Administration of Human Derived Upper gut Commensal Prevotella histicola delays the onset of type 1 diabetes in NOD mice
Abstract Background 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 defi...
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| Format: | Article |
| Language: | English |
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BMC
2022-01-01
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| Series: | BMC Microbiology |
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| Online Access: | https://doi.org/10.1186/s12866-021-02406-9 |
| _version_ | 1798034563145924608 |
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| author | Eric Marietta Irina Horwath Stephanie Meyer Shahryar Khaleghi-Rostamkolaei Eric Norman David Luckey Baskar Balakrishnan Ashutosh Mangalam Rok Seon Choung Veena Taneja Joseph A. Murray |
| author_facet | Eric Marietta Irina Horwath Stephanie Meyer Shahryar Khaleghi-Rostamkolaei Eric Norman David Luckey Baskar Balakrishnan Ashutosh Mangalam Rok Seon Choung Veena Taneja Joseph A. Murray |
| author_sort | Eric Marietta |
| collection | DOAJ |
| description | Abstract Background 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. Results 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. Conclusions 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. |
| first_indexed | 2024-04-11T20:45:58Z |
| format | Article |
| id | doaj.art-189314fcc280420eb8b943affa892836 |
| institution | Directory Open Access Journal |
| issn | 1471-2180 |
| language | English |
| last_indexed | 2024-04-11T20:45:58Z |
| publishDate | 2022-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Microbiology |
| spelling | doaj.art-189314fcc280420eb8b943affa8928362022-12-22T04:04:02ZengBMCBMC Microbiology1471-21802022-01-0122111010.1186/s12866-021-02406-9Administration of Human Derived Upper gut Commensal Prevotella histicola delays the onset of type 1 diabetes in NOD miceEric Marietta0Irina Horwath1Stephanie Meyer2Shahryar Khaleghi-Rostamkolaei3Eric Norman4David Luckey5Baskar Balakrishnan6Ashutosh Mangalam7Rok Seon Choung8Veena Taneja9Joseph A. Murray10Department of Gastroenterology and Hepatology (Celiac Disease), Mayo ClinicDepartment of Gastroenterology and Hepatology (Celiac Disease), Mayo ClinicDepartment of Gastroenterology and Hepatology (Celiac Disease), Mayo ClinicDepartment of Gastroenterology and Hepatology (Celiac Disease), Mayo ClinicDepartment of Gastroenterology and Hepatology (Celiac Disease), Mayo ClinicDepartment of Immunology, Mayo ClinicDepartment of Immunology, Mayo ClinicDepartment of Immunology, University of IowaDepartment of Gastroenterology and Hepatology (Celiac Disease), Mayo ClinicDepartment of Immunology, Mayo ClinicDepartment of Gastroenterology and Hepatology (Celiac Disease), Mayo ClinicAbstract Background 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. Results 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. Conclusions 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.https://doi.org/10.1186/s12866-021-02406-9DiabetesprevotellaHisticolaMicrobiomeNon-obese |
| spellingShingle | Eric Marietta Irina Horwath Stephanie Meyer Shahryar Khaleghi-Rostamkolaei Eric Norman David Luckey Baskar Balakrishnan Ashutosh Mangalam Rok Seon Choung Veena Taneja Joseph A. Murray Administration of Human Derived Upper gut Commensal Prevotella histicola delays the onset of type 1 diabetes in NOD mice BMC Microbiology Diabetes prevotella Histicola Microbiome Non-obese |
| title | Administration of Human Derived Upper gut Commensal Prevotella histicola delays the onset of type 1 diabetes in NOD mice |
| title_full | Administration of Human Derived Upper gut Commensal Prevotella histicola delays the onset of type 1 diabetes in NOD mice |
| title_fullStr | Administration of Human Derived Upper gut Commensal Prevotella histicola delays the onset of type 1 diabetes in NOD mice |
| title_full_unstemmed | Administration of Human Derived Upper gut Commensal Prevotella histicola delays the onset of type 1 diabetes in NOD mice |
| title_short | Administration of Human Derived Upper gut Commensal Prevotella histicola delays the onset of type 1 diabetes in NOD mice |
| title_sort | administration of human derived upper gut commensal prevotella histicola delays the onset of type 1 diabetes in nod mice |
| topic | Diabetes prevotella Histicola Microbiome Non-obese |
| url | https://doi.org/10.1186/s12866-021-02406-9 |
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