Small intestinal microbial dysbiosis underlies symptoms associated with functional gastrointestinal disorders

George B. Saffouri; Robin R. Shields-Cutler; Jun Chen; Yi Yang; Heather R. Lekatz; Vanessa L. Hale; Janice M. Cho; Eric J. Battaglioli; Yogesh Bhattarai; Kevin J. Thompson; Krishna K. Kalari; Gaurav Behera; Jonathan C. Berry; Stephanie A. Peters; Robin Patel; Audrey N. Schuetz; Jeremiah J. Faith; Michael Camilleri; Justin L. Sonnenburg; Gianrico Farrugia; Jonathan R. Swann; Madhusudan Grover; Dan Knights; Purna C. Kashyap

doi:10.1038/s41467-019-09964-7

Small intestinal microbial dysbiosis underlies symptoms associated with functional gastrointestinal disorders

George B. Saffouri, Robin R. Shields-Cutler, Jun Chen, Yi Yang, Heather R. Lekatz, Vanessa L. Hale, Janice M. Cho, Eric J. Battaglioli, Yogesh Bhattarai, Kevin J. Thompson, Krishna K. Kalari, Gaurav Behera, Jonathan C. Berry, Stephanie A. Peters, Robin Patel, Audrey N. Schuetz, Jeremiah J. Faith, Michael Camilleri, Justin L. Sonnenburg, Gianrico FarrugiaJonathan R. Swann, Madhusudan Grover, Dan Knights, Purna C. Kashyap

Biotechnology Institute

Research output: Contribution to journal › Article › peer-review

145 Scopus citations

Abstract

Small intestinal bacterial overgrowth (SIBO) has been implicated in symptoms associated with functional gastrointestinal disorders (FGIDs), though mechanisms remain poorly defined and treatment involves non-specific antibiotics. Here we show that SIBO based on duodenal aspirate culture reflects an overgrowth of anaerobes, does not correspond with patient symptoms, and may be a result of dietary preferences. Small intestinal microbial composition, on the other hand, is significantly altered in symptomatic patients and does not correspond with aspirate culture results. In a pilot interventional study we found that switching from a high fiber diet to a low fiber, high simple sugar diet triggered FGID-related symptoms and decreased small intestinal microbial diversity while increasing small intestinal permeability. Our findings demonstrate that characterizing small intestinal microbiomes in patients with gastrointestinal symptoms may allow a more targeted antibacterial or a diet-based approach to treatment.

Original language	English (US)
Article number	2012
Journal	Nature communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-09964-7
State	Published - Dec 1 2019

Bibliographical note

Funding Information:
This work was made possible by funding from NIH DK111850 (PCK), DK114007 (PCK), DK115950 (MC), DK103911 (MG), and the Center for Individualized Medicine and Department of Medicine, Mayo Clinic, Rochester, MN (PCK).

Funding Information:
Competing interests: Robin Patel: Dr. Patel reports grants from CD Diagnostics, BioFire, Curetis, Merck, Hutchison Biofilm Medical Solutions, Accelerate Diagnostics, Allergan, and The Medicines Company. Dr. Patel is or has been a consultant to Curetis, Specific Technologies, Selux Dx, GenMark Diagnostics, PathoQuest, Heraeus Medical and Genentech; monies are paid to Mayo Clinic. In addition, Dr. Patel has a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an anti-biofilm substance issued. Dr. Patel receives travel reimbursement from ASM and IDSA and an editor’s stipend from ASM and IDSA, and honoraria from the NBME, Up-to-Date and the Infectious Diseases Board Review Course. Michael Camilleri: Research support from Allergan to study effects of eluxadoline in IBS-diarrhea and bile acid malabsorption. Dan Knights: DK serves as CEO and holds equity in CoreBiome, a company involved in the commercialization of microbiome analysis. The University of Minnesota also has financial interests in CoreBiome under the terms of a license agreement with CoreBiome. These interests have been reviewed and managed by the University of Minnesota in accordance with its Conflict-of-Interest policies. Purna Kashyap: Advisory board uBiome, ad hoc advisory board Salix Pharmaceuticals. The remaining authors declare no competing interests.

Publisher Copyright:
© 2019, The Author(s).

