Sophisticated molecular techniques are now unravelling differences in gut microbionta between IBS patients and healthy controls. Growing evidence suggests that, in IBS, the epithelial barrier, gut microbionta, food antigens and bile acid cause abnormal responses in the key regulators of sensorimotor functions, the HPA axis, immune system and enteric nervous system. The brain-gut axis is ruled by neural pathways, hormones and the immune system, which are all affected in IBS.
In IBS, pain is both the commonest symptom and the most difficult to treat, causing considerable morbidity, but the mechanism is still speculative. Increased epithelial barrier permeability is considered an early event leading to low grade immune cell infiltration. Causes for the ‘leaky’ gut are unclear but genetics, dysbiosis (microbial imbalance) and food allergies have been postulated.
Immune activation has a considerable role in some patients with IBS, with mast cells considered the key component for inducing low grade immune activation. Injury and inflammation induce sensitisation of neural pathways of the enteric nervous system.
Transient receptor potential cation channels (TRPs) are implicated in the pathogenesis of hyperalgesia. IBS patients have increased levels of specific polyunsaturated fatty acids stimulating the TRP subfamily, generating visceral hypersensitivity. High TNF and TRPV1 expression can be correlated to increased rectal sensitivity, postulating a similar mechanism in the gut of IBS patients.
Gut microbionta is a diverse ecosystem of enormous complexity that is largely ill-defined regarding its contribution to human health. Dysbiosis in IBS has been recognised and experimental models show microbionta from IBS patients can induce visceral hypersensitivity, impaired intestinal permeability and altered GI transit time.
A link between stress and gut permeability shows a reciprocal association in IBS between the brain, gut, immune system and microbionta. Recent studies have investigated mind-altering microorganisms and the impact of gut microbionta on brain and behaviour. These disease-relevant brain alterations in IBS patients need further study.
A further association between joint hypermobility syndrome, a connective tissue disease, and GI problems raises the question of whether connective tissue is the missing link. With better understanding of the mechanism of IBS, alternative therapy strategies such as immunosuppressants and neuropathic analgesia can be considered.