Gut microbiota and intestinal permeability in older adults and their roles in cognitive frailty

The rapid growth of the global ageing population has led to a surge in age-associated syndromes including cognitive frailty (CF). CF is characterised by the coexistence of physical frailty and mild cognitive impairment (MCI) without dementia, which poses major risks for mortality, hospitalisation, and reduced quality of life. Ageing is often accompanied by gut frailty, marked by low-grade inflammation and reduced gut microbiota diversity and composition (dysbiosis), which may impair brain function and increase susceptibility to CF. To date, there remains very limited integrative research in this area. The present study aimed at exploring the changes in gut microbiota as well as intestinal permeability and inflammatory markers in older adults through a multi-tiered research approach, which included systematic review and meta-analysis as well as comprehensive microbiome sequencing and statistical analyses. The present systematic review and meta-analysis found that previous studies on intestinal permeability in older adults (n = 10) focused predominantly on faecal calprotectin (an intestinal inflammatory marker). Although elevated faecal calprotectin was consistently observed in cases (diseases) versus controls, findings on intestinal permeability markers such as alpha-1antitrypsin and zonulin remain limited, inconsistent, and largely underexplored in the context of ageing. These findings highlight the urgent need for robust validation of faecal markers as surrogate tools for monitoring intestinal health in clinical practice.