Research Paper Volume 13, Issue 5 pp 6330—6345

Age-dependent remodeling of gut microbiome and host serum metabolome in mice

Chia-Shan Wu1,2, , Sai Deepak Venkata Muthyala1, , Cory Klemashevich3, , Arinzechukwu Uchenna Ufondu4, , Rani Menon4, , Zheng Chen5, , Sridevi Devaraj6,7, , Arul Jayaraman4, , Yuxiang Sun1,2, ,

  • 1 Department of Nutrition, Texas A&M University, College Station, TX 77843, USA
  • 2 USDA/ARS Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA
  • 3 Integrated Metabolomics Analysis Core, Texas A&M University, College Station, TX 77843, USA
  • 4 Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, TX 77843, USA
  • 5 Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA
  • 6 Department of Pathology, Texas Children’s Hospital, Houston, TX 77030, USA
  • 7 Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA

Received: September 10, 2020       Accepted: January 4, 2021       Published: February 17, 2021
How to Cite

Copyright: © 2021 Wu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


The interplay between microbiota and host metabolism plays an important role in health. Here, we examined the relationship between age, gut microbiome and host serum metabolites in male C57BL/6J mice. Fecal microbiome analysis of 3, 6, 18, and 28 months (M) old mice showed that the Firmicutes/Bacteroidetes ratio was highest in the 6M group; the decrease of Firmicutes in the older age groups suggests a reduced capacity of gut microflora to harvest energy from food. We found age-dependent increase in Proteobacteria, which may lead to altered mucus structure more susceptible to bacteria penetration and ultimately increased intestinal inflammation. Metabolomic profiling of polar serum metabolites at fed state in 3, 12, 18 and 28M mice revealed age-associated changes in metabolic cascades involved in tryptophan, purine, amino acids, and nicotinamide metabolism. Correlation analyses showed that nicotinamide decreased with age, while allantoin and guanosine, metabolites in purine metabolism, increased with age. Notably, tryptophan and its microbially derived compounds indole and indole-3-lactic acid significantly decreased with age, while kynurenine increased with age. Together, these results suggest a significant interplay between bacterial and host metabolism, and gut dysbiosis and altered microbial metabolism contribute to aging.


F/B: Firmicutes/Bacteroidetes; LC-MS: liquid chromatography high resolution accurate mass spectrometry; LEfSE: Linear discriminant analysis Effect Size; M: months; NAD+: nicotinamide adenine dinucleotide; OUT: operation taxonomic units; PCA: Principal Component Analysis; PCoA: Principal Coordinate Analysis; V4: variable region 4.