Crohn’s disease (CD) is a chronic inflammatory condition of diverse aetiology in which host genetics and the gut microbiome may interact to regulate susceptibility. People with CD tend to have higher numbers of a type of gut bacteria known as adherent-invasive Escherichia coli (AIEC) in their guts. Besides this, acute infectious gastroenteritis caused by Salmonella or other enteric pathogens, increase the long-term risk of CD. However, the mechanistic basis for this relationship to disease onset is still unknown.
A recent study, led by Prof. Brian K. Coombes from the Department of Biochemistry and Biomedical Sciences at the McMaster University in Hamilton, Ontario (Canada), has found that AIEC colonization along with acute infectious gastroenteritis worsened clinical outcome and increased mortality in mice, and also that the infectious diarrhoea caused by microbes promoted growth of AIEC and heightened the inflammatory state in the gut.
The researchers infected some mice with an AIEC strain collected from a person with CD and left some mice uninfected. Then they exposed the mice to Salmonella enterica serovar Typhimurium (S. Typhimurium) or Citrobacter rodentium to invoke acute infectious gastroenteritis.
After exposure to the diarrhoea-causing bacteria, mice that had been infected with AIEC experienced greater symptom severity, as well as increased growth of AIEC. Overall these results indicated that prior colonization by AIEC worsened the clinical outcome of infectious gastroenteritis and, furthermore, the acute infectious gastroenteritis created a specialized niche permissive for the AIEC pathobiont with enhanced fitness under inflamed conditions. In addition, prior AIEC colonization led to heightened cellular and proinflammatory cytokine responses in the cecum following S. Typhimurium infection. The researchers concluded that colonization with AIEC creates an inflammatory environment in the gut that worsens the severity of gastroenteritis and further promotes AIEC growth.
“This work”, the authors summarize, “addresses how AIEC persists in the inflamed gut and makes a novel connection to a perplexing risk factor in Crohn’s disease, which is acute infectious gastroenteritis. Based on this work, AIEC status might be an important measure in the management of Crohn’s disease risk in individuals following episodes of food poisoning.”
In summary, this study shows that symptoms in the post-infectious period after acute infectious gastroenteritis are driven by the expansion of the resident AIEC pathobiont. These results suggest that people colonized by AIEC at the time of acute infectious gastroenteritis may be at greater risk for CD onset and, thus, developing novel diagnostic methods to help identify AIEC-colonized individuals may create opportunities for prevention of CD.
Small CL, Xing L, McPhee JB, Law HT, Coombes BK. Acute infectious gastroenteritis potentiates a Crohn’s disease pathobiont to fuel ongoing inflammation in the post-infectious period. PLoS Pathog. 2016; