Chronic oral exposure to glycated whey proteins increases survival of aged male NOD mice with autoimmune prostatitis by regulating the gut microbiome and anti-inflammatory responses

Abstract

Glycated whey proteins have been shown to be protective against type 1 diabetes in our previous studies, suggesting their potential application as medical food. To determine if the protection could be extended to other autoimmune diseases, aged male non-obese diabetic (NOD) mice that develop a wide spectrum of autoimmune pathologies, including spontaneous autoimmune prostatitis, were used. After a 6-month oral exposure to whey protein-derived early glycation products (EGPs), EGP-treated NOD mice had an increased survival rate, decreased macrophage infiltration in the anterior lobe and decreased inflammation in the prostate when compared to the mice that received non-reacted controls. The systemic immunity was regulated towards anti-inflammation, evidenced by an increase in serum IL-10 level and decreases in total splenocytes, splenic M1 macrophages, CD4⁺ T cells, CD8⁺ T cells and B cells. Consistent with an overall anti-inflammatory status, the gut microbiome was altered in abundance but not diversity, with increased Allobaculum, Anaerostipes, Bacteroides, Parabacteroides and Prevotella and decreased Adlercreutzia and Roseburia at the genus level. Moreover, increased Bacteroides acidifaciens correlated with most of the immune parameters measured. Collectively, chronic oral exposure to EGPs produced an anti-inflammatory effect in aged male NOD mice, which might contribute to the protective effects against spontaneous autoimmune prostatitis and/or other organ specific autoimmune diseases.