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
- PubMed: 36261888
- DOI: 10.1080/19490976.2022.2136467
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
Supplement | Health Outcome | Effect Type | Effect Size |
---|---|---|---|
Lactiplantibacillus plantarum LP-01 | Delayed Onset of Type 1 Diabetes | Beneficial | Moderate |
Lactiplantibacillus plantarum LP-01 | Enhanced Antioxidant Defense | Beneficial | Moderate |
Lactiplantibacillus plantarum LP-01 | Improved Stress Response | Beneficial | Moderate |
Lactiplantibacillus plantarum LP-1 | Delayed Onset of Type 1 Diabetes | Beneficial | Moderate |
Lactiplantibacillus plantarum LP-1 | Enhanced Antioxidant Defense | Beneficial | Moderate |
Lactiplantibacillus plantarum LP-1 | Reduced ER Stress Responses in β-cells | Beneficial | Moderate |