Fecal microbiota transplantation for ulcerative colitis: a prospective clinical study

Yan Tian, Yan Zhou, Sisi Huang, Jun Li, Kui Zhao, Xiaohui Li, Xiangchen Wen, Xiao-An Li, Yan Tian, Yan Zhou, Sisi Huang, Jun Li, Kui Zhao, Xiaohui Li, Xiangchen Wen, Xiao-An Li

Abstract

Background: Fecal microbiota transplantation may contribute to disease remission in ulcerative colitis; however, the factors that determine the effects of treatment remain unknown. The aim of the present study was to prospectively investigate the clinical efficacy of fecal microbiota transplantation in patients with ulcerative colitis and identify the bacterial signatures associated with clinical remission.

Methods: A total of 20 patients with ulcerative colitis were included in this prospective and uncontrolled study. All patients underwent gastroscopy five times, once every 3 weeks. Clinical indices were used to assess the efficacy of fecal microbiota transplantation, as well as the Mayo score, a score used to evaluate the extent of intestinal mucosal lesions in patients with ulcerative colitis. The changes in intestinal flora were detected by 16S ribosomal RNA-sequencing, and the relationship between ulcerative colitis and intestinal flora was analyzed.

Results: After treatment, clinical index scores for diarrhea, abdominal pain, and blood stool decreased significantly (p < 0.05). Erythrocyte sedimentation rate and C-reactive protein levels had not changed significantly; however, the clinical index score for intestinal mucosal lesions and the Mayo score decreased significantly. In addition, 16S ribosomal RNA-sequencing revealed that the intestinal flora in patients diagnosed with ulcerative colitis was different from that of donors.

Conclusion: Fecal microbiota transplantation has a potential therapeutic value for the treatment of ulcerative colitis as it changes the abundance of bacterial flora and improves the scores for diarrhea, abdominal pain, and mucous membrane lesions in patients with this disease.

Trial registration: The clinical trial was retrospectively registered with ClinicalTrials.gov ( NCT03016780 ) on January 11th, 2017.

Keywords: Fecal microbiota transplantation; Intestinal flora; Intestinal microorganisms; Ulcerative colitis.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Enteroscopic findings of intestinal mucosa of a patient before and after treatment (a); Hematoxylin-eosin staining of intestinal mucosa before and after treatment (b);b reflect the infiltration of inflammatory cells in the intestinal mucosa before and after treatment. PatientA, PatientB, PatientC represent three patients. Scale bar = 200 μm
Fig. 2
Fig. 2
Relative abundance of fecal microbiota in patients with ulcerative colitis before and after treatment at phylum and genus level. Different colors represent different bacterial species. a 10 most abundant species in patients and donors at the phylum level; b 20 most abundant species in patients and donors at the genus level; c 10 most abundant species in patients at the phylum level according to different treatment stages; d 20 most abundant species in patients at the genus level according to different treatment stages
Fig. 3
Fig. 3
Venn diagram analysis of bacteria populations in patients with ulcerative colitis and healthy donors. The number in each region represents the number of operational taxonomic units shared between sample groups or unique to the sample group. The histogram represents the total number within each sample set
Fig. 4
Fig. 4
Dilution curve of alpha-diversity. The alpha-diversity index based on the number of sequencing reads. Different samples are represented by different color lines
Fig. 5
Fig. 5
Principal component analysis of donors and patients with ulcerative colitis during each treatment period. PC1, PC2, and PC3 represent the three principal components, and the percentage indicates the contribution of the principal component to the sample difference. Each dot represents one sample, and each color represents one group
Fig. 6
Fig. 6
Linear discriminant analysis (LDA) scores of donors and patients with ulcerative colitis during each treatment period (for specimens with an LDA score > 2)

