Abstract
BACKGROUND: Frailty is a public health problem for ageing society, however, evidence is lacking regarding its impact on intestinal functions. We aimed to examine prospective relationships of frailty and pre-frailty in middle-aged and older adults with incident irritable bowel syndrome (IBS) in a large-scale population-based cohort. METHODS: Participants (aged 37-73 years) free of IBS, coeliac disease, inflammatory bowel disease and any cancer at baseline were included, using data from the UK Biobank (collected 2006-2010, 22 assessment centres). Participants without available primary care data were excluded. Frailty status was assessed using Fried phenotype including five criteria (weight loss, exhaustion, low grip strength, low physical activity, slow walking pace). Participants who met at least three criteria were defined as frail, and those who fulfilled one or two criteria were defined as pre-frail. Primary outcome was incident IBS. Cox proportional hazard model was conducted to examine the associated risk of incident IBS. FINDINGS: Among 176,423 participants (mean age 56.19 years), 7994 (4.5%) and 78,957 (44.8%) were frail and pre-frail at baseline. During a median of 13.2-year follow-up, 4155 cases of incident IBS were identified. Compared with non-frail individuals, those with frail (HR = 1.80, 95% CI: 1.59-2.04) and pre-frail (HR = 1.21, 1.14-1.30) showed significantly higher risk of developing IBS after multivariable adjustment (P(trend) < 0.001). Specifically, the positive association was not only observed in older adults (HR = 1.69, 1.37-2.08 for frail; 1.24, 1.12-1.39 for pre-frail), but also in middle-aged adults (HR = 1.90, 1.62-2.22 for frail; 1.19, 1.10-1.30 for pre-frail), both with P(trend) < 0.001. Further sensitivity analysis and subgroup analysis indicated similar results. INTERPRETATION: Frailty and pre-frailty in middle-aged and older adults are associated with increased risk of incident clinical diagnosis of IBS. FUNDING: National Natural Science Foundation of China (No. 82070550) & National Key Research and Development Program of China (2022YFC2504002, 2022YFC2504003).