Lactiplantibacillus plantarum 299v supplementation modulates β-cell ER stress and antioxidative defense pathways and prevents type 1 diabetes in gluten-free BioBreeding rats
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
Affiliations
Pinar Sargin
The Max McGee Research Center for Juvenile Diabetes, Children’s Research Institute of Children’s Hospital of Wisconsin, Milwaukee, WI, USA
Mark F. Roethle
The Max McGee Research Center for Juvenile Diabetes, Children’s Research Institute of Children’s Hospital of Wisconsin, Milwaukee, WI, USA
Shuang Jia
The Max McGee Research Center for Juvenile Diabetes, Children’s Research Institute of Children’s Hospital of Wisconsin, Milwaukee, WI, USA
Tarun Pant
The Max McGee Research Center for Juvenile Diabetes, Children’s Research Institute of Children’s Hospital of Wisconsin, Milwaukee, WI, USA
Ashley E. Ciecko
The Max McGee Research Center for Juvenile Diabetes, Children’s Research Institute of Children’s Hospital of Wisconsin, Milwaukee, WI, USA
Samantha N. Atkinson
Center for Microbiome Research, Medical College of Wisconsin, Milwaukee, WI, USA
Nita H. Salzman
Center for Microbiome Research, Medical College of Wisconsin, Milwaukee, WI, USA
Ru-Jeng Teng
Department of Pediatrics, Division of Neonatology, the Medical College of Wisconsin, Milwaukee, WI, USA
Yi-Guang Chen
The Max McGee Research Center for Juvenile Diabetes, Children’s Research Institute of Children’s Hospital of Wisconsin, Milwaukee, WI, USA
Susanne M. Cabrera
The Max McGee Research Center for Juvenile Diabetes, Children’s Research Institute of Children’s Hospital of Wisconsin, Milwaukee, WI, USA
Martin J. Hessner
The Max McGee Research Center for Juvenile Diabetes, Children’s Research Institute of Children’s Hospital of Wisconsin, Milwaukee, WI, USA
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.
