Impact of Psychopathology and Gut Microbiota on Disease Progression in Ulcerative Colitis: A Five-Year Follow-Up Study

Abstract

Psychological distress and gut dysbiosis play key roles in IBD. This study investigated whether specific psychopathological and gut microbiota features predict adverse outcomes in UC patients. This retrospective cohort study included 35 UC patients recruited in 2019. Baseline assessments involved clinical interviews, psychiatric evaluations, and stool sampling. In 2024, follow-up interviews and medical record reviews assessed disease progression, including biologic therapy failure, hospitalization, surgery, and diagnosis changes. Disease activity was measured via the Mayo score. Psychological testing included MMPI-2, STAI-Y2, GSES, CD-RISC, and TAS-20. Patients with biological therapy failure showed increased levels of Proteobacteria, Fusobacteria, Enterobacteriaceae, and Trabulsiella, while Firmicutes were less abundant. UC-related hospitalized patients had lower levels of Rikenellaceae, Ruminococcaceae, Faecalibacterium, Lachnospira, Methanobrevibacter, and Phascolarctobacterium compared to non-hospitalized patients. Hospitalized patients scored higher on the Sc clinical scale and the OBS and HEA content scales. Acidaminococcus and Bilophila were more abundant in patients who underwent surgery. PCA revealed differences between patients with and without biological failure. Logistic regression found that Fusobacteria were negatively correlated with the failure of three or more biologics, while Hy and Pd were positively correlated. Pa and Pt were negatively correlated with multifailure. Obsessiveness, health concerns, somatization, and reduced SCFA-producing bacteria may predict UC-related adverse outcomes.

Keywords: disease activity; gut microbiota; gut–brain-axis; psychopathology; ulcerative colitis.

Figure 1

Gut microbiota differences between patient groups. (A) Patients who experienced a failure of biological therapy (Fail1) showed significantly increased levels of Proteobacteria, Fusobacteria, Enterobacteriaceae, and Trabulsiella, and decreased Firmicutes compared to patients who did not experience failure (nFail1). (B) Patients hospitalized for complications related to ulcerative colitis (Hos) exhibited lower levels of Euryarchaeota, Rikenellaceae, Ruminococcaceae, Faecalibacterium, Lachnospira, Methanobrevibacter, Parabacteroides, Phascolarctobacterium, and Collinsella compared to non-hospitalized patients (nHos). (C) Patients who underwent surgery for UC (Sur) had higher levels of Acidaminococcus and Bilophila compared to non-surgical patients (nSur). (D) Patients with a diagnosis change to Crohn’s disease (Ch) had lower levels of Coprococcus compared to those with no diagnosis change (nCh).

Figure 2

Psychometric scale differences between patient groups. (A) Hospitalized patients (Hos) had higher scores on the Sc (Schizophrenia) clinical scale, as well as on the OBS (Obsessiveness) and HEA (Health Concerns) content scales, compared to non-hospitalized patients (nHos). (B) Patients with a diagnosis change to CD (Ch) scored lower on the STAI Y2 (trait anxiety), higher on the Mf (Masculinity–Femininity) clinical scale, and lower on the Sc (Schizophrenia) clinical scale and the BIZ (Bizarre Mentation) content scale compared to those without a diagnosis change (nCh). Gray dashed lines indicate the clinical threshold (T-score ≥ 65) above which scores are generally considered clinically significant.

Figure 3

Principal Component Analysis (PCA) of gut microbiota at the phylum level. The PCA conducted on the phyla of the gut microbiota revealed significant differences between patients who experienced the failure of biological therapy (Fail1) and those who did not (nFail1), as indicated by PERMANOVA (p < 0.001), with an explained variance of 42.3%.