Aged Gut Microbiota Contributes to Systemical Inflammaging after Transfer to Germ-Free Mice.

Floris Fransen,Theo Borghuis,Mark V Boekschoten,Marien I De Jonge,Christa ,Sahar El Aidy,Marijke M Faas,Paul De Vos,Adriaan A Van Beek,Huub F J Savelkoul,Floor Hugenholtz,Hauke Smidt

doi:10.3389/fimmu.2017.01385

Abstract

Advanced age is associated with chronic low-grade inflammation, which is usually referred to as inflammaging. Elderly are also known to have an altered gut microbiota composition. However, whether inflammaging is a cause or consequence of an altered gut microbiota composition is not clear. In this study, gut microbiota from young or old conventional mice was transferred to young germ-free (GF) mice. Four weeks after gut microbiota transfer immune cell populations in spleen, Peyer’s patches, and mesenteric lymph nodes from conventionalized GF mice were analyzed by flow cytometry. In addition, whole-genome gene expression in the ileum was analyzed by microarray. Gut microbiota composition of donor and recipient mice was analyzed with 16S rDNA sequencing. Here, we show by transferring aged microbiota to young GF mice that certain bacterial species within the aged microbiota promote inflammaging. This effect was associated with lower levels of Akkermansia and higher levels of TM7 bacteria and Proteobacteria in the aged microbiota after transfer. The aged microbiota promoted inflammation in the small intestine in the GF mice and enhanced leakage of inflammatory bacterial components into the circulation was observed. Moreover, the aged microbiota promoted increased T cell activation in the systemic compartment. In conclusion, these data indicate that the gut microbiota from old mice contributes to inflammaging after transfer to young GF mice.

Highlights

The gut microbiota is a highly complex and diverse community of bacteria that closely interacts with the epithelium and underlying immune cells in the gut [1]
The mice were sacrificed and the frequency of the different CD4+ T helper (Th) subsets were identified in the Peyer’s patches (PPs), mesenteric lymph nodes (MLNs), and the spleen by flow cytometry
In the PPs and MLNs no differences were observed in Th frequencies, except for Th1 cells in PPs, which were significantly higher in GF mice after transfer of the old microbiota (Figure 1D) when compared with GF mice after transfer of microbiota of young mice

Summary

Introduction

The gut microbiota is a highly complex and diverse community of bacteria that closely interacts with the epithelium and underlying immune cells in the gut [1]. The bacterial divisions that dominate the human gut microbiota are Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria [2]. The dominance of these bacterial divisions is evolutionary conserved and has been confirmed. Aged Gut Microbiota Induces Inflammaging in different mammalian species [3, 4]. It has become clear that the gut microbiota has a major impact on the immune system, metabolism, and even behavior of the host [5]. An imbalance in gut microbiota composition (dysbiosis) has been associated with several immunological, metabolic, and mental disorders [6]. For the majority of these diseases it remains unclear whether dysbiosis is a cause or consequence of the disease

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