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

Date Published: May 16, 2018

Publisher: Impact Journals

Author(s): Benthe van der Lugt, Fenni Rusli, Carolien Lute, Andreas Lamprakis, Ethel Salazar, Mark V. Boekschoten, Guido J. Hooiveld, Michael Müller, Jacques Vervoort, Sander Kersten, Clara Belzer, Dieuwertje E.G. Kok, Wilma T. Steegenga.


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.

Partial Text

Aging is a complex process characterized by a time-dependent loss of physical fitness accompanied by an increased risk of morbidities [1]. The increase in life expectancy and the increased prevalence of age-related pathologies [1] demands further insight into the mechanisms underlying the aging process.

In the present study, we report that aging is associated with pronounced changes in gut microbiota composition and colonic gene expression. In agreement with the current literature, we found an increase in potential pathobionts and a decrease in health-promoting bacteria during aging, which could potentially contribute to the development of age-related pathologies [12,22]. In contrast to the mild effects of aging on colonic gene expression that we found several years ago [23], we now report much stronger effects, probably because we included older mice (28 months instead of 21 months of age). Moreover, by applying an integrative approach, we show that several bacterial genera strongly correlated with colonic gene expression, providing evidence for potential host-microbe interactions.




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