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Role of an unclassified Lachnospiraceae in the pathogenesis of type 2 diabetes: a longitudinal study of the urine microbiome and metabolites

Recent investigations have revealed that the human microbiome plays an essential role in the occurrence of type 2 diabetes (T2D). However, despite the importance of understanding the involvement of the microbiota throughout the body in T2D, most studies have focused specifically on the intestinal mi...

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Autores principales: Kim, Kangjin, Lee, Sanghun, Park, Sang-Chul, Kim, Nam-Eun, Shin, Chol, Lee, Seung Ku, Jung, Youngae, Yoon, Dankyu, Kim, Hyeonjeong, Kim, Sanghyun, Hwang, Geum-Sook, Won, Sungho
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9440228/
https://www.ncbi.nlm.nih.gov/pubmed/35931735
http://dx.doi.org/10.1038/s12276-022-00816-x
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author Kim, Kangjin
Lee, Sanghun
Park, Sang-Chul
Kim, Nam-Eun
Shin, Chol
Lee, Seung Ku
Jung, Youngae
Yoon, Dankyu
Kim, Hyeonjeong
Kim, Sanghyun
Hwang, Geum-Sook
Won, Sungho
author_facet Kim, Kangjin
Lee, Sanghun
Park, Sang-Chul
Kim, Nam-Eun
Shin, Chol
Lee, Seung Ku
Jung, Youngae
Yoon, Dankyu
Kim, Hyeonjeong
Kim, Sanghyun
Hwang, Geum-Sook
Won, Sungho
author_sort Kim, Kangjin
collection PubMed
description Recent investigations have revealed that the human microbiome plays an essential role in the occurrence of type 2 diabetes (T2D). However, despite the importance of understanding the involvement of the microbiota throughout the body in T2D, most studies have focused specifically on the intestinal microbiota. Extracellular vesicles (EVs) have been recently found to provide important evidence regarding the mechanisms of T2D pathogenesis, as they act as key messengers between intestinal microorganisms and the host. Herein, we explored microorganisms potentially associated with T2D by tracking changes in microbiota-derived EVs from patient urine samples collected three times over four years. Mendelian randomization analysis was conducted to evaluate the causal relationships among microbial organisms, metabolites, and clinical measurements to provide a comprehensive view of how microbiota can influence T2D. We also analyzed EV-derived metagenomic (N = 393), clinical (N = 5032), genomic (N = 8842), and metabolite (N = 574) data from a prospective longitudinal Korean community-based cohort. Our data revealed that GU174097_g, an unclassified Lachnospiraceae, was associated with T2D (β = −189.13; p = 0.00006), and it was associated with the ketone bodies acetoacetate and 3-hydroxybutyrate (r = −0.0938 and −0.0829, respectively; p = 0.0022 and 0.0069, respectively). Furthermore, a causal relationship was identified between acetoacetate and HbA1c levels (β = 0.0002; p = 0.0154). GU174097_g reduced ketone body levels, thus decreasing HbA1c levels and the risk of T2D. Taken together, our findings indicate that GU174097_g may lower the risk of T2D by reducing ketone body levels.
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spelling pubmed-94402282022-09-16 Role of an unclassified Lachnospiraceae in the pathogenesis of type 2 diabetes: a longitudinal study of the urine microbiome and metabolites Kim, Kangjin Lee, Sanghun Park, Sang-Chul Kim, Nam-Eun Shin, Chol Lee, Seung Ku Jung, Youngae Yoon, Dankyu Kim, Hyeonjeong Kim, Sanghyun Hwang, Geum-Sook Won, Sungho Exp Mol Med Article Recent investigations have revealed that the human microbiome plays an essential role in the occurrence of type 2 diabetes (T2D). However, despite the importance of understanding the involvement of the microbiota throughout the body in T2D, most studies have focused specifically on the intestinal microbiota. Extracellular vesicles (EVs) have been recently found to provide important evidence regarding the mechanisms of T2D pathogenesis, as they act as key messengers between intestinal microorganisms and the host. Herein, we explored microorganisms potentially associated with T2D by tracking changes in microbiota-derived EVs from patient urine samples collected three times over four years. Mendelian randomization analysis was conducted to evaluate the causal relationships among microbial organisms, metabolites, and clinical measurements to provide a comprehensive view of how microbiota can influence T2D. We also analyzed EV-derived metagenomic (N = 393), clinical (N = 5032), genomic (N = 8842), and metabolite (N = 574) data from a prospective longitudinal Korean community-based cohort. Our data revealed that GU174097_g, an unclassified Lachnospiraceae, was associated with T2D (β = −189.13; p = 0.00006), and it was associated with the ketone bodies acetoacetate and 3-hydroxybutyrate (r = −0.0938 and −0.0829, respectively; p = 0.0022 and 0.0069, respectively). Furthermore, a causal relationship was identified between acetoacetate and HbA1c levels (β = 0.0002; p = 0.0154). GU174097_g reduced ketone body levels, thus decreasing HbA1c levels and the risk of T2D. Taken together, our findings indicate that GU174097_g may lower the risk of T2D by reducing ketone body levels. Nature Publishing Group UK 2022-08-05 /pmc/articles/PMC9440228/ /pubmed/35931735 http://dx.doi.org/10.1038/s12276-022-00816-x Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Kim, Kangjin
Lee, Sanghun
Park, Sang-Chul
Kim, Nam-Eun
Shin, Chol
Lee, Seung Ku
Jung, Youngae
Yoon, Dankyu
Kim, Hyeonjeong
Kim, Sanghyun
Hwang, Geum-Sook
Won, Sungho
Role of an unclassified Lachnospiraceae in the pathogenesis of type 2 diabetes: a longitudinal study of the urine microbiome and metabolites
title Role of an unclassified Lachnospiraceae in the pathogenesis of type 2 diabetes: a longitudinal study of the urine microbiome and metabolites
title_full Role of an unclassified Lachnospiraceae in the pathogenesis of type 2 diabetes: a longitudinal study of the urine microbiome and metabolites
title_fullStr Role of an unclassified Lachnospiraceae in the pathogenesis of type 2 diabetes: a longitudinal study of the urine microbiome and metabolites
title_full_unstemmed Role of an unclassified Lachnospiraceae in the pathogenesis of type 2 diabetes: a longitudinal study of the urine microbiome and metabolites
title_short Role of an unclassified Lachnospiraceae in the pathogenesis of type 2 diabetes: a longitudinal study of the urine microbiome and metabolites
title_sort role of an unclassified lachnospiraceae in the pathogenesis of type 2 diabetes: a longitudinal study of the urine microbiome and metabolites
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9440228/
https://www.ncbi.nlm.nih.gov/pubmed/35931735
http://dx.doi.org/10.1038/s12276-022-00816-x
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