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Fecal and Mucosa-Associated Intestinal Microbiota in Patients with Diarrhea-Predominant Irritable Bowel Syndrome

Digestive Diseases and Sciences volume 63, pages 1890–1899 (2018)Cite this article

Abstract

Background

Irritable bowel syndrome (IBS) has been associated with changes in the intestinal microbiota. Only a few studies have explored differences in the mucosa-associated microbiota between IBS patients and healthy controls (HC).

Aims

To characterize and compare the microbiota in mucosal and fecal samples from carefully selected patients with IBS-D and HC.

Methods

The cohort was composed of 23 diarrhea-predominant IBS (IBS-D) patients and 24 HC. Fresh stool samples were collected from participants prior to the collection of colonic mucosal samples from an unprepped bowel. After DNA extraction, 16S rRNA genes were sequenced by 454 pyrosequencing and analyzed using the QIIME pipeline.

Results

The fecal microbiota (luminal niche) of IBS-D patients was found to have reduced enteric richness compared to HC (P < 0.05), whereas no differences were observed between the two groups within the mucosal microbiota. Within the luminal niche, the relative proportions of Faecalibacterium genus were found to be lower in IBS-D than in HC and the Dorea genus was higher in IBS-D. None of the taxa proportions were significantly different in IBS-D patients versus HC using an FDR of ≤ 0.1 when analyzing samples that appeared in > 25% samples of either niche.

Conclusion

Fecal and mucosal microbiota of IBS-D patients and HC are very similar and are not sufficient to explain the reported altered physiology and symptomatology of IBS-D. Future studies should investigate intestinal microbiome-dependent functional activity in addition to the fecal and mucosal-associated microbial composition.

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References

  1. Blumberg R, Powrie F. Microbiota, disease, and back to health: a metastable journey. Sci Transl Med. 2012;4:37rv7.

    Article  CAS  Google Scholar 

  2. Eckburg PB, Bik EM, Bernstein CN, et al. Diversity of the human intestinal microbial flora. Science. 2005;308:1635–1638.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Zoetendal EG, von Wright A, Vilpponen-Salmela T, et al. Mucosa-associated bacteria in the human gastrointestinal tract are uniformly distributed along the colon and differ from the community recovered from feces. Appl Environ Microbiol. 2002;68:3401–3407.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Ringel Y, Maharshak N, Ringel-Kulka T, et al. High throughput sequencing reveals distinct microbial populations within the mucosal and luminal niches in healthy individuals. Gut Microbes. 2015;6:173–181.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Tap J, Derrien M, Tornblom H, et al. Identification of an intestinal microbiota signature associated with severity of irritable bowel syndrome. Gastroenterology. 2017;152:e8.

    Article  Google Scholar 

  6. Durban A, Abellan JJ, Jimenez-Hernandez N, et al. Structural alterations of faecal and mucosa-associated bacterial communities in irritable bowel syndrome. Environ Microbiol Rep. 2012;4:242–247.

    Article  PubMed  CAS  Google Scholar 

  7. Soldi S, Vasileiadis S, Uggeri F, et al. Modulation of the gut microbiota composition by rifaximin in non-constipated irritable bowel syndrome patients: a molecular approach. Clin Exp Gastroenterol. 2015;8:309–325.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Bhattarai Y, Muniz Pedrogo DA, Kashyap PC. Irritable bowel syndrome: a gut microbiota-related disorder? Am J Physiol Gastrointest Liver Physiol. 2017;312:G52–G62.

    Article  PubMed  Google Scholar 

  9. Rajilic-Stojanovic M, Biagi E, Heilig HG, et al. Global and deep molecular analysis of microbiota signatures in fecal samples from patients with irritable bowel syndrome. Gastroenterology. 2011;141:1792–1801.

    Article  PubMed  CAS  Google Scholar 

  10. Codling C, O’Mahony L, Shanahan F, et al. A molecular analysis of fecal and mucosal bacterial communities in irritable bowel syndrome. Dig Dis Sci. 2010;55:392–397.

    Article  PubMed  Google Scholar 

  11. Kassinen A, Krogius-Kurikka L, Makivuokko H, et al. The fecal microbiota of irritable bowel syndrome patients differs significantly from that of healthy subjects. Gastroenterology. 2007;133:24–33.

    Article  PubMed  CAS  Google Scholar 

  12. Shukla R, Ghoshal U, Dhole TN, et al. Fecal microbiota in patients with irritable bowel syndrome compared with healthy controls using real-time polymerase chain reaction: an evidence of dysbiosis. Dig Dis Sci. 2015;60:2953–2962.

