P0152 Distinct faecal metabolic profiles associated with endoscopic remission in ulcerative colitis patients following faecal microbiota transplantation
Authors: Jiwa F , Jitsumara M , Hugo S , Takis P , Ghiboub M , Kinross J , Harris D , Hitchings M 
Published: January 2025

Background

While FMT has shown promise in inducing remission in ulcerative colitis (UC) patients, there are still high rates of non-response (1). Identifying patterns associated with treatment response may help optimize FMT and improve the management of UC patients by identifying FMT's underlying mechanisms. This study aimed to examine the faecal metabolic profile of UC patients post-FMT to identify key metabolites and metabolic pathways linked to treatment response.

Methods

Faecal samples were collected from 18 treatment-naïve UC patients recruited from a single-centre, single-blinded randomised controlled trial (ISRCTN58082603). All patients received antibiotics and bowel lavage before randomisation into three groups: (1) a single FMT enema (n=7), (2) five consecutive FMT enemas over five days (n=7), and (3) a control group receiving only antibiotics and bowel lavage (n=4). Samples were collected at baseline (week 0) and at weeks 1, 4, 8, and 12 post-treatment. Treatment response was defined as endoscopic remission or a drop of ≥2 points in the partial Mayo score. Faecal samples were analysed using 1H-NMR spectroscopy. Univariate statistics analysis was performed on processed spectral data using Metaboanalyst 5.0.

Results

Among 18 patients (median age 42, range 18-70; 7 (39%) male), 3 of 14 in the FMT groups and 2 in the control group achieved endoscopic remission. Faecal metabolic profiles were available for 58 samples at week (W) 0, W4, W8 and W12, showing a total of 23 targeted metabolites. Although no individual metabolites were significantly changed across groups and all timepoints, pathway-specific analysis revealed distinct metabolic shifts in responders post-FMT. Responders showed a reduction in purine metabolism and alanine synthesis, whereas non-responders’ metabolic profile remained comparable to baseline (W0), suggesting these pathways may play a role in remission induction. Disturbances in purine metabolism have been linked to inflammatory conditions, including inflammatory bowel disease (IBD) and bacterial purine metabolism is a target of thiopurine drugs commonly used in IBD therapy (2, 3).

Conclusion

Alterations in purine and alanine metabolism are associated with clinical response in UC patients following FMT, underscoring their potential role in mediating treatment effects. Ongoing analysis, including taxonomic profiling, aims to further explore the relationship between these pathways and the gut microbiome may provide insights into the underlying mechanisms driving FMT-induced remission.

References

1.Imdad A, Pandit NG, Zaman M, Minkoff NZ, Tanner-Smith EE, Gomez-Duarte OG, et al. Fecal transplantation for treatment of inflammatory bowel disease. Cochrane Database Syst Rev. 2023;4(4):Cd012774.

2.Oancea I, Movva R, Das I, Aguirre de Cárcer D, Schreiber V, Yang Y, et al. Colonic microbiota can promote rapid local improvement of murine colitis by thioguanine independently of T lymphocytes and host metabolism. Gut. 2017;66(1):59-69.

3.Crittenden S, Cheyne A, Adams A, Forster T, Robb CT, Felton J, et al. Purine metabolism controls innate lymphoid cell function and protects against intestinal injury. Immunol Cell Biol. 2018;96(10):1049-59.