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

Abstract

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. Outmore » 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.« less

Authors:
 [1];  [1];  [1];  [1];  [2];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [3];  [1];  [3]
+ Show Author Affiliations
  1. Nanjing Medical University (China)
  2. Nanjing Medical University (China); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
  3. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
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
OSTI Identifier:
1896678
Grant/Contract Number:  
AC02-05CH11231; BE2016800; QNRC2016674; 201715015; ZDB2020034; M2021056
Resource Type:
Accepted Manuscript
Journal Name:
Frontiers in Cellular and Infection Microbiology
Additional Journal Information:
Journal Volume: 12; Journal ID: ISSN 2235-2988
Publisher:
Frontiers Research Foundation
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; fecal microbiota transplantation; type 2 diabetes mellitus; therapeutic biomarker; prospective cohort study; gut microbiome

Citation Formats

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, and Chang, Hang. Prospective Study Reveals Host Microbial Determinants of Clinical Response to Fecal Microbiota Transplant Therapy in Type 2 Diabetes Patients. United States: N. p., 2022. Web. doi:10.3389/fcimb.2022.820367.
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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. Prospective Study Reveals Host Microbial Determinants of Clinical Response to Fecal Microbiota Transplant Therapy in Type 2 Diabetes Patients. United States. https://doi.org/10.3389/fcimb.2022.820367
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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, and Chang, Hang. Fri . "Prospective Study Reveals Host Microbial Determinants of Clinical Response to Fecal Microbiota Transplant Therapy in Type 2 Diabetes Patients". United States. https://doi.org/10.3389/fcimb.2022.820367. https://www.osti.gov/servlets/purl/1896678.
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@article{osti_1896678,
title = {Prospective Study Reveals Host Microbial Determinants of Clinical Response to Fecal Microbiota Transplant Therapy in Type 2 Diabetes Patients},
author = {Ding, Dafa and Yong, Huijuan and You, Na and Lu, Wei and Yang, Xu and Ye, Xiaolong and Wang, Yayun and Cai, Tingting and Zheng, Xiaoling and Chen, Hui and Cui, Bota and Zhang, Faming and Liu, Xingyin and Mao, Jian-Hua and Lu, Yibing and Chang, Hang},
abstractNote = {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.},
doi = {10.3389/fcimb.2022.820367},
journal = {Frontiers in Cellular and Infection Microbiology},
number = ,
volume = 12,
place = {United States},
year = {Fri Mar 25 00:00:00 EDT 2022},
month = {Fri Mar 25 00:00:00 EDT 2022}
}
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Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
https://doi.org/10.3389/fcimb.2022.820367
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Figures / Tables:

FIGURE 1 FIGURE 1 : The composition of fecal microbiome is altered in T2DM patients. (A) A graphic illustration of the perspective cohort study design to evaluate clinical outcomes in T2DM patients following FMT. (B) The relative abundance of the major microbial families in T2DM patients and controls. (C) Maximally collapsing metricmore » learning (MCML) analysis of family-level T2DM gut microbiomes. Seventeen T2DM samples (green cross) and 20 control samples (res open circle). The p-value was obtained from permutational multivariate analysis of variance (PERMANOVA). (D) Boxplot of relative abundance of 12 families that showed the significant difference between T2DM and control. The p-values were obtained by Mann–Whitney test. Boxes represent the median and interquartile ranges between the first and third quartiles. The dots represent outliers.« less
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