Obesity and the gut microbiome: pathophysiological aspects

While there is a large volume of literature describing a role for obesity as a risk factor for breast cancer and many other cancers, in the main a causal relationship has not been established. If the study is limited to breast cancer risk, it has been suggested that the increase in sex steroid formation that occurs in postmenopausal women plays a role. Obesity is known to be associated with chronic low grade inflammation, but no reason for this association has been offered in the past. The gut microbiome, while known to be enormous, has not in the past been considered as a metabolic role player in the body. This is now recognized to be the case. Recent studies have found the obesity is correlated with an alteration in the gut microbiome. In obese individual there is a change in the relative proportions of the two major classes of bacteria - bacteroides and firmacutes - with the latter dominant in obesity and resulting in the formation of increased amounts of metabolic endotoxins like deoxycholic acid and lipopolysaccharides (LPS). Obese individuals show a decrease in the concentration of Akkermansia muciniphila in the mucus that lines the intestinal wall, resulting in thinner mucus and a weakened intestinal lining and permitting metabolic endotoxins formed by other bacterial flora like LPS to enter the blood steam and cause the chronic inflammation associated with obesity. The change in the microbiome profile results in increases in bacterial strains that are more efficient at generating energy, leading to increased obesity. In mice, it has been shown that introducing gut bacterial flora from the cecum of obese mice into germ-free mice results in increased obesity with lesser food consumption while the reverse, introducing bacterial flora from lean mice results in a loss in weight. This raises the attractive possibility that manipulating the gut microbiome could facilitate weight loss or prevent obesity in humans.