Year: 2022
Type: article
Abstract: ABSTRACT Objective This study examined the host-microbe changes underpinning treatment response to hyperbaric oxygen therapy (HBOT) in ulcerative colitis. Design Pre- and post-intervention mucosal tissue and fecal samples from two clinical trials, along with fecal samples from healthy controls and fecal and mucosal tissue from disease severity matched UC controls. Mucosal tissue bulk-RNA sequencing, digital spatial profiling (DSP) for single-cell RNA and protein analysis, and immunohistochemistry was performed, in addition to 16S rRNA, shotgun metagenomics, metabolomics, and metaproteomics of fecal samples. Fecal colonization experiments in IL10 -/- germ-free mice were performed to confirm observations. Results Proteomics identified associations between HBOT response status and neutrophil degranulation, with specificity of effect for azurophilic granules. DSP identified a specific HBOT effect on reducing neutrophil STAT3, which was confirmed by immunohistochemistry. HBOT decreased microbial diversity with an accompanying proportional increase in Firmicutes and a secondary bile acid lithocholic acid. The reduction in diversity was due to reductions in mucinophiles, with differences in Akkermansia muciniphila strains being associated with HBOT response status. Proteomics observed an accompanying effect for HBOT on MUC2. Colonization of IL10 -/- with stool obtained from HBOT responders resulted in lower colitis activity compared to stool obtained from HBOT non-responders, with no differences in STAT3 expression, suggesting complementary but independent host and microbial responses. Conclusion 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.
Authors: 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, 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
Language: English
Topic: Inflammatory Bowel Disease
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
Funders: Kenneth Rainin Foundation, Crohn's and Colitis Foundation, Georgia Clinical and Translational Science Alliance, European Commission, Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, Université de Paris, National Institutes of Health, University of California, San Diego, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Advancing Translational Sciences
Awards: EMULBIONT: Impact of dietary food additive EMULsifiers on pathoBIONT’s pathogenic potential in chronic inflammatory diseases: from mechanism to prevention, G1228297150, G1963894250, Macrophage Polarization in Response to Infections and Inflammation, Using single-cell RNA-seq to interrogate host immunity to pathogens, UC San Diego Clinical and Translational Research Institute, G3186420570, G3305682634, G3462717068, G3795641072, G4180218856, G434337789, G4656594441, G4707887143, G4782157933, G4950536974, Hyperbaric Oxygen Therapy for Ulcerative Colitis Patients Hospitalized for Moderate to Severe Flares: A Multi-Center, Randomized, Double-Blind, Sham Controlled Trial (HBOT-UC), Modulation of Macrophage Polarization by Heterotrimeric G proteins: Implications of Gastrointestinal Inflammation, Role of proteasome activity in adaptive immunity, Graduate Training in Cellular and Molecular Pharmacology, G6453366704, G698963419, G7016406969, Using single-cell approaches to study inflammatory bowel disease, Training Grant in Gastroenterology, Precision therapeutics of inflammatory bowel disease guided by Boolean logic, G8471630636, Université de Paris, Molecular Determinants of Tissue-resident Memory T cell Fate in Acute and Chronic Infection, UC San Diego Clinical and Translational Research Institute, G9000106685, G9000220295, G9000250858, San Diego Digestive Diseases Research Center, San Diego IRACDA Scholars Program, Excellence in SImulation of Weather and Climate in Europe
OpenAlex ID: W4224308954