Age Associated Microbiome and Microbial Metabolites Modulation and Its Association With Systemic Inflammation in a Rhesus Macaque Model
Aging is associated with declining immunity and inflammation as well as alterations in the gut microbiome with a decrease of beneficial microbes and increase in pathogenic ones. The aim of this study was to investigate the age associated gut microbiome in relation to immunologic and metabolic profil...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.748397/full |
| _version_ | 1819152404548943872 |
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| author | Suresh Pallikkuth Roberto Mendez Kyle Russell Tirupataiah Sirupangi Daniel Kvistad Rajendra Pahwa Francois Villinger Santanu Banerjee Santanu Banerjee Santanu Banerjee Savita Pahwa |
| author_facet | Suresh Pallikkuth Roberto Mendez Kyle Russell Tirupataiah Sirupangi Daniel Kvistad Rajendra Pahwa Francois Villinger Santanu Banerjee Santanu Banerjee Santanu Banerjee Savita Pahwa |
| author_sort | Suresh Pallikkuth |
| collection | DOAJ |
| description | Aging is associated with declining immunity and inflammation as well as alterations in the gut microbiome with a decrease of beneficial microbes and increase in pathogenic ones. The aim of this study was to investigate the age associated gut microbiome in relation to immunologic and metabolic profile in a non-human primate (NHP) model. 12 geriatric (age 19-24 years) and 4 young adult (age 3-4 years) Rhesus macaques were included in this study. Immune cell subsets were characterized in peripheral blood mononuclear cells (PBMC) by flow cytometry and plasma cytokines levels were determined by bead based multiplex cytokine analysis. Stool samples were collected by ileal loop and investigated for microbiome analysis by shotgun metagenomics. Serum, gut microbial lysate, and microbe-free fecal extract were subjected to metabolomic analysis by mass-spectrometry. Our results showed that the gut microbiome in geriatric animals had higher abundance of Archaeal and Proteobacterial species and lower Firmicutes than the young adults. Highly abundant microbes in the geriatric animals showed a direct association with plasma biomarkers of inflammation and immune activation such as neopterin, CRP, TNF, IL-2, IL-6, IL-8 and IFN-γ. Significant enrichment of metabolites that contribute to inflammatory and cytotoxic pathways was observed in serum and feces of geriatric animals compared to the young adults. We conclude that aging NHP undergo immunosenescence and age associated alterations in the gut microbiome that has a distinct metabolic profile. Aging NHP can serve as a model for investigating the relationship of the gut microbiome to particular age-associated comorbidities and for strategies aimed at modulating the microbiome. |
| first_indexed | 2024-12-22T14:48:45Z |
| format | Article |
| id | doaj.art-6e657527f80041978608f45177f8190e |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-22T14:48:45Z |
| publishDate | 2021-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-6e657527f80041978608f45177f8190e2022-12-21T18:22:23ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-10-011210.3389/fimmu.2021.748397748397Age Associated Microbiome and Microbial Metabolites Modulation and Its Association With Systemic Inflammation in a Rhesus Macaque ModelSuresh Pallikkuth0Roberto Mendez1Kyle Russell2Tirupataiah Sirupangi3Daniel Kvistad4Rajendra Pahwa5Francois Villinger6Santanu Banerjee7Santanu Banerjee8Santanu Banerjee9Savita Pahwa10Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL, United StatesDepartment of Surgery, University of Miami Miller School of Medicine, Miami, FL, United StatesDepartment of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL, United StatesNew Iberia Research Center, University of Louisiana at Lafayette, New Iberia, LA, United StatesDepartment of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL, United StatesDepartment of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL, United StatesNew Iberia Research Center, University of Louisiana at Lafayette, New Iberia, LA, United StatesDepartment of Surgery, University of Miami Miller School of Medicine, Miami, FL, United StatesMiami Integrative Metabolomics Research Center (MIMRC), University of Miami Miller School of Medicine, Miami, FL, United StatesCenter for Scientific Review, National Institute of Health, Bethesda, MD, United StatesDepartment of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL, United StatesAging is associated with declining immunity and inflammation as well as alterations in the gut microbiome with a decrease of beneficial microbes and increase in pathogenic ones. The aim of this study was to investigate the age associated gut microbiome in relation to immunologic and metabolic profile in a non-human primate (NHP) model. 12 geriatric (age 19-24 years) and 4 young adult (age 3-4 years) Rhesus macaques were included in this study. Immune cell subsets were characterized in peripheral blood mononuclear cells (PBMC) by flow cytometry and plasma cytokines levels were determined by bead based multiplex cytokine analysis. Stool samples were collected by ileal loop and investigated for microbiome analysis by shotgun metagenomics. Serum, gut microbial lysate, and microbe-free fecal extract were subjected to metabolomic analysis by mass-spectrometry. Our results showed that the gut microbiome in geriatric animals had higher abundance of Archaeal and Proteobacterial species and lower Firmicutes than the young adults. Highly abundant microbes in the geriatric animals showed a direct association with plasma biomarkers of inflammation and immune activation such as neopterin, CRP, TNF, IL-2, IL-6, IL-8 and IFN-γ. Significant enrichment of metabolites that contribute to inflammatory and cytotoxic pathways was observed in serum and feces of geriatric animals compared to the young adults. We conclude that aging NHP undergo immunosenescence and age associated alterations in the gut microbiome that has a distinct metabolic profile. Aging NHP can serve as a model for investigating the relationship of the gut microbiome to particular age-associated comorbidities and for strategies aimed at modulating the microbiome.https://www.frontiersin.org/articles/10.3389/fimmu.2021.748397/fullage and microbesage and metabolitesmicrobiome and metabolitesimmunity and microbiomeage and immunity |
| spellingShingle | Suresh Pallikkuth Roberto Mendez Kyle Russell Tirupataiah Sirupangi Daniel Kvistad Rajendra Pahwa Francois Villinger Santanu Banerjee Santanu Banerjee Santanu Banerjee Savita Pahwa Age Associated Microbiome and Microbial Metabolites Modulation and Its Association With Systemic Inflammation in a Rhesus Macaque Model Frontiers in Immunology age and microbes age and metabolites microbiome and metabolites immunity and microbiome age and immunity |
| title | Age Associated Microbiome and Microbial Metabolites Modulation and Its Association With Systemic Inflammation in a Rhesus Macaque Model |
| title_full | Age Associated Microbiome and Microbial Metabolites Modulation and Its Association With Systemic Inflammation in a Rhesus Macaque Model |
| title_fullStr | Age Associated Microbiome and Microbial Metabolites Modulation and Its Association With Systemic Inflammation in a Rhesus Macaque Model |
| title_full_unstemmed | Age Associated Microbiome and Microbial Metabolites Modulation and Its Association With Systemic Inflammation in a Rhesus Macaque Model |
| title_short | Age Associated Microbiome and Microbial Metabolites Modulation and Its Association With Systemic Inflammation in a Rhesus Macaque Model |
| title_sort | age associated microbiome and microbial metabolites modulation and its association with systemic inflammation in a rhesus macaque model |
| topic | age and microbes age and metabolites microbiome and metabolites immunity and microbiome age and immunity |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.748397/full |
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