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Colonic transit time is related to bacterial metabolism and mucosal turnover in the gut

Abstract

Little is known about how colonic transit time relates to human colonic metabolism and its importance for host health, although a firm stool consistency, a proxy for a long colonic transit time, has recently been positively associated with gut microbial richness. Here, we show that colonic transit time in humans, assessed using radio-opaque markers, is associated with overall gut microbial composition, diversity and metabolism. We find that a long colonic transit time associates with high microbial richness and is accompanied by a shift in colonic metabolism from carbohydrate fermentation to protein catabolism as reflected by higher urinary levels of potentially deleterious protein-derived metabolites. Additionally, shorter colonic transit time correlates with metabolites possibly reflecting increased renewal of the colonic mucosa. Together, this suggests that a high gut microbial richness does not per se imply a healthy gut microbial ecosystem and points at colonic transit time as a highly important factor to consider in microbiome and metabolomics studies.

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Figure 1: Colonic transit time correlates to gut microbial diversity and composition.
Figure 2: Identified urinary metabolites associated with colonic transit time.
Figure 3: Associations between microbial metabolites and the relative abundances of bacterial OTUs.
Figure 4: Graphical summary of the main observations.

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Acknowledgements

The authors thank K.V. Vibefelt for helping out with DNA extraction and N. Bicen for performing the PCR and sequencing. The sequencing was carried out by the DTU in-house facility (DTU Multi-Assay Core, DMAC), Technical University of Denmark. This work was funded by the Danish Council for Strategic Research (grant no. 11-116163; Center for Gut, Grain and Greens), by the Technical University of Denmark and by the personal Danisco Award (to T.R.L.). The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent research centre at the University of Copenhagen and is partly funded by an unrestricted donation from the Novo Nordisk Foundation.

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M.I.B., R.J.G., H.V., T.H., T.S.-P., O.P., L.L., M.K., R.G. and T.R.L. assembled the cohort and developed protocols and infrastructure to obtain the biological samples and clinical metadata. M.H.S. measured the colonic transit time. L.B.S.H., V.C. and M.D.D. prepared the faecal samples, extracted DNA and performed 16S rRNA gene sequencing. L.B.S.H. performed the 16S data analyses, with contributions from V.C. H.M.R. and H.L.F. prepared the urine samples, performed the urine metabolic profiling and identified the urinary metabolites. H.M.R. performed the statistical correlation analyses with contributions from L.B.S.H., D.R.P. and H.B.N. H.M.R., M.I.B., H.B.N., L.B.S.H., T.S.-P., R.G., M.K. and T.R.L. interpreted the data. H.M.R. and T.R.L. wrote the manuscript and all authors read, revised and approved the final manuscript.

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Correspondence to Tine R. Licht.

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Supplementary Tables 1-6, Supplementary Figures 1-14 and Supplementary References. (PDF 2035 kb)

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Roager, H., Hansen, L., Bahl, M. et al. Colonic transit time is related to bacterial metabolism and mucosal turnover in the gut. Nat Microbiol 1, 16093 (2016). https://doi.org/10.1038/nmicrobiol.2016.93

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