Skip to main content
SpringerLink
Log in

Proinflammatory Sulfur-Reducing Bacteria Are More Abundant in Colonic Biopsies of Patients with Microscopic Colitis Compared to Healthy Controls

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Background

Microscopic colitis (MC), a subtype of inflammatory bowel disease, is a chronic condition of unknown etiology. Recent evidence has linked MC with intriguing changes in the stool microbiota, which may be linked to disease pathogenesis. The composition of the mucosal microbiome in patients with MC remains unclear.

Methods

We performed a cross-sectional study comparing colonic tissue samples from patients with MC to those of healthy controls at the Michael E. DeBakey VA Medical Center. We included adults older than 18 who underwent a colonoscopy with biopsies to evaluate chronic diarrhea. Cases were defined by histology consistent with MC and controls by the absence of histologic disease. We conducted structured chart review to exclude other gastrointestinal diseases and obtain demographic (age, sex, race) and clinical (duration of symptoms and concurrent medications) information for cases and controls. We extracted bacterial DNA from formalin-fixed paraffin-embedded tissue samples and sequenced the v4 region of the 16S rRNA gene. Operational taxonomic unit (OTU) clustering was performed using UPARSE, and OTUs were assigned using the SILVA database. Statistical analysis was performed in QIIME and LEfSe. Comparisons with FDR-adjusted p values of less than 0.05 were considered statistically significant.

Results

We included 20 MC patients and 20 controls with mean ages of 62 and 54, respectively. Most cases were White (95%), 60% had symptoms for greater than 12 months, and 50% were taking PPIs and NSAIDs at the time of their diagnosis. Compared to controls, MC patients had a significant increase in the proinflammatory sulfur-reducing bacterial family Desulfovibrionales. The Coriobacteriaceae family, abundant in the healthy gut, was significantly decreased in MC cases. There was also an increase in the genus Actinomyces in MC patients on PPI and an increase in the class Bacilli among those taking NSAIDs.

Discussion

Patients with MC have an increase in the proinflammatory family Desulfovibrionales. Actinomyces and Bacilli were associated with medications (PPI and NSAID) known to increase the risk of MC. Our findings may have important implications for understanding the pathogenesis of MC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Tong J, Zheng Q, Zhang C, Lo R, Shen J, Ran Z. Incidence, prevalence, and temporal trends of microscopic colitis: a systematic review and meta-analysis. Am J Gastroenterol. 2015;110:265–276. (quiz 277).

    Article  PubMed  Google Scholar 

  2. Nyhlin N, Wickbom A, Montgomery SM, Tysk C, Bohr J. Long-term prognosis of clinical symptoms and health-related quality of life in microscopic colitis: a case-control study. Aliment Pharmacol Ther. 2014;39:963–972.

    Article  CAS  PubMed  Google Scholar 

  3. El-Salhy M, Gundersen D, Hatlebakk JG, Hausken T. Clinical presentation, diagnosis, pathogenesis and treatment options for lymphocytic colitis (Review). Int J Mol Med. 2013;32:263–270.

    Article  PubMed  Google Scholar 

  4. Fischer H, Holst E, Karlsson F, et al. Altered microbiota in microscopic colitis. Gut. 2015;64:1185–1186.

    Article  PubMed  Google Scholar 

  5. Rajilić-Stojanović M, Shanahan F, Guarner F, de Vos WM. Phylogenetic analysis of dysbiosis in ulcerative colitis during remission. Inflamm Bowel Dis. 2013;19:481–488.

    Article  PubMed  Google Scholar 

  6. Zoetendal EG, von Wright A, Vilpponen-Salmela T, Ben-Amor K, Akkermans AD, de Vos WM. 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  CAS  PubMed  PubMed Central  Google Scholar 

  7. Edgar RC. UPARSE: highly accurate OTU sequences from microbial amplicon reads. Nat Methods. 2013;10:996–998.

    Article  CAS  PubMed  Google Scholar 

  8. Cole JR, Wang Q, Fish JA, et al. Ribosomal Database Project: data and tools for high throughput rRNA analysis. Nucleic Acids Res. 2014;42:D633–D642.

    Article  CAS  PubMed  Google Scholar 

  9. Quast C, Pruesse E, Yilmaz P, et al. The SILVA ribosomal RNA gene database project: improved data processing and web-based tools. Nucleic Acids Res. 2013;41:D590–D596.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  PubMed Central  Google Scholar 

  12. Rowan F, Docherty NG, Murphy M, Murphy B, Coffey JC, O‘Connell PR. Desulfovibrio bacterial species are increased in ulcerative colitis. Dis Colon Rectum. 2010;53:1530–1536.

    Article  PubMed  Google Scholar 

  13. Loubinoux J, Bronowicki JP, Pereira IA, Mougenel JL, Le Faou AE. Sulfate-reducing bacteria in human feces and their association with inflammatory bowel diseases. FEMS Microbiol Ecol. 2002;40:107–112.

    Article  CAS  PubMed  Google Scholar 

  14. Lennon G, Balfe A, Bambury N, et al. Correlations between colonic crypt mucin chemotype, inflammatory grade and Desulfovibrio species in ulcerative colitis. Colorectal Dis. 2014;16:O161–O169.

