Porphyromonas gingivalis induces entero-hepatic metabolic derangements with alteration of gut microbiota in a type 2 diabetes mouse model

Abstract Periodontal infection is thought to generate systemic inflammation, thus aggravating diabetes. Furthermore, orally administered periodontal pathogens may directly alter the gut microbiota. To elucidate this, using an obese db/db diabetes mice, orally treated with Porphyromonas gingivalis ( Pg ), we screened for Pg -specific peptides in intestinal fecal specimens and examined whether Pg localization affected the intestinal microbiota profile altering gut metabolite levels. Finally, we screened whether deterioration of fasting hyperglycemia was related to changes in intrahepatic glucose metabolism, using proteome and metabolome analyses. As results; (1) Oral Pg treatment aggravated both fasting and postprandial hyperglycemia ( P < 0.05) with a significant ( P < 0.01) increase in dental alveolar bone resorption. (2) Pg -specific peptides were identified in fecal specimens after oral Pg treatment and intestinal Pg profoundly altered gut microbiome profiles at the phylum, family, and genus levels. Prevotella showed the largest increase in abundance. Furthermore, Pg -treatment significantly altered intestinal metabolite levels. (3) Fasting hyperglycemia was associated with increases in gluconeogenesis-related enzyme and metabolite levels without changes in proinflammatory cytokine expressions and insulin resistance. This work reveals that oral Pg administration induced gut microbiota changes, leading to entero-hepatic metabolic derangements, thereby aggravating hyperglycemia in an obese type 2 diabetes mouse model.