Gut frailty: the core of reversing frailty

Abstract

Imbalances in gut microbiota have been implicated in numerous age-related degenerative diseases and unhealthy aging. Frail individuals often exhibit severe malnutrition and gastrointestinal dysfunction. Recent studies have demonstrated a correlation between physical frailty, cognitive decline, gastrointestinal function, and intestinal microbiota, leading to the introduction of the concept of 'gut frailty'. However, the mechanisms by which intestinal weakness influences frail individuals and contributes to the onset of frailty remain unclear. We hypothesize that gut frailty encompasses not only the deterioration of gastrointestinal function but also the ecological imbalance of gut microbiota, which disrupts the normal aging process. This condition may impact frailty through several critical pathways, particularly those involving the gut-brain and gut-muscle axes, and constitutes a central and essential factor in the development of frailty. This perspective suggests the potential of targeting gut frailty as a therapeutic strategy in the context of Geroscience, highlighting its role beyond mere participation in the frailty process.

Keywords: Frailty; gut frailty; gut microbiota; gut–brain axis; gut–muscle axis.

Figure 1.

The hypothesized physiological and pathological mechanisms are delineated, with gut frailty, attributed to alterations in the gut microbiota, identified as a core element in the development of both somatic and cognitive frailty. The composition and metabolic activity of the gut microbiota are modulated by a range of environmental factors, such as dietary intake, pharmaceutical interventions, and physical activity.