Role of gut luminal microplastics in Ulcerative Colitis physiopathology – UCplastic

Ulcerative colitis (UC) is a chronic inflammatory bowel disease caused by genetic and environmental factors. The latter act firstly as neonatal primers: their exposure during the perinatal period disturbs early maturation of gut microbiota and immune system and induces an increased susceptibility to colitis, called pathological imprinting. Environmental factors act secondly as colitis triggers, causing or worsening colitis development in patients with genetic susceptibility or pathological imprinting. Our hypothesis is that gut luminal microplastics (MPs), which are increasingly present because of expanding human oral MP exposure, belong to environmental UC primers and/or triggers. Indeed, pilot studies detected MPs in neonatal and adult feces, and accumulating data show that ingestion of MPs promote gut inflammation and dysbiosis in mice. Our main aims are:1) To identify in human feces the MPs with pro-inflammatory and pro-dysbiotic properties. Nano-and microplastics will be characterized in control and UC patient feces and correlated with inflammatory calprotectin level and dysbiosis parameters. Combined analyzes will identify a cocktail of MPs with pro-inflammatory and pro-dysbiotic properties thereafter called pro-UC MP cocktail. 2) To assess MP effects on UC pathogenesis either as neonatal primer of UC susceptibility and/or as promoting UC trigger. Pregnant mice will be exposed to the pro-UC MP cocktail and the effects on gut immune response, permeability, microbiota, nano-and microplastic presence in feces, and susceptibility to experimental colitis will be assessed in male and female offspring. These parameters as well as fecal metabolome will be also assessed in response to the pro-UC MP cocktail exposure in gnotobiotic mice colonized with humanized microbiota from control or UC patients. This multidisciplinary project will provide new essential knowledge on human exposure to MPs and their impact on gut homeostasis, particularly in the UC pathophysiology.