Abstract

Type 1 autoimmune diabetes is an autoimmune disease characterized by specific destruction of pancreatic β-cells producing insulin. Recent studies have shown that gut microbiota and immunity are closely linked to systemic immunity, affecting the balance between pro-inflammatory and regulatory immune responses. Altered gut microbiota may be causally related to the development of immune-mediated diseases, and probiotics have been suggested to have modulatory effects on inflammatory diseases and immune disorders. We studied whether a probiotic combination that has immunomodulatory effects on several inflammatory diseases can reduce the incidence of diabetes in non-obese diabetic (NOD) mice, a classical animal model of human T1D. When Immune Regulation and Tolerance 5 (IRT5), a probiotic combination comprising Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus reuteri, Bifidobacterium bifidium, and Streptococcus thermophiles, was administered 6 times a week for 36 weeks to NOD mice, beginning at 4 weeks of age, the incidence of diabetes was significantly reduced. Insulitis score was also significantly reduced, and β-cell mass was conversely increased by IRT5 administration. IRT5 administration significantly reduced gut permeability in NOD mice. The proportion of total regulatory T cells was not changed by IRT5 administration; however, the proportion of CCR9+ regulatory T (Treg) cells expressing gut-homing receptor was significantly increased in pancreatic lymph nodes (PLNs) and lamina propria of the small intestine (SI-LP). Type 1 T helper (Th1) skewing was reduced in PLNs by IRT5 administration. IRT5 could be a candidate for an effective probiotic combination, which can be safely administered to inhibit or prevent type 1 diabetes (T1D).

Highlights

  • Type 1 autoimmune diabetes is a classical organ-specific autoimmune disease resulting from immune-mediated destruction of pancreatic β-cells producing insulin

  • Since Immune Regulation and Tolerance 5 (IRT5), a combination of 5 bacteria (Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus reuteri, Bifidobacterium bifidium, and Streptococcus thermophilus) has been shown to be effective against several autoimmune and inflammatory disorders [20, 21], we administered 5 × 108 cfu IRT5 to female non-obese diabetic (NOD) mice by oral gavage six times a week for 36 weeks beginning at 4 weeks of age and monitored blood glucose level

  • The incidence of diabetes was significantly reduced in NOD mice treated with IRT5 compared to control NOD mice treated with PBS (Figure 1A)

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Summary

Introduction

Type 1 autoimmune diabetes is a classical organ-specific autoimmune disease resulting from immune-mediated destruction of pancreatic β-cells producing insulin. Regarding specific microorganisms that can influence autoimmune diabetes, Lactobacillus johnsonii, Lactobacillus casei, Bacillus cereus, Akkermansia muciniphila, Segmented Filamentous Bacteria (SFB), a specific strain of Clostridium butyricum or probiotic comprising such bacteria have been reported to reduce the incidence of diabetes in NOD mice or BB rat, a rat model of autoimmune diabetes by modulating cytokine profile, Treg cells, Th cell polarization, or barrier function [5,6,7,8,9,10] Viruses, such as norovirus or lymphocytic choriomeningitis virus (LCMV) have been shown to inhibit the development of autoimmune diabetes in NOD mice [11, 12]

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