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

Area of Science:

• Gastroenterology
• Microbiology
• Immunology

Background:

• Ulcerative colitis (UC) is a chronic inflammatory bowel disease.
• Hyperbaric oxygen therapy (HBOT) shows promise for moderate-to-severe UC.
• The host and microbial responses to HBOT in UC are not fully understood.

Purpose of the Study:

• To investigate the molecular mechanisms of HBOT in UC.
• To analyze host and microbial changes induced by HBOT.
• To identify factors influencing HBOT response in UC patients.

Main Methods:

• Multi-omic analysis (metaproteomics, metabolomics, 16S rRNA sequencing, metagenomics, RNA sequencing, DSP) of patient samples.
• Immunohistochemistry and colonization experiments in IL10-/- UC mouse models.
• Analysis of mucosal biopsies, tissue, and fecal samples from HBOT clinical trials.

Main Results:

• HBOT reduced neutrophil STAT3 and azurophilic granule activity in UC patients.
• Microbial diversity decreased, with increased Firmicutes and lithocholic acid.
• Loss of mucus-adherent bacteria led to increased MUC2; Akkermansia muciniphila strain variations correlated with HBOT response.

Conclusions:

• HBOT ameliorates UC by modulating host neutrophil responses and gut microbiota.
• Intestinal microbiota, particularly A. muciniphila strains, may influence HBOT non-response.
• Host and microbial responses to HBOT are complementary and independent.