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Saffouri, G. B., Shields-Cutler, R. R., Chen, J., Yang, Y., Lekatz, H. R., Hale, V. L., Cho, J. M., Battaglioli, E. J., Bhattarai, Y., Thompson, K. J., Kalari, K. K., Behera, G., Berry, J. C., Peters, S. A., Patel, R., Schuetz, A. N., Faith, J. J., Camilleri, M., Sonnenburg, J. L., ... Kashyap, P. C. (2019). Small intestinal microbial dysbiosis underlies symptoms associated with functional gastrointestinal disorders. Nature communications, 10(1), Article 2012. https://doi.org/10.1038/s41467-019-09964-7

Saffouri, GB, Shields-Cutler, RR, Chen, J, Yang, Y, Lekatz, HR, Hale, VL, Cho, JM, Battaglioli, EJ, Bhattarai, Y, Thompson, KJ, Kalari, KK, Behera, G, Berry, JC, Peters, SA, Patel, R, Schuetz, AN, Faith, JJ, Camilleri, M, Sonnenburg, JL, Farrugia, G, Swann, JR, Grover, M, Knights, D & Kashyap, PC 2019, 'Small intestinal microbial dysbiosis underlies symptoms associated with functional gastrointestinal disorders', Nature communications, vol. 10, no. 1, 2012. https://doi.org/10.1038/s41467-019-09964-7

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abstract = "Small intestinal bacterial overgrowth (SIBO) has been implicated in symptoms associated with functional gastrointestinal disorders (FGIDs), though mechanisms remain poorly defined and treatment involves non-specific antibiotics. Here we show that SIBO based on duodenal aspirate culture reflects an overgrowth of anaerobes, does not correspond with patient symptoms, and may be a result of dietary preferences. Small intestinal microbial composition, on the other hand, is significantly altered in symptomatic patients and does not correspond with aspirate culture results. In a pilot interventional study we found that switching from a high fiber diet to a low fiber, high simple sugar diet triggered FGID-related symptoms and decreased small intestinal microbial diversity while increasing small intestinal permeability. Our findings demonstrate that characterizing small intestinal microbiomes in patients with gastrointestinal symptoms may allow a more targeted antibacterial or a diet-based approach to treatment.",

author = "Saffouri, {George B.} and Shields-Cutler, {Robin R.} and Jun Chen and Yi Yang and Lekatz, {Heather R.} and Hale, {Vanessa L.} and Cho, {Janice M.} and Battaglioli, {Eric J.} and Yogesh Bhattarai and Thompson, {Kevin J.} and Kalari, {Krishna K.} and Gaurav Behera and Berry, {Jonathan C.} and Peters, {Stephanie A.} and Robin Patel and Schuetz, {Audrey N.} and Faith, {Jeremiah J.} and Michael Camilleri and Sonnenburg, {Justin L.} and Gianrico Farrugia and Swann, {Jonathan R.} and Madhusudan Grover and Dan Knights and Kashyap, {Purna C.}",

note = "Funding Information: This work was made possible by funding from NIH DK111850 (PCK), DK114007 (PCK), DK115950 (MC), DK103911 (MG), and the Center for Individualized Medicine and Department of Medicine, Mayo Clinic, Rochester, MN (PCK). Funding Information: Competing interests: Robin Patel: Dr. Patel reports grants from CD Diagnostics, BioFire, Curetis, Merck, Hutchison Biofilm Medical Solutions, Accelerate Diagnostics, Allergan, and The Medicines Company. Dr. Patel is or has been a consultant to Curetis, Specific Technologies, Selux Dx, GenMark Diagnostics, PathoQuest, Heraeus Medical and Genentech; monies are paid to Mayo Clinic. In addition, Dr. Patel has a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an anti-biofilm substance issued. Dr. Patel receives travel reimbursement from ASM and IDSA and an editor{\textquoteright}s stipend from ASM and IDSA, and honoraria from the NBME, Up-to-Date and the Infectious Diseases Board Review Course. Michael Camilleri: Research support from Allergan to study effects of eluxadoline in IBS-diarrhea and bile acid malabsorption. Dan Knights: DK serves as CEO and holds equity in CoreBiome, a company involved in the commercialization of microbiome analysis. The University of Minnesota also has financial interests in CoreBiome under the terms of a license agreement with CoreBiome. These interests have been reviewed and managed by the University of Minnesota in accordance with its Conflict-of-Interest policies. Purna Kashyap: Advisory board uBiome, ad hoc advisory board Salix Pharmaceuticals. The remaining authors declare no competing interests. Publisher Copyright: {\textcopyright} 2019, The Author(s).",

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Small intestinal microbial dysbiosis underlies symptoms associated with functional gastrointestinal disorders

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