Saturday, September 7, 2013

GUT BACTERIA FROM THIN HUMANS MAY BE THE CURE FOR OBESITY IN FAT HUMANS

More and more research is demonstrating the beneficial roles played by the bacteria that reside within our intestines in the control, regulation, and modulation of normal physiological status and that disruption in the ratios of certain types of bacteria are associated with disease states such as obesity and type 2 diabetes, and the associated increase in intestinal inflammation and gut barrier disruption this causes. Indeed, I have written about this area of research in the pages of this blog earlier this year:


As always you can read more about the correlation between obesity and gut bacteria in the Obesity page of themedicalbiochemistrypage.org


A recent paper just published in the prestigious journal Science demonstrates that administration of bacteria from thin human feces prevents obesity in mice even when they are fed a high-fat diet.



This most elegant study study compared the effects of the administration of uncultured (feces) or culturable bacteria from twins that were both obese or who were both lean, to mice. These types of studies are designed to ascertain precisely what types of bacteria, and especially how these bacteria, effect the differences in metabolism observed in lean versus obese individuals. Previous work, for example, has shown that transplanting fecal bacteria from healthy donors to recipients with metabolic syndrome (MetS) results in the amelioration of insulin-resistance. In this current study, the bacteria (feces) from obese twins resulted in significantly greater increases in body mass and adiposity (fat) in the mice than did the bacteria (feces) from lean twins. These changes in overall metabolism in the mice were correlated to differences in the metabolic profiles of the bacteria. Bacteria in the gut metabolize (ferment) undigested fiber into short-chain fatty acids (SCFA) which exert important metabolic effects on host tissue such as the intestine. These SCFA were increased in the mice fed bacteria from lean twins relative to those fed bacteria from obese twins. The mice fed obese bacteria also showed higher levels of amino acid metabolism including essential and branched-chain amino acids (BCAA). This pattern of amino acid metabolism by the obese bacteria in these mice is very similar to elevations seen in BCAA and related amino acids observed in obese and insulin-resistant versus lean and insulin-sensitive humans. In addition, bacterial metabolism of bile acids into molecules that down-regulated host FXR receptorsignaling was significantly higher with lean bacteria than with the obese bacteria. The significance of this latter observation relates to the role of FXR-regulated bile acid synthesis and how this relates to serum cholesterol levels since bile acid synthesis is the major means for excretion of cholesterol. Activation of intestinal FXR induces expression of intestinal fibroblast growth factor 15 (FGF15) which is then secreted to the portal circulation where it binds to, and activates the liver fibroblast growth factor receptor 4 (FGFR4). This activation then results in inhibited expression of the rate-limiting enzyme in bile acid biosynthesis, cholesterol 7-a-hydroxylase (CYP7A1) resulting in lower rates of bile acid synthesis. Therefore, the observation that mice fed lean bacteria have reduced levels of activated FXR in the gut can be directly correlated to increased bile acid synthesis and increased disposition of cholesterol. Indeed, studies have shown that over-expression of CYP7A1 can prevent diet-induced obesity and insulin resistance. An additional finding in this study was that when mice fed lean twin bacteria were housed with mice fed obese twin bacteria the latter mice had reduced fat mass and adiposity accumulation compared to mice fed obese twin bacteria that were not co-housed with lean bacteria fed mice.



TAKE HOME from this study: it could be argued that an easy (but potentially distasteful, pun intended) solution to obesity is just to consume a small amount of feces from skinny humans. Given that most, if not all, of the bacteria in our guts are anaerobic, due to the lack of oxygen in the gut, it is difficult to culture the beneficial strains so that they can be delivered in the diet. In addition, there are 500 to 1000 different species of bacteria in the gut making it highly laborious to separate and culture each and every individual strain. However, in spite of these limitations it is clear that very soon there will be available methods to treat obese and type 2 diabetic individuals with cocktails of beneficial gut microbiota. Look for this to be the next HUGE market in the alternative medical and dietary supplement market. Already, numerous yogurt manufacturers are making claims to the health benefits of the probiotic cultures in their yogurt.

1 comment: