A metagenomic prospective cohort study on gut microbiome composition and clinical infection in small bowel transplantation

ABSTRACT

Two-thirds of small-bowel transplantation (SBT) recipients develop bacteremia, with the majority of infections occurring within 3 months post-transplant. Sepsis-related mortality occurs in 31% of patients and is commonly caused by bacteria of gut origin, which are thought to translocate across the implanted organ. Serial post-transplant surveillance endoscopies provide an opportunity to study whether the composition of the ileal and colonic microbiota can predict the emergence as well as the pathogen of subsequent clinical infections in the SBT patient population. Five participants serially underwent aspiration of ileal and colonic bowel effluents at transplantation and during follow-up endoscopy either until death or for up to 3 months post-SBT. We performed whole-metagenome sequencing (WMS) of 40 bowel effluent samples and compared the results with clinical infection episodes. Microbiome composition was concordant between participants and timepoint-matched ileal and colonic samples. Four out of five (4/5) participants had clinically significant infections thought to be of gut origin. Bacterial translocation from the gut was observed in 3/5 patients with bacterial infectious etiologies. In all three cases, the pathogens had demonstrably colonized the gut between 1–10 days prior to invasive clinical infection. Recipients with better outcomes received donor grafts with higher alpha diversity. There was an increase in the number of antimicrobial resistance genes associated with longer hospital stay for all participants. This metagenomic study provides preliminary evidence to support the pathogen translocation hypothesis of gut-origin sepsis in the SBT cohort. Ileal and colonic microbiome compositions were concordant; therefore, fecal metagenomic analysis could be a useful surveillance tool for impeding infection with specific gut-residing pathogens.

KEYWORDS:

• Small bowel transplantation
• bacterial translocation
• gut microbiome
• sepsis
• antibiotics
• gut-origin sepsis
• metagenomics
• antimicrobial resistance

Acknowledgments

We thank the transplant nursing team for their assistance in this study. Most importantly, heart-felt thanks were expressed to the participants for selflessly supporting this study.

Disclosure statement

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

Authors contributions

Conception and design: EGK, JBS, SB, JPD

Recruitment of participants: KA, TD, RB

Collection of samples and clinical data: RB, HS, DM, LS, CR, JW, NR, IA, AB

Processing of samples: CC, RB, JPD, SF, LK

Analysis and interpretation of data: AM, EH, RB, JK, EGK

Drafting initial paper: RB, AM, EGK

Revising the final paper: RB, AM, CC, JPD, SF, JK, LK, EH, GD, HS, DM, LS, CR, JW, NR, IA, AB, KA, TD, JBS, SB, EGK

Data availability statement

The authors confirm that the data supporting the findings of this study are available in the article and its supplementary materials. The microbial WMS reads for 40 patient samples and WGS reads for 3 bacterial isolates have been deposited in the NCBI Sequence Read Archive under BioProject accession PRJNA1004534.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2024.2323232

Additional information

Funding

This work was supported by Addenbrooke’s Charitable Trust, Cambridge University Hospitals, Grant number 1543. This research was supported by the NIHR Cambridge Biomedical Research Centre (NIHR203312). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.