Obesity alters gut microbial ecology

Abstract

We have analyzed 5,088 bacterial 16S rRNA gene sequences from the distal intestinal (cecal) microbiota of genetically obese ob/ob mice, lean ob/+ and wild-type siblings, and their ob/+ mothers, all fed the same polysaccharide-rich diet. Although the majority of mouse gut species are unique, the mouse and human microbiota(s) are similar at the division (superkingdom) level, with Firmicutes and Bacteroidetes dominating. Microbial-community composition is inherited from mothers. However, compared with lean mice and regardless of kinship, ob/ob animals have a 50% reduction in the abundance of Bacteroidetes and a proportional increase in Firmicutes. These changes, which are division-wide, indicate that, in this model, obesity affects the diversity of the gut microbiota and suggest that intentional manipulation of community structure may be useful for regulating energy balance in obese individuals. The sequences reported in this paper have been deposited in the GenBank database [accession nos. DQ 014552--DQ 015671 (mothers) and AY 989911--AY 993908 (offspring)].

Figures

Fig. 1.

Bacterial diversity in the distal gut (ceca) of C57BL/6 mice. (A) Phylogenetic tree of 5,088 mouse ceca-associated 16S rRNA sequences reported in this study and 11,831 human colon-associated 16S rRNA sequences from ref. . Data from bacteria harvested from both mammalian hosts were obtained by using the same 16S rRNA gene-directed primers and PCR cycle numbers. The bar represents 15% sequence divergence. (B) Phylogenetic tree of the Bacteria showing described divisions (wedges, n = 55). Divisions detected in this study are indicated by the mouse symbol. Divisions detected in a large survey of the human colonic microbiota (11) are indicated by the human-head symbol. “H” denotes additional divisions represented in the human fecal microbiota, as determined from GenBank entries (1). Divisions dominant in mice and humans are colored red, rarer divisions are blue, and undetected divisions are black. The bar indicates changes per nucleotide. (C) Maximum-parsimony tree, showing representative taxa of the Cyanobacteria in green, including chloroplast sequences from Eukaryotes. Sequences detected in the gastrointestinal tracts of animals are in brown, and those detected in other environments are in purple (for additional information about taxa used to construct and root, but not shown in, the tree, see Supporting Methods. Nodes within the tree that are supported [bootstrap values (BT) of >70% and Bayesian posterior probabilities (BPP) of >90%] are indicated by filled squares. BT/BPP is explicitly stated for the basal node. The bar represents 0.1 nucleotide substitutions per site.

Fig. 2.

Effects of kinship and obesity on gut microbial ecology. (A) Unweighted-pair-group method with arithmetic-mean (UPGMA) tree, based on pairwise differences between the cecal microbial communities of each mouse (UniFrac metric, based on 5,088 sequences). Dark blue, mother 1 and her offspring (M1-); pink, mother 2 and offspring; light blue, M3 and offspring. mothers 1 and 3 are siblings from different litters. Mother 2 had two sequential litters (M2A- and M2B-). All nodes are robust with respect to the specific mice included (jackknife values >0.95 for all nodes, representing the percentage of time the node was present when a randomly chosen mouse was removed from the distance matrix for n = 1,000 replicates). Nodes denoted by a square are robust to sequence number (jackknife values >0.67, representing the number of times the node was present when 200 sequences were randomly chosen from each mouse for n = 100 replicates, excluding mice M2A-1 and M2A-2, which had <200 sequences). (B) Community similarity between the microbiota of mouse pairs belonging to different families (≠ fam), the same family (= fam), different phenotypes [obese or lean, (≠ pheno)], or the same phenotype (= pheno). Community similarity was calculated for taxa (defined by percentage of conserved sequence identities, ranging from 86% to 99%, excluding hypervariable regions of the gene in the alignment) by using the Chao-Jaccard abundance-based similarity index (16). This index estimates the similarity of communities, based on the probability (taking into account community coverage) of a taxon belonging to one community or another or both. Identical communities have an index of 1. Values shown are means for each category. Error bars are standard errors among the similarity indices between all pairs of mice in each category. (C) Proportion of Bacteroidetes and Firmicutes in the cecal microbiota of lean vs. obese mice. Mean values ± SEM are plotted. *, P < 0.05 within the division.