Probiotics of Lacticaseibacillus paracasei SD1 and Lacticaseibacillus rhamnosus SD11 attenuate inflammation and β-cell death in streptozotocin-induced type 1 diabetic mice

Abstract

Probiotics provide health benefits in various aspects and are believed to modulate the immune system by balancing gut microbiota homeostasis, termed the “microbiota-immune axis”. Recent evidence supports that several Lactobacillus strains possess glucose-lowering and anti-inflammatory effects in an animal model of type 1 diabetes (T1D). Although probiotics of Lacticaseibacillus paracasei SD1 (SD1) and Lacticaseibacillus rhamnosus SD11 (SD11) exert human oral health benefits by reducing harmful bacterial populations, their clinical application regarding hypoglycemic-related traits as well as the underlying mechanisms are still lacking. In this report, we used multiple low doses of streptozotocin (STZ)-induced diabetic BALB/c mice to explore the effects of SD1 and SD11 supplementation on the regulation of markers related to T1D. Experimental mice were randomly assigned into five groups, non-STZ + V, STZ + V, STZ + SD1, STZ + SD11, and STZ + SDM (mixture of SD1 and SD11), and physiological data were measured every week. Blood and pancreas samples were collected at 4- and 8-weeks. Our results indicate that supplementation with SD1, SD11, or SDM for 8 weeks significantly improved body weights, glycemic levels, glucose tolerance, insulin levels, and lipid profiles. Probiotic administration also preserved islet integrity and increased β-cell mass in STZ-injected mice, as well as prevented infiltration of macrophages, CD4+, and CD8+ T cells into the islets. Significantly, SD1 and SD11 suppressed the levels of IL1-β, TNF-α and IFN-γ and increased IL-10, which is concomitant with the inhibition of cleaved caspase 3, caspase 9, caspase 8, proapoptotic Bax, NF-κBp65, pSTAT1, and iNOS. Additionally, the survival ability of β-cells was mediated by upregulated anti-apoptotic Bcl2. We conclude that SD1 and SD11 attenuate STZ-induced diabetic mice by stabilizing glycemic levels and reducing inflammation, thereby protecting β-cells. Among the probiotic treatment groups, SD11 revealed the best results in almost all parameters, indicating its potential use for alleviating hyperglycemia-associated symptoms.