Age Associated Microbiome and Microbial Metabolites Modulation and Its Association With Systemic Inflammation in a Rhesus Macaque Model

Suresh Pallikkuth, Roberto Mendez, Kyle Russell, Tirupataiah Sirupangi, Daniel Kvistad, Rajendra Pahwa, Francois Villinger, Santanu Banerjee, Savita Pahwa

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article number748397
JournalFrontiers in immunology
Volume12
DOIs
StatePublished - Oct 19 2021

Keywords

  • age and immunity
  • age and metabolites
  • age and microbes
  • immunity and microbiome
  • microbiome and metabolites

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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