Effects of bowel preparation on the human gut microbiome and metabolome

Naoyoshi Nagata, Mari Tohya, Shinji Fukuda, Wataru Suda, Suguru Nishijima, Fumihiko Takeuchi, Mitsuru Ohsugi, Tetsuro Tsujimoto, Tomoka Nakamura, Akira Shimomura, Naohiro Yanagisawa, Yuya Hisada, Kazuhiro Watanabe, Koh Imbe, Junichi Akiyama, Masashi Mizokami, Tohru Miyoshi-Akiyama, Naomi Uemura, Masahira Hattori, Naoyoshi Nagata, Mari Tohya, Shinji Fukuda, Wataru Suda, Suguru Nishijima, Fumihiko Takeuchi, Mitsuru Ohsugi, Tetsuro Tsujimoto, Tomoka Nakamura, Akira Shimomura, Naohiro Yanagisawa, Yuya Hisada, Kazuhiro Watanabe, Koh Imbe, Junichi Akiyama, Masashi Mizokami, Tohru Miyoshi-Akiyama, Naomi Uemura, Masahira Hattori

Abstract

Large bowel preparation may cause a substantial change in the gut microbiota and metabolites. Here, we included a bowel prep group and a no-procedure control group and evaluated the effects of bowel prep on the stability of the gut microbiome and metabolome as well as on recovery. Gut microbiota and metabolome compositions were analyzed by 16S rRNA sequencing and capillary electrophoresis time-of-flight mass spectrometry, respectively. Analysis of coefficients at the genus and species level and weighted UniFrac distance showed that, compared with controls, microbiota composition was significantly reduced immediately after the prep but not at 14 days after it. For the gut metabolome profiles, correlation coefficients between before and immediately after the prep were significantly lower than those between before and 14 days after prep and were not significantly different compared with those for between-subject differences. Thirty-two metabolites were significantly changed before and immediately after the prep, but these metabolites recovered within 14 days. In conclusion, bowel preparation has a profound effect on the gut microbiome and metabolome, but the overall composition recovers to baseline within 14 days. To properly conduct studies of the human gut microbiome and metabolome, fecal sampling should be avoided immediately after bowel prep.

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Gut microbiota α-diversity as measured by the Shannon index before, during, and after bowel preparation. Note: Boxes represent the interquartile range (IQR) and lines inside show the median. Whiskers denote the lowest and highest values within 1.5 times the IQR.
Figure 2
Figure 2
Gut microbial composition across different sampling times in the bowel prep group vs control group. (A) Spearman’s correlation coefficients of gut microbial composition at the genus level. (B) Spearman’s correlation coefficients of gut microbial composition at the species level. (C) Weighted UniFrac distances of gut microbial composition. Note: Boxes represent the interquartile range (IQR) and lines inside show the median. Whiskers denote the lowest and highest values within 1.5 times the IQR.
Figure 3
Figure 3
Principal coordinate analysis (PCoA) plot in microbiome and metabolome. (A) PCoA plot of weighted UniFrac distances for samples between bowel prep group and controls in microbioal analysis. (B) PCoA plot of weighted UniFrac distances for samples in bowel prep group in microbial analysis. (C) PCoA plot, unit variance scaling in bowel prep group in metabolome analysis.
Figure 4
Figure 4
Spearman’s correlation coefficients of fecal metabolome profiles before bowel prep (Day 0), immediately after bowel prep (Day 1), and 14 days after bowel prep (Day 14). Note: Boxes represent the interquartile range (IQR) and lines inside show the median. Whiskers denote the lowest and highest values within 1.5 times the IQR.
Figure 5
Figure 5
Timing of fecal sample collection in the bowel prep group and control group.

