Improved hygiene leading to reduced exposure to microorganisms has been identified as one possible cause for the recent epidemic of chronic inflammatory diseases in westernised countries. The essence of the hygiene hypothesis that argues that rising incidence of chronic inflammatory diseases may be, at least in part, the result of lifestyle and environmental changes that have made us too “clean” for our own good, so causing changes in our microbiota.
The composition of the gut microbiota then causes an inappropriate increase in intestinal permeability, amongst other things.
During the past decade, a growing body of research has shown that this imbalance in gut microbiota and loss of mucosal barrier function in the gastrointestinal (GI) tract may substantially affect antigen trafficking, ultimately influencing the close two-way interaction between gut microbiome and our immune system. This then predisposes to a “hyper-belligerent” immune system, driving systemic inflammation and, ultimately, driving chronic inflammatory diseases.
The pathogenic role of increased gut permeability is supported by pre-clinical and clinical studies that
have shown that the zonulin family, a group of proteins modulating gut permeability, is implicated in a
variety of chronic inflammatory diseases. Zonulin dysfunction has been linked to autoimmune, infective,
metabolic, and tumoral diseases.
Zonulin is a modulator of both epithelial and endothelial barrier functions and its role in health and
disease remains an object of active research. Gut dysbiosis causes the release of zonulin leading to the
passage of luminal contents across the epithelial barrier causing the release of pro-inflammatory
cytokines that themselves cause increased permeability establishing a vicious loop leading to massive
influx of dietary and microbial antigens triggering the activation of T-cells.
This fascinating topic was the focus for a recent review by famed leaky gut researchers Alessio Fasano.
This great review highlights the benefits of utilising nutritional, herbal, dietary, and lifestyle treatment
strategies that help to restore gut flora balance and repair the GI tract barrier as part of any treatment
plan for chronic inflammatory diseases.
REFERENCE
Fasano A. All disease begins in the (leaky) gut: role of zonulin-mediated gut permeability in the
pathogenesis of some chronic inflammatory diseases. F1000 Research 2020;9:69