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

PLoS One. 2023 Apr 11;18(4):e0284303. doi: 10.1371/journal.pone.0284303. eCollection 2023.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Death
  • Diabetes Mellitus, Experimental* / drug therapy
  • Diabetes Mellitus, Type 1*
  • Glucose / therapeutic use
  • Humans
  • Inflammation
  • Lacticaseibacillus
  • Lacticaseibacillus paracasei*
  • Lacticaseibacillus rhamnosus*
  • Mice
  • Probiotics* / pharmacology
  • Streptozocin

Substances

  • Streptozocin
  • Glucose

Supplementary concepts

  • Syndactyly, Type I

Grants and funding

The authors declare no conflicts of interest. This research was financially supported by National Science, Research and Innovation Fund (NSRF) and Prince of Songkla University (Grant No. SCI6505115S) and received partial support from the Center of Excellence for Trace Analysis and Biosensor (TAB-CoE), Faculty of Science, Prince of Songkla University. 1. First and corresponding author: JN 2. Second author: PK 3. Third author: SP 4. Forth author: RT JN has received research grants from National Science, Research and Innovation Fund (NSRF) and Prince of Songkla University (Grant No. SCI6505115S) as principal investigator and partial support from the Center of Excellence for Trace Analysis and Biosensor (TAB-CoE), Faculty of Science, Prince of Songkla University. PK, SP, and RT have received research grant from National Science, Research and Innovation Fund (NSRF) and Prince of Songkla University (Grant No. SCI6505115S) as co-investigators. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.