Sara K. Fenton, Veronika K. Pettersen,a, Terje Vasskog,b, Kenneth Lindstedt
a Host-Microbe Interaction Research Group,Department of Medical Biology, UiT the Arctic University of Norway
b Natural Products and Medicinal Chemistry Research Group, Department of Pharmacy, UiT the Arctic University of
Norway
Email: sfe024@uit.no
Klebsiella pneumoniae (Kp) is a major opportunistic and nosocomial pathogen increasingly associated with antimicrobial resistance and high clinical mortality.1 Of particular concern, carbapenem-resistant K. pneumoniae (CRKp) have been recognised by the World Health Organisation (WHO) as a moderate global health threat. 2,3 Kp is a well-known asymptomatic coloniser of the human gastrointestinal tract, creating a critical reservoir for infection and transmission. However, the mechanisms that determine whether Kp persists or is suppressed in the gut remain poorly understood. Within the intestinal ecosystem, colonisation resistance is thought to arise partly through metabolic competition, but the specific metabolites and pathways involved are largely unknown1,4
Faecal Microbiota Transplantation (FMT) has emerged as a promising approach to restore microbiome function and a functional metabolism in dysbiotic conditions such as irritable bowel syndrome (IBS).5 IBS is a functional gastrointestinal disorder characterised by abdominal pain and altered bowel habits, often associated with disturbances in the gut microbiota. Dysbiosis in IBS can impact microbial metabolism and small-molecule mediators, processes crucial to colonisation resistance.6
This project is based on the REFIT2 clinical trial, a randomised, double-blind study investigating FMT as a treatment for IBS.7 The trial provides an opportunity to link alterations in the faecal metabolome to changes in Kp colonisation following FMT, exploring more in depth how microbiome-driven metabolic changes may influence gut colonisation by opportunistic pathogens like Kp. Pre- and post-FMT stool samples from REFIT2 participants will be analysed using liquid chromatography–tandem mass spectrometry (LC-MS/MS), applying both untargeted and targeted metabolomic approaches. The resulting data will be processed using advanced analytical software to identify metabolic shifts associated with Kp suppression or persistence.
By combining metabolomic data with microbiological results, we hopefully will be able to identify key metabolites and pathways involved in how the gut microbiome prevents colonization of opportunistic pathogens. The findings may help guide future microbiome-based or metabolite-targeted strategies to reduce infections caused by multidrug-resistant K. pneumoniae.
References:
1.Wyres, K. L., Lam, M. M. C. & Holt, K. E. Population genomics of Klebsiella pneumoniae. Nat Rev Microbiol 18, 344-359 (2020). https://doi.org/10.1038/s41579-019-0315-1 2.World Health Organization. (2024, July 31). Antimicrobial resistance, hypervirulent Klebsiella pneumoniae – Global situation. Disease Outbreak News. https://www.who.int/emergencies/disease-outbreak-news/item/2024-DON527 3.Xu, L., Sun, X. & Ma, X. Systematic review and meta-analysis of mortality of patients infected with carbapenem-resistant Klebsiella pneumoniae. Ann Clin Microbiol Antimicrob 16, 18 (2017). https://doi.org/10.1186/s12941-017-0191-3 4.Gorrie, C. L. et al. Gastrointestinal Carriage Is a Major Reservoir of Klebsiella pneumoniae Infection in Intensive Care Patients. Clin Infect Dis 65, 208-215 (2017). https://doi.org/10.1093/cid/cix270 5. Leikanger, I. S., Kolstad, C., Valle, P. C., & Goll, R. (2018). Faecal microbiota transplantation versus placebo for moderate-to-severe irritable bowel syndrome: a double-blind, randomised, placebo-controlled, parallel-group, single-centre trial. The lancet. Gastroenterology & hepatology, 3(1), 17–24. https://doi.org/10.1016/S2468-1253(17)30338 6.Shaikh, S. D., Sun, N., Canakis, A., Park, W. Y., & Weber, H. C. (2023). Irritable Bowel Syndrome and the Gut Microbiome: A Comprehensive Review. Journal of clinical medicine, 12(7), 2558. https://doi.org/10.3390/jcm12072558 7. Goll, R., & Johnsen, P. H. (2025, September 26). Behandling av irritabel tarm syndrom med tarmflora fra frisk donor. REFIT2 – en norsk multisenter fase III studie. Cristin. https://www.cristin.no/