The human small intestinal microbiota is driven by rapid uptake and conversion of simple carbohydrates

Abstract

The human gastrointestinal tract (GI tract) harbors a complex community of microbes. The microbiota composition varies between different locations in the GI tract, but most studies focus on the fecal microbiota, and that inhabiting the colonic mucosa. Consequently, little is known about the microbiota at other parts of the GI tract, which is especially true for the small intestine because of its limited accessibility. Here we deduce an ecological model of the microbiota composition and function in the small intestine, using complementing culture-independent approaches. Phylogenetic microarray analyses demonstrated that microbiota compositions that are typically found in effluent samples from ileostomists (subjects without a colon) can also be encountered in the small intestine of healthy individuals. Phylogenetic mapping of small intestinal metagenome of three different ileostomy effluent samples from a single individual indicated that Streptococcus sp., Escherichia coli, Clostridium sp. and high G+C organisms are most abundant in the small intestine. The compositions of these populations fluctuated in time and correlated to the short-chain fatty acids profiles that were determined in parallel. Comparative functional analysis with fecal metagenomes identified functions that are overrepresented in the small intestine, including simple carbohydrate transport phosphotransferase systems (PTS), central metabolism and biotin production. Moreover, metatranscriptome analysis supported high level in-situ expression of PTS and carbohydrate metabolic genes, especially those belonging to Streptococcus sp. Overall, our findings suggest that rapid uptake and fermentation of available carbohydrates contribute to maintaining the microbiota in the human small intestine.

Figure 1

(a) Relative contribution of different microbial groups that are present in samples derived from the small intestine and feces of four and two healthy individuals, respectively, and those from five healthy ileostomists. The taxonomic classification is performed as described previously (Rajilić-Stojanović et al., 2009). The tree represents the Euclidian clustering of the HITChip probe profiles. A–K encode the subjects; eff, jen, ile, ter, fec encode ileostomy effluent, jenunum, ileum, terminal ileum, and feces, respectively. Microbial groups that are 2.5% of the total community in at least one of the samples are represented in the legend. (b) Principle component analysis of the microbiotas based on the HITChip probe signal profiles. Sample identities are identical as in Figure 1a. The two first components and their respective percentage of variation they explain are indicated.

Figure 2

KEGG modules plotted at the metabolic pathways. Pathways that are overrepresented in small intestine versus colon are indicated in blue; pathways that are overrepresented in metatranscriptome versus metagenome are indicated in yellow; overrepresented pathways in metatranscriptome and small intestine are indicated in green. The fermentation pathways and PTS are highlighted in boxes.

Figure 3

Phylogenetic representation of the reads. The size of the bullets represents the relative abundance of the reads per phylogenetic position. Highly abundant phylogenetic groups are indicated. (a) Representation of GS-FLX reads that showed hits to genes involved in central (purple) and glycan (green) metabolism. (b) Representation of the cDNA reads that showed hits to PTS. The colors indicate the different types of PTS.

Figure 4

Small intestinal microbiome model based on the 16S rRNA, metabolite, metagenome and metatranscriptome data.