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: Metabolic and Clinical Consequences page of my website.
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 receptor signaling 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.
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