Human Microbiome and Frailty: From Observations of Clinically Relevant Associations to Insights into Biological Mechanisms
Nearly all surfaces of the human body are colonized by communities of microbes such as bacteria, viruses, and fungi. Collectively called microbiota, microbiome colonizes both internal surfaces such as the gut, oral cavity, and bladder, as well as surfaces exposed to the outside world such as the skin. Nonetheless, most microbiome studies have focused on the gut, using low-resolution sequencing techniques such as 16S ribosomal RNA. Despite these limitations many reports have described deleterious microbiome changes or dysbiosis in individuals with diseases as varied as cancer, diabetes mellitus, and cardiovascular conditions. While qualitatively similar changes have been described in the context of aging, growing evidence indicates that these associations are stronger in relationship to frailty. Most recently, studies assessing microbiome across multiple different tissues using metagenome sequencing have revealed features of dysbiosis that were particularly prominent in the skin and were more strongly associated with frailty in nursing home residents than with chronological aging. Moreover, these approaches have revealed the presence of antibiotic resistance in nosocomial pathogens (like methicillin-resistant Staphylococcus aureus) with considerably clinical implications. Finally, efforts to link microbiome data to evaluations of relevant immune responses are also beginning to shed insights into biological aging and frailty pathophysiology.
