Microbiota and mucosal gene expression of fecal microbiota transplantation or placebo treated patients with chronic pouchitis

ABSTRACT

Altered microbiota and impaired host immune function have been linked to the pathogenesis of pouchitis. We used 16S rRNA gene sequencing and RNA sequencing data from a previous randomized clinical trial (RCT) on fecal microbiota transplantation (FMT) therapy in 26 chronic pouchitis patients with one-year follow-up. We analyzed changes in both luminal and mucosal microbiota composition, as well as in host mucosal gene expression to gain insights into the host–microbiota interactions possibly underlying clinical outcomes of the patients. Antibiotic type and pattern of use were significant drivers of the luminal microbiota at baseline. Differential gene expression analysis indicated transition from ileal to colonic gene expression in the pouch, and upregulation in inflammation- and immune system-related pathways in the pouch. At 4 weeks, the non-relapsed FMT patients had a lower microbiota dissimilarity to the donor than the non-relapsed placebo patients (p = .02). While two FMT-treated patients showed a shift toward the donor’s microbiota during the one-year follow-up, the overall FMT microbiota modulation effect was low. Patient’s luminal and mucosal microbiota profiles were unstable in both FMT and placebo groups. Expression of the chemokine receptor CXCR4 was downregulated at 52 weeks compared to the baseline in the non-relapsed patients in both FMT and placebo groups. Microbiota modulation by FMT seems to be low in this patient group. The microbiota composition or alterations did not explain the relapse status of the patients. Some evidence for remission-related host gene expression pattern was found; specifically, CXCR4 expression may have a role in sustained remission.

KEYWORDS:

• Fecal microbiota transplantation
• ulcerative colitis
• pouchitis
• inflammatory bowel disease
• microbiota
• gene expression

Acknowledgments

Open access funded by Helsinki University Library.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Authors’ contributions

AHL, EKK, LR-S, PA, and RS conceived and designed the clinical study. AHL, EKK, LR-S and RS conducted the clinical study and collected samples. EKK collected the patient data. AKH, IK, JJ and RS designed the sample analysis. AKH and IK conducted the laboratory analysis and performed the bioinformatic and statistical analysis. RS and JJ supervised the analysis. AKH, IK, JJ and RS interpreted the results and wrote the manuscript. All authors revised the manuscript. All authors read and approved the final manuscript.

Data availability statement

The datasets generated and/or analyzed during the current study are available in the European Nucleotide Archive (ENA) repository with the accession number PRJEB52304 or by request.

Supplemental material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2023.2295445.

Additional information

Funding

The study was supported by Academy of Finland (grant no. 323156 for RS), Sigrid Juselius Foundation (Senior Researcher’s grant for RS), University of Helsinki (Doctoral School in Health Sciences funding for AH), Helsinki University Hospital and Mary and Georg C. Ehrnroth Fund (Helsinki University Hospital Research Fund and Mary and Georg C. Ehrnroth Fund grants for EK) and the Competitive State Research Financing (for PA). The research was independent of the funding sources.