Fight Aging!

Changes in the gut microbiome over the course of aging occur in parallel to a decline in immune function. The direction of causation is unclear, as both systems influence one another. Indeed, causation can exist in both directions simultaneously, as there are a great many distinct mechanisms involved in the interactions between gut microbes and the host immune system. The balance of evidence at the moment favors gut microbes as the cause and immune issues as the consequence. The results here add to those of other studies that suggest it is shifts in the gut microbe populations that drive significant dysfunction in the immune system, and that these shifts can be reversed (at least temporarily) via comparatively simple, brute-force strategies.

One of the organs that is significantly affected by age is the gastrointestinal tract and the gut-associated microbiome. These commensal microorganisms are essential for health, affecting the functions of multiple bodily systems, such as host metabolism, brain functions, and the immune response. Older individuals have age-related alterations in gut microbial composition, which have been associated with increased frailty, reduced cognitive performance, immune inflammaging and an increased susceptibility to intestinal disorders.

What drives these age-associated changes in the gut microbiota remains unknown. The microbiome is shaped by many factors including host genetics, early life events, diet, and the gut immune system. While some of these factors remain relatively constant throughout life, the function of the immune system is known to deteriorate with age. This prompts the hypothesis that dysbiosis of the intestinal microbiome in older individuals may be driven by altered cross-talk between the host immune system and the microbiota. The gut immune system can regulate the composition of the microbiome by the production of immunoglobulin A (IgA) antibodies that coat commensal bacteria. In the gastrointestinal tract, IgA antibodies are either produced by short-lived plasma cells in the lamina propria or from plasma cells that arise from germinal centre (GC) reactions in Peyer's patches (PPs).

Studies indicate clearly that the microbiome is causally influenced by the GC reaction. In the case of the gut-associated defects seen with advancing age in the GC reaction and gut microbiota, however, the direction of causation is unclear. Here, we report that the defective GC reaction in aged mice could be boosted by direct faecal transplantation from adult donors and by oral administration of cholera toxin. This demonstrates that the age-dependent defect in the gut GC reaction is not irreversible, but can be corrected by changing the microbiota or by delivery of a bacterial derived toxin.

Link: https://doi.org/10.1038/s41467-019-10430-7