References

    1. Geremia A, Biancheri P, Allan P, et al. Innate and adaptive immunity in inflammatory bowel disease. Autoimmun Rev. 2014;13(1):3–10. doi: 10.1016/j.autrev.2013.06.004.
    1. Khan S, Imran A, Malik A, et al. Bacterial imbalance and gut pathologies: association andcontribution of E. coli in inflammatory bowel disease. Crit Rev Clin Lab Sci. 2018;29:1–17.
    1. Hvas Christian L., Bendix Mia, Dige Anders, Dahlerup Jens F., Agnholt Jørgen. Current, experimental, and future treatments in inflammatory bowel disease: a clinical review. Immunopharmacology and Immunotoxicology. 2018;40(6):446–460. doi: 10.1080/08923973.2018.1469144.
    1. Levy M, Kolodziejczyk AA, Thaiss CA, et al. Dysbiosis and the immune system. Nat Rev Immunol. 2017;17(4):219–232. doi: 10.1038/nri.2017.7.
    1. Kostic AD, Xavier RJ, Gevers D. The microbiome in inflammatory bowel disease: current status and the future ahead. Gastroenterology. 2014;146:1489–1499. doi: 10.1053/j.gastro.2014.02.009.
    1. Manichanh C, Borruel N, Casellas F, et al. The gut microbiota in IBD. Nat Rev Gastroenterol Hepatol. 2012;9(10):599–608. doi: 10.1038/nrgastro.2012.152.
    1. Ng SC, Tang W, Leong RW, et al. Environmental risk factors in inflammatory bowel disease: a population-based case-control study in Asia-Pacific. Gut. 2015;64(7):1063–1071. doi: 10.1136/gutjnl-2014-307410.
    1. Chang PV, Hao L, Offermanns S, et al. The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition. Proc Natl Acad Sci U S A. 2014;111(6):2247–2252. doi: 10.1073/pnas.1322269111.
    1. Yan ZX, Gao XJ, Li T, et al.Fecal microbiota transplantation in experimental ulcerative colitis reveals associated gut microbial and host metabolic reprogramming. Appl Environ Microbiol. 2018;84(14):26-51.
    1. Axelrad Jordan E., Olén Ola, Askling Johan, Lebwohl Benjamin, Khalili Hamed, Sachs Michael C., Ludvigsson Jonas F. Gastrointestinal Infection Increases Odds of Inflammatory Bowel Disease in a Nationwide Case–Control Study. Clinical Gastroenterology and Hepatology. 2019;17(7):1311-1322.e7. doi: 10.1016/j.cgh.2018.09.034.
    1. Schirmer M, Denson L, Vlamakis H, et al. Compositional and Temporal Changes in the Gut Microbiome of Pediatric Ulcerative Colitis Patients Are Linked to Disease Course. Cell Host Microbe. 2018;24(4):600–610.e4. doi: 10.1016/j.chom.2018.09.009.
    1. Barrett JS, Canale KE, Gearry RB, et al. Probiotic effects on intestinal fermentation patterns in patients with irritable bowel syndrome. World J Gastroenterol. 2008;14(32):5020–5024. doi: 10.3748/wjg.14.5020.
    1. D'Odorico I, Di Bella S, Monticelli J, et al. Role of fecal microbiota transplantation in inflammatory bowel disease. J Dig Dis. 2018;19(6):322–334. doi: 10.1111/1751-2980.12603.
    1. Angelberger S, Reinisch W, Makristathis A, et al. Temporal bacterial community dynamics vary among ulcerative colitis patients after fecal microbiota transplantation. Am J Gastroenterol. 2013;108(10):1620–1630. doi: 10.1038/ajg.2013.257.
    1. Damman CJ, Miller SI, Surawicz CM, et al. The microbiome and inflammatory bowel disease: is there a therapeutic role for fecal microbiota transplantation? Am J Gastroenterol. 2012;107(10):1452–1459. doi: 10.1038/ajg.2012.93.
    1. Jitsumura M, Cunningham AL, Hitchings MD, et al. Protocol for faecal microbiota transplantation in ulcerative colitis (FMTUC): a randomised feasibility study. BMJ Open. 2018;8(10):e021987.
    1. Sham HP, Bazett M, Bosiljcic M, et al. Immune Stimulation Using a Gut Microbe-Based Immunotherapy Reduces Disease Pathology and Improves Barrier Function in Ulcerative Colitis. Front Immunol. 2018;9:2211. doi: 10.3389/fimmu.2018.02211.
    1. Uygun A, Ozturk K, Demirci H, et al. Fecal micr obiota transplantation is a rescue treatment modality for refractory ulcerative colitis. Medicine (Baltimore) 2017;96(16):e6479. doi: 10.1097/MD.0000000000006479.
    1. Borody TJ, Campbell J. Fecal microbiota transplantation: current status and future directions. Expert Rev Gastroenterol Hepatol. 2011;5(6):653–655. doi: 10.1586/egh.11.71.
    1. Brandt LJ, Aroniadis OC, Mellow M, et al. Long-term follow-up of colonoscopic fecal microbiota transplant for recurrent Clostridium difficile infection. Am J Gastroenterol. 2012;107(7):1079–1087. doi: 10.1038/ajg.2012.60.
    1. Kump PK, Gröchenig H, Lackner S, et al. Alteration of intestinal Dysbiosis by fecal microbiota transplantation does not induce remission in patients with chronic active ulcerative colitis. Inflamm Bowel Dis. 2013;19(10):2155–2165. doi: 10.1097/MIB.0b013e31829ea325.
    1. Schirmer M, Franzosa EA, Lloyd-Price J, et al. Dynamics of metatranscription in the inflammatory bowel disease gut microbiome. Nat Microbiol. 2018;3(3):337–346. doi: 10.1038/s41564-017-0089-z.

Source: PubMed

3
Abonnieren