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Lactiplantibacillus plantarum 299v supplementation modulates β-cell ER stress and antioxidative defense pathways and prevents type 1 diabetes in gluten-free BioBreeding rats

  • 2022-10-19
  • Gut Microbes 14(1)
    • Pinar Sargin
    • Mark F. Roethle
    • S. Jia
    • Tarun Pant
    • Ashley E. Ciecko
    • Samantha Atkinson
    • N. Salzman
    • R. Teng
    • Yi-Guang Chen
    • S. Cabrera
    • M. Hessner

Abstract

The increasing incidence of Type 1 diabetes has coincided with the emergence of the low-fiber, high-gluten Western diet and other environmental factors linked to dysbiosis. Since Lactiplantibacillus plantarum 299 v (Lp299v) supplementation improves gut barrier function and reduces systemic inflammation, we studied its effects in spontaneously diabetic DR_lyp/lyp_ rats provided a normal cereal diet (ND) or a gluten-free hydrolyzed casein diet (HCD). All rats provided ND developed diabetes (62.5±7.7 days); combining ND with Lp299v did not improve survival. Diabetes was delayed by HCD (72.2±9.4 days, p = .01) and further delayed by HCD+Lp299v (84.9±14.3 days, p < .001). HCD+Lp299v pups exhibited increased plasma propionate and butyrate levels, which correlated with enriched fecal Bifidobacteriaceae and Clostridiales taxa. Islet transcriptomic and histologic analyses at 40-days of age revealed that rats fed HCD expressed an autophagy profile, while those provided HCD+Lp299v expressed ER-associated protein degradation (ERAD) and antioxidative defense pathways, including Nrf2. Exposing insulinoma cells to propionate and butyrate promoted the antioxidative defense response but did not recapitulate the HCD+Lp299v islet ERAD transcriptomic profile. Here, both diet and microbiota influenced diabetes susceptibility. Moreover, Lp299v supplement modulated antioxidative defense and ER stress responses in β-cells, potentially offering a new therapeutic direction to thwart diabetes progression and preserve insulin secretion.

Keywords: Lactiplantibacillus plantarum; Nrf2; Type 1 diabetes; antioxidative defense; beta cell; endoplasmic reticulum stress; probiotic supplement; unfolded protein response.

Research Insights

SupplementHealth OutcomeEffect TypeEffect Size
Lactiplantibacillus plantarum LP-01Delayed Onset of Type 1 DiabetesBeneficial
Moderate
Lactiplantibacillus plantarum LP-01Enhanced Antioxidant DefenseBeneficial
Moderate
Lactiplantibacillus plantarum LP-01Improved Stress ResponseBeneficial
Moderate
Lactiplantibacillus plantarum LP-1Delayed Onset of Type 1 DiabetesBeneficial
Moderate
Lactiplantibacillus plantarum LP-1Enhanced Antioxidant DefenseBeneficial
Moderate
Lactiplantibacillus plantarum LP-1Reduced ER Stress Responses in β-cellsBeneficial
Moderate

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