Objective: Inflammatory bowel diseases (IBDs) are complex chronic inflammatory disorders of the gastro-intestinal (GI) tract with uncertain etiology. IBDs comprise two idiopathic disorders: Crohn’s disease (CD) and ulcerative colitis (UC). The aetiology, severity and progression of such disorders are still poorly understood but thought to be influenced by multiple factors (including genetic, environmental, immunological, physiological, psychological factors and gut microbiome) and their interactions. The overarching aim of this review is to evaluate the extent and nature of the interrelationship between these factors with the disease course. A broader conceptual and longitudinal framework of possible neuro-visceral integration, core microbiome analysis and immune modulation assessment may be useful in accurately documenting and characterizing the nature and temporal continuity of crosstalk between these factors and the role of their interaction (s) in IBD disease activity. Characterization of these interactions holds the promise of identifying novel diagnostic, interventions, and therapeutic strategies.Material and Methods: A search of published literature was conducted by exploring PubMed, EMBASE, MEDLINE, Medline Plus, CDSR library databases. Following search terms relating to key question were set for the search included: “Inflammatory bowel diseases,” “gut microbiota,” “psychological distress and IBD,” “autonomic reactivity and IBD,” “immune modulation,” “chronic inflammation,” “gut inflammation,” “enteric nervous system,” “gut nervous system,” “Crohn’s disease,” “Ulcerative colitis”, “depression and IBD”, “anxiety and IBD”, “quality of life in IBD patients,” “relapse in IBDs,” “remission in IBDs,” “IBD disease activity,” “brain-gut-axis,” “microbial signature in IBD,” “validated questionnaires in IBD,” “IBD activity indices,” “IBD aetiology,” “IBDs and stress,” “epidemiology of IBDs”, “autonomic nervous system and gut inflammation”, “IBD and environment,” “genetics of IBDs,” “pathways of immune response in IBDs,” “sleep disturbances in IBD,” “hypothalamic-pituitary-adrenal axis (HPA),” “sympatho-adrenal axis,” “CNS and its control of gut function” “mucosal immune response,” “commensal and pathogenic bacteria in the gut,” “innate and adaptive immunity.” Studies evaluating any possible associations between gut microbiome, psychological state, immune modulation, and autonomic function with IBDs were identified. Commonly cited published literatures with high quality research methodology/results and additional articles from bibliographies of recovered papers were examined and included where relevant.Results: Although there is a substantial literature identifying major contributing factors with IBD, there has been little attempt to integrate some factors over time and assess their interplay and relationship with IBD disease activity. Such contributing factors include genetic and environmental factors, gut microbiota composition and function, physiological factors, psychological state and gut immune response. Interdependences are evident across psychological and biological factors and IBD disease activity. Although from the available evidence, it is implausible that a single explanatory model could elucidate the interplay between such factors and the disease course as well as the sequence of the effect during the pathophysiology of IBD.Conclusion: Longitudinal monitoring of IBD patients and integrating data related to the contributing/risk factors including psychological state, physiological conditions, inflammatory/immune modulations, and microbiome composition/function, could help to explain how major factors associate and interrelate leading to exacerbation of symptoms and disease activity. Identifying the temporal trajectory of biological and psychosocial disturbances may also help to assess their effects and interdependence on individuals’ disease status. Moreover, this allows greater insight into understanding the temporal progressions of subclinical events as potential ground for disease severity in IBD. Furthermore, understanding the interaction between these risk factors may help better interventions in controlling the disease, reducing the costs related to disease management, further implications for clinical practice and research approaches in addition to improving patients’ mental health and quality of life.

Background Therapeutic aims in IBDs are to induce remission through rapidly effective treatment. Conventional therapeutic methods including immunosuppression have been available for more than half a century with biological therapies the treatment of choice in patients who fail immunosuppressive drugs. There has been little attempt to longitudinally examine the differences in biopsychological factors and their associations with treatment modalities in IBD patients. Methods 50 IBD participants (24 UC, 26 CD) in clinical remission were followed for 12 months. Complete longitudinal datasets including demography, disease status (HBI, Mayo score), monthly stool and blood samples for inflammatory biomarkers, monthly validated scores of psychological state, baseline physiological state and autonomic function were collected for analysis of association. Microbiome analysis was performed using V4 16SrRNA for identification of microbial phylogenetic relationships. Patients were grouped on whether or not they were in remission on biological agents. Results CD: There was a larger magnitude of change in linear trends of anxiety (p = 0.007) in CD patients on non-biologic treatment. Quality of life (QOL), health-related quality of life (HRQOL) and faecal calprotectin measures were similar regardless of treatment. Longitudinal quadratic trends of CRP were significantly different between the two (p = 0.039) with the larger magnitude of change in non-biologic groups. CD patients had similar microbial profile when compared between two treatment groups. UC: Similar distributions of longitudinal psychological measures were found in two treatment groups, although results suggested significant linear trend (p = 0.019) in QOL scores but not with HRQOL. Faecal calprotectin had significant longitudinal linear trend (p = 0.016) with significant interaction between biologic therapy and this trend (p = 0.023). CRP had significant quadratic trend (p = 0.005) with strong interaction between biologic therapy and this trend (p = 0.009). Microbial α diversity was significantly different between two groups of treatments (Shannon; p = 0.041, evenness; p = 0.045) with biologic group having more diverse and more even microbial community. Conclusion Baseline biological and psychological factors were mostly similarly distributed between the two treatment options in remissive IBD patients, however biological therapy significantly influenced longitudinal trends of some psychological, inflammatory and microbiome dynamics, especially in UC. This suggests an underlying interrelationship between mode of treatment and biopsychological trajectories which might overshadow response to the treatment, requiring further assessment.

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BackgroundThis study examines longitudinal bio-psychological dynamics and their interplay in IBD patients undergoing conventional and biological therapies.MethodsFifty 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.ResultsResults 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.ConclusionA 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.