Cellular and Molecular Gastroenterology and Hepatology (Jan 2022)
The Host-Microbiome Response to Hyperbaric Oxygen Therapy in Ulcerative Colitis PatientsSummary
- Carlos G. Gonzalez,
- Robert H. Mills,
- Melissa C. Kordahi,
- Marvic Carrillo-Terrazas,
- Henry Secaira-Morocho,
- Christella E. Widjaja,
- Matthew S. Tsai,
- Yash Mittal,
- Brian A. Yee,
- Fernando Vargas,
- Kelly Weldon,
- Julia M. Gauglitz,
- Clara Delaroque,
- Consuelo Sauceda,
- Leigh-Ana Rossitto,
- Gail Ackermann,
- Gregory Humphrey,
- Austin D. Swafford,
- Corey A. Siegel,
- Jay C. Buckey, Jr.,
- Laura E. Raffals,
- Charlotte Sadler,
- Peter Lindholm,
- Kathleen M. Fisch,
- Mark Valaseck,
- Arief Suriawinata,
- Gene W. Yeo,
- Pradipta Ghosh,
- John T. Chang,
- Hiutung Chu,
- Pieter Dorrestein,
- Qiyun Zhu,
- Benoit Chassaing,
- Rob Knight,
- David J. Gonzalez,
- Parambir S. Dulai
Affiliations
- Carlos G. Gonzalez
- Department of Pharmacology, University of California, San Diego, California; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, California; Department of Pediatrics, University of California, San Diego, California
- Robert H. Mills
- Department of Pharmacology, University of California, San Diego, California; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, California; Department of Pediatrics, University of California, San Diego, California
- Melissa C. Kordahi
- INSERM U1016, team “Mucosal microbiota in chronic inflammatory diseases”, CNRS UMR 8104, Université de Paris, Paris, France
- Marvic Carrillo-Terrazas
- Department of Pharmacology, University of California, San Diego, California; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, California
- Henry Secaira-Morocho
- School of Life Sciences, Arizona State University, Tempe, Arizona; Biodesign Center for Fundamental and Applied Microbiomics, Arizona State University, Tempe, Arizona
- Christella E. Widjaja
- Division of Gastroenterology, University of California San Diego, San Diego, California
- Matthew S. Tsai
- Division of Gastroenterology, University of California San Diego, San Diego, California
- Yash Mittal
- Division of Gastroenterology, University of California San Diego, San Diego, California
- Brian A. Yee
- Department of Cellular and Molecular Medicine, University of California San Diego, San Diego, California; Institute for Genomic Medicine, University of California San Diego, San Diego, California
- Fernando Vargas
- Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, California
- Kelly Weldon
- Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, California; Department of Computer Science and Engineering, University of California San Diego, San Diego, California
- Julia M. Gauglitz
- Department of Pediatrics, University of California, San Diego, California
- Clara Delaroque
- INSERM U1016, team “Mucosal microbiota in chronic inflammatory diseases”, CNRS UMR 8104, Université de Paris, Paris, France
- Consuelo Sauceda
- Department of Pharmacology, University of California, San Diego, California
- Leigh-Ana Rossitto
- Department of Pharmacology, University of California, San Diego, California
- Gail Ackermann
- Department of Pediatrics, University of California, San Diego, California
- Gregory Humphrey
- Department of Pediatrics, University of California, San Diego, California
- Austin D. Swafford
- Department of Computer Science and Engineering, University of California San Diego, San Diego, California
- Corey A. Siegel
- Section of Gastroenterology and Hepatology, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire
- Jay C. Buckey, Jr.
