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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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Autores principales: Pallikkuth, Suresh, Mendez, Roberto, Russell, Kyle, Sirupangi, Tirupataiah, Kvistad, Daniel, Pahwa, Rajendra, Villinger, Francois, Banerjee, Santanu, Pahwa, Savita
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8560971/
https://www.ncbi.nlm.nih.gov/pubmed/34737748
http://dx.doi.org/10.3389/fimmu.2021.748397
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author Pallikkuth, Suresh
Mendez, Roberto
Russell, Kyle
Sirupangi, Tirupataiah
Kvistad, Daniel
Pahwa, Rajendra
Villinger, Francois
Banerjee, Santanu
Pahwa, Savita
author_facet Pallikkuth, Suresh
Mendez, Roberto
Russell, Kyle
Sirupangi, Tirupataiah
Kvistad, Daniel
Pahwa, Rajendra
Villinger, Francois
Banerjee, Santanu
Pahwa, Savita
author_sort Pallikkuth, Suresh
collection PubMed
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.
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spelling pubmed-85609712021-11-03 Age Associated Microbiome and Microbial Metabolites Modulation and Its Association With Systemic Inflammation in a Rhesus Macaque Model Pallikkuth, Suresh Mendez, Roberto Russell, Kyle Sirupangi, Tirupataiah Kvistad, Daniel Pahwa, Rajendra Villinger, Francois Banerjee, Santanu Pahwa, Savita Front Immunol Immunology 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. Frontiers Media S.A. 2021-10-19 /pmc/articles/PMC8560971/ /pubmed/34737748 http://dx.doi.org/10.3389/fimmu.2021.748397 Text en Copyright © 2021 Pallikkuth, Mendez, Russell, Sirupangi, Kvistad, Pahwa, Villinger, Banerjee and Pahwa https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Pallikkuth, Suresh
Mendez, Roberto
Russell, Kyle
Sirupangi, Tirupataiah
Kvistad, Daniel
Pahwa, Rajendra
Villinger, Francois
Banerjee, Santanu
Pahwa, Savita
Age Associated Microbiome and Microbial Metabolites Modulation and Its Association With Systemic Inflammation in a Rhesus Macaque Model
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 Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8560971/
https://www.ncbi.nlm.nih.gov/pubmed/34737748
http://dx.doi.org/10.3389/fimmu.2021.748397
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