Lactobacillus johnsonii N6.2 improves glycemia and reduces diabetes-induced organ injury in db/db mice

Jul 16, 2026

Diabetes mellitus is a complex metabolic disorder marked by hyperglycemia and multiple comorbidities, including liver, kidney, and nervous system dysfunction, alongside frequent microbiota alterations. Using a db/db mouse model of type 2 diabetes, the study evaluates Lactobacillus johnsonii N6.2, including metabolomics of liver tissue, RNA-seq with qRT-PCR validation, and hepatocyte lipid testing with extracellular vesicles. Treatment improves glycemic levels and reduces diabetes-related pancreatic, liver, and kidney injury, with biomarker signatures implicating vitamin K pathway modulation, increased FGF21, and shifts in circadian genes.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages16

Reading Time40 min

Abstract

Introduction

Background on diabetes and comorbidities

Role of microbiota and probiotics

Prior evidence and study rationale

Journal of Endocrinology (2025) 267 e250184 [https://doi.org/10.1530/JOE-25-0184](https://doi.org/10.1530/JOE-25-0184) RESEARCH Received 12 May 2025 Accepted 30 September 2025 Available online 3 October 2025 Version of Record published 21 October 2025 | Lactobacillus johnsonii N6.2 improves glycemia and reduces diabetes-induced organ injury in the db/db mice model Monica F Torrez Lamberti􀀁1, Sharon Thompson1, Natalie A Harrison1, Christopher L Gardner1, Danilo R da Silva1, Leandro D Teixeira1, Kanthi Kiran Kondepudi1,2, Claudio F Gonzalez1, Sasanka S Chukkapalli3,4 and Graciela L Lorca􀀁1 1Department of Microbiology and Cell Science, Genetics Institute, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, USA 2Food and Nutrition Biotechnology Division, National Agri-Food and Biomanufacturing Institute (BRIC-NABI), S. A. S. Nagar, Mohali, Punjab, India 3Department of Biomedical Engineering, Texas A&M University, College Station, Texas, USA 4Department of Oral Biology, University of Florida, Gainesville, USA Correspondence should be addressed to G L Lorca: glorca@uﬂ.edu | | --- | | Abstract Diabetes mellitus is a complex metabolic disorder characterized by hyperglycemia and the associated comorbidities. Type 2 diabetes is also associated with the 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 the 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 and 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. Keywords: Lactobacillus johnsonii N6 . 2; probiotics; db/db mice; diabetes type 2; human HepG2 cell line; extracellular vesicles | Introduction Diabetes mellitus (DM) is a complex metabolic disorder that branches into two main types, diabetes mellitus type 1 (T1D) and diabetes mellitus type 2 (T2D) . According to the Centers for Disease Control and Prevention (CDC), 38.4 million people have diabetes in the United States (11.6%), and a total of 97.6 million people aged 18 years or older have prediabetes (38% of the adult US population) (1). The main symptom of diabetes is hyperglycemia; however, broader impacts are linked to the associated comorbidities, such as vascular and non-vascular complications in both T1D and T2D (2) . T2D is also associated with increased occurrence of cancer, infections, liver disease, mental and nervous system disorders, coronary heart disease and strokes (3) . Obesity is among the risk factors for developing T2D, with one-third of obese individuals developing T2D (4) . According to the World Health Organization (WHO), the prevalence of obesity has increased to 1 in 8 worldwide, Published by Bioscientiﬁca Ltd. [https://joe.bioscienti](https://joe.bioscienti)ﬁ[ca.com](ca.com) © 2025 the author(s) M F Torrez Lamberti et al. Journal of Endocrinology (2025) 267 e250184 [https://doi.org/10.1530/JOE-25-0184](https://doi.org/10.1530/JOE-25-0184) where adult o

FAQs

What is the main goal of administering Lactobacillus johnsonii N6.2 in this study?

To assess whether the probiotic improves glycemic control and reduces organ injury associated with type 2 diabetes in the db/db mouse model.

Which experimental approaches are used to evaluate metabolic and molecular effects?

The study uses liver metabolomics, RNA-seq from liver and visceral adipose tissue with qRT-PCR validation, and additional assessment of hepatocyte lipid accumulation using probiotic extracellular vesicles.

What biomarkers and pathways were identified to explain Lactobacillus johnsonii N6.2 activity?

Analyses indicated modulation of the vitamin K pathway, upregulation of FGF21, and alterations in selected circadian genes.

Jul 16, 2026

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