Gut-Derived Endotoxin and Telomere Length Attrition in Adults with and without Type 2 Diabetes
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
Affiliations
Nasser M. Al-Daghri
Chair for Biomarkers of Chronic Diseases, Biochemistry Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia
Saba Abdi
Chair for Biomarkers of Chronic Diseases, Biochemistry Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia
Shaun Sabico
Chair for Biomarkers of Chronic Diseases, Biochemistry Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia
Abdullah M. Alnaami
Chair for Biomarkers of Chronic Diseases, Biochemistry Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia
Kaiser A. Wani
Chair for Biomarkers of Chronic Diseases, Biochemistry Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia
Mohammed G. A. Ansari
Chair for Biomarkers of Chronic Diseases, Biochemistry Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia
Malak Nawaz Khan Khattak
Chair for Biomarkers of Chronic Diseases, Biochemistry Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia
Nasiruddin Khan
Department of Food Science and Human Nutrition, College of Applied and Health Sciences, A’Sharqiyah University, Ibra 400, Oman
Gyanendra Tripathi
Human Sciences Research Centre, School of Human Sciences, University of Derby, Derby DE22 1GB, UK
George P. Chrousos
University Research Institute of Maternal and Child Health and Precision Medicine, UNESCO Chair on Adolescent Health Care, National and Kapodistrian University of Athens, 11527 Athens, Greece
Philip G. McTernan
Department of Biosciences, School of Science and Technology, Nottingham Trent University, Nottingham NG1 8NS, UK
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: n = 387) and without (non-diabetic (ND) controls: n = 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, p = 0.01) was inversely associated with TL, noting that endotoxin and triglycerides predicted 18% of the variance perceived in TL (p p = 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.
