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Abstract
Background Bile acids (BAs) can be metabolized by gut microbiota. As dysbiosis has been reported in inflammatory bowel diseases (IBD), we aim to investigate the correlation between IBD-associated dysbiosis and BAs metabolism and its influence on clinical response after the introduction of fecal microbiota transplantation (FMT).
Methods Patients with active IBD (37 UC and 69 CD) undergoing FMT and 24 matched individuals without IBD were enrolled. We explored changes in the serum metabolic and fecal microbial signatures of groups and the association between baseline serum metabolomic profiles, microbiota, and patient outcomes. Non-targeted LC-MS and 16s rRNA sequencing were used for blood and stool samples. In the mice model, Primary BAs (cholic acid and chenodeoxycholic acid) were given to DSS-induced acute enteritis mice and antibiotic-disturbed mice. DAI score, colon length, spleen index and pathological score were evaluated.
Results Patients with IBD and BAM (bile acid malabsorption) had significant differences in network connections between fecal microbiomes and metabolomes compared with controls (IDDF2024-ABS-0041 Figure 1, IDDF2024-ABS-0041 Figure 2); these were accompanied by differences in clinical efficacy before and after FMT. The BAM group (especially CD patients with a history of ileal resection, ileal type/ileocolonic type, who had the highest prevalence of BAM) had a higher proportion of improvement in abdominal pain and diarrhea after FMT compared to non-BAM, along with a significant decrease of serum 7α-hydroxy-4-cholesten-3-one (C4). (IDDF2024-ABS-0041 Figure 3). A random forest classifier was constructed with 18 or top 4 differential OTUs to predict the occurrence of BAM in IBD patients, showing an area under the curve of 0.92 and 0.83, respectively, with the F1-score and accuracy remaining unchanged. (IDDF2024-ABS-0041 Figure 4, IDDF2024-ABS-0041 Figure 5). Altered BAs transformation affected by IBD-associated dysbiosis (IDDF2024-ABS-0041 Figure 6) could participate in the chronic inflammation loop, lipid and glucose metabolism of IBD and eroded anti-inflammatory effects. Administration of high doses of exogenous primary BAs can exacerbate colitis in mice, whether in the DSS-induced acute colitis model or the antibiotic-mediated dysbiosis model.
Conclusions Multi-omics analysis and random forest prediction would assist physicians in using FMT in IBD patients with BAM.