    Article  PubMed  Google Scholar 

  13. Carroll IM, Ringel-Kulka T, Siddle JP, et al. Alterations in composition and diversity of the intestinal microbiota in patients with diarrhea-predominant irritable bowel syndrome. Neurogastroenterol Motil. 2012;24:e248.

    Article  Google Scholar 

  14. Ringel-Kulka T, Benson AK, Carroll IM, et al. Molecular characterization of the intestinal microbiota in patients with and without abdominal bloating. Am J Physiol Gastrointest Liver Physiol. 2016;310:G417–G426.

    Article  PubMed  Google Scholar 

  15. Carroll IM, Chang YH, Park J, et al. Luminal and mucosal-associated intestinal microbiota in patients with diarrhea-predominant irritable bowel syndrome. Gut Pathog. 2010;2:19.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Rangel I, Sundin J, Fuentes S, et al. The relationship between faecal-associated and mucosal-associated microbiota in irritable bowel syndrome patients and healthy subjects. Aliment Pharmacol Ther. 2015;42:1211–1221.

    Article  PubMed  CAS  Google Scholar 

  17. Preheim SP, Perrotta AR, Friedman J, et al. Computational methods for high-throughput comparative analyses of natural microbial communities. Methods Enzymol. 2013;531:353–370.

    Article  PubMed  CAS  Google Scholar 

  18. Arthur JC, Gharaibeh RZ, Uronis JM, et al. VSL#3 probiotic modifies mucosal microbial composition but does not reduce colitis-associated colorectal cancer. Sci Rep. 2013;3:2868.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Caporaso JG, Kuczynski J, Stombaugh J, et al. QIIME allows analysis of high-throughput community sequencing data. Nat Methods. 2010;7:335–336.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. McDonald D, Price MN, Goodrich J, et al. An improved Greengenes taxonomy with explicit ranks for ecological and evolutionary analyses of bacteria and archaea. ISME J. 2012;6:610–618.

    Article  PubMed  CAS  Google Scholar 

  21. Lozupone C, Knight R. UniFrac: a new phylogenetic method for comparing microbial communities. Appl Environ Microbiol. 2005;71:8228–8235.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Carroll IM, Ringel-Kulka T, Siddle JP, et al. Characterization of the fecal microbiota using high-throughput sequencing reveals a stable microbial community during storage. PLoS ONE. 2012;7:e46953.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Lozupone C, Lladser ME, Knights D, et al. UniFrac: an effective distance metric for microbial community comparison. ISME J. 2011;5:169–172.

    Article  PubMed  Google Scholar 

  24. Segata N, Izard J, Waldron L, et al. Metagenomic biomarker discovery and explanation. Genome Biol. 2011;12:R60.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Langille MG, Zaneveld J, Caporaso JG, et al. Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences. Nat Biotechnol. 2013;31:814–821.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Carding S, Verbeke K, Vipond DT, et al. Dysbiosis of the gut microbiota in disease. Microb Ecol Health Dis. 2015;26:26191.

    PubMed  Google Scholar 

  27. Hong SN, Rhee PL. Unraveling the ties between irritable bowel syndrome and intestinal microbiota. World J Gastroenterol. 2014;20:2470–2481.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Carroll IM, Ringel-Kulka T, Keku TO, et al. Molecular analysis of the luminal- and mucosal-associated intestinal microbiota in diarrhea-predominant irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol. 2011;301:G799–G807.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Rangel I, Sundin J, Fuentes S, et al. The relationship between faecal-associated and mucosal-associated microbiota in irritable bowel syndrome patients and healthy subjects. Aliment Pharmacol Ther. 2015;42:1211–1221.

    Article  PubMed  CAS  Google Scholar 

  30. Manichanh C, Rigottier-Gois L, Bonnaud E, et al. Reduced diversity of faecal microbiota in Crohn’s disease revealed by a metagenomic approach. Gut. 2006;55:205–211.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Hod K, Dickman R, Sperber A, et al. Assessment of high-sensitivity CRP as a marker of micro-inflammation in irritable bowel syndrome. Neurogastroenterol Motil. 2011;23:1105–1110.

    Article  PubMed  CAS  Google Scholar 

  32. Hod K, Ringel-Kulka T, Martin CF, et al. High-sensitive C-reactive protein as a marker for inflammation in irritable bowel syndrome. J Clin Gastroenterol. 2016;50:227–232.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Zhang Z, Geng J, Tang X, et al. Spatial heterogeneity and co-occurrence patterns of human mucosal-associated intestinal microbiota. ISME J. 2014;8:881–893.

