Abstract

 

Functional gastrointestinal disorders (FGD), characterized by altered bowel transit, impaired intestinal barrier function, and visceral pain, are highly prevalent in a wide range of complex chronic diseases affecting the pelvic organs-brain axis, such as endometriosis or following spinal cord injury. Better understanding underlying mechanisms combining translational as well as mechanistical studies remains a major aim to identify novel therapeutic targets. Furthermore, due to the complexity of symptoms in these pathologies, better stratifying patients to address adequate treatment remains a major clinical issue.

Among key actors involved in FGD is the enteric nervous system whose alterations remains largely unknown and whose capacity to be targeted to improve FGD is still largely unexplored. Among novel putative targets involved in FGD are mediators of the HPA axis, especially glucocorticoids (GC), that have been widely associated to Irritable bowel syndrome a prototypical FGD. However, the specific role of GC upon ENS alterations in FGD remains largely unexplored.

Another major contributor to FGD and also source of therapeutic targets is the gut microbiota. Besides playing an increasingly recognized causal role in disorders of gut brain interactions and source of biomarkers of disease evolution, the gut microbiota represents also a source of innovative therapeutical targets or biomarkers of treatment response, in particular via its production of combinatory bacterial metabolites (that can also be encapsulated with bacteria derived EVs to reach gut distant organs). However, whether the gut microbiota contributes to FGD in endometriosis and SCI associated comorbidities, in particular of gut and urological origin, remains unexplored.