Ulcerative Colitis in Response to Fecal Microbiota Transplantation via Modulation of Gut Microbiota and Th17/Treg Cell Balance

Chunlan Huang; Qixiang Mei; Lihong Lou; Zehua Huang; Yang Fu; Junjie Fan; Jingjing Wang; Nuoming Yin; Yi Zheng; Yingying Lu; Yue Zeng

doi:10.3390/cells11111851

Ulcerative Colitis in Response to Fecal Microbiota Transplantation via Modulation of Gut Microbiota and Th17/Treg Cell Balance

Cells. 2022 Jun 5;11(11):1851. doi: 10.3390/cells11111851.

Authors

Chunlan Huang¹, Qixiang Mei¹, Lihong Lou², Zehua Huang^{1

3}, Yang Fu^{1

3}, Junjie Fan¹, Jingjing Wang³, Nuoming Yin^{1

3}, Yi Zheng⁴, Yingying Lu¹, Yue Zeng^{1

3}

Affiliations

¹ Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China.
² International Medical Care Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
³ Shanghai Key Laboratory of Pancreatic Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China.
⁴ Department of Gastroenterology, Fifth People's Hospital of Zunyi, Zunyi 563000, China.

Abstract

Background: Fecal microbiota transplantation (FMT) may contribute to disease remission in ulcerative colitis (UC). We studied the microbiota change and its regulation on T cells after FMT. Methods: Patients with mild to moderately active UC were included to receive FMT. The intestinal histopathological changes and barrier function were evaluated. The fecal samples of donors and patients were analyzed by 16S rRNA gene-based microbiota analysis, and the colon Th17 and Treg cells were assessed. Results: Fifteen patients completed the 8-week-follow-up. A total of 10 patients (66.7%) were in the responders (RE) group and five in the non-responders (NR) group. The Nancy histological index and fecal calprotectin decreased (p < 0.001, p = 0.06, respectively) and Occludin and Claudin1 increased in the RE group. The abundance of Faecalibaterium increased significantly by 2.3-fold in the RE group at week 8 (p = 0.043), but it was suppressed in the NR group. Fecal calprotectin (r = −0.382, p = 0.003) and Nancy index (r = −0.497, p = 0.006) were correlated inversely with the abundance of Faecalibacterium, respectively. In the RE group the relative mRNA expression of RORγt decreased and Foxp3 increased. Significantly decreased CD4+ RORγt+ Th17 and increased CD4+ Foxp3+ Treg were also observed in the RE group. The relative abundance of Faecalibacterium correlated with CD4+ RORγt+ Th17 (r = −0.430, p = 0.018) and CD4+ Foxp3+ Treg (r = 0.571, p = 0.001). Conclusions: The long-term Faecalibaterium colonization following FMT plays a crucial role in UC remission by alleviating intestinal inflammation. This anti-inflammatory effect of Faecalibacterium may be achieved by regulating the imbalance of Th17/Treg levels in UC.

Keywords: T cell; fecal microbiota transplantation; ulcerative colitis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Colitis, Ulcerative* / pathology
Fecal Microbiota Transplantation
Forkhead Transcription Factors
Gastrointestinal Microbiome*
Humans
Leukocyte L1 Antigen Complex / pharmacology
Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics
RNA, Ribosomal, 16S
T-Lymphocytes, Regulatory / pathology
Transcription Factors*

Substances

Forkhead Transcription Factors
Leukocyte L1 Antigen Complex
Nuclear Receptor Subfamily 1, Group F, Member 3
RNA, Ribosomal, 16S
Transcription Factors
negative elongation factor

Grants and funding

This study was funded by the Clinical Research Cultivating Program of the Shanghai Hospital Development Center (SHDC12017X09); the Foundation of Shanghai Jiao Tong University School of Medicine for the Research-oriented Doctors (No. 20181813); the Clinical Research Plan of the Shanghai Hospital Development Center (SHDC2020CR2014A) and the National Natural Science Foundation of China (No. 81970555).