    Article  PubMed  Google Scholar 

  34. Saulnier DM, Riehle K, Mistretta TA, et al. Gastrointestinal microbiome signatures of pediatric patients with irritable bowel syndrome. Gastroenterology. 2011;141:1782–1791.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Leclercq S, Matamoros S, Cani PD, et al. Intestinal permeability, gut-bacterial dysbiosis, and behavioral markers of alcohol-dependence severity. Proc Natl Acad Sci USA. 2014;111:E4485–E4493.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Jeffery IB, O’Toole PW, Ohman L, et al. An irritable bowel syndrome subtype defined by species-specific alterations in faecal microbiota. Gut. 2012;61:997–1006.

    Article  PubMed  Google Scholar 

  37. Tana C, Umesaki Y, Imaoka A, et al. Altered profiles of intestinal microbiota and organic acids may be the origin of symptoms in irritable bowel syndrome. Neurogastroenterol Motil. 2010;22:e114–e115.

    Google Scholar 

  38. Kabeerdoss J, Jayakanthan P, Pugazhendhi S, et al. Alterations of mucosal microbiota in the colon of patients with inflammatory bowel disease revealed by real time polymerase chain reaction amplification of 16S ribosomal ribonucleic acid. Indian J Med Res. 2015;142:23–32.

    PubMed  PubMed Central  CAS  Google Scholar 

  39. Martin R, Miquel S, Chain F, et al. Faecalibacterium prausnitzii prevents physiological damages in a chronic low-grade inflammation murine model. BMC Microbiol. 2015;15:67.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Quevrain E, Maubert MA, Michon C, et al. Identification of an anti-inflammatory protein from Faecalibacterium prausnitzii, a commensal bacterium deficient in Crohn’s disease. Gut. 2016;65:415–425.

    Article  PubMed  CAS  Google Scholar 

  41. Kotlowski R, Bernstein CN, Sepehri S, et al. High prevalence of Escherichia coli belonging to the B2 + D phylogenetic group in inflammatory bowel disease. Gut. 2007;56:669–675.

    Article  PubMed  CAS  Google Scholar 

  42. Spiller RC. Inflammation as a basis for functional GI disorders. Best Pract Res Clin Gastroenterol. 2004;18:641–661.

    Article  PubMed  CAS  Google Scholar 

  43. Pozuelo M, Panda S, Santiago A, et al. Reduction of butyrate- and methane-producing microorganisms in patients with Irritable Bowel Syndrome. Sci Rep. 2015;5:12693.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Funding

This study was funded by the U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases-K23 DK075621 (YR).

Author information

Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, 7340 MBRB Building, 111 Mason Farm Road, Chapel Hill, NC, 27599, USA

    Nitsan Maharshak, Yehuda Ringel, Ashley Lundqvist, R. Balfour Sartor & Ian M. Carroll

  2. Department of Gastroenterology and Hepatology, Meir Medical Center, Affiliated with Tel Aviv University, 59 Tshernichovsky St., 4428164, Kfar Saba, Israel

    Yehuda Ringel

  3. Bacteriotherapy Clinic, Department of Gastroenterology and Liver Diseases, Tel Aviv Medical Center Affiliated with the Sackler Faculty of Medicine, Tel Aviv University, 6 Weizmann St., Tel Aviv, Israel

    Nitsan Maharshak & David Katibian

  4. Division of Gastroenterology and Hepatology, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, 7309A MBRB Building, 111 Mason Farm Road, Chapel Hill, NC, 27599, USA

    R. Balfour Sartor

  5. Department of Maternal and Child Health, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, 404A Rosenau, Chapel Hill, NC, 27599, USA

    Tamar Ringel-Kulka

Authors
  1. Nitsan Maharshak
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  2. Yehuda Ringel
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  3. David Katibian
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  4. Ashley Lundqvist
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  5. R. Balfour Sartor
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  6. Ian M. Carroll
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  7. Tamar Ringel-Kulka
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Corresponding author

Correspondence to Yehuda Ringel.

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Cite this article

Maharshak, N., Ringel, Y., Katibian, D. et al. Fecal and Mucosa-Associated Intestinal Microbiota in Patients with Diarrhea-Predominant Irritable Bowel Syndrome. Dig Dis Sci 63, 1890–1899 (2018). https://doi.org/10.1007/s10620-018-5086-4

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  • DOI: https://doi.org/10.1007/s10620-018-5086-4

Keywords

  • Fecal microbiota
  • Mucosal microbiota
  • Microbiome
  • Irritable bowel syndrome
  • Diarrhea