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© Benoît Chassaing
Interaction microbiote-mucus à la surface de l’épithélium colique humain
Publication : Cellular and molecular gastroenterology and hepatology

The Host-Microbiome Response to Hyperbaric Oxygen Therapy in Ulcerative Colitis Patients.

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Cellular and molecular gastroenterology and hepatology - 01 Jan 2022

Gonzalez CG, Mills RH, Kordahi MC, Carrillo-Terrazas M, Secaira-Morocho H, Widjaja CE, Tsai MS, Mittal Y, Yee BA, Vargas F, Weldon K, Gauglitz JM, Delaroque C, Sauceda C, Rossitto LA, Ackermann G, Humphrey G, Swafford AD, Siegel CA, Buckey JC, Raffals LE, Sadler C, Lindholm P, Fisch KM, Valaseck M, Suriawinata A, Yeo GW, Ghosh P, Chang JT, Chu H, Dorrestein P, Zhu Q, Chassaing B, Knight R, Gonzalez DJ, Dulai PS

Link to Pubmed [PMID] – 35378331

Link to DOI – 10.1016/j.jcmgh.2022.03.008

Cell Mol Gastroenterol Hepatol 2022 ; 14(1): 35-53

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.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.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.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.