Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), affects over 2 million people worldwide . Although biological therapies have significantly improved the treatment outcomes for UC, nearly two-thirds of patients experience diminishing drug responses over time, making it crucial to explore novel therapeutic approaches targeting the underlying pathophysiology of UC. UC is associated with alterations in gut microbiota, reduced microbial diversity, and changes in the relative abundance of dominant bacterial populations. Specifically, UC patients exhibit a marked decrease in gut microbiota diversity at the species level, with a reduction in Firmicutes (e.g., Clostridium butyricum) and an increase in Actinobacteria, Proteobacteria (e.g., Escherichia coli), Enterobacteriaceae, Streptococcus, and Bacteroides . Given the association between gut microbiota alterations and IBD activity, several studies have proposed microbiota-based therapies, particularly fecal microbiota transplantation (FMT), as a treatment for UC.

FMT involves the infusion of fecal material from healthy donors into patients to restore gut microbiota balance. It is currently recognized as an effective treatment for recurrent or refractory Clostridium difficile infections. Numerous studies suggest that FMT, as a therapeutic tool to regulate gut microbial homeostasis, holds potential in treating UC and other diseases, although the biochemical and/or immune mechanisms underlying its effects remain unclear . Paramsothy et al. demonstrated the efficacy of autologous FMT compared to placebo, utilizing a protocol involving colonoscopy-guided FMT followed by daily enemas for 5 days per week over 8 weeks. However, the high financial burden of this approach limits its broader clinical application. Another study revealed that donor FMT prepared anaerobically for 1-week treatment led to a higher likelihood of remission at 8 weeks compared to autologous FMT. Further research is needed to assess its safety and maintain long-term remission rates.

Our team's high-quality research findings indicate that the gut microbiota of populations in Yunnan's ethnic minority regions exhibits significantly higher diversity and regional specificity compared to urban populations. This has potential value in enhancing FMT efficacy. Previous studies revealed ethnic and regional differences in IBD prevalence in Yunnan Province, with lower rates among the Dai, Bai, and Miao ethnic groups compared to the Han population. An analysis of contributing factors highlighted the protective role of traditional ethnic diets, which increase gut microbial and viral diversity and probiotics content, thereby reducing UC prevalence. Based on this, the differences between donors in FMT may affect treatment outcomes, emphasizing the importance of identifying "high-quality" donors who maximize efficacy and minimize adverse reactions.

Inclusion Criteria:

1. Age between 14 and 79 years (inclusive), any gender.
2. Diagnosed with ulcerative colitis (UC) per established clinical, endoscopic, and histological standards, with a disease duration of over 3 months.
3. Active mild-to-moderate UC, defined by a Mayo score of 4-10, including an endoscopic score ≥1 and a physician's global assessment score ≤2.
4. Stable baseline medication consisting of 5-aminosalicylic acid (mesalamine).
5. Signed written informed consent.

Exclusion Criteria:

1. Participants unable to provide informed consent, answer questionnaires, or supply samples.

2. Pregnant women or those attempting to conceive.

3. Participants unwilling to use effective contraception throughout the study.

4. Participants deemed in remission by investigators.

5. Evidence or history of toxic megacolon.

6. Isolated rectal inflammation (<5 cm in extent).

7. Diagnosed with Crohn's disease or indeterminate colitis.

8. Participants with perianal diseases (e.g., fistulae, anal fissures).

9. History of significant gastrointestinal surgery (e.g., colectomy) ：

   • Minor surgeries will be reviewed case by case.
   • Patients with appendectomy within 3 months will be excluded.

10. Antibiotic use within the past 4 weeks for any reason, including for UC.

11. Steroid dependence requiring >20 mg prednisone or >9 mg budesonide daily at enrollment.

12. Recent or anticipated usage of prohibited drugs during the study period, including:

    • Rectal corticosteroids within 2 weeks prior to the first FMT.
    • Biologics (e.g., infliximab, adalimumab, vedolizumab) within 4 weeks prior to the first FMT.
    • Other major immunosuppressants (e.g., calcineurin inhibitors, antitumor drugs) within 12 weeks prior to treatment.
    • Probiotics within 4 weeks before the first FMT.
    • Experimental drugs or protocols within 12 weeks before the first FMT.
    • Anti-tuberculosis (TB or MAC) treatment within 4 weeks before the first FMT.

Permitted Medications:

Participants may continue using the following medications if doses are stable within specified timeframes before the first FMT:

• Oral 5-aminosalicylic acid (stable for 4 weeks).
• Azathioprine and methotrexate (≥90 days of use with stable doses for 4 weeks).
• Oral prednisone (≤20 mg/day, stable for 2 weeks, gradually tapered at a rate of 2.5 mg/week to discontinue by week 8).

Subjects should maintain the same doses of oral 5-aminosalicylates, thiopurines, and methotrexate during the study. For oral prednisolone, the dose had to be tapered off gradually, at a rate of 2.5mg per week, so that subjects were no longer exposed to steroids until week 8.

Prohibited Medications:

• Rectal corticosteroids (2 weeks before and throughout the study).
• Antibiotics, antifungals, antivirals, probiotics, or prebiotics (4 weeks before and throughout the study).
• Biologics or calcineurin inhibitors (12 weeks before and throughout the study). Participants using prohibited medications during the study will remain enrolled, and outcomes will still be evaluated. All prohibited medication usage will be recorded.

The collection of AEs, including serious adverse events (SAEs), will begin from the first administration of FMT. Routine AE collection will continue until week 1.Since participants will transition to standard care after week 1, AEs occurring beyond this period will not be collected.

These symptoms are typically mild and resolve within three days post-FMT. Unless symptoms persist for more than three days or become more severe, they will not be recorded as AEs.Sore throat. Fever. Increase of CRP. Diarrhea. Increased in stool frequency. Loose stool. Abdominal discomfort. Abdominal distention. Abdominal pain. Abdominal fullness. Bloating. Belching. Cramping. Gassiness. Fatigue. Vomiting. Excessive flatulence. Constipation. Decreased appetite. Headache. Nausea. Borborygmus.