    Article  CAS  PubMed  Google Scholar 

  15. Png CW, Lindén SK, Gilshenan KS, et al. Mucolytic bacteria with increased prevalence in IBD mucosa augment in vitro utilization of mucin by other bacteria. Am J Gastroenterol. 2010;105:2420–2428.

    Article  CAS  PubMed  Google Scholar 

  16. Derrien M, Collado MC, Ben-Amor K, Salminen S, de Vos WM. The Mucin degrader Akkermansia muciniphila is an abundant resident of the human intestinal tract. Appl Environ Microbiol. 2008;74:1646–1648.

    Article  CAS  PubMed  Google Scholar 

  17. Kang CS, Ban M, Choi EJ, et al. Extracellular vesicles derived from gut microbiota, especially Akkermansia muciniphila, protect the progression of dextran sulfate sodium-induced colitis. PLoS ONE. 2013;8:e76520.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Reunanen J, Kainulainen V, Huuskonen L, et al. Akkermansia muciniphila adheres to enterocytes and strengthens the integrity of the epithelial cell layer. Appl Environ Microbiol. 2015;81:3655–3662.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Jackson MA, Goodrich JK, Maxan ME, et al. Proton pump inhibitors alter the composition of the gut microbiota. Gut. 2016;65:749–756.

    Article  CAS  PubMed  Google Scholar 

  20. Sokol H, Pigneur B, Watterlot L, et al. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc Natl Acad Sci USA. 2008;105:16731–16736.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Fujimoto T, Imaeda H, Takahashi K. Decreased abundance of Faecalibacterium prausnitzii in the gut microbiota of Crohn’s disease. J Gastroenterol Hepatol. 2013;28:613–619.

    Article  CAS  PubMed  Google Scholar 

  22. Human Microbiome Project, C. Structure, function and diversity of the healthy human microbiome. Nature. 2012;486:207–214.

    Article  CAS  Google Scholar 

  23. Li G, Yang M, Zhou K, et al. Diversity of duodenal and rectal microbiota in biopsy tissues and luminal contents in healthy volunteers. J Microbiol Biotechnol. 2015;25:1136–1145.

    Article  CAS  PubMed  Google Scholar 

  24. Watt E, Gemmell MR, Berry S, et al. Extending colonic mucosal microbiome analysis-assessment of colonic lavage as a proxy for endoscopic colonic biopsies. Microbiome. 2016;4:61.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Tannock GW. The bowel microbiota and inflammatory bowel diseases. Int J Inflamm. 2010;2010:954051.

    Article  Google Scholar 

  26. Huttenhower C, Kostic AD, Xavier RJ. Inflammatory bowel disease as a model for translating the microbiome. Immunity. 2014;40:843–854.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Kostic AD, Xavier RJ, Gevers D. The microbiome in inflammatory bowel disease: current status and the future ahead. Gastroenterology. 2014;146:1489–1499.

    Article  CAS  PubMed  Google Scholar 

  28. Berry D, Reinisch W. Intestinal microbiota: a source of novel biomarkers in inflammatory bowel diseases? Best Pract Res Clin Gastroenterol. 2013;27:47–58.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

(1) The research reported here was supported in part by resources at the VA HSR&D Center for Innovations in Quality, Effectiveness and Safety (#CIN 13-413), at the Michael E. DeBakey VA Medical Center, Houston, TX (JKH). (2) No writing assistance was used in the preparation of this manuscript.

Author information

Authors and Affiliations

  1. Department of Medicine, Baylor College of Medicine, 2002 Holcombe Blvd MCL-111D, Houston, TX, 77030, USA

    Valentine Millien, Jason Hou & Rajesh Shah

  2. Department of Pathology, Baylor College of Medicine, Houston, TX, USA

    Daniel Rosen

  3. Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA

    Jason Hou & Rajesh Shah

Authors
  1. Valentine Millien
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daniel Rosen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jason Hou
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rajesh Shah
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

VM contributed in study design, data analysis, and authorship of the manuscript. She has approved of the final draft submission. DR contributed in study design, sample preparation, and authorship of the manuscript. He has approved of the final draft submission. JH contributed in authorship and editorial input. He has approved of the final draft submission. RS contributed in the study design, data abstraction, data analysis, and authorship of the manuscript. He has approved of the final draft submission.

Corresponding author

Correspondence to Rajesh Shah.

Ethics declarations

Conflict of interest

(1) JH has served as a speaker for AbbVie, Janssen, a consultant for UCB, and served on an advisory board for Pfizer. JH has received research funding from AbbVie, Janssen, Pfizer, Celgene, and RedHill Biopharma. (2) VM, DR, and RS have no financial disclosures.

Additional information

The views expressed in this article are those of the author(s) and do not necessarily represent the views of the Department of Veterans Affairs.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 17 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Millien, V., Rosen, D., Hou, J. et al. Proinflammatory Sulfur-Reducing Bacteria Are More Abundant in Colonic Biopsies of Patients with Microscopic Colitis Compared to Healthy Controls. Dig Dis Sci 64, 432–438 (2019). https://doi.org/10.1007/s10620-018-5313-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-018-5313-z

Keywords

Search

Navigation