Background Inflammatory bowel disease (IBD) primarily encompasses Crohn’s disease (CD) and ulcerative colitis (UC), both of which are chronic, incurable conditions that can progress to enteritis-associated colorectal cancer, significantly impacting patients’ quality of life and mental well-being. Although the etiology remains incompletely understood, numerous studies have indicated that the progression of IBD is associated with genetic susceptibility, immune dysfunction, and microbial dysbiosis. In comparison to healthy individuals, IBD patients exhibit reduced gut microbiota richness characterized by a decrease in certain beneficial bacteria such as Firmicutes and Bacteroidetes while displaying an increase in Proteobacteria. Consequently, fecal microbiota transplantation (FMT), as a relatively safe and sustainable therapeutic approach, can introduce the intestinal flora from healthy donors into patients’ gastrointestinal tract to enhance the diversity and abundance of gut bacteria while restoring immune homeostasis within the host intestinal mucosa; however, the precise mechanism underlying this process remains unclear.

Methods Patients diagnosed with active UC (Mayo total score 4-10 and endoscopic subscore ≥1) were randomly selected from the patient pool at the First Affiliated Hospital of Kunming Medical University. One week after undergoing colonoscopy FMT, patients were assessed as follows: Patients were followed up at 1 week, 8 weeks, 12 weeks, 24 weeks, and 48 weeks for biochemical tests, colonoscopy examinations, and analysis of intestinal flora. The primary outcome measure was clinical remission, defined by achieving both endoscopic remission or remission at 12 weeks (Mayo total score ≤2 and subscore ≤1, along with a minimum decrease of one point in the endoscopic score by week 12.

Results We collected the stool samples to explore the microbiome-wide protein expression and lysine crotonylation (Kcr) during the IBD patient’s FMT treatment. We observed that all patients experienced a reduction in inflammation to some extent after FMT treatment, regardless of whether they achieved clinical benefits. In addition, alterations in microbiota composition and enterotype were also observed during FMT treatment, which impacted the treatment outcomes of FMT.

Conclusions Many microbial protein Kcr sites on metabolic enzymes exhibited significant correlation with the expression of human inflammation-related factors, which might affect the patients’ therapeutic outcomes.