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)
Summary
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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