Microbiome−host proteostasis crosstalk—An emerging perspective on mechanisms and interventions toward healthy longevity

Proteostasis and the gut microbiota are two major determinants of host health and longevity. Proteostasis ensures proper protein folding and degradation thereby preventing the accumulation of unwanted proteins. Similarly, microbiota contribute to host metabolism, immunity, and protection from pathogens. However, as aging progresses, the proteostasis network declines, and the composition and functionality of gut microbiota are altered, often resulting in dysbiosis. While the impact of the microbiota on various aspects of host physiology is extensively studied, its specific influence on host protein quality control remains relatively underexplored. In this review, we provide an integrated overview of the relationship between microbiota and host proteostasis. Accumulating findings, particularly from C. elegans models, provide substantial support for the concept that microbiota-derived factors (vitamins and RNA) can shape host proteostasis and influence aging-related phenotypes. We discuss emerging evidence showing that microbial communities and their metabolites can either support or impair cellular proteostasis, highlighting their potential as prebiotics or dietary intervention candidates for promoting healthy aging. Understanding the intricate interplay between microbiota and proteostasis opens new avenues for designing microbiota-based strategies for healthy aging.