Heterochronic faecal transplantation boosts gut germinal centres in aged mice

Abstract

Ageing is a complex multifactorial process associated with a plethora of disorders, which contribute significantly to morbidity worldwide. One of the organs significantly affected by age is the gut. Age-dependent changes of the gut-associated microbiome have been linked to increased frailty and systemic inflammation. This change in microbial composition with age occurs in parallel with a decline in function of the gut immune system; however, it is not clear whether there is a causal link between the two. Here we report that the defective germinal centre reaction in Peyer’s patches of aged mice can be rescued by faecal transfers from younger adults into aged mice and by immunisations with cholera toxin, without affecting germinal centre reactions in peripheral lymph nodes. This demonstrates that the poor germinal centre reaction in aged animals is not irreversible, and that it is possible to improve this response in older individuals by providing appropriate stimuli.

Microbial Stimulation Reverses the Age-Related Decline in M Cells in Aged Mice

“…This indicates that the exposure of aged mice to used bedding from young mice did not result in a large change in microbiota alpha diversity. These data are consistent with data from a similar study of aged C57BL/6 mice exposed to young bedding that also reported that ageing was not associated with a reduction in bacterial diversity (Stebbeg et al, 2019).…”

“…IgA responses depend on the development of GC responses in the Peyer’s patch, and GC B and Tfh cells are also reduced in M cell deficient mice (Rios et al, 2016). Consistent with the decline in M cell maturation (Kobayashi et al, 2013), Peyer’s patch GC B and Tfh cells are also reduced in aged mice (Stebbeg et al, 2019). The decline in Peyer’s patch GC B and Tfh cells in aged mice could be reversed by transfer of a young microbiota (Stebbeg et al, 2019), consistent with the results of this study.…”

“…Consistent with the decline in M cell maturation (Kobayashi et al, 2013), Peyer’s patch GC B and Tfh cells are also reduced in aged mice (Stebbeg et al, 2019). The decline in Peyer’s patch GC B and Tfh cells in aged mice could be reversed by transfer of a young microbiota (Stebbeg et al, 2019), consistent with the results of this study. It is therefore likely that the increased GC B and Tfh cells observed in aged mice after young microbiota transfer is dependent on increased M cell maturation.…”

The role of the microbiota in sedentary lifestyle disorders and ageing: lessons from the animal kingdom

“…Studies in our laboratory of rats up to two years of age showed clear age-related microbiome alteration and increase in alpha diversity [79], with an increase in short-chain fatty acid production that contrasted with the decline in frail older human subjects [69]. Older mice also have a different gut microbiome to older mice, and interestingly, co-housing or faecal transfer from adult to aged mice alters microbiome and boosts germinal centre response [80]. The altered gut epithelial gene expression pattern of older mice [81] was correlated with differential abundance of particular species and increased proportional abundance of so-called pathobionts, species such as Escherichia coli and other Proteobacteria that are opportunistic pathogens.…”

All You Can Feed: Some Comments on Production of Mouse Diets Used in Biomedical Research with Special Emphasis on Non-Alcoholic Fatty Liver Disease Research

“…It was demonstrated some years ago that the composition of the commensal gut microbiota in humans correlates with diet and health in the elderly [91]. Moreover, in aged mice some of the alterations associated with aging can be rescued by fecal transfer [92]. In this context, it should be noted that the eating of fresh feces, which is a natural behavior of mice, is possibly not only helpful to better absorb nutrients/minerals they need to stay healthy, but is further a requirement to slow down the aging processes caused by nutritional deficiencies.…”