Introduction

Irritable bowel syndrome (IBS) is defined as a disorders of gut–brain interaction, which shows a high comorbidity tendency with anxiety and depression. Berberine has been suggested in previous studies to alleviate IBS-like symptoms, however, there is currently a lack of research investigating the clinical efficacy of berberine, its modulation of gut microbiota, and its influence on brain functional regulation in IBS patients with comorbid anxiety and depression.

Aims & Methods

We conducted a double-blind, randomized, placebo-controlled clinical trial to evaluate the therapeutic efficacy of berberine on clinical symptoms in patients with IBS comorbid depression and (or) anxiety. Eligible participants with IBS based on Rome IV criteria and comorbid anxiety/depression based on HAMA/HAMD criteria were recruited. Participants were randomly assigned to receive berberine (300mg tid) or placebo for 8 weeks. Follow-up assessments occurred at 4 and 8 weeks. We collected stool samples from patients and performed resting-state functional magnetic resonance imaging (rs-fMRI) for patients and healthy controls (HCs) recruited at the same period at baseline and after 8 weeks of treatment. Fractional amplitude of low-frequency fluctuations (fALFF) was used to assess brain activation.

Results

78 patients (40 berberine, 38 placebo) showed no significant baseline differences. Berberine had higher drug response rates at 4 weeks (61.86% vs. 32.26%, p=0.027) and 8 weeks (73.53% vs. 32.26%, p=0.003). Berberine also had higher drug efficacy rates for anxiety at 8 weeks (79.4% vs. 29.0%, p<0.001). Adverse reactions (constipation, nausea) were higher with berberine (35.00% vs. 13.16%, p=0.025) but not severe. Metagenomic sequencing revealed that, berberine decreased pathogenic bacteria (Eubacterium, Faecalibacterium, Collinsella, Streptococcus, Lachnospira) and increased beneficial bacteria (Bacteroides uniformis etc.). Correlations indicated associations between Streptococcus, Eubacterium and diarrhea and abdominal pain. Berberine suppressed flagella assembly and bacterial chemotaxis, accordingly reduced invasiveness by decreasing the abundance of Eubacterium and Streptococcus, and improved gastrointestinal symptoms. Also berberine may reduce the function of pyrimidine metabolism, one-carbon pool folate, and glycerophospholipid metabolism by suppressing the abundance of Collinsella, Faecalibacterium and enriching Bacteroides uniformis. Patients exhibited decreased activity in several brain regions compared to HC, while increasing activity in brain regions (cingulate gyrus, supplementary motor area, superior frontal gyrus, etc.) after berberine intake was shown. Placebo group showed limited activity increase. Activity in different brain regions negatively correlated with abdominal pain, anxiety scores.

Conclusion

Berberine significantly improves gastrointestinal symptoms and psychometric scale score in IBS patients comorbid depression and (or) anxiety. Berberine reduces the abundance of pathogenetic bacteria, suppresses bacterial chemotaxis, flagella assembly and accordingly decreases bacteria invasiveness, which correlate with symptom improvement. Berberine may affect metabolic pathways linked to anxiety and depression improvement. Following berberine intervention, the activity in these hypoactive brain regions significantly recovers. Moreover, berberine enhances the activity in brain regions related to the functionality of the whole-body action-cognition network and control network, which may serve as important neurobiological foundations for berberine's treatment of the gut-brain comorbidity.

Disclosure

There are no financial conflicts of interest to disclose

Introduction

Avoidant/restrictive food intake disorder (ARFID) is characterized by reduced dietary intake leading to medical and/or psychosocial impairment, independent of body image concerns. Its prevalence in gastrointestinal (GI) disorders remains unclear despite frequent symptom-induced restrictive eating behaviors.

Aims & Methods

We aim to assess the prevalence and characteristics of ARFID in patients with various GI disorders compared to healthy volunteers (HV), and its associations with symptom severity, extraintestinal somatic symptoms and depression.
Data from 92 HV and 467 GI patients across seven tertiary care diagnostic categories —including irritable bowel syndrome (IBS, n=88), functional dyspepsia (FD, n=83), (refractory slow transit) constipation (n=59), reflux (n=107), globus (n=45), (non-obstructive) dysphagia (n=37), and achalasia (n=48)—were analyzed. Questionnaires included Rome IV criteria, ARFID screening, extraintestinal symptoms and depression scores (PHQ-12/9). Positive NIAS screening (NIAS+) was defined as meeting any subscale cutoff (≥10 for Picky Eating, ≥9 for Appetite, and ≥10 for Fear). Medical and/or psychosocial impairment in NIAS+ individuals was evaluated using the ARFID DSM-5 checklist. ARFID+ was defined as NIAS+ plus DSM-5 impairment. Odds ratios were calculated using a multiple logistic regression model with three-level hierarchical approach. Odds of fulfilling ARFID or NIAS criteria between DGBI diagnoses (step 1) were adjusted for z-scores of symptom severity (step 2) and extra-intestinal somatic symptoms and depression (step 3). Esophageal and non-esophageal disorders were analyzed separately.

Results

Table 1 shows demographics and characteristics of patients. Compared to HV, ARFID+ was significantly associated with IBS (OR: 15.00, p < 0.001), FD (OR: 10.59, p = 0.002), constipation (OR: 18.21, p < 0.001), dysphagia (OR: 7.03, p = 0.024) and reflux (OR: 5.16, p = 0.036), but not with achalasia and globus. Within disease categories, there were no differences in the odds of ARFID+ after adjusting for symptom severity (step 2) and for comorbid extraintestinal symptoms and depression (step 3). Increase in PHQ9, contributed independently to the presence of ARFID in non-esophageal disorders (OR: 1.11, p = 0.009).

Conclusion

ARFID symptoms are prevalent across various GI disorders. While mechanical factors may drive ARFID in esophageal conditions, psychological factors (e.g., depression) may play a role in ARFID in non-esophageal disorders. Further research is needed to establish the contribution of mechanical factors to ARFID in esophageal conditions. Routine ARFID screening is crucial to address psychosocial and nutritional impacts in GI patients.