Species–function relationships shape ecological properties of the human gut microbiome

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Despite recent progress, the organization and ecological properties of the intestinal microbial ecosystem remain under-investigated. Here, using a manually curated metabolic module framework for (meta-)genomic data analysis, we studied species–function relationships in gut microbial genomes and microbiomes. Half of gut-associated species were found to be generalists regarding overall substrate preference, but we observed significant genus-level metabolic diversification linked to bacterial life strategies. Within each genus, metabolic consistency varied significantly, being low in Firmicutes genera and higher in Bacteroides. Differentiation of fermentable substrate degradation potential contributed to metagenomic functional repertoire variation between individuals, with different enterotypes showing distinct saccharolytic/proteolytic/lipolytic profiles. Finally, we found that module-derived functional redundancy was reduced in the low-richness Bacteroides enterotype, potentially indicating a decreased resilience to perturbation, in line with its frequent association to dysbiosis. These results provide insights into the complex structure of gut microbiome-encoded metabolic properties and emphasize the importance of functional and ecological assessment of gut microbiome variation in clinical studies.

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Figure 1: Gut reference species' saccharolytic, proteolytic and lipolytic fermentation potential.
Figure 2: Gut metabolic diversification of input, central and ouput functions.
Figure 3: Metabolic consistency between species belonging to the same genus.
Figure 4: Saccharolytic, lipolytic and proteolytic potential diversification across the enteroscape (277 MetaHIT samples).
Figure 5: Enterotype-associated differences in ecosystem resilience and stability indicators (277 MetaHIT samples).


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This research was funded by FP7 METACARDIS HEALTH-F4-2012- 305312 and IWT-SBO 100016. S.V.S. is funded by Marie Curie Actions FP7 People COFUND Proposal 267139 (acronym OMICS@VIB) and the Fund for Scientific Research-Flanders (FWO-V). S.C., M.V.C. and G.L.M. are funded by FWO-V. D.V. is funded by the Agency for Innovation by Science and Technology (IWT). The authors thank Dr Greenblum and collaborators and Dr Korem and collaborators for providing data.

Author information

S.V.S. and G.F. contributed equally to this work. S.V.S. and G.F. designed the study, collected and processed data, performed the analyses and wrote the paper. G.F., S.V.S., D.V., M.V.C. and Y.D. curated the gut-specific metabolic modules. J.R. designed the study and co-wrote the paper. Y.D., R.G.Y., F.H. and S.O. participated in data collection and processing. G.L.M., Y.D., R.G.Y., S.O., D.V. and S.C. participated in statistical analyses. Y.D. participated in graphical representation design.

Correspondence to Jeroen Raes.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Information

Supplementary Figures 1–9, Supplementary Data legends 1–3, Supplementary Table legends 1–11. (PDF 3080 kb)

Supplementary Data 1

Gut-specific metabolic modules formatted for easy integration into bioinformatics pipelines (TXT 25 kb)

Supplementary Data 2

Gut reference genomes phylogenetic tree (TXT 14 kb)

Supplementary Information

Supplementary Tables 1–11 (XLSX 666 kb)

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Vieira-Silva, S., Falony, G., Darzi, Y. et al. Species–function relationships shape ecological properties of the human gut microbiome. Nat Microbiol 1, 16088 (2016) doi:10.1038/nmicrobiol.2016.88

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