New evidence to inform clinical decisions

Introduction: Anxiety and depression are common in disorders of gut-brain interaction (DGBI). (1) Digital brain-gut behavioral therapy (BGBT) is a validated intervention, but psychological outcomes remain understudied. We evaluated whether a 6-week BGBT program is associated with psychological symptom change in users with irritable bowel syndrome.

Methods: 64,025 users with baseline data who completed a 6-week BGBT program were retrospectively analyzed. The PHQ-4 was administered at baseline and program end (average 6-weeks) yielding a composite score (0–12; bands: none 0–2, mild 3–5, moderate 6–8, severe 9–12) and two subscales, GAD-2 (anxiety, 0–6) and PHQ-2 (depression, 0–6), each positive at ≥3. Outcomes were percentage reduction, screening conversion (≥3 to <3), severity band shifts, and Cohen’s d. Secondary analyses modelled time-to-resolution (Kaplan-Meier). Attrition was assessed by baseline completer vs non-completer comparison, with inverse probability weighting (IPW) for sensitivity.

Results: Completion was associated with significant reductions: GAD-2 (36.3%, 3.68 to 2.34; d = 0.77), PHQ-2 (37.6%, 2.42 to 1.51; d = 0.52), and PHQ-4 composite (36.8%, 6.10 to 3.85; d = 0.72). Positivity halved for anxiety (GAD-2 ≥3: 68.2% to 34.1%) and depression (PHQ-2 ≥3: 41.3% to 20.0%). Among screen-positive users, 57.2% on GAD-2 (N = 43,643) and 64.5% on PHQ-2 (N = 26,469) dropped below threshold. On PHQ-4, 66.1% with baseline distress (≥mild) shifted to a lower band, rising by severity: 50.3% mild, 72.8% moderate, 77.7% severe. Median time-to-resolution was 34 days (GAD-2) and 27 days (PHQ-2). Baseline psychological symptoms were near-identical in completers and dropouts (GAD-2: d = 0.08; PHQ-2: d = 0.12), though dropouts reported more abdominal pain and bloating. IPW-adjusted estimates matched unweighted results (±0.1pp). Higher baseline somatic severity predicted greater improvement among completers (anxiety: 0.749 vs 0.655, high vs low abdominal pain; p < 0.001).

Discussion: Digitally delivered BGBT is associated with meaningful reductions in anxiety and depression, with over half of screen-positive users measuring below threshold within six weeks. Baseline somatic severity was associated with attrition but not attenuated response among completers. Improving retention in high somatic-burden users may extend these benefits.

1. Trindade IA, et al. Am J Gastroenterol 2024;119:165-175.

Background: Anxiety and depression frequently co-occur with irritable bowel syndrome (IBS), and clinicians often assume that psychological comorbidity may attenuate response to behavioural interventions, potentially leading to deferral of brain-gut therapy in favour of pharmacological or dietary management. Whether baseline psychological distress influences abdominal pain outcomes in digital gut-directed hypnotherapy (GDH) has not been examined at scale.

Materials and Methods: Retrospective cohort analysis of de-identified data from Nerva, a six-week daily digital brain-gut behavioural therapy program for IBS (May 2020–May 2026). Of 228,876 paid users, 76,138 recorded both initial and end-of-program abdominal pain scores (0–100 mm visual analogue scale) with complete Patient Health Questionnaire-4 (PHQ-4) data and comprised the analysis cohort (mean age 46 ± 16 years; n=48,544 with known age). PHQ-4 total scores (range 0–12) were categorised into severity groups: none (0–2; n=11,943), mild (3–5; n=23,514), moderate (6–8; n=21,760), and severe (9–12; n=18,921). The primary outcome was the proportion achieving ≥30% abdominal pain reduction, aligned with established clinically meaningful thresholds in IBS. A Cochran–Armitage test assessed trend in responder rates across ordered severity groups.

Results: Mean baseline abdominal pain increased with PHQ-4 severity (50.9 to 66.4 mm). Despite this gradient, the ≥30% pain responder rate was consistent across all groups, ranging from 52.2% to 53.6% with no significant trend (p for trend=0.13).

Conclusions: Among 76,138 IBS program completers with paired symptom data, baseline psychological comorbidity as measured by the PHQ-4 did not influence abdominal pain response to digital GDH. Over half of completers in every severity category, including those with severe psychological symptoms, achieved clinically meaningful pain reduction. Interpretation should consider potential selection bias related to program completion and availability of paired symptom data. These data suggest that baseline psychological comorbidity should not deter clinicians from recommending digital GDH for IBS.

Background: A long-standing paradigm holds that brain-gut behavioural therapy is primarily indicated for patients whose symptoms are driven by psychological distress rather than dietary triggers. Consequently, patients identifying food-only triggers are often directed toward restrictive diets rather than behavioural care. No large-scale study has compared outcomes of brain-gut behavioural therapy across self-reported trigger profiles.

