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

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 DRlyp/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.

• Authors: Pinar Sargin, Mark F Roethle, Shuang Jia, Tarun Pant, Ashley E Ciecko, Samantha N Atkinson, Nita H Salzman, Ru-Jeng Teng, Yi-Guang Chen, Susanne M Cabrera, Martin J Hessner
• Journal: Gut microbes (Gut Microbes) 2022 Jan-Dec Vol. 14 Issue 1 Pg. 2136467 ISSN: 1949-0984 [Electronic] United States
• PMID: 36261888 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural)

Chemical References

• NF-E2-Related Factor 2
• Antioxidants
• Caseins
• Propionates
• Butyrates

Topics

• Rats
• Animals
• Diabetes Mellitus, Type 1 (prevention & control, metabolism)
• Lactobacillus plantarum
• NF-E2-Related Factor 2
• Antioxidants
• Caseins
• Propionates
• Gastrointestinal Microbiome
• Dietary Supplements
• Butyrates