Intestinal Microbe-Metabolite Network Associated with The Efficacy of Fecal Microbiota Transplantation Therapy in Inflammatory Bowel Disease

ABSTRACT:

BACKGROUND: Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is a type of recurrent and incurable disease, which can lead to the loss of workability, increase cancer risk and bring serious economic burden to patients. Abnormal intestinal microbe interaction contributes to the pathogenesis of IBD, and abnormal host-microbe cometabolites are considered to be one of the causes of dysbiosis of microbe interaction. Fecal microbial transplantation (FMT) is an effective strategy for IBD treatment, but it is unclear how FMT changes intestinal microbial interaction, which to some extent leads to the erratic efficacy of FMT application. It is of great significance to further explore the host-microbiota interaction mode during FMT treatment, which can provide a basis for improving the efficacy of FMT.

METHODS: 37 IBD patients (including 15 UC and 22 CD) and 16 healthy donors were recruited from October 2019 to May 2021. 15 UC patients received FMT treatment and 12 of them with therapeutic reactions. 15 CD patients received pure FMT treatment, 9 of them present therapeutic reaction, and 2 of them present clinical unresponsive. 7 CD patients received scheduled ileocolic resection. 2 FMT unresponsive CD patients and 7 postoperative CD patients received infliximab (IFX)-FMT combination treatment, and 5 of them present therapeutic reactions. Clinical evaluation was performed after 14 weeks of FMT treatment. Fecal samples were collected at baseline timepoint (prior treatment) and post-FMT timepoint. 16S sequencing was used to obtain the microbiome information of subjects. LC-MS-based quantitative targeting strategy was used to collect host-microbe cometabolite information. Spearman correlation network analysis was used to construct IBD prognosis marker-microbe-metabolite ternary interaction network.

RESULTS: FMT therapy, but not IFX therapy, shifted α- and β-diversity of intestinal microbiota in patients with UC and CD toward that of healthy donors. Between subjects with and without clinical response both in UC and CD cohort, β-diversity did not vary significantly but α-diversity showed a significantly difference. On the other hand, FMT therapy can shift host-microbe co-metabolic profiles of baseline subjects toward that of healthy donors, so can IFX-FMT combination therapy in operative or FMT unresponsive CD subjects. After excluding microbes or metabolites unrelated to the FMT treatment response, we found that the remaining microbes or metabolites had nonnegligible associations with the baseline characteristics of the subjects (including age, gender, onset time, inflammatory degree, etc.). On the contrary, we did not find enough association between IBD prognostic indicators (including CRP, calprotectin, and MAYO or CDAI score) and FMT response-related microbes or metabolites. Nevertheless, we constructed the IBD prognosis marker-FMT response related microbe-FMT response related metabolite ternary interaction network and found that the number of associations increased significantly after FMT treatment relative to baseline subjects.

CONCLUSION: It may take the intestinal microbe-metabolite interaction network as the standard or indicator for donor-receptor matching during FMT therapy, rather than simply considering the differences of bacteria or metabolites between donor and receptor.

INSTRUMENT(S): Liquid Chromatography MS -

PROVIDER: MTBLS3909 | MetaboLights | 2026-03-11

REPOSITORIES: MetaboLights