Age-associated intestinal permeability and microbial translocation as promotors of T cell ageing

Description

Altered gut microbiota composition with advancing age (microbial dysbiosis) is accompanied by increased intestinal membrane permeability and systemic translocation of microbial products. Concurrently, ageing leads to remodelling of the immune system, termed immunesenescence, which attenuates the host’s ability to mount robust immune responses against pathogens. However, the relationship between age-related microbial dysbiosis, intestinal permeability and immunesenescence remains poorly understood. To further investigate, deep immunophenotyping and microbiome analysis were performed on young adults with low microbial translocation (MT) (n=27) and older adults with low MT (n=24) and high MT (n=31). Our results revealed that older adults with high MT display a greater proportion of peripheral activated (CD69+ve), senescent (CD28veCD57+ve) and regulatory (Foxp3+ve) T cells. Importantly, we observed a positive association between surrogate markers of microbial translocation (occludin) and thymic output as well as immunological (IMM-AGE) scores. Moreover, immune cells from aged participants with high MT
displayed other hallmarks of ageing, including impaired autophagy, inflammation and exhaustion. Furthermore, aged germ-free mice are protected from intestinal barrier dysfunction in addition to features of thymic involution (adipose deposition, altered thymic microenvironment) and immunesenescence. Together, these findings provide evidence for investigating the potential of microbiome-based therapies in combating T cell ageing.

Period	6 Jul 2022
Held at	Federation of European Biochemical Societies (FEBS)
Degree of Recognition	International