An obesity-associated gut microbiome with increased capacity for energy harvest.

David Robertson

David Robertson

David Robertson

+ -1 Evaluators

This study implicates the nature of the gut microbiome as a determinant of the pathophysiology of obesity, and perhaps other conditions. In spite of great diversity in the microbial content of the gut, 90% of bacteria are in the Bacteroidetes and Firmicutes divisions. The relative portion of these two divisions in the gut influence energy release from food. The obese mouse microbiome is found here to harvest energy from the diet more effectively, and the relative abundance of Bacteroidetes in gut tracked with weight loss. Speculative but well worth studying will be the extent of causality here, or the larger question of the role of intestinal flora in other traits such as interindividual differences in water or salt absorption and oral drug handling.

Joel Elmquist

Joel Elmquist

Joel Elmquist

+ -1 Evaluators

This is one of the most provocative papers to be published in the field of obesity research in some time. The evidence provided in this paper demonstrates that obese and non-obese mice have alterations in bacterial populations that apparently affect energy availability and utilization and the body weight of the host. Similar to advances in the field of neuroimmunology, the paper also highlights the need to increase the understanding how the nervous system monitors the levels and activity of microorganisms. The results also require a rethinking of the physiology underlying coordinated control of energy homeostasis.

Matthias Maiwald

Matthias Maiwald

Matthias Maiwald

+ -1 Evaluators

This exciting paper reveals that there is a relationship between intestinal microbial flora and obesity. The authors examined and compared the intestinal 'microbiomes' of genetically obese versus non-obese mice by metagenomic sequence analysis. Two bacterial divisions predominated in the intestinal flora: the Firmicutes and the Bacteroidetes. Obese mice had a significantly larger proportion of Firmicutes than non-obese ones, and the non-obese ones had more Bacteroidetes than the obese ones. Analysis of metabolic pathways from the intestinal microbiomes also revealed a greater frequency in obese mice of genes coding for enzymes that are involved in the breakdown of complex carbohydrates, thereby suggesting an increased capacity for energy harvest from nutrients. Intestinal content from the caecum of obese and non-obese mice was also transferred into germ-free raised mice and resulted in greater weight gain in mice inoculated with 'obese' intestinal content. Similar observations regarding the frequency of Firmicutes and Bacteroidetes were also made in groups of naturally obese and non-obese humans and published in an accompanying paper in the same journal issue {1} -- there, the frequency of Bacteroidetes increased after a weight-loss program. These findings clearly show that the intestinal flora is involved in the pathogenesis of obesity; however, the exact nature of this association remains unclear, especially if the shift in flora composition is a cause or a consequence of obesity. Reference: {1} Ley et al. Nature 2006, 444:1022-3 [PMID:17183309].

Liang Tong

Liang Tong

Liang Tong

+ -1 Evaluators

This paper reports that the gut microbiota can contribute to the obese state of the host. The microbiota in obese individuals, rich in Firmicutes, appear to be more efficient at extracting energy from the diet. It remains to be determined how the lean/obese state of the host can dictate the composition of the gut microbiota.

Joanna Goldberg

Joanna Goldberg

Joanna Goldberg

+ -1 Evaluators

With the New Year, our resolutions naturally focus on losing weight. This is one of two reports (see also {1}) in this issue of Nature from Jeffrey I. Gordon and colleagues at Washington University School of Medicine that suggest that our own microbiota need to be included in the discussion.

In the paper by Ley et al. {1} 12 obese people were randomly assigned to either a fat-restricted diet or a carbohydrate-restricted diet.

The composition of their gut microbiota was monitored during the year of this study by sequencing the 16S rRNA genes of stool samples. Before the diet, obese individuals had fewer bacteria of the phylum Bacteroidetes and more bacteria of the phylum Firmicutes, than did lean controls. Depending on the diet, once an individual lost 2-6% body fat, the relative abundance of Bacteroidetes increased, with the concomitant decrease in abundance of Firmicutes. To decipher the mechanism of this observation, the present paper reports the sequence of the metagenome of the distal gut of genetically obese mice
and their lean littermates. The bacteria in the obese mice had an increase in the number of genes encoding enzymes for the degradation of indigestible dietary polysaccharides, suggesting that these mice had greater ability to extract energy from the food they ingested compared to lean mice. When the microbiota from either obese or lean mice was transferred to germ-free mice, those receiving the obese community of bacteria exhibited a significantly greater percentage in body fat over two weeks compared to those mice that received the lean community of bacteria. Together these reports, as well as the accompanying News and Views {2}, suggest that we need to adjust our ideas about exactly what causes obesity and what can be done to treat or prevent it.

Marc Lecuit

Marc Lecuit

Marc Lecuit

+ -1 Evaluators

This study from the laboratory of Jeffrey I. Gordon, together with an accompanying study published in the same issue {1}, is remarkable as it clearly establishes a link between gut microflora composition and obesity, both in mice and humans.

Significantly, it shows that, in mice, the 'obese' microbiome has an increased capacity to harvest energy from the diet, a finding that may sound counterintuitive: the microbiota seem indeed to be more efficient in obese individuals who already have the most stored
energy, and shifts to being less efficient as the subjects lose weight.

In addition, the authors also demonstrate that this trait is transmissible, since colonization of germ-free mice with an 'obese microbiota' results in a significantly greater increase in total body fat than colonization with a 'lean microbiota'. Among the many important questions arising from these studies, one can list the
following: firstly, what is the quantitative and qualitative
contribution of diet composition on the shaping of the microbiota, and its consequence in terms of energy harvest; secondly, what is the actual role of gut microbiota on the developing obesity epidemics; and lastly, would it be theoretically possible to alter
microbiota composition as a therapeutic approach against obesity? These questions will certainly be subject to intense investigations in the near future. Please also refer to previous articles on the same theme {2,3,4}.

Stefan Kaufmann

Stefan Kaufmann

Stefan Kaufmann

+ -1 Evaluators

In this paper, the authors demonstrate the link between obesity and the composition of the microbiome in the gut. The microbiome of obese mice has a higher abundance of genes that encode enzymes which gain energy from the diet, for example, by degrading otherwise indigestible dietary components. Such enzymes are more prevalent in species of the phylum Firmicutes as compared to species of the phylum Bacteroidetes. Hence, composition of the gut microbiome influences obesity through differential abundance of the metabolic potential of the respective gut flora.

Joseph Heitman

Joseph Heitman

Joseph Heitman

+ -1 Evaluators

Obesity could be an infectious disease! The microbiome resident in the gastrointestinal tract of obese mice lacking the hormone leptin (ob/ob animals) was found to differ from their lean wild-type littermates. Transplantation of the obesity-associated microbiome into recipient animals resulted in an increased body fat composition, suggesting that the microbiome can be associated with differences in the efficiency with which calories can be harvested from ingested nutrients. Given the relatively recent appreciation that human maladies as complex as ulcer disease can be the result of infectious disease, these studies raise the exciting possibility that antimicrobial therapy might be implemented to alter the microbiome and tip the balance towards weight balance, or even weight loss, with no sacrifice in caloric intake.

David Bilder

David Bilder

David Bilder

+ -1 Evaluators

This is one of several papers from the Gordon lab that use metagenomic sequencing to point to a distinctive phylogenetic distribution of gut microbial flora associated with obese mice. Here, several lines of evidence indicate that the microbiome of obese mice is more efficient at extracting energy from food intake, although the overall effect on weight gain (tested in microbiome transplantation experiments) is quite small. The results provide a nice example of host-microbe interactions significant to adult physiology and homeostasis.