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Research Paper|Volume 10, Issue 5|pp 930—950

Integrative analysis of gut microbiota composition, host colonic gene expression and intraluminal metabolites in aging C57BL/6J mice

Benthe van der Lugt1, Fenni Rusli1, Carolien Lute1, Andreas Lamprakis1, Ethel Salazar1, Mark V. Boekschoten1, Guido J. Hooiveld1, Michael Müller2, Jacques Vervoort3, Sander Kersten1, Clara Belzer4, Dieuwertje E.G. Kok1, Wilma T. Steegenga1
  • 1Division of Human Nutrition, Wageningen University and Research, 6708 WE, Wageningen, The Netherlands
  • 2Nutrigenomics and Systems Nutrition, Norwich Medical School, University of East Anglia, Norwich NR4 7UA, United Kingdom
  • 3Laboratory of Biochemistry, Wageningen University and Research, 6708 WE, Wageningen, The Netherlands
  • 4Laboratory of Microbiology, Wageningen University and Research, 6708 WE, Wageningen, The Netherlands
Received: March 20, 2018Accepted: April 26, 2018Published: May 16, 2018
https://doi.org/10.18632/aging.101439

Copyright: © 2018 van der Lugt 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.

Abstract

The aging process is associated with diminished colonic health. In this study, we applied an integrative approach to reveal potential interactions between determinants of colonic health in aging C57BL/6J mice. Analysis of gut microbiota composition revealed an enrichment of various potential pathobionts, including Desulfovibrio spp., and a decline of the health-promoting Akkermansia spp. and Lactobacillus spp. during aging. Intraluminal concentrations of various metabolites varied between ages and we found evidence for an increased gut permeability at higher age. Colonic gene expression analysis suggested that during the early phase of aging (between 6 and 12 months), expression of genes involved in epithelial-to-mesenchymal transition and (re)organization of the extracellular matrix were increased. Differential expression of these genes was strongly correlated with Bifidobacterium spp. During the later phase of aging (between 12 and 28 months), gene expression profiles pointed towards a diminished antimicrobial defense and were correlated with an uncultured Gastranaerophilales spp. This study demonstrates that aging is associated with pronounced changes in gut microbiota composition and colonic gene expression. Furthermore, the strong correlations between specific bacterial genera and host gene expression may imply that orchestrated interactions take place in the vicinity of the colonic wall and potentially mediate colonic health during aging.