Faculty Collaboration Database

Lactiplantibacillus plantarum 299v supplementation modulates β-cell ER stress and antioxidative defense pathways and prevents type 1 diabetes in gluten-free BioBreeding rats. Gut Microbes 2022;14(1):2136467

Date

10/21/2022

Pubmed ID

36261888

Pubmed Central ID

PMC9586621

DOI

10.1080/19490976.2022.2136467

Scopus ID

2-s2.0-85140364986 (requires institutional sign-in at Scopus site)   3 Citations

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.

Author List

Sargin P, Roethle MF, Jia S, Pant T, Ciecko AE, Atkinson SN, Salzman NH, Teng RJ, Chen YG, Cabrera SM, Hessner MJ

Authors

Samantha N. Atkinson PhD Bioinformatics Analyst III in the Microbiology and Immunology department at Medical College of Wisconsin
Susanne M. Cabrera MD Associate Professor in the Pediatrics department at Medical College of Wisconsin
Yi-Guang Chen PhD Professor in the Pediatrics department at Medical College of Wisconsin
Martin J. Hessner PhD Professor in the Pediatrics department at Medical College of Wisconsin
Nita H. Salzman MD, PhD Director, Professor in the Pediatrics department at Medical College of Wisconsin
Ru-Jeng Teng MD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Antioxidants
Butyrates
Caseins
Diabetes Mellitus, Type 1
Dietary Supplements
Gastrointestinal Microbiome
Lactobacillus plantarum
NF-E2-Related Factor 2
Propionates
Rats