Translational research into gut microbiota: new horizons on obesity treatment: updated 2014

Abstract

Obesity is currently a pandemic of worldwide proportions affecting millions of people. Recent stu dies have proposed the hypothesis that mechanisms not directly related to the human genome could be involved in the genesis of obesity, due to the fact that, when a population undergoes the same nutritional stress, not all individuals present weight gain related to the diet or become hyperglycemic. The human intestine is colonized by millions of bacteria which form the intestinal flora, known as gut flora. Studies show that lean and overweight human may present a difference in the composition of their intestinal flora; these studies suggest that the intestinal flora could be involved in the development of obesity. Several mechanisms explain the correlation between intestinal flora and obesity. The intestinal flora would increase the energetic extraction of non-digestible polysaccharides. In addition, the lipopolysaccharide from intestinal flora bacteria could trigger a chronic sub-clinical inflammatory process, leading to obesity and diabetes. Another mechanism through which the intestinal flora could lead to obesity would be through the regulation of genes of the host involved in energy storage and expenditure. In the past five years data coming from different sources established causal effects between intestinal microbiota and obesity/insulin resistance, and it is clear that this area will open new avenues of therapeutic to obesity, insulin resistance and DM2. Arch Endocrinol Metab. 2015;59(2):154-60

The highly variable microbiota associated to intestinal mucosa correlates with growth and hypoxia resistance of sea bass, Dicentrarchus labrax, submitted to different nutritional histories

“…The present experiment attempted to evaluate the short and long-term influence of two kinds of nutritional deficiencies on the bacterial community associated with intestinal mucosa in sea bass individuals. When animals are subjected to nutritional stress, not all individuals may react in a similar way, partly depending on intestinal microbiota [19]. A common garden approach was used to test the effects of possible social interaction and inter-individual contamination.…”

Inflammatory Links Between High Fat Diets and Diseases

“…Therefore, elevated release of LPS and/or increased FFAs levels led to elevated production of pro-inflammatory cytokines [i.e., interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α] in the gut ( 13 – 17 ). The second step may consist in increased delivery of intestinal LPS, pro-inflammatory cytokines, and FFAs into the systemic circulation and portal circulation, thus leading to a systemic low-grade inflammation ( 15 , 18 ). Elevated plasma FFAs and LPS can upregulate the expression of TLRs in circulating macrophages, enabling macrophages to be activated (M1 phenotype), which in turn produce proinflammmatory cytokines ( 11 , 12 ).…”

Changes in serum levels of lipopolysaccharides and CD26 in patients with Crohn's disease

“…Once LPS is released systemically, monocytes and phagocytic cells produce large amounts of cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-8 23. Conditions associated with abnormal intestinal permeability may increase LPS absorption and induce a state of metabolic endotoxemia characterized by elevated serum LPS concentration 45. The origin of metabolic endotoxemia is still unclear, but it is strongly suggested that it may be associated with changes in the gut microbiota, especially in diets with high fat content, leading to increased activation of inflammatory pathways and impaired insulin signaling 1…”

“…It has also been speculated that LPS may be related to the etiology of inflammation in CD. With increased bowel permeability, gut bacterial overgrowth occurs in IBD 45. The combination of abnormal microbiota and a damaged mucosal barrier may increase serum LPS levels 7…”