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Background The relationship between non-alcoholic fatty liver degree as well as non-alcoholic fatty liver disease (NAFLD) and irritable bowel syndrome (IBS) remains poorly understood. We aimed to investigate the prospective association of non-alcoholic fatty liver degree as well as NAFLD with incident IBS in a large-scale population-based cohort. Methods Participants free of IBS, coeliac disease, inflammatory bowel disease, alcoholic liver disease, and any cancer at baseline from the UK Biobank were included. Non-alcoholic fatty liver degree was measured by a well-validated fatty liver index (FLI), with FLI ≥ 60 as an indicator of NAFLD. Primary outcome was incident IBS. Cox proportional hazard model was used to investigate the associated risk of incident IBS. Results Among 396,838 participants (mean FLI was 48.29 ± 30.07), 153,203(38.6%) were with NAFLD diagnosis at baseline. During a median of 12.4-year follow-up, 7129 cases of incident IBS were identified. Compared with non-NAFLD, NAFLD patients showed a 13% higher risk of developing IBS (HR = 1.13, 95%CI: 1.05–1.17) after multivariable adjustment. Compared with the lowest, the highest FLI quartile was associated with a significantly increased risk of IBS (HRQ4 VS Q1 = 1.21, 1.13–1.30, Ptrend Conclusions High degree of non-alcoholic fatty liver as well as non-alcoholic fatty liver disease is associated with increased risk of incident IBS. Further studies are warranted to confirm the findings and elucidate the underlying biological mechanisms.

Additional file 2. FigureS1. Restricted cubic splinefor the association of baseline fatty liver index with incident IBS. Figure S2. Risk of incident IBSassociated with NAFLD type (lean, non-obese and obese NAFLD).

Additional file 1. Table S1. ICD codes and Field ID definingdiseases in UKB. Table S2. Baseline characteristicsaccording to diagnosis of NAFLD or not by predefined cutoff of FLI in UKBiobank cohort. Table S3.Sensitivity analysis regarding risk of IBS according to per SD change anddiagnosis of NAFLD or not by predefined cutoff of FLI. Table S4. Sensitivityanalysis regarding risk of IBS according to per SD change and diagnosis ofNAFLD or not by predefined cutoff of baseline hepatic steatosis index.

Human nectin—like 1 (NECL1) full—length cDNA was cloned by bioinformatics method when searching for candidate membrane proteins interacting with members of protein 4.1 family. The cytoplasmic and extracellular regions of NECLl were expressed in and purified from E.coli, and the polyclonal antibody was produced. Interaction between the cytoplasmic region of NECLl and the 30 kD membrane binding domain of protein 4.1 on red blood cell (4.1R) was demonstrated by IAsys—biosensor system and GST pull—down experiment. Results of biotin—labeled peptide ELISA further demonstrated the key amino acids for the binding. The interaction research of NECLl's cytoplasmic domain provides basis for further study of the functions of NECL1 in nervous system. Supported by National Natural Science Foundation of China (Grant No. 50271027), Fujian International Cooperation Foundation (Grant No.20021018), and Fujian Natural Science Foundation (Grant Nos. E0310023 and 2002J010)