Gut-Derived Endotoxin and Telomere Length Attrition in Adults with and without Type 2 Diabetes

Premature aging, as denoted by a reduced telomere length (TL), has been observed in several chronic inflammatory diseases, such as obesity and type 2 diabetes mellitus (T2DM). However, no study to date has addressed the potential inflammatory influence of the gut-derived Gram-negative bacterial frag...

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Autores principales:	Nasser M. Al-Daghri, Saba Abdi, Shaun Sabico, Abdullah M. Alnaami, Kaiser A. Wani, Mohammed G. A. Ansari, Malak Nawaz Khan Khattak, Nasiruddin Khan, Gyanendra Tripathi, George P. Chrousos, Philip G. McTernan
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	telomere length endotoxin inflammation type 2 diabetes mellitus Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/6e31841260c842c495cf189c79552959
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spelling	oai:doaj.org-article:6e31841260c842c495cf189c795529592021-11-25T16:53:53ZGut-Derived Endotoxin and Telomere Length Attrition in Adults with and without Type 2 Diabetes10.3390/biom111116932218-273Xhttps://doaj.org/article/6e31841260c842c495cf189c795529592021-11-01T00:00:00Zhttps://www.mdpi.com/2218-273X/11/11/1693https://doaj.org/toc/2218-273XPremature aging, as denoted by a reduced telomere length (TL), has been observed in several chronic inflammatory diseases, such as obesity and type 2 diabetes mellitus (T2DM). However, no study to date has addressed the potential inflammatory influence of the gut-derived Gram-negative bacterial fragments lipopolysaccharide, also referred to as endotoxin, and its influence on TL in low-grade inflammatory states such as type 2 diabetes mellitus (T2DM). The current study therefore investigated the influence of endotoxin and inflammatory factors on telomere length (TL) in adults with (T2DM: <i>n</i> = 387) and without (non-diabetic (ND) controls: <i>n</i> = 417) obesity and T2DM. Anthropometric characteristics were taken, and fasted blood samples were used to measure biomarkers, TL, and endotoxin. The findings from this study highlighted across all participants that circulating endotoxin (r = −0.17, <i>p</i> = 0.01) was inversely associated with TL, noting that endotoxin and triglycerides predicted 18% of the variance perceived in TL (<i>p</i> < 0.001). Further stratification of the participants according to T2DM status and sex highlighted that endotoxin significantly predicted 19% of the variance denoted in TL among male T2DM participants (<i>p</i> = 0.007), where TL was notably influenced. The influence on TL was not observed to be impacted by anti-T2DM medications, statins, or anti-hypertensive therapies. Taken together, these results show that TL attrition was inversely associated with circulating endotoxin levels independent of the presence of T2DM and other cardiometabolic factors, suggesting that low-grade chronic inflammation may trigger premature biological aging. The findings further highlight the clinical relevance of mitigating the levels of circulating endotoxin (e.g., manipulation of gut microbiome) not only for the prevention of chronic diseases but also to promote healthy aging.Nasser M. Al-DaghriSaba AbdiShaun SabicoAbdullah M. AlnaamiKaiser A. WaniMohammed G. A. AnsariMalak Nawaz Khan KhattakNasiruddin KhanGyanendra TripathiGeorge P. ChrousosPhilip G. McTernanMDPI AGarticletelomere lengthendotoxininflammationtype 2 diabetes mellitusMicrobiologyQR1-502ENBiomolecules, Vol 11, Iss 1693, p 1693 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	telomere length endotoxin inflammation type 2 diabetes mellitus Microbiology QR1-502
spellingShingle	telomere length endotoxin inflammation type 2 diabetes mellitus Microbiology QR1-502 Nasser M. Al-Daghri Saba Abdi Shaun Sabico Abdullah M. Alnaami Kaiser A. Wani Mohammed G. A. Ansari Malak Nawaz Khan Khattak Nasiruddin Khan Gyanendra Tripathi George P. Chrousos Philip G. McTernan Gut-Derived Endotoxin and Telomere Length Attrition in Adults with and without Type 2 Diabetes
description	Premature aging, as denoted by a reduced telomere length (TL), has been observed in several chronic inflammatory diseases, such as obesity and type 2 diabetes mellitus (T2DM). However, no study to date has addressed the potential inflammatory influence of the gut-derived Gram-negative bacterial fragments lipopolysaccharide, also referred to as endotoxin, and its influence on TL in low-grade inflammatory states such as type 2 diabetes mellitus (T2DM). The current study therefore investigated the influence of endotoxin and inflammatory factors on telomere length (TL) in adults with (T2DM: <i>n</i> = 387) and without (non-diabetic (ND) controls: <i>n</i> = 417) obesity and T2DM. Anthropometric characteristics were taken, and fasted blood samples were used to measure biomarkers, TL, and endotoxin. The findings from this study highlighted across all participants that circulating endotoxin (r = −0.17, <i>p</i> = 0.01) was inversely associated with TL, noting that endotoxin and triglycerides predicted 18% of the variance perceived in TL (<i>p</i> < 0.001). Further stratification of the participants according to T2DM status and sex highlighted that endotoxin significantly predicted 19% of the variance denoted in TL among male T2DM participants (<i>p</i> = 0.007), where TL was notably influenced. The influence on TL was not observed to be impacted by anti-T2DM medications, statins, or anti-hypertensive therapies. Taken together, these results show that TL attrition was inversely associated with circulating endotoxin levels independent of the presence of T2DM and other cardiometabolic factors, suggesting that low-grade chronic inflammation may trigger premature biological aging. The findings further highlight the clinical relevance of mitigating the levels of circulating endotoxin (e.g., manipulation of gut microbiome) not only for the prevention of chronic diseases but also to promote healthy aging.
format	article
author	Nasser M. Al-Daghri Saba Abdi Shaun Sabico Abdullah M. Alnaami Kaiser A. Wani Mohammed G. A. Ansari Malak Nawaz Khan Khattak Nasiruddin Khan Gyanendra Tripathi George P. Chrousos Philip G. McTernan
author_facet	Nasser M. Al-Daghri Saba Abdi Shaun Sabico Abdullah M. Alnaami Kaiser A. Wani Mohammed G. A. Ansari Malak Nawaz Khan Khattak Nasiruddin Khan Gyanendra Tripathi George P. Chrousos Philip G. McTernan
author_sort	Nasser M. Al-Daghri
title	Gut-Derived Endotoxin and Telomere Length Attrition in Adults with and without Type 2 Diabetes
title_short	Gut-Derived Endotoxin and Telomere Length Attrition in Adults with and without Type 2 Diabetes
title_full	Gut-Derived Endotoxin and Telomere Length Attrition in Adults with and without Type 2 Diabetes
title_fullStr	Gut-Derived Endotoxin and Telomere Length Attrition in Adults with and without Type 2 Diabetes
title_full_unstemmed	Gut-Derived Endotoxin and Telomere Length Attrition in Adults with and without Type 2 Diabetes
title_sort	gut-derived endotoxin and telomere length attrition in adults with and without type 2 diabetes
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/6e31841260c842c495cf189c79552959
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Gut-Derived Endotoxin and Telomere Length Attrition in Adults with and without Type 2 Diabetes

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