Dietary advanced glycation end-products elicit toxicological effects by disrupting gut microbiome and immune homeostasis

Abstract

The aging immune system is characterized by a low-grade chronic systemic inflammatory state (“inflammaging”) marked by elevated serum levels of inflammatory molecules such as interleukin (IL)-6 and C-reactive protein (CRP). These inflammatory markers were also reported to be strong predictors for the development/severity of Type 2 diabetes, obesity, and COVID-19. The levels of these markers have been positively associated with those of advanced glycation end-products (AGEs) generated via non-enzymatic glycation and oxidation of proteins and lipids during normal aging and metabolism. Based on the above observations, it is clinically important to elucidate how dietary AGEs modulate inflammation and might thus increase the risk for aging-exacerbated diseases. The present narrative review discusses the potential pro-inflammatory properties of dietary AGEs with a focus on the inflammatory mediators CRP, IL-6 and ferritin, and their relations to aging in general and Type 2 diabetes in particular. In addition, underlying mechanisms – including those related to gut microbiota and the receptors for AGEs, and the roles AGEs might play in affecting physiologies of the healthy elderly, obese individuals, and diabetics are discussed in regard to any greater susceptibility to COVID-19.

Keywords:

• Advanced glycation end-products
• inflammation
• aging
• Type 2 diabetes
• gut microbiome

Acknowledgments

The authors greatly appreciate Dr. Steven D. Holladay (Department Head, Professor, Department of Veterinary Biomedical Sciences at the University of Georgia) for his critical comments.

Disclosure statement

The authors declare no conflicts of interest. The authors alone are responsible for the content of this manuscript.

Additional information

Funding

This work was supported by grants from the National Institutes of Health [NIH R41DK121553, NIH R41AT009523, R21ES24487] and USDA National Institute of Food and Agriculture [2016-67021-24994] (project accession no. 1009090).