Materials and Methods: Retrospective cohort analysis of de-identified data from Nerva, a six-week daily digital brain-gut behavioural therapy program for irritable bowel syndrome. Users with completed onboarding and six-week outcome data were included (n=26,008; mean age 38 ± 12 years; 84% female). At onboarding, users self-classified their predominant symptom trigger as food only (n=4,016), stress only (n=5,512), or combined food and stress (n=16,480). Baseline symptom severity was comparable across groups (p>0.05). Outcomes: (1) average weekly session adherence; (2) proportion achieving global symptom improvement, defined as a ≥2-point reduction on a 0–10 severity scale at six weeks. Between-group comparisons used t-tests and chi-square tests; logistic regression assessed the association between combined trigger status and improvement, adjusting for age, gender, and baseline severity. Individual-level comorbidity data were unavailable, limiting confounder adjustment.

Results: There was no significant difference between food-only and stress-only users in weekly adherence (2.53 versus 2.54 sessions; p=0.86) or proportion reporting improvement (23.0% versus 23.4%; p=0.63). The combined group demonstrated modestly higher adherence (+0.17 sessions per week; p<0.001) and a higher improvement rate (28.0%; odds ratio 1.19; 95% CI 1.11–1.28; p<0.001). The adherence difference, although statistically significant, may not represent a clinically meaningful difference.

Conclusions: These data do not support the assumption that brain-gut behavioural therapy is less suitable for users who identify food rather than stress as their predominant trigger; food-only and stress-only users showed similar engagement and symptom improvement outcomes. A combined trigger profile was associated with modestly higher improvement, though absence of confounder data warrants cautious interpretation.

Introduction: Gut-directed hypnotherapy (GDH) is an effective treatment for disorders of gut–brain interaction, including irritable bowel syndrome (IBS). App-based delivery of GDH has demonstrated comparable efficacy to face-to-face treatment. However, its impact in individuals with co-morbid gastrointestinal (GI) conditions such as Crohn's disease and ulcerative colitis (UC) is not well understood. This study evaluated outcomes following the app-delivered GDH program, Nerva, in people with IBS with and without co-morbid GI conditions.

Methods: Individuals enrolling in the Nerva 6-week app-based GDH program were asked at baseline whether they had a co-morbid GI condition. Respondents indicating Crohn's disease or UC were classified accordingly, while those reporting no co-morbid GI condition (none) served as the comparison group. Outcomes were assessed at program completion, including responder status (≥30% improvement in abdominal pain) and change in total psychological symptom score as measured by the PHQ-4. Subgroup analyses were conducted by sex and age (≤50 vs >50 years). In total, 2,843 reported no co-morbid GI condition, 100 reported Crohn's disease, and 151 reported UC.

Results: Of the total sample, 2,843 individuals reported no co-morbid GI condition (80% female, aged 13-94 y), 100 reported Crohn's disease (82% female, 18-82 y), and 151 reported UC (79% female, 14-83 y). Responder rates were comparable across diagnostic groups (none 58%, Crohn's 52%, UC 60%; p=0.26, one-way ANOVA). Across sex, responder rates were broadly similar, although males with UC demonstrated a numerically higher responder rate (69%) than other subgroups. By age, responder rates were similar across groups for users ≤50 years, whereas individuals with UC aged >50 years had the highest responder rate (70%). Psychological improvements were likewise consistent across groups, with males and females showing comparable changes and only minimal (non-significant) differences between those with no co-morbid GI condition, Crohn's disease, and UC.

Discussion: App-delivered GDH via Nerva has comparable responder rates and psychological benefit individuals with IBS-like symptoms and co-morbid Crohn's disease or UC to those without co-morbid GI conditions. This suggests GDH may be a feasible and effective option for managing functional symptoms in IBD populations, where treatment gaps remain. Controlled studies are warranted to confirm efficacy and examine demographic moderators of response.

Background: Digital brain-gut behavioural therapy is effective at managing irritable bowel syndrome (IBS), but clinical adoption in older adults remains low, partly due to assumptions that smartphone-delivered therapies are less suitable for this population. Data evaluating engagement and clinical outcomes of digital GDH in older adults remain limited.

Materials and Methods: Retrospective cohort analysis of de-identified data from Nerva, a six-week daily digital brain-gut therapy program for IBS (July 2019–May 2026; data extracted May 1, 2026). Enrolled users with known age were included (n=131,900; mean age 42 ± 15 years; 70% female; 41% US, 19% Australia, 16% UK). Users were stratified by age band (<45, 45–54, 55–64, 65–74, 75–84, 85+). Abdominal pain was assessed via a 0–100 mm visual analogue scale (VAS). Clinically significant response was defined as a ≥30% VAS reduction. Outcomes: (1) program completion rate; (2) ≥30% abdominal pain VAS responder rate among users with valid paired scores.

