-2, the endocannabinoid system and specific bacteria (e.g., Bifidobacterium spp.) have been investigated. Moreover, the advent of probiotic and prebiotic treatments appears to be a promising "pharmaco-nutritional" approach to reversing the host metabolic alterations linked to the dysbiosis observed in obesity. Although novel powerful molecular system biology approaches have offered great insight into this "small world within", more studies are needed to unravel how specific changes in the gut microbial community might affect or counteract the development of obesity and related disorders.

Cani PD ，Delzenne NM 《-》

Interplay between obesity and associated metabolic disorders: new insights into the gut microbiota.

Cani PD ，Delzenne NM 《-》

Gut microbiota controls adipose tissue expansion, gut barrier and glucose metabolism: novel insights into molecular targets and interventions using prebiotics.

Geurts L ，Neyrinck AM ，Delzenne NM ，Knauf C ，Cani PD ... -  《-》

The gut microbiota, obesity and insulin resistance.

The human gut is densely populated by commensal and symbiotic microbes (the "gut microbiota"), with the majority of the constituent microorganisms being bacteria. Accumulating evidence indicates that the gut microbiota plays a significant role in the development of obesity, obesity-associated inflammation and insulin resistance. In this review we discuss molecular and cell biological mechanisms by which the microbiota participate in host functions that impact the development and maintenance of the obese state, including host ingestive behavior, energy harvest, energy expenditure and fat storage. We additionally explore the diverse signaling pathways that regulate gut permeability and bacterial translocation to the host and how these are altered in the obese state to promote the systemic inflammation ("metabolic endotoxemia") that is a hallmark of obesity and its complications. Fundamental to our discussions is the concept of "crosstalk", i.e., the biochemical exchange between host and microbiota that maintains the metabolic health of the superorganism and whose dysregulation is a hallmark of the obese state. Differences in community composition, functional genes and metabolic activities of the gut microbiota appear to distinguish lean vs obese individuals, suggesting that gut 'dysbiosis' contributes to the development of obesity and/or its complications. The current challenge is to determine the relative importance of obesity-associated compositional and functional changes in the microbiota and to identify the relevant taxa and functional gene modules that promote leanness and metabolic health. As diet appears to play a predominant role in shaping the microbiota and promoting obesity-associated dysbiosis, parallel initiatives are required to elucidate dietary patterns and diet components (e.g., prebiotics, probiotics) that promote healthy gut microbiota. How the microbiota promotes human health and disease is a rich area of investigation that is likely to generate fundamental discoveries in energy metabolism, molecular endocrinology and immunobiology and may lead to new strategies for prevention of obesity and its complications.

Shen J ，Obin MS ，Zhao L 《-》

Crosstalk between the gut microbiota and the endocannabinoid system: impact on the gut barrier function and the adipose tissue.

Obesity is associated with type 2 diabetes, insulin resistance and low grade inflammation. The gut microbiota is now considered as one of the most important environmental factors impacting on host physiology and metabolism. We have recently pointed out the role of this 'organ' on the onset of insulin resistance and the low grade inflammatory tone characterizing obesity. Among the mechanisms, we have introduced the novel concept of metabolic endotoxaemia as factor triggering low grade inflammation and associated disorders. More recently, two novel mechanisms involved in the development of gut permeability and adipose tissue plasticity have been identified. Specific attention has been paid to the role of the glucagon-like peptide 2 and the endocannabinoid system. This review briefly discusses the role of prebiotics as a key tool to modulate the gut microbiota, the gut barrier function, inflammation and the insulin resistance associated with obesity.

Cani PD 《-》