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Distinct signatures of gut microbiota and metabolites in different types of diabetes: a population-based cross-sectional study
BACKGROUND: Patients with type 1 diabetes (T1D) and type 2 diabetes (T2D) present intestinal disturbances. Recent epidemiological data have showed that, worldwide, over half of newly diagnosed T1D patients were adults. However, the gut microbial alterations in adult-onset T1D are unclear. We aimed t...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10430172/ https://www.ncbi.nlm.nih.gov/pubmed/37593224 http://dx.doi.org/10.1016/j.eclinm.2023.102132 |
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author | Hu, Jingyi Ding, Jin Li, Xia Li, Jun Zheng, Tingting Xie, Lingxiang Li, Chenyu Tang, Yingxin Guo, Keyu Huang, Juan Liu, Shanshan Yan, Jianru Peng, Weijun Hou, Can Wen, Li Xu, Aimin Zhou, Zhiguang Xiao, Yang |
author_facet | Hu, Jingyi Ding, Jin Li, Xia Li, Jun Zheng, Tingting Xie, Lingxiang Li, Chenyu Tang, Yingxin Guo, Keyu Huang, Juan Liu, Shanshan Yan, Jianru Peng, Weijun Hou, Can Wen, Li Xu, Aimin Zhou, Zhiguang Xiao, Yang |
author_sort | Hu, Jingyi |
collection | PubMed |
description | BACKGROUND: Patients with type 1 diabetes (T1D) and type 2 diabetes (T2D) present intestinal disturbances. Recent epidemiological data have showed that, worldwide, over half of newly diagnosed T1D patients were adults. However, the gut microbial alterations in adult-onset T1D are unclear. We aimed to identify the signatures of gut microbiota and metabolites in patients with adult-onset T1D systematically, comparing with T2D patients and healthy controls (HCs). METHODS: This study enrolled 218 subjects from February 2019 to April 2022 (discovery cohort: 36 HCs, 51 patients with adult-onset T1D and 56 patients with T2D; validation cohort: 28 HCs, 27 patients with adult-onset T1D and 20 patients with T2D). Gut microbial profiles of the study subjects were investigated by metagenomic sequencing, and their faecal and serum metabolites were measured with targeted metabolomics. The study was registered on ClinicalTrials.gov (NCT05252728). FINDINGS: Patients with adult-onset T1D had significant differences in the composition of bacteria and their metabolites, characterized by notable depletion of short-chain fatty acid-producing bacteria, especially Eubacterium rectale. This was associated with a severe loss of phenolic acids and their derivatives, including gallic acid (associated with glucose metabolism) and 3,4-dihydroxyhydrocinnamic acid (linked with glucose metabolism and pancreatic beta cell autoimmunity). A predictive model based on six bacteria and six metabolites simultaneously discriminated adult-onset T1D from T2D and HCs with high accuracy. Interestingly, bacterial-viral or bacterial-fungal trans-kingdom relationships, especially positive correlations between bacteriophages and beneficial bacteria, were significantly reduced in adult-onset T1D compared to HCs. INTERPRETATION: Adult-onset T1D patients exhibit unique changes in host-microbiota-metabolite interactions. Gut microbiota and metabolite-based algorithms could be used as additional tools for differential diagnosis of different types of diabetes and beyond. FUNDING: 10.13039/501100012166National Key Research and Development Program of China, the 10.13039/501100001809National Natural Science Foundation of China. |
format | Online Article Text |
id | pubmed-10430172 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-104301722023-08-17 Distinct signatures of gut microbiota and metabolites in different types of diabetes: a population-based cross-sectional study Hu, Jingyi Ding, Jin Li, Xia Li, Jun Zheng, Tingting Xie, Lingxiang Li, Chenyu Tang, Yingxin Guo, Keyu Huang, Juan Liu, Shanshan Yan, Jianru Peng, Weijun Hou, Can Wen, Li Xu, Aimin Zhou, Zhiguang Xiao, Yang eClinicalMedicine Articles BACKGROUND: Patients with type 1 diabetes (T1D) and type 2 diabetes (T2D) present intestinal disturbances. Recent epidemiological data have showed that, worldwide, over half of newly diagnosed T1D patients were adults. However, the gut microbial alterations in adult-onset T1D are unclear. We aimed to identify the signatures of gut microbiota and metabolites in patients with adult-onset T1D systematically, comparing with T2D patients and healthy controls (HCs). METHODS: This study enrolled 218 subjects from February 2019 to April 2022 (discovery cohort: 36 HCs, 51 patients with adult-onset T1D and 56 patients with T2D; validation cohort: 28 HCs, 27 patients with adult-onset T1D and 20 patients with T2D). Gut microbial profiles of the study subjects were investigated by metagenomic sequencing, and their faecal and serum metabolites were measured with targeted metabolomics. The study was registered on ClinicalTrials.gov (NCT05252728). FINDINGS: Patients with adult-onset T1D had significant differences in the composition of bacteria and their metabolites, characterized by notable depletion of short-chain fatty acid-producing bacteria, especially Eubacterium rectale. This was associated with a severe loss of phenolic acids and their derivatives, including gallic acid (associated with glucose metabolism) and 3,4-dihydroxyhydrocinnamic acid (linked with glucose metabolism and pancreatic beta cell autoimmunity). A predictive model based on six bacteria and six metabolites simultaneously discriminated adult-onset T1D from T2D and HCs with high accuracy. Interestingly, bacterial-viral or bacterial-fungal trans-kingdom relationships, especially positive correlations between bacteriophages and beneficial bacteria, were significantly reduced in adult-onset T1D compared to HCs. INTERPRETATION: Adult-onset T1D patients exhibit unique changes in host-microbiota-metabolite interactions. Gut microbiota and metabolite-based algorithms could be used as additional tools for differential diagnosis of different types of diabetes and beyond. FUNDING: 10.13039/501100012166National Key Research and Development Program of China, the 10.13039/501100001809National Natural Science Foundation of China. Elsevier 2023-08-03 /pmc/articles/PMC10430172/ /pubmed/37593224 http://dx.doi.org/10.1016/j.eclinm.2023.102132 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Articles Hu, Jingyi Ding, Jin Li, Xia Li, Jun Zheng, Tingting Xie, Lingxiang Li, Chenyu Tang, Yingxin Guo, Keyu Huang, Juan Liu, Shanshan Yan, Jianru Peng, Weijun Hou, Can Wen, Li Xu, Aimin Zhou, Zhiguang Xiao, Yang Distinct signatures of gut microbiota and metabolites in different types of diabetes: a population-based cross-sectional study |
title | Distinct signatures of gut microbiota and metabolites in different types of diabetes: a population-based cross-sectional study |
title_full | Distinct signatures of gut microbiota and metabolites in different types of diabetes: a population-based cross-sectional study |
title_fullStr | Distinct signatures of gut microbiota and metabolites in different types of diabetes: a population-based cross-sectional study |
title_full_unstemmed | Distinct signatures of gut microbiota and metabolites in different types of diabetes: a population-based cross-sectional study |
title_short | Distinct signatures of gut microbiota and metabolites in different types of diabetes: a population-based cross-sectional study |
title_sort | distinct signatures of gut microbiota and metabolites in different types of diabetes: a population-based cross-sectional study |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10430172/ https://www.ncbi.nlm.nih.gov/pubmed/37593224 http://dx.doi.org/10.1016/j.eclinm.2023.102132 |
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