The Interplay Between Use of Biological Therapies, Psychological State, and the Microbiome in IBD

Abstract

Background: This study examines longitudinal bio-psychological dynamics and their interplay in IBD patients undergoing conventional and biological therapies.

Methods: Fifty IBD participants (24 UC, 26 CD) in clinical remission were followed for 12 months. Complete longitudinal datasets, biological samples, validated scores of psychological status were collected monthly for analysis of association. Microbiome analysis was performed to identify microbial dynamics and signatures. Patients were grouped on disease phenotype (CD, UC) and mode of treatment (biological therapies, non-biological treatment). General linear models, mixed models, cluster analysis, and analyses of variance were used to examine the longitudinal trends of the variables and their associations over time. Results were corrected for multiple testing.

Results: Results substantiated different interactions between biological therapy and longitudinal trends of inflammatory biomarkers in remission CD and UC patients as well as significant differences between CD and UC patients in their psychological measures during clinical remission, with UC patients having inferior condition compared to CD. A significant reduction in microbial diversity in CD patients compared to UC was identified. Results characterized considerable differences in longitudinal microbial profile between those taking and not taking biological treatment in UC patients, but not in CD patients.

Conclusion: A different trajectory of interdependence was identified between psychological state, sleep, and microbial dynamics with mode of treatment when compared between CD and UC patients. Further studies should investigate the causal relationships between bio-psychological factors for improved treatment purposes.

Keywords: Crohn's disease; gut microbiome; inflammatory bowel disease; psychological state; ulcerative colitis.

Figure 1

Non-parametric analysis quantifying F-calprotectin (A) and C-reactive protein (CRP) (B) at baseline and across diagnosis. Analysis did not show significant differences in measures of both CRP and FC in CD and UC participants at baseline assessment.

Figure 2

Phylum composition in baseline analysis (CD, UC). Phylum composition relative abundance for baseline analysis in all CD, UC participants. Only the top 5 phyla are shown. Numbers indicate the p-value from the Wilcoxon tests.

Figure 3

UC patients: strong negative relationship between microbial evenness and depression scores (p < 0.001), meaning that lower microbial evenness was strongly associated with higher depression scores in UC cohort.

Figure 4

Microbial community composition at family level in patients in remission. (A) CD, and (B) UC. Only families with a relative abundance ≥2% in any sample are shown.

Figure 5

CD participants- microbial α diversity and treatment modalities. Measures of microbial α diversity between treatment options in CD group (Comprising remission and relapse) including: (A) Shannon's index (diversity); (B) Pielou's evenness; and (C) Chao1 index (richness). Analysis did not show any significant differences between the two groups over time.

Figure 6

Microbial community composition at family level in IBD patients across two treatment options including changes in FC concentration over time in (A) CD, and (B) UC. Only families with a relative abundance ≥2% in any sample are shown.

Figure 7

Differences in some microbial family abundances between the two treatment options in CD group (biologics vs. non-biologic). Only significantly different families are shown (Wilcoxon, p ≤ 0.05).

Figure 8

CD participants-Microbial biomarkers. OTUs microbial biomarkers for CD groups with two treatment options including biologic treatment (Yes) and non-biologic treatments (No) (OTUs and Genus information on Supplementary Table 14).

Figure 9

Differences in some microbial family abundances between the two treatment options in UC group. Only significant results are shown (Wilcoxon, p ≤ 0.05).

Figure 10

UC participants- microbial a diversity and treatment modalities. Measures of microbial alpha diversity between treatment options in UC group (comprising remission and relapse) including: (A) Shannon's index (diversity); (B) Pielou's evenness; and (C) Chao1 index (richness).

Figure 11

UC participants-Microbial biomarkers. OTUs microbial biomarkers for UC groups with two treatment options (biologic as Yes and non-biologic treatments as No) (OTUs and Genus information on Supplementary Information No. 14).