Amelioration of Autoimmune Diabetes of NOD Mice by Immunomodulating Probiotics

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).

Modification of Intestinal Microbiota Dysbiosis by Low-Dose Interleukin-2 in Dermatomyositis: A Post Hoc Analysis From a Clinical Trial Study

“…The microbial community of patients is always influenced by various environmental and clinical factors, such as demography, diet, complications, etc . Therefore, we chose the NOD mice, a model for autoimmune diseases ( Aoki et al., 2005 ; Kim et al., 2020 ), to better evaluate the influence of IL-2 treatment on gut microbiota. The Shannon and equitability indexes in each sample revealed that alpha diversity were changed after low-dose IL-2 therapy ( Supplementary Figure 2A ) .…”

Insights from Bacteroides Species in Children with Type 1 Diabetes

“…Several studies have reported the beneficial role of different Lactobacillus species on delaying the development of T1D or reducing its complications, using mice models [ 83 , 84 , 85 , 86 ]. In the current study the fecal samples of T1D children showed lower numbers of Lactobacillus spp.…”

Immunomodulatory Potential of Lactobacillus acidophilus: Implications in Bone Health

“…Conditioned media of LA inhibits IL-1β stimulated decrease in occludin and increase in claudin-1 expression and thus preserve intestinal permeability by normalizing the expression of occludin and claudin-1 [89]. Probiotic combination of LA, L. reuteri, L. casei, Streptococcus thermophiles and Bifidobacterium bifidum significantly reduced diabetes incidence and gut permeability [90]. Administration of probiotics LA and Bifidobacterium infantis to the pregnant women daily from embryonic day 15-to 2-week-old postnatally maintained the intestinal integrity of preweaned offspring.…”