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| Status |
Public on Oct 01, 2022 |
| Title |
Probiotic supplementation with Lactiplantibacillus plantarum 299v modulates ER and oxidative stress pathways in ?-cells and prevents Type 1 diabetes in gluten-free BioBreeding Rats |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by array
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| Summary |
Type 1 diabetes (T1D) is an autoimmune disease characterized by destruction of the pancreatic β-cells. T1D pathogenesis has a strong genetic basis. However, in recent decades, the prevalence of high-risk HLA haplotypes among new diagnoses has declined, the age of onset has decreased, and T1D incidence has increased. These changes are consistent with increased environmental pressure and coincide with introduction of the Western diet, widespread antibiotic use and reduced breast feeding. These factors are thought to drive intestinal dysbiosis, increased gut permeability and systemic inflammation. Notably, our studies of T1D families and the BioBreeding (BB) rat have identified a peripheral inflammatory state associated with diabetes susceptibility that is consistent with microbial antigen exposure and pattern recognition receptor ligation. Lactiplantibacillus plantarum 299v (Lp299v), a probiotic strain, is reported to increase plasma and stool levels of anti-inflammatory short chain fatty acids (SCFA) and promote IL-10 signaling in colonic derived macrophages and T-cells.
Here we investigated the effect of Lp299v supplement on T1D progression and inflammatory phenotypes in diabetes prone BB DRlyp/lyp rats. Rats were weaned at 21 days onto a normal cereal diet (ND) or a gluten-free hydrolyzed casein diet (HCD), with and without daily Lp299v supplementation. All DRlyp/lyp ND rats developed T1D by day 83 (mean time to onset of 62.8+/-7.9 days). DRlyp/lyp ND+Lp299v rats exhibited an insignificant delay in T1D onset (62.6+/-6.5 days), however 8% remained diabetes-free to day 130. Providing DRlyp/lyp rats HCD prevented T1D in 17% of rats (to age 130 days) and significantly delayed onset (mean time to onset 72.8+/-7.3 days, p<0.001). Providing DRlyp/lyp rats HCD+Lp299v prevented T1D in 25% of rats and more robustly delayed onset (mean time to onset 84.9 +/-14.3 days, p<0.001). While multiplex ELISA failed to detect significantly altered plasma cytokine/chemokine levels at 40 days of life, plasma induced transcription revealed greatest normalization of systemic inflammation in the HCD+Lp299v group. Plasma SCFA levels (propionate and butyrate, p<0.01) were elevated in the HCD+Lp299v group compared to the ND group. Global gene expression analysis of pancreatic islets was conducted at 40 days, prior to insulitis. Endoplasmic reticulum (ER) stress has been implicated in the formation of islet neoantigens that may underlie the initial loss of immune tolerance in T1D. Under one or both diets, Lp299v favorably modulated islet expression levels of pathways and transcripts related to inflammation and innate immunity (Cxcl9, Cxcl10), oxidative stress (Gsta1, Gsta4, Gstp1, Gstk1), as well as ER stress and unfolded protein response (Cirbp, Edem1, Hspa1a, Atf4). These ongoing studies add to a growing understanding that inherited susceptibility can be modulated by diet and microbiota.
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| Overall design |
Pancreatic islets were isolated from 40 day old rats of BB DRlyp/lyp ND, DRlyp/lyp ND+Lp299v, DRlyp/lyp HCD, DRlyp/lyp HCD+Lp299v, and Flyp/lyp ND and run global gene expression analysis.
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| Contributor(s) |
Sargin P, Roethle MF, Jia S, Dew K, Laib T, Atkinson SN, Teng R, Hessner M |
| Citation(s) |
36261888 |
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| Submission date |
Mar 14, 2022 |
| Last update date |
Oct 28, 2022 |
| Contact name |
Martin Hessner |
| E-mail(s) |
[email protected]
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| Organization name |
Medical College of Wisconsin
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| Department |
Pediatrics
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| Lab |
Max McGee National Research Center for Juvenile Diabetes
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| Street address |
8701 Watertown Plank Road
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| City |
Milwaukee |
| State/province |
WI |
| ZIP/Postal code |
53226 |
| Country |
USA |
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| Platforms (1) |
| GPL1355 |
[Rat230_2] Affymetrix Rat Genome 230 2.0 Array |
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| Samples (15)
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| GSM5953775 |
Day40 DRlyp/lyp Rat fed with a normal cereal diet from age of day21, rep1 |
| GSM5953776 |
Day40 DRlyp/lyp Rat fed with a gluten-free hydrolyzed bovine casein diet (HCD) from age of day21, rep1 |
| GSM5953777 |
Day40 DRlyp/lyp Rat fed with a normal cereal diet plus Lp299v from age of day21, rep1 |
| GSM5953778 |
Day40 DRlyp/lyp Rat fed with a gluten-free hydrolyzed bovine casein diet (HCD) plus Lp299v from age of day21, rep1 |
| GSM5953779 |
Day40 Flyp/lyp Rat fed with a normal cereal diet from age of day21, rep1 |
| GSM5953780 |
Day40 DRlyp/lyp Rat fed with a normal cereal diet from age of day21, rep2 |
| GSM5953781 |
Day40 DRlyp/lyp Rat fed with a gluten-free hydrolyzed bovine casein diet (HCD) from age of day21, rep2 |
| GSM5953782 |
Day40 DRlyp/lyp Rat fed with a normal cereal diet plus Lp299v from age of day21, rep2 |
| GSM5953783 |
Day40 DRlyp/lyp Rat fed with a gluten-free hydrolyzed bovine casein diet (HCD) plus Lp299v from age of day21, rep2 |
| GSM5953784 |
Day40 Flyp/lyp Rat fed with a normal cereal diet from age of day21, rep2 |
| GSM5953785 |
Day40 DRlyp/lyp Rat fed with a normal cereal diet from age of day21, rep3 |
| GSM5953786 |
Day40 DRlyp/lyp Rat fed with a gluten-free hydrolyzed bovine casein diet (HCD) from age of day21, rep3 |
| GSM5953787 |
Day40 DRlyp/lyp Rat fed with a normal cereal diet plus Lp299v from age of day21, rep3 |
| GSM5953788 |
Day40 DRlyp/lyp Rat fed with a gluten-free hydrolyzed bovine casein diet (HCD) plus Lp299v from age of day21, rep3 |
| GSM5953789 |
Day40 Flyp/lyp Rat fed with a normal cereal diet from age of day21, rep3 |
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| Relations |
| BioProject |
PRJNA816162 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE198617_RAW.tar |
35.2 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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