Prospective Study Reveals Host Microbial Determinants of Clinical Response to Fecal Microbiota Transplant Therapy in Type 2 Diabetes Patients
BackgroundIncreasing 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.Me...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-03-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2022.820367/full |
| _version_ | 1811334145405616128 |
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| author | Dafa Ding Huijuan Yong Na You Wei Lu Xu Yang Xu Yang Xu Yang Xiaolong Ye Yayun Wang Tingting Cai Xiaoling Zheng Hui Chen Bota Cui Faming Zhang Xingyin Liu Jian-Hua Mao Jian-Hua Mao Yibing Lu Hang Chang Hang Chang |
| author_facet | Dafa Ding Huijuan Yong Na You Wei Lu Xu Yang Xu Yang Xu Yang Xiaolong Ye Yayun Wang Tingting Cai Xiaoling Zheng Hui Chen Bota Cui Faming Zhang Xingyin Liu Jian-Hua Mao Jian-Hua Mao Yibing Lu Hang Chang Hang Chang |
| author_sort | Dafa Ding |
| collection | DOAJ |
| description | BackgroundIncreasing 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.MethodsWe 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.ResultsWe 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.ConclusionOur 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. |
| first_indexed | 2024-04-13T17:03:29Z |
| format | Article |
| id | doaj.art-a0b836b0aabd431e8fba8c5e4e6a4733 |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-04-13T17:03:29Z |
| publishDate | 2022-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-a0b836b0aabd431e8fba8c5e4e6a47332022-12-22T02:38:33ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882022-03-011210.3389/fcimb.2022.820367820367Prospective Study Reveals Host Microbial Determinants of Clinical Response to Fecal Microbiota Transplant Therapy in Type 2 Diabetes PatientsDafa Ding0Huijuan Yong1Na You2Wei Lu3Xu Yang4Xu Yang5Xu Yang6Xiaolong Ye7Yayun Wang8Tingting Cai9Xiaoling Zheng10Hui Chen11Bota Cui12Faming Zhang13Xingyin Liu14Jian-Hua Mao15Jian-Hua Mao16Yibing Lu17Hang Chang18Hang Chang19Department of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaKey Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, ChinaBiological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA, United StatesBiomedical Data Science Center, Lawrence Berkeley National Laboratory, Berkeley, CA, United StatesDepartment of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaMedical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaMedical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Pathogen Biology-Microbiology Division, Key Laboratory of Pathogen of Jiangsu Province, Nanjing Medical University, Nanjing, ChinaBiological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA, United StatesBiomedical Data Science Center, Lawrence Berkeley National Laboratory, Berkeley, CA, United StatesDepartment of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaBiological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA, United StatesBiomedical Data Science Center, Lawrence Berkeley National Laboratory, Berkeley, CA, United StatesBackgroundIncreasing 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.MethodsWe 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.ResultsWe 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.ConclusionOur 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.https://www.frontiersin.org/articles/10.3389/fcimb.2022.820367/fullfecal microbiota transplantationtype 2 diabetes mellitustherapeutic biomarkerprospective cohort studygut microbiome |
| spellingShingle | Dafa Ding Huijuan Yong Na You Wei Lu Xu Yang Xu Yang Xu Yang Xiaolong Ye Yayun Wang Tingting Cai Xiaoling Zheng Hui Chen Bota Cui Faming Zhang Xingyin Liu Jian-Hua Mao Jian-Hua Mao Yibing Lu Hang Chang Hang Chang Prospective Study Reveals Host Microbial Determinants of Clinical Response to Fecal Microbiota Transplant Therapy in Type 2 Diabetes Patients Frontiers in Cellular and Infection Microbiology fecal microbiota transplantation type 2 diabetes mellitus therapeutic biomarker prospective cohort study gut microbiome |
| title | Prospective Study Reveals Host Microbial Determinants of Clinical Response to Fecal Microbiota Transplant Therapy in Type 2 Diabetes Patients |
| title_full | Prospective Study Reveals Host Microbial Determinants of Clinical Response to Fecal Microbiota Transplant Therapy in Type 2 Diabetes Patients |
| title_fullStr | Prospective Study Reveals Host Microbial Determinants of Clinical Response to Fecal Microbiota Transplant Therapy in Type 2 Diabetes Patients |
| title_full_unstemmed | Prospective Study Reveals Host Microbial Determinants of Clinical Response to Fecal Microbiota Transplant Therapy in Type 2 Diabetes Patients |
| title_short | Prospective Study Reveals Host Microbial Determinants of Clinical Response to Fecal Microbiota Transplant Therapy in Type 2 Diabetes Patients |
| title_sort | prospective study reveals host microbial determinants of clinical response to fecal microbiota transplant therapy in type 2 diabetes patients |
| topic | fecal microbiota transplantation type 2 diabetes mellitus therapeutic biomarker prospective cohort study gut microbiome |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2022.820367/full |
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