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Gut microbiota and type 1 diabetes: a two-sample bidirectional Mendelian randomization study
OBJECTIVE: The real causal relationship between human gut microbiota and T1D remains unclear and difficult to establish. Herein, we adopted a two-sample bidirectional mendelian randomization (MR) study to evaluate the causality between gut microbiota and T1D. METHODS: We leveraged publicly available...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10258312/ https://www.ncbi.nlm.nih.gov/pubmed/37313342 http://dx.doi.org/10.3389/fcimb.2023.1163898 |
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author | Luo, Manjun Sun, Mengting Wang, Tingting Zhang, Senmao Song, Xinli Liu, Xiaoying Wei, Jianhui Chen, Qian Zhong, Taowei Qin, Jiabi |
author_facet | Luo, Manjun Sun, Mengting Wang, Tingting Zhang, Senmao Song, Xinli Liu, Xiaoying Wei, Jianhui Chen, Qian Zhong, Taowei Qin, Jiabi |
author_sort | Luo, Manjun |
collection | PubMed |
description | OBJECTIVE: The real causal relationship between human gut microbiota and T1D remains unclear and difficult to establish. Herein, we adopted a two-sample bidirectional mendelian randomization (MR) study to evaluate the causality between gut microbiota and T1D. METHODS: We leveraged publicly available genome-wide association study (GWAS) summary data to perform MR analysis. The gut microbiota-related GWAS data from 18,340 individuals from the international consortium MiBioGen were used. The summary statistic data for T1D (n = 264,137) were obtained from the latest release from the FinnGen consortium as the outcome of interest. The selection of instrumental variables conformed strictly to a series of preset inclusion and exclusion criteria. MR-Egger, weighted median, inverse variance weighted (IVW), and weighted mode methods were used to assess the causal association. The Cochran’s Q test, MR-Egger intercept test, and leave-one-out analysis were conducted to identify heterogeneity and pleiotropy. RESULTS: At the phylum level, only Bacteroidetes was indicated to have causality on T1D (OR = 1.24, 95% CI = 1.01-1.53, P = 0.044) in the IVW analysis. When it comes to their subcategories, Bacteroidia class (OR = 1.28, 95% CI = 1.06-1.53, P = 0.009, P (FDR) = 0.085), Bacteroidales order (OR = 1.28, 95% CI = 1.06-1.53, P = 0.009, P (FDR) = 0.085), and Eubacterium eligens group genus (OR = 0.64, 95% CI = 0.50-0.81, P = 2.84×10(-4), P (FDR) = 0.031) were observed to have a causal relationship with T1D in the IVW analysis. No heterogeneity and pleiotropy were detected. CONCLUSIONS: The present study reports that Bacteroidetes phylum, Bacteroidia class, and Bacteroidales order causally increase T1D risk, whereas Eubacterium eligens group genus, which belongs to the Firmicutes phylum, causally decreases T1D risk. Nevertheless, future studies are warranted to dissect the underlying mechanisms of specific bacterial taxa’s role in the pathophysiology of T1D. |
format | Online Article Text |
id | pubmed-10258312 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-102583122023-06-13 Gut microbiota and type 1 diabetes: a two-sample bidirectional Mendelian randomization study Luo, Manjun Sun, Mengting Wang, Tingting Zhang, Senmao Song, Xinli Liu, Xiaoying Wei, Jianhui Chen, Qian Zhong, Taowei Qin, Jiabi Front Cell Infect Microbiol Cellular and Infection Microbiology OBJECTIVE: The real causal relationship between human gut microbiota and T1D remains unclear and difficult to establish. Herein, we adopted a two-sample bidirectional mendelian randomization (MR) study to evaluate the causality between gut microbiota and T1D. METHODS: We leveraged publicly available genome-wide association study (GWAS) summary data to perform MR analysis. The gut microbiota-related GWAS data from 18,340 individuals from the international consortium MiBioGen were used. The summary statistic data for T1D (n = 264,137) were obtained from the latest release from the FinnGen consortium as the outcome of interest. The selection of instrumental variables conformed strictly to a series of preset inclusion and exclusion criteria. MR-Egger, weighted median, inverse variance weighted (IVW), and weighted mode methods were used to assess the causal association. The Cochran’s Q test, MR-Egger intercept test, and leave-one-out analysis were conducted to identify heterogeneity and pleiotropy. RESULTS: At the phylum level, only Bacteroidetes was indicated to have causality on T1D (OR = 1.24, 95% CI = 1.01-1.53, P = 0.044) in the IVW analysis. When it comes to their subcategories, Bacteroidia class (OR = 1.28, 95% CI = 1.06-1.53, P = 0.009, P (FDR) = 0.085), Bacteroidales order (OR = 1.28, 95% CI = 1.06-1.53, P = 0.009, P (FDR) = 0.085), and Eubacterium eligens group genus (OR = 0.64, 95% CI = 0.50-0.81, P = 2.84×10(-4), P (FDR) = 0.031) were observed to have a causal relationship with T1D in the IVW analysis. No heterogeneity and pleiotropy were detected. CONCLUSIONS: The present study reports that Bacteroidetes phylum, Bacteroidia class, and Bacteroidales order causally increase T1D risk, whereas Eubacterium eligens group genus, which belongs to the Firmicutes phylum, causally decreases T1D risk. Nevertheless, future studies are warranted to dissect the underlying mechanisms of specific bacterial taxa’s role in the pathophysiology of T1D. Frontiers Media S.A. 2023-05-29 /pmc/articles/PMC10258312/ /pubmed/37313342 http://dx.doi.org/10.3389/fcimb.2023.1163898 Text en Copyright © 2023 Luo, Sun, Wang, Zhang, Song, Liu, Wei, Chen, Zhong and Qin https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cellular and Infection Microbiology Luo, Manjun Sun, Mengting Wang, Tingting Zhang, Senmao Song, Xinli Liu, Xiaoying Wei, Jianhui Chen, Qian Zhong, Taowei Qin, Jiabi Gut microbiota and type 1 diabetes: a two-sample bidirectional Mendelian randomization study |
title | Gut microbiota and type 1 diabetes: a two-sample bidirectional Mendelian randomization study |
title_full | Gut microbiota and type 1 diabetes: a two-sample bidirectional Mendelian randomization study |
title_fullStr | Gut microbiota and type 1 diabetes: a two-sample bidirectional Mendelian randomization study |
title_full_unstemmed | Gut microbiota and type 1 diabetes: a two-sample bidirectional Mendelian randomization study |
title_short | Gut microbiota and type 1 diabetes: a two-sample bidirectional Mendelian randomization study |
title_sort | gut microbiota and type 1 diabetes: a two-sample bidirectional mendelian randomization study |
topic | Cellular and Infection Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10258312/ https://www.ncbi.nlm.nih.gov/pubmed/37313342 http://dx.doi.org/10.3389/fcimb.2023.1163898 |
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