Dataset Information

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

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.

SUBMITTER: Gonzalez CG

PROVIDER: S-EPMC9117812 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

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

Gonzalez Carlos G CG Mills Robert H RH Kordahi Melissa C MC Carrillo-Terrazas Marvic M Secaira-Morocho Henry H Widjaja Christella E CE Tsai Matthew S MS Mittal Yash Y Yee Brian A BA Vargas Fernando F Weldon Kelly K Gauglitz Julia M JM Delaroque Clara C Sauceda Consuelo C Rossitto Leigh-Ana LA Ackermann Gail G Humphrey Gregory G Swafford Austin D AD Siegel Corey A CA Buckey Jay C JC Raffals Laura E LE Sadler Charlotte C Lindholm Peter P Fisch Kathleen M KM Valaseck Mark M Suriawinata Arief A Yeo Gene W GW Ghosh Pradipta P Chang John T JT Chu Hiutung H Dorrestein Pieter P Zhu Qiyun Q Chassaing Benoit B Knight Rob R Gonzalez David J DJ Dulai Parambir S PS

Cellular and molecular gastroenterology and hepatology 20220401 1

<h4>Background & aims</h4>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.<h4>Methods</h4>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 shotg ...[more]

PMID: 35378331

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Project description:BackgroundChronic wounds are common and present a health problem with significant effect on quality of life. Various pathologies may cause tissue breakdown, including poor blood supply resulting in inadequate oxygenation of the wound bed. Hyperbaric oxygen therapy (HBOT) has been suggested to improve oxygen supply to wounds and therefore improve their healing.ObjectivesTo assess the benefits and harms of adjunctive HBOT for treating chronic ulcers of the lower limb.Search methodsFor this second update we searched the Cochrane Wounds Group Specialised Register (searched 18 February 2015); the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2015, Issue 1); Ovid MEDLINE (1946 to 17 February 2015); Ovid MEDLINE (In-Process & Other Non-Indexed Citations, 17 February 2015); Ovid EMBASE (1974 to 17 February 2015); and EBSCO CINAHL (1982 to 17 February 2015).Selection criteriaRandomised controlled trials (RCTs) comparing the effect on chronic wound healing of therapeutic regimens which include HBOT with those that exclude HBOT (with or without sham therapy).Data collection and analysisThree review authors independently evaluated the risk of bias of the relevant trials using the Cochrane methodology and extracted the data from the included trials. We resolved any disagreement by discussion.Main resultsWe included twelve trials (577 participants). Ten trials (531 participants) enrolled people with a diabetic foot ulcer: pooled data of five trials with 205 participants showed an increase in the rate of ulcer healing (risk ratio (RR) 2.35, 95% confidence interval (CI) 1.19 to 4.62; P = 0.01) with HBOT at six weeks but this benefit was not evident at longer-term follow-up at one year. There was no statistically significant difference in major amputation rate (pooled data of five trials with 312 participants, RR 0.36, 95% CI 0.11 to 1.18). One trial (16 participants) considered venous ulcers and reported data at six weeks (wound size reduction) and 18 weeks (wound size reduction and number of ulcers healed) and suggested a significant benefit of HBOT in terms of reduction in ulcer area only at six weeks (mean difference (MD) 33.00%, 95% CI 18.97 to 47.03, P < 0.00001). We identified one trial (30 participants) which enrolled patients with non-healing diabetic ulcers as well as venous ulcers ("mixed ulcers types") and patients were treated for 30 days. For this "mixed ulcers" there was a significant benefit of HBOT in terms of reduction in ulcer area at the end of treatment (30 days) (MD 61.88%, 95% CI 41.91 to 81.85, P < 0.00001). We did not identify any trials that considered arterial and pressure ulcers.Authors' conclusionsIn people with foot ulcers due to diabetes, HBOT significantly improved the ulcers healed in the short term but not the long term and the trials had various flaws in design and/or reporting that means we are not confident in the results. More trials are needed to properly evaluate HBOT in people with chronic wounds; these trials must be adequately powered and designed to minimise all kinds of bias.

Dataset Information

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

Background & aims

Methods

Results

Conclusions

Publications

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

Similar Datasets

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