Physiological mechanisms of unexplained (functional) gastrointestinal disorders

Abstract

Functional gastrointestinal disorders (FGIDs) encompass a range of complex conditions with similar clinical characteristics and no overt pathology. Recent recognition of sub‐clinical pathologies in FGIDs, in conjunction with physiological and biochemical abnormalities including increased intestinal permeability, microbial profile alterations, differences in metabolites and extra‐intestinal manifestations of disease, call into question the designation of these conditions as ‘functional’. This is despite significant heterogeneity in both symptom profile and specifics of reported physiological abnormalities hampering efforts to determine defined mechanisms that drive onset and chronicity of symptoms. Instead, the literature demonstrates these conditions are disorders of homeostatic imbalance, with disruptions in both host and microbial function and metabolism. This imbalance is also associated with extraintestinal abnormalities including psychological comorbidities and fatigue that may be a consequence of gastrointestinal disruption. Given the exploitation of such abnormalities will be crucial for improved therapeutic selection, an enhanced understanding of the relationship between alterations in function of the gastrointestinal tract and the response of the immune system is of interest in identifying mechanisms that drive FGID onset and chronicity. Considerations for future research should include the role of sex hormones in regulating physiological functions and treatment responses in patients, as well as the importance of high‐level phenotyping of clinical, immune, microbial and physiological parameters in study cohorts. There is opportunity to examine the functional contribution of the microbiota and associated metabolites as a source of mechanistic insight and targets for therapeutic modulation. image

Network Pharmacology Exploration Reveals Gut Microbiota Modulation as a Common Therapeutic Mechanism for Anti-Fatigue Effect Treated with Maca Compounds Prescription

“…Therefore, fatigue may be a consequence of gastrointestinal imbalance, and targeting on specific intestinal bacteria and gut microbial ecosystem modulation may be a worthwhile therapeutic strategy in fatigue management [9,34]. Although such associations between gut microbiota and the MCP are established, the underlying mechanisms by which the microbiota and the host interact remain unknown.…”

Multi-omics analysis reveals the metabolic regulators of duodenal low-grade inflammation in a functional dyspepsia model

“…The duodenal microenvironment has emerged as an important player in the pathophysiological mechanisms of FD, in which both locally microbial community disorder, host and microbial metabolism and host innate immunity are involved ( 27 ). These imbalances may in part be mediated by specific microbiome-associated metabolites ( 28 ). A recent study showed that the metabolic functional prediction of oral and gastric microbiome based on 16S rRNA sequencing data.…”

Circadian Rhythms and Melatonin Metabolism in Patients With Disorders of Gut-Brain Interactions

“…While there is no consensus regarding the specific differences and mechanisms at play, it is clear that sex differences exist in circadian rhythms and melatonin metabolism ( Cipolla-Neto et al, 2021 ) which may in part explain the higher prevalence of DGBIs in women ( Burns et al, 2021 ). In healthy women, the intrinsic circadian period of melatonin and body temperature are shorter ( Duffy et al, 2011 ) and females also tend to wake up earlier, with morning chronotypes ( Adan and Natale, 2002 ; Cain et al, 2010 ).…”

“…Importantly, over 40% of the global population experience GI symptoms associated with these conditions ( Sperber et al, 2021 ), highlighting the need to better understand the mechanisms underlying symptom onset and chronicity. Further, alterations in immune profiles, microbiota composition and physiology of the GIT are linked to DGBIs ( Burns et al, 2021 ), all of which are associated with chronodisruption and as such, it is likely that altered circadian rhythms are involved in the pathophysiology of these conditions. This review aims to discuss the evidence for circadian abnormalities in DGBIs with a focus on FD and IBS.…”