Change in irritable bowel syndrome symptom severity among members of a multi-omic digital food-as-medicine program: a retrospective single-arm cohort study with estimates corrected for regression to the mean

Background: Real-world evidence on food-as-medicine programs for irritable bowel syndrome (IBS) is scarce, and single-arm evaluations overstate improvement because of regression to the mean (RTM). We estimated change in the IBS Symptom Severity Scale (IBS-SSS, 0-500) in a multi-omics personalized digital health food-as-medicine program, unadjusted and RTM-corrected. Methods: Retrospective single-arm cohort. Of 15,933 members with a valid baseline, 2,254 had a follow-up reading and 1,683 one at least 14 days after baseline. Change at 4, 12 (primary) and 26 weeks was estimated by baseline severity stratum, unadjusted and RTM-corrected by analysis of covariance. A responder fell by at least 50 points (the minimal clinically important difference benchmark). Sensitivity analyses covered equity, inverse-probability weighting and delta-based tipping-point analyses for members without a reading in each landmark window, a negative-control stratum and medication. The association of weight loss and dietary nutrient density with symptom change was evaluated within and between members. Results: At 12 weeks (n = 430) IBS-SSS fell by 43.88 points unadjusted (95% confidence interval [CI] -52.44 to -35.32; p < 0.001) and by 47.73 RTM-corrected (-55.48 to -39.98; p < 0.001); 720 of 1,339 symptomatic members (53.8%; 95% CI 51.1 to 56.4) fell by at least 50 points, and the proportion of responders rose with baseline severity, from 41.0% in the mild stratum (226/551) and 59.4% in the moderate stratum (336/566) to 71.2% in the severe stratum (158/222), staying at 73% to 76% in the severe stratum at each landmark. Larger improvement in more severe members persisted after RTM correction (severe stratum, n = 37: unadjusted -127.43, RTM-corrected -60.71, 95% CI -97.75 to -23.68, p = 0.001). A higher meal nutrient density was associated with lower IBS-SSS within a members own trajectory (p = 0.018) while weight change was not (p = 0.361). Follow-up differed by age, sex, income and ethnicity; subgroup differences in RTM-corrected 12-week change were not significant (age p = 0.458, sex 0.749, income 0.486, ethnicity 0.170). RTM-corrected estimates moved by less than 2 points with weighting for members without a reading, and their change would have had to be 39 to 73 points worse than observed before the mean change reached zero. Baseline medication use and starting a GLP-1 receptor agonist did not explain symptom changes. Conclusions: IBS-SSS fell significantly among program participants, with steeper improvement in the more severe group, even after RTM correction. Improvement occurred in all subgroups, with mostly non-significant differences, though follow-up differed by subgroup and the ethnicity result depended on missing-data handling; overall estimates were robust to the assumptions evaluated. These associations from a self-selected single-arm cohort warrant replication in independent studies.