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The Host-Microbiome Response to Hyperbaric Oxygen Therapy in Ulcerative Colitis Patients.
Gonzalez, Carlos G; Mills, Robert H; Kordahi, Melissa C; Carrillo-Terrazas, Marvic; Secaira-Morocho, Henry; Widjaja, Christella E; Tsai, Matthew S; Mittal, Yash; Yee, Brian A; Vargas, Fernando; Weldon, Kelly; Gauglitz, Julia M; Delaroque, Clara; Sauceda, Consuelo; Rossitto, Leigh-Ana; Ackermann, Gail; Humphrey, Gregory; Swafford, Austin D; Siegel, Corey A; Buckey, Jay C; Raffals, Laura E; Sadler, Charlotte; Lindholm, Peter; Fisch, Kathleen M; Valaseck, Mark; Suriawinata, Arief; Yeo, Gene W; Ghosh, Pradipta; Chang, John T; Chu, Hiutung; Dorrestein, Pieter; Zhu, Qiyun; Chassaing, Benoit; Knight, Rob; Gonzalez, David J; Dulai, Parambir S.
Afiliación
  • Gonzalez CG; 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.
  • Mills RH; 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.
  • Kordahi MC; INSERM U1016, team "Mucosal microbiota in chronic inflammatory diseases", CNRS UMR 8104, Université de Paris, Paris, France.
  • Carrillo-Terrazas M; Department of Pharmacology, University of California, San Diego, California; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, California.
  • Secaira-Morocho H; School of Life Sciences, Arizona State University, Tempe, Arizona; Biodesign Center for Fundamental and Applied Microbiomics, Arizona State University, Tempe, Arizona.
  • Widjaja CE; Division of Gastroenterology, University of California San Diego, San Diego, California.
  • Tsai MS; Division of Gastroenterology, University of California San Diego, San Diego, California.
  • Mittal Y; Division of Gastroenterology, University of California San Diego, San Diego, California.
  • Yee BA; 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.
  • Vargas F; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, California.
  • Weldon K; 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.
  • Gauglitz JM; Department of Pediatrics, University of California, San Diego, California.
  • Delaroque C; INSERM U1016, team "Mucosal microbiota in chronic inflammatory diseases", CNRS UMR 8104, Université de Paris, Paris, France.
  • Sauceda C; Department of Pharmacology, University of California, San Diego, California.
  • Rossitto LA; Department of Pharmacology, University of California, San Diego, California.
  • Ackermann G; Department of Pediatrics, University of California, San Diego, California.
  • Humphrey G; Department of Pediatrics, University of California, San Diego, California.
  • Swafford AD; Department of Computer Science and Engineering, University of California San Diego, San Diego, California.
  • Siegel CA; Section of Gastroenterology and Hepatology, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire.
  • Buckey JC; Center for Hyperbaric Medicine, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire.
  • Raffals LE; Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
  • Sadler C; Division of Hyperbaric Medicine, Department of Emergency Medicine, University of California San Diego, San Diego, California.
  • Lindholm P; Division of Hyperbaric Medicine, Department of Emergency Medicine, University of California San Diego, San Diego, California.
  • Fisch KM; Center for Computational Biology and Bioinformatics, University of California San Diego, San Diego, California.
  • Valaseck M; Department of Pathology, University of California San Diego, San Diego, California.
  • Suriawinata A; Section of Gastroenterology and Hepatology, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire.
  • Yeo GW; 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.
  • Ghosh P; 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.
  • Chang JT; Division of Gastroenterology, University of California San Diego, San Diego, California.
  • Chu H; 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 Die
  • Dorrestein P; 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.
  • Zhu Q; School of Life Sciences, Arizona State University, Tempe, Arizona; Biodesign Center for Fundamental and Applied Microbiomics, Arizona State University, Tempe, Arizona.
  • Chassaing B; INSERM U1016, team "Mucosal microbiota in chronic inflammatory diseases", CNRS UMR 8104, Université de Paris, Paris, France.
  • Knight R; 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.
  • Gonzalez DJ; 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.
  • Dulai PS; Division of Gastroenterology, University of California San Diego, San Diego, California; Division of Gastroenterology, Northwestern University, Chicago, Illinois. Electronic address: parambir.dulai@northwestern.edu.
Cell Mol Gastroenterol Hepatol ; 14(1): 35-53, 2022.
Article en En | MEDLINE | ID: mdl-35378331
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Colitis Ulcerosa / Microbiota / Oxigenoterapia Hiperbárica Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Cell Mol Gastroenterol Hepatol Año: 2022 Tipo del documento: Article
Texto completo
Añadir a Mi BVS
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XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Colitis Ulcerosa / Microbiota / Oxigenoterapia Hiperbárica Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Cell Mol Gastroenterol Hepatol Año: 2022 Tipo del documento: Article