A Potential Role for Stress-Induced Microbial Alterations in IgA-Associated Irritable Bowel Syndrome with Diarrhea

Sunaina Rengarajan, Kathryn A. Knoop, Arvind Rengarajan, Jiani N. Chai, Jose G. Grajales-Reyes, Vijay K. Samineni, Emilie V. Russler-Germain, Prabha Ranganathan, Alessio Fasano, Gregory S. Sayuk, Robert W. Gereau, Andrew L. Kau, Dan Knights, Purna C. Kashyap, Matthew A. Ciorba, Rodney D. Newberry, Chyi Song Hsieh

Research output: Contribution to journalArticlepeer-review

Abstract

Rengarajan et al. show that stress in mice causes fecal dysbiosis, which is sufficient to induce diarrhea, intestinal barrier defect, and increased antibacterial IgA. IBS-D patients also display fecal dysbiosis and increased antibacterial IgA that is unique from healthy or IBD patients. This IgA response correlates with somatic symptom severity.

Original languageEnglish (US)
Article number100124
JournalCell Reports Medicine
Volume1
Issue number7
DOIs
StatePublished - Oct 20 2020

Bibliographical note

Funding Information:
The Washington University Digestive Disease Research Cores Center is supported by NIH grant P30DK052574 . C.-S.H. is supported by NIH grants 1R01AI140755 and 1R01AI136515 , BWF , ICTS (Washington University ), and the Wolff Professorship . M.A.C. is supported by DK109384 , CA206039 , and the Daniel H. Present Senior Research Award from the Crohn’s and Colitis Foundation . A.L.K. is supported by NIAID K08 AI113184 and the AAAAI Foundation . V.K.S. is supported by NIDDK R01DK116178 to R.W.G. IV, the Urology Care Foundation Research Scholars Program , the Kailash Kedia Research Scholar Award , and NIDDK Career Development Award K01 DK115634 . P.C.K. is supported by NIH grant DK114007 , P.C.K. and D.K. are supported by the Minnesota Partnership for Biotechnology and Medical Genomics . The Center for Genome Sciences and Systems Biology at Washington University in St. Louis is partially supported by NCI Cancer Center Support Grant P30 CA91842 to the Siteman Cancer Center and by ICTS/CTSA grant UL1TR002345 from the National Center for Research Resources (NCRR), a component of the NIH , and the NIH Roadmap for Medical Research . S.R. and E.V.R.-G. are supported by NIH grant T32 GM007200-42 .

Funding Information:
We would like to thank the patients and relatives who contributed samples to this collection and the team of research staff including Kelly Monroe and Darren Nix (Digestive Diseases Research Cores Center, Washington University School of Medicine) who contributed to subject recruitment and specimen acquisition. We would also like to thank Jessica Hoisington-Lopez at the Center for Genome Sciences and Systems Biology at Washington University School of Medicine for Miseq sequencing expertise and Jingquin Luo (Division of Biostatistics, Washington University) for advice regarding the statistical analyses. We thank the Genome Technology Access Center in the Department of Genetics at Washington University School of Medicine for help with the genomic analysis. We would like to thank Ryan McDonough and Natalia Jaeger for assistance and expertise with the GF experiments. The Washington University Digestive Disease Research Cores Center is supported by NIH grant P30DK052574. C.-S.H. is supported by NIH grants 1R01AI140755 and 1R01AI136515, BWF, ICTS (Washington University), and the Wolff Professorship. M.A.C. is supported by DK109384, CA206039, and the Daniel H. Present Senior Research Award from the Crohn's and Colitis Foundation. A.L.K. is supported by NIAID K08 AI113184 and the AAAAI Foundation. V.K.S. is supported by NIDDK R01DK116178 to R.W.G. IV, the Urology Care Foundation Research Scholars Program, the Kailash Kedia Research Scholar Award, and NIDDK Career Development Award K01 DK115634. P.C.K. is supported by NIH grant DK114007, P.C.K. and D.K. are supported by the Minnesota Partnership for Biotechnology and Medical Genomics. The Center for Genome Sciences and Systems Biology at Washington University in St. Louis is partially supported by NCI Cancer Center Support Grant P30 CA91842 to the Siteman Cancer Center and by ICTS/CTSA grant UL1TR002345 from the National Center for Research Resources (NCRR), a component of the NIH, and the NIH Roadmap for Medical Research. S.R. and E.V.R.-G. are supported by NIH grant T32 GM007200-42. S.R. K.A.K. G.S.S. R.W.G. IV, A.L.K. M.A.C. R.D.N. and C.-S.H. conceived the project and/or designed the experiments. A.F. provided the celiac sprue fecal specimens. D.K. and P.C.K. provided ROC IBS fecal specimens. A.R. P.R. G.S.S. M.A.C. and R.D.N. designed and assisted in patient recruitment and specimen collection in STL. A.L.K. also assisted with GF expertise. S.R. K.A.K. A.R. J.N.C. J.G.G. V.K.S. and E.V.R.-G. performed experiments and S.R. K.A.K. A.R. J.N.C. J.G.G. and V.K.S. analyzed the data. S.R. and C.-S.H. wrote the manuscript. The authors declare no competing interests. D.K. serves as Senior Scientific Advisor to Diversigen, a company involved in the commercialization of microbiome analysis. Diversigen is now a wholly owned subsidiary of OraSure. P.C.K. is on the advisory board of Novome Biotechnologies and is an ad hoc consultant for Pendulum Therapeutics, IP Group, and Otsuka Pharmaceuticals. These interests have been reviewed and managed by the respective institutions in accordance with their conflict-of-interest policies.

Publisher Copyright:
© 2020 The Author(s)

Keywords

  • IgA
  • host:commensal immunity
  • irritable bowel syndrome
  • stress

PubMed: MeSH publication types

  • Journal Article

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