Association of intestinal leakage with frailty in patients with age-related diseases

Abstract Purpose Frailty is a geriatric syndrome that precedes disability and is a common finding in patients with chronic obstructive pulmonary disease (COPD), chronic heart failure (CHF), and Alzheimer’s disease (AD). The contribution of increased intestinal permeability to frailty phenotype in patients with COPD, CHF, and AD is poorly known. Methods We conducted a cross-sectional, multicenter study of older men, including controls and patients with COPD, CHF, and AD (n = 37—48/group). We used Fried's cardiovascular health study (CHS) criteria to measure frailty and measured plasma zonulin levels as a biomarker of intestinal permeability. We also measured plasma c-reactive protein (CRP), 8-isoprostanes, and creatine kinase (CK) levels as markers of inflammation, oxidative stress, and muscle damage, respectively. Results Frail patients exhibited higher plasma zonulin than pre-frail patients, irrespective of disease type (all p < 0.05). Plasma zonulin exhibited significant positive associations with CHS frailty index, which were strongest in the control group, followed by CHF, COPD, and AD patients, respectively (all p < 0.05). Plasma zonulin demonstrated significantly high areas under the curve in diagnosing frailty in controls and patients with COPD, CHF, and AD (all p < 0.05). In the frail vs. pre-frail comparisons, we also found elevated plasma CK levels in CHF and AD patients, elevated CRP levels in COPD patients, and elevated 8-isoprostanes in AD patients (all p < 0.05). Conclusion Together, our data indicate the potential contribution of the disrupted intestinal mucosal barrier and elevated plasma zonulin to frailty phenotype in patients with COPD, CHF, and AD.