References

    1. ASGE Standards of Practice Committee et al. Bowel preparation before colonoscopy. Gastrointest. Endosc. 81, 781–794 (2015).
    1. Sawaya S, et al. Microsatellite tandem repeats are abundant in human promoters and are associated with regulatory elements. PLoS One. 2013;8:e54710. doi: 10.1371/journal.pone.0054710.
    1. Gorkiewicz G, et al. Alterations in the colonic microbiota in response to osmotic diarrhea. PLoS One. 2013;8:e55817. doi: 10.1371/journal.pone.0055817.
    1. Shobar RM, et al. The Effects of Bowel Preparation on Microbiota-Related Metrics Differ in Health and in Inflammatory Bowel Disease and for the Mucosal and Luminal Microbiota Compartments. Clin. Transl. Gastroenterol. 2016;7:e143. doi: 10.1038/ctg.2015.54.
    1. Drago L, Toscano M, De Grandi R, Casini V, Pace F. Persisting changes of intestinal microbiota after bowel lavage and colonoscopy. Eur. J. Gastroenterol. Hepatol. 2016;28:532–537. doi: 10.1097/MEG.0000000000000581.
    1. Harrell L, et al. Standard colonic lavage alters the natural state of mucosal-associated microbiota in the human colon. PLoS One. 2012;7:e32545. doi: 10.1371/journal.pone.0032545.
    1. O’Brien CL, Allison GE, Grimpen F, Pavli P. Impact of colonoscopy bowel preparation on intestinal microbiota. PLoS One. 2013;8:e62815. doi: 10.1371/journal.pone.0062815.
    1. Nishimoto Y, et al. High stability of faecal microbiome composition in guanidine thiocyanate solution at room temperature and robustness during colonoscopy. Gut. 2016;65:1574–1575. doi: 10.1136/gutjnl-2016-311937.
    1. Jalanka J, et al. Effects of bowel cleansing on the intestinal microbiota. Gut. 2015;64:1562–1568. doi: 10.1136/gutjnl-2014-307240.
    1. Rooks MG, Garrett WS. Gut microbiota, metabolites and host immunity. Nat. Rev. Immunol. 2016;16:341–352. doi: 10.1038/nri.2016.42.
    1. Tropini C, et al. Transient Osmotic Perturbation Causes Long-Term Alteration to the Gut Microbiota. Cell. 2018;173:1742–1754.e17. doi: 10.1016/j.cell.2018.05.008.
    1. Fouhy F, et al. The effects of freezing on faecal microbiota as determined using MiSeq sequencing and culture-based investigations. PLoS One. 2015;10:e0119355. doi: 10.1371/journal.pone.0119355.
    1. Kim SW, et al. Robustness of gut microbiota of healthy adults in response to probiotic intervention revealed by high-throughput pyrosequencing. DNA Res. 2013;20:241–253. doi: 10.1093/dnares/dst006.
    1. Dohmoto M. Preparation for colonoscopy using 1,000 ml Magcorol P isotonic solution in the absence of dietary restrictions or use of purgatives on the preceding day. Rev. Gastroenterol. Peru. 2007;27:376–381.
    1. Nagao-Kitamoto H, et al. Functional Characterization of Inflammatory Bowel Disease-Associated Gut Dysbiosis in Gnotobiotic Mice. Cell. Mol. Gastroenterol. Hepatol. 2016;2:468–481. doi: 10.1016/j.jcmgh.2016.02.003.
    1. Shibagaki N, et al. Aging-related changes in the diversity of women’s skin microbiomes associated with oral bacteria. Sci. Rep. 2017;7:10567-017–10834-9. doi: 10.1038/s41598-017-10834-9.
    1. Lozupone C, Lladser ME, Knights D, Stombaugh J, Knight R. UniFrac: an effective distance metric for microbial community comparison. ISME J. 2011;5:169–172. doi: 10.1038/ismej.2010.133.
    1. van den Berg, R. A., Hoefsloot, H. C., Westerhuis, J. A., Smilde, A. K. & van der Werf, M. J. Centering, scaling, and transformations: improving the biological information content of metabolomics data. BMC Genomics7, 142-2164-7-142 (2006).

Source: PubMed

3
Se inscrever