Journal article
Administration of Human Derived Upper gut Commensal Prevotella histicola delays the onset of type 1 diabetes in NOD mice
BMC microbiology, Vol.22(1), pp.8-8
01/04/2022
DOI: 10.1186/s12866-021-02406-9
PMCID: PMC8729070
PMID: 34983374
Abstract
Type 1 diabetes (T1D) is an autoimmune disease that is increasing in prevalence worldwide. One of the contributing factors to the pathogenesis of T1D is the composition of the intestinal microbiota, as has been demonstrated. in T1D patients, with some studies demonstrating a deficiency in their levels of Prevotella. We have isolated a strain of Prevotella histicola from a duodenal biopsy that has anti-inflammatory properties, and in addition, alters the development of autoimmune diseases in mouse models. Therefore, our hypothesis is that the oral administration of P. histicola might delay the development of T1D in the non-obese diabetic (NOD) mice. To assess this, we used the following materials and methods. Female NOD mice (ages 5-8 weeks) were administered every other day P. histicola that was cultured in-house. Blood glucose levels were measured every other week. Mice were sacrificed at various time points for histopathological analysis of the pancreas. Modulation of immune response by the commensal was tested by analyzing regulatory T-cells and NKp46+ cells using flow cytometry and intestinal cytokine mRNA transcript levels using quantitative RT-PCR. For microbial composition, 16 s rRNA gene analysis was conducted on stool samples collected at various time points.
Administration of P. histicola in NOD mice delayed the onset of T1D. Beta diversity in the fecal microbiomes demonstrated that the microbial composition of the mice administered P. histicola was different from those that were not treated. Treatment with P. histicola led to a significant increase in regulatory T cells with a concomitant decrease in NKp46+ cells in the pancreatic lymph nodes as compared to the untreated group after 5 weeks of treatment.
These observations suggest that P. histicola treatment delayed onset of diabetes by increasing the levels of regulatory T cells in the pancreatic lymph nodes. This preliminary work supports the rationale that enteral exposure to a non pathogenic commensal P. histicola be tested as a future therapy for T1D.
Details
- Title: Subtitle
- Administration of Human Derived Upper gut Commensal Prevotella histicola delays the onset of type 1 diabetes in NOD mice
- Creators
- Eric Marietta - Department of Dermatology, Mayo Clinic, Rochester, MN, USAIrina Horwath - Department of Gastroenterology and Hepatology (Celiac Disease), Mayo Clinic, Rochester, MN, USAStephanie Meyer - Department of Gastroenterology and Hepatology (Celiac Disease), Mayo Clinic, Rochester, MN, USAShahryar Khaleghi-Rostamkolaei - Department of Gastroenterology and Hepatology (Celiac Disease), Mayo Clinic, Rochester, MN, USAEric Norman - Department of Gastroenterology and Hepatology (Celiac Disease), Mayo Clinic, Rochester, MN, USADavid Luckey - Department of Immunology, Mayo Clinic, Rochester, MN, USABaskar Balakrishnan - Department of Immunology, Mayo Clinic, Rochester, MN, USAAshutosh Mangalam - Department of Immunology, University of Iowa, Iowa City, Iowa, USARok Seon Choung - Department of Gastroenterology and Hepatology (Celiac Disease), Mayo Clinic, Rochester, MN, USAVeena Taneja - Department of Immunology, Mayo Clinic, Rochester, MN, USAJoseph A Murray - Department of Immunology, Mayo Clinic, Rochester, MN, USA. Murray.Joseph@mayo.edu
- Resource Type
- Journal article
- Publication Details
- BMC microbiology, Vol.22(1), pp.8-8
- DOI
- 10.1186/s12866-021-02406-9
- PMID
- 34983374
- PMCID
- PMC8729070
- NLM abbreviation
- BMC Microbiol
- ISSN
- 1471-2180
- eISSN
- 1471-2180
- Grant note
- P30 DK084567 / NIDDK NIH HHS
- Language
- English
- Date published
- 01/04/2022
- Academic Unit
- Pathology; Iowa Neuroscience Institute
- Record Identifier
- 9984210348802771
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