Results: Of 131,900 enrolled users, 13,454 (10.2%) were aged ≥65. Older adults demonstrated higher engagement: program completion increased from 34% (<45) to 61% (65–74; p<0.001). Among 51,940 users with valid paired VAS scores, the ≥30% abdominal pain responder rate was 51.0% (<45; 95% CI 50.4–51.6) compared with 58.8% (65–74; 57.5–60.0; p<0.001). The responder rate was also significantly higher in the 45–54 (53.6%), 55–64 (57.8%), and 75–84 (55.4%) age bands (all p<0.001 vs <45). The 85+ band (45.0%; 36.4–53.9) did not differ significantly from <45 (p=0.23; n=120).

Conclusions: Older adults with IBS demonstrated higher engagement and improved abdominal pain outcomes with digital GDH compared with younger users. These data suggest that digital GDH is feasible and associated with meaningful engagement across the adult age spectrum, including older populations.

Introduction: Gut-directed hypnotherapy is an evidence-based treatment for irritable bowel syndrome (IBS), but adherence to digital programs remains a challenge. We examined whether structured clinic follow-ups with an advanced practice provider will enhance the completion rates of an app-based gut-directed hypnotherapy program, in a tertiary care Neurogastroenterology practice.

Methods: We retrospectively analyzed 80 consecutive IBS patients who enrolled in the 6-week app-based gut-directed hypnotherapy program. After identifying the appropriate patients, app information was sent to the patients along with scheduled visits. The protocol included an initial consultation visit, mid-point check-in (week 3), and completion follow-up (week 6) by a specialized nurse practitioner. Patients completed the Visual Analogue Scale for IBS and the Patient Health Questionnaire 4 (PHQ-4). We examined clinical characteristics, program completion and the association between follow-up visit attendance and completion rate of the app-based therapy.

Results: The cohort represented a complex IBS population (61.3% IBS-constipation) with high psychological comorbidity (78.8%) and prolonged symptom duration > 5 years (62.5%). Overall program completion rate was 46.2% compared to 24% in general self-directed app users (p<0.001). Patients attending all three visits were more likely to complete the program than those attending only one to two visits (67.6% vs 22.6%, p=0.0005). Visit number correlated with completion rate (Spearman ρ=0.43, p=0.0003; Kendall τ=0.41, p=0.0005). No baseline characteristic, subtype, duration, psychological comorbidity, and baseline severity, predicted completion rate. Completers achieved a 31.4% reduction in GI symptoms with a large effect size (d=−1.00), which was comparable to 38.9% reduction (d=−0.96) in general population (p=0.23). Anxiety outcomes were similarly comparable with improvement in 38.1% (d=−0.86) versus 36.5% (d=−0.72) in general population (p=0.62).

Discussion: In this tertiary care IBS cohort, structured follow-ups were associated with completion rates of an app-based gut-directed hypnotherapy program. Despite the greater clinical complexity, those who completed the program demonstrated large and clinically meaningful symptom reductions. Larger studies are needed to confirm that clinical engagement improves symptom outcomes using digital behavioral therapy in IBS.

Introduction: Digital brain-gut behavioral therapy (d-BGBT) may expand access to evidence-based treatment for irritable bowel syndrome (IBS), but equitable access depends on awareness and is often shaped by clinician referral. Prior data suggest that men are less often clinician-referred despite self-directed interest and similar benefit to women. Whether referral patterns vary by provider gender or provider-patient gender pairing is unknown. We evaluated gender-based differences in clinician referral patterns for d-BGBT.

Methods: We performed a retrospective analysis of deidentified adults using a d-BGBT program for IBS across Australia, the United States, and the United Kingdom. Gender distribution was compared between all d-BGBT users and clinician-referred users. Among clinician-referred users with provider and patient gender data, referrals were categorized by provider-patient gender dyad. The primary outcome was referrals to male versus female patients by provider gender. Secondary outcomes included paid-program conversion and completion.

Results: A total of 790,304 users had gender data, of whom 42,845 (5.4%) were clinician-referred. Among clinician-referred users, men accounted for 20.0% compared with 26.8% of all d-BGBT users; women accounted for 78.7% compared with 72.1% overall (p<0.001). Among 25,517 referrals with provider-patient gender dyad data, 20,748 (81.3%) were from female providers and 4,769 (18.7%) from male providers. Referral patterns differed by provider gender: female providers referred 16.4% male and 83.6% female patients, compared with 31.3% male and 68.7% female patients among male providers (p<0.001). Gender concordance was not associated with higher conversion or completion.

Discussion: Men represented more than one-quarter of all d-BGBT users but only one-fifth of clinician-referred users, suggesting a referral-specific access gap despite interest in d-BGBT. Provider gender was associated with referral patterns, though this may reflect practice composition and unmeasured case-mix. Gender concordance did not meaningfully improve conversion or completion. Provider and patient gender may influence whether d-BGBT is selected as a therapeutic option. Prospective studies are under development to clarify why referral rates differ despite similar efficacy outcomes between men and women with IBS. ChatGPT was used to assist with language refinement, clarity, and formatting. All analyses, interpretations, conclusions, and final content were reviewed and approved by the authors.