Prospective Study Reveals Host Microbial Determinants of Clinical Response to Fecal Microbiota Transplant Therapy in Type 2 Diabetes Patients

Ding, Dafa; Yong, Huijuan; You, Na; Lu, Wei; Yang, Xu; Ye, Xiaolong; Wang, Yayun; Cai, Tingting; Zheng, Xiaoling; Chen, Hui; Cui, Bota; Zhang, Faming; Liu, Xingyin; Mao, Jian-Hua; Lu, Yibing; Chang, Hang

doi:10.3389/fcimb.2022.820367

Title: Prospective Study Reveals Host Microbial Determinants of Clinical Response to Fecal Microbiota Transplant Therapy in Type 2 Diabetes Patients

Journal Article · 25 March 2022 · Frontiers in Cellular and Infection Microbiology

DOI: https://doi.org/10.3389/fcimb.2022.820367 · OSTI ID:1896678

Ding, Dafa ^[1]; Yong, Huijuan ^[1]; You, Na ^[1]; Lu, Wei ^[1]; Yang, Xu ^[2]; Ye, Xiaolong ^[1]; Wang, Yayun ^[1]; Cai, Tingting ^[1]; Zheng, Xiaoling ^[1]; Chen, Hui ^[1]; Cui, Bota ^[1]; Zhang, Faming ^[1]; Liu, Xingyin ^[1]; Mao, Jian-Hua ^[3]; Lu, Yibing ^[1]; Chang, Hang ^[3]

Nanjing Medical University (China)
Nanjing Medical University (China); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

Increasing evidence shows that alterations in gut microbiome (GM) contribute to the development of type 2 diabetes mellitus (T2DM), and fecal microbiota transplantation (FMT) successfully treats various human diseases. However, the benefits of FMT therapy to T2DM patients remain unknown. We enrolled 17 patients with T2DM for nonblinded, one-armed intervention trial of FMT. A total of 20 healthy individuals were recruited as the baseline control. HbA1c% and metabolic parameter change were evaluated in 17 T2DM patients 12 weeks after they received FMT from healthy donors. The GM composition was characterized by 16S rRNA gene amplicon sequencing from fecal samples prior to and 12 weeks after FMT treatment. We found that the GM of T2DM patients was reconstituted by FMT. We observed a statistically significant decrease in HbA1c% (from 7.565 ± 0.148 to 7.190 ± 0.210, p<0.01), blood glucose (from 8.483 ± 0.497 to 7.286 ± 0.454 mmol/L, p<0.01), and uric acid (from 309.4 ± 21.5 to 259.1 ± 15.8 µmol/L, p<0.01) while a significant increase in postprandial C-peptide (from 4.503 ± 0.600 to 5.471 ± 0.728 ng/ml, p<0.01) at 12 weeks after FMT. Closely evaluating the changes in these assays, we found individual variability in response to FMT treatment. Out of 17 T2DM patients, 11 were found to significantly improve T2DM symptoms. The FMT responders have significantly higher levels of the family Rikenellaceae and the genus Anaerotruncus (family Ruminococcaceae) in their pretreated fecal in comparison to nonresponders, which could predict the clinical response with an area under the curve of 0.83. Our findings suggest that certain T2DM patients can potentially benefit from FMT, and the pretreated abundance of Rikenellaceae and Anaerotruncus in the fecal of patients may serve as potential biomarkers for selecting T2DM patients to receive FMT.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER); Major Research and Development Project of Jiangsu; Jiangsu Youth Medical Talents Project; Nanjing Science Technology Plan Project; Jiangsu Provincial Health and Health Commission

Grant/Contract Number:: AC02-05CH11231; BE2016800; QNRC2016674; 201715015; ZDB2020034; M2021056

OSTI ID:: 1896678

Journal Information:: Frontiers in Cellular and Infection Microbiology, Vol. 12; ISSN 2235-2988

Publisher:: Frontiers Research FoundationCopyright Statement

Country of Publication:: United States

Language:: English

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