Obesity alters gut microbial ecology

Abstract

The 10 trillion to 100 trillion microorganisms that populate our adult intestines benefit us in a number of ways (1). One benefit is that they allow us to extract calories from otherwise indigestible common polysaccharides in our diet. This benefit occurs because components of the microbiota are able to adaptively deploy a large array of glycoside hydrolases and polysaccharide lysases that we humans do not encode in our genome (2, 3) (http://afmb.cnrs-mrs.fr/CAZY/). Furthermore, studies using germ-free and colonized normal and knockout mice fed a standard, polysaccharide-rich rodent-chow diet indicate that this mutualistic host-microbe relationship allows the extracted energy to be stored in adipocytes through a pathway that involves microbial regulation of the intestinal epithelial expression of fasting-induced adipocyte protein (Fiaf), a circulating inhibitor of lipoprotein lipase (LPL) (4). Microbial fermentation of dietary polysaccharides to monosaccharides and short-chain fatty acids in the distal gut and their subsequent absorption stimulate de novo synthesis of triglycerides in the liver. Microbial suppression of Fiaf in the gut epithelium results in reduced levels of this circulating LPL inhibitor, increased LPL activity in adipocytes, and enhanced storage of liver-derived triacyglycerols in fat cells (4).

Although the root cause of obesity is excess caloric intake compared with expenditure, differences in gut microbial ecology between humans may be an important factor affecting energy homeostasis; i.e., individuals predisposed to obesity may have gut microbial communities that promote more efficient extraction and/or storage of energy from a given diet, compared with these communities in lean individuals. This hypothesis raises a number of basic questions about gut microbial ecology in humans and mice. For example, how do the distal-gut microbiotas of the two hosts compare? Does kinship play an important role in the composition of the microbial community? Does adiposity affect community structure, and, if so, at what taxonomic level do these effects occur, and do they reflect a heretofore unappreciated form of homeostatic feedback between the microbiota and host energy balance?

Although information is limited, a current conceptualization of bacterial diversity in the human gut is that there is a restricted suite of highly adapted bacteria, likely inherited from the immediate family and, possibly, filtered by host genotype (5). Studies are needed to characterize the rules controlling microbial diversity in the human gut. Remarkably, a comprehensive enumeration of the gut microbiota has not yet been reported for Mus musculus, even though this mammalian species provides a very attractive model for systematically exploring the roles of host genotype, maternal exposure, diet, and energy balance on intestinal microbial ecology. Therefore, in this report, we use C57BL/6 mice, homozygous for a mutation in the leptin gene (ob/ob) that produces a stereotyped, fully penetrant obesity phenotype (6, 7), and their lean ob/+ and +/+ siblings, to show that microbial-community composition in the distal intestine changes at a division-wide level in response to increasing adiposity. This finding provides another perspective about the link between the gut microbiota and host energy balance.

Acknowledgments

Notes

Author contributions: R.E.L., F.B., and J.I.G. designed research; R.E.L., F.B., and P.T. performed research; C.A.L. and R.D.K. contributed new reagents/analytic tools; R.E.L., F.B., P.T., C.A.L., R.D.K., and J.I.G. analyzed data; and R.E.L., C.A.L., and J.I.G. wrote the paper.

Data deposition: The sequences reported in this paper have been deposited in the GenBank database [accession nos. DQ014552-DQ015671 (mothers) and AY989911-AY993908 (offspring)].