A Review of Inflammatory Bowel Disease: A Model of Microbial, Immune and Neuropsychological Integration

Abstract

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.

Potential role of MALT1 as a candidate biomarker of disease surveillance and treatment response prediction in inflammatory bowel disease patients

“…(c) The dysregulation of MALT1 was positively correlated with microbial pathogens, which had been reported to be associated with the inflammatory status in IBD patients. 48 , 49 , 50 Therefore, MALT1 was related to inflammation indexes in IBD patients.…”

Inflammatory bowel disease biomarkers of human gut microbiota selected via different feature selection methods

“…IBD, comprising Crohns disease (CD) and ulcerative colitis (UC), is a gut-related disorder that affects the intestinal tract. The most widely reported symptoms of IBD involve diarrhea, intermittent nausea and vomiting, rectal bleeding, and abdominal pain or tenderness ( Tavakoli et al, 2021 ; Baumgart & Sandborn, 2007 ; Strober et al, 2007 ). Most of these symptoms occur due to intestinal damage which happens as a result of the exaggerated inflammatory response.…”

Gut Bacteria and Neuropsychiatric Disorders

“…Zanoli et al [112] reported an association between depression, Crohn's disease, and cardiovascular complications. Common symptoms associated with IBD is diarrhea, rectal bleeding, intermittent nausea and abdominal pain or tenderness [57]. Although the authors [112] did not associate changes in gut microbiota with any of these symptoms, it is likely that an imbalanced microbiome did play a role.…”

“…Chemical signals generated by EECs, either directly or in response to microbial metabolites, travel through the ENS and regulates digestion, salivation, lacrimation, urination, defecation and sexual arousal [56]. A clear association exists between chronic stress and gut inflammation disorders, such as IBD and IBS [57]. Signals from the CNS are sent back to EECs and gut microbiota via the ENS and peripheric nervous system (PNS) [58].…”