- Center for Hyperbaric Medicine, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire
- Laura E. Raffals
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
- Charlotte Sadler
- Division of Hyperbaric Medicine, Department of Emergency Medicine, University of California San Diego, San Diego, California
- Peter Lindholm
- Division of Hyperbaric Medicine, Department of Emergency Medicine, University of California San Diego, San Diego, California
- Kathleen M. Fisch
- Center for Computational Biology and Bioinformatics, University of California San Diego, San Diego, California
- Mark Valaseck
- Department of Pathology, University of California San Diego, San Diego, California
- Arief Suriawinata
- Section of Gastroenterology and Hepatology, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire
- Gene W. Yeo
- Department of Cellular and Molecular Medicine, University of California San Diego, San Diego, California; Institute for Genomic Medicine, University of California San Diego, San Diego, California
- Pradipta Ghosh
- Division of Gastroenterology, University of California San Diego, San Diego, California; Department of Cellular and Molecular Medicine, University of California San Diego, San Diego, California
- John T. Chang
- Division of Gastroenterology, University of California San Diego, San Diego, California
- Hiutung Chu
- Department of Pathology, University of California San Diego, San Diego, California; Center for Microbiome Innovation, University of California San Diego, San Diego, California; Chiba University-UC San Diego Center for Mucosal Immunology, Allergy and Vaccines (cMAV), University of California, San Diego, La Jolla, California
- Pieter Dorrestein
- Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, California; Department of Pediatrics, University of California, San Diego, California; Center for Microbiome Innovation, University of California San Diego, San Diego, California
- Qiyun Zhu
- School of Life Sciences, Arizona State University, Tempe, Arizona; Biodesign Center for Fundamental and Applied Microbiomics, Arizona State University, Tempe, Arizona
- Benoit Chassaing
- INSERM U1016, team “Mucosal microbiota in chronic inflammatory diseases”, CNRS UMR 8104, Université de Paris, Paris, France
- Rob Knight
- Department of Computer Science and Engineering, University of California San Diego, San Diego, California; Department of Pediatrics, University of California, San Diego, California; Center for Microbiome Innovation, University of California San Diego, San Diego, California
- David J. Gonzalez
- Department of Pharmacology, University of California, San Diego, California; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, California; Center for Microbiome Innovation, University of California San Diego, San Diego, California
- Parambir S. Dulai
- Division of Gastroenterology, University of California San Diego, San Diego, California; Division of Gastroenterology, Northwestern University, Chicago, Illinois; Correspondence Address correspondence to: Parambir S. Dulai, MD, Division of Gastroenterology & Hepatology, Northwestern University Feinberg School of Medicine, Arkes Pavilion, 676 North St Clair Street, 14th Floor, Chicago, Illinois 60611. fax: (858) 657-5022.
- Journal volume & issue
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Vol. 14,
no. 1
pp. 35 – 53
Abstract
Background & Aims: Hyperbaric oxygen therapy (HBOT) is a promising treatment for moderate-to-severe ulcerative colitis. However, our current understanding of the host and microbial response to HBOT remains unclear. This study examined the molecular mechanisms underpinning HBOT using a multi-omic strategy. Methods: Pre- and post-intervention mucosal biopsies, tissue, and fecal samples were collected from HBOT phase 2 clinical trials. Biopsies and fecal samples were subjected to shotgun metaproteomics, metabolomics, 16s rRNA sequencing, and metagenomics. Tissue was subjected to bulk RNA sequencing and digital spatial profiling (DSP) for single-cell RNA and protein analysis, and immunohistochemistry was performed. Fecal samples were also used for colonization experiments in IL10-/- germ-free UC mouse models. Results: Proteomics identified negative associations between HBOT response and neutrophil azurophilic granule abundance. DSP identified an HBOT-specific reduction of neutrophil STAT3, which was confirmed by immunohistochemistry. HBOT decreased microbial diversity with a proportional increase in Firmicutes and a secondary bile acid lithocholic acid. A major source of the reduction in diversity was the loss of mucus-adherent taxa, resulting in increased MUC2 levels post-HBOT. Targeted database searching revealed strain-level associations between Akkermansia muciniphila and HBOT response status. Colonization of IL10-/- with stool obtained from HBOT responders resulted in lower colitis activity compared with non-responders, with no differences in STAT3 expression, suggesting complementary but independent host and microbial responses. Conclusions: HBOT reduces host neutrophil STAT3 and azurophilic granule activity in UC patients and changes in microbial composition and metabolism in ways that improve colitis activity. Intestinal microbiota, especially strain level variations in A muciniphila, may contribute to HBOT non-response.
