Abstract

Abstract Background Anxiety and/or depression (A/D) have been identified as significant co-morbidities of ulcerative colitis (UC), and even considered as extraintestinal manifestations, with emerging evidence to support the role for gut microbial dysbiosis in the natural history for both UC and A/D. However, there is a paucity of knowledge regarding the specific attributes of the gut bacteriome in individuals with UC with concomitant A/D. Aims To explore the connection between the gut bacteriome and A/D in a cohort of patients with UC. Methods This cross-sectional study included 29 participants diagnosed with UC either in remission or with mild to severe disease. To test for depression and anxiety, participants completed the Patient Health Questionnaire-8 (PHQ-8) and General Anxiety Disorder-7 (GAD-7) respectively. Participants provided a stool sample for microbiome analysis and the fecal bacteriome was assessed using metagenomic shotgun sequencing. Results Among the 29 patients, 55% were female (n=16) and 45% were male (n=13), 34.5 % (n=10) had a Partial Mayo Score over 5 indicating moderate-severe disease activity (median 3, IQR 1-6). Mean age was 38.3 years (± 12.2 years). Sixty-nine percent were on 5-ASA, 42.9% on steroids, 31.0% on Anti-TNF, and 20.7% on immunomodulators. Mean FCP was 976.4 μg/g (± 1589.2). Forty-four percent (n=12) screened positive for anxiety with a median GAD-7 score of 5.0 (IQR: 1-8), while 26% screened positive for depression with a median PHQ-8 of 3 (IQR: 3-10). Principal Coordinate Analysis (PCoA) reveals distinct clustering between UC patients with or without A/D (Figure 1). Regarding the microbial analyses, the log fold change of Firmicutes bacterium CAG:424, Holdemanella biformis, Blautia hansenii, Bifidobacterium pullorum, Anaerostipes caccae, and Ruminococcus gnavus exhibited positive associations with both A/D, whereas Roseburia sp. CAG:303, Prevotella copri, and Bacteroides stercoris demonstrated negative associations. Uniquely, Faecalicoccus pleomorphus and Lachnospira pectinoschiza showed negative associations only with the PHQ-8. Conclusions Our research affirms the presence of anxiety and depression in a cohort of UC patients. The severity of A/D measured by the GAD-7 and PHQ-8 were linked to the levels of specific fecal microbes. We introduce several novel species that warrant further examination in UC patients with and without A/D. As this was an exploratory study, the findings need replication in a larger sample size. PCoA results reveal distinct bacterial clustering patterns between individuals with minimal anxiety/depression (absence) versus those with mild/moderate/severe anxiety and depression as measured by GAD-7 and PHQ-8. Funding Agencies None

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