Lactobacillus johnsonii N6.2 Improves Glycemia, and Reduces Diabetes-induced Organ Injury in the db/db Mice Model.

Abstract

Diabetes mellitus is a complex metabolic disorder characterized by hyperglycemia as well as the associated comorbidities. Type 2 diabetes is also associated with dysfunction of liver, kidney and nervous system. In addition, an altered microbiota is frequently observed in subjects with Type 2 diabetes. In this study a db/db (diabetic) mouse model of Type 2 diabetes was used to elucidate the beneficial effects of the probiotic Lactobacillus johnsonii N6.2. To evaluate metabolic effects, we performed metabolomics on liver samples, and RNA-seq from liver and visceral adipose tissue, followed by qRT-PCR validation. Using L. johnsonii N6.2 extracellular vesicles we evaluated lipid accumulation in hepatocytes. Finally, the gut microbiome of db/db mice was profiled using 16S rRNA sequencing. We observed that administration of the probiotic improved glycemic levels and decreased diabetes scores, as well as Type 2 diabetes-associated injury to the pancreas, liver and kidneys. Liver metabolomic and transcriptome analyses identified biomarkers of L. johnsonii N6.2 activity, including modulation of the vitamin K pathway, upregulation of FGF21-, a key regulator of glucose and lipid metabolism, and alternations in selected circadian genes. This study elucidates the beneficial effects of L. johnsonii N6.2, against the common symptoms of type 2 diabetes, highlighting its potential as an adjuvant therapeutic agent.