Obesity, Diabetes, and Gut Microbiota The hygiene hypothesis expanded?

The connection between gut microbiota and energy homeostasis and inflammation and its role in the pathogenesis of obesity-related disorders are increasingly recognized. Animals models of obesity connect an altered microbiota composition to the development of obesity, insulin resis-tance, and diabetes in the host through several mechanisms: increased energy harvest from the diet, altered fatty acidmetabolism and composition in adipose tissue and liver, modulation of gut peptide YY and glucagon-like peptide (GLP)-1 secretion, activation of the lipopolysaccharide toll-like receptor-4 axis, andmodulation of intestinal barrier integrity byGLP-2. Instrumental for gut microbiota manipulation is the understanding of mechanisms regulating gut microbiota composition. Several factors shape the gut microflora during infancy: mode of delivery, type of infant feeding, hospitalization, and prematurity. Furthermore, the key importance of antibiotic use and dietary nutrient composition are increasingly recognized. The role of theWestern diet in promoting an obesogenic gut microbiota is being confirmation in subjects. Following encour-aging results in animals, several short-term randomized controlled trials showed the benefit of prebiotics and probiotics on insulin sensitivity, inflammatory markers, postprandial incretins, and glucose tolerance. Future research is needed to unravel the hormonal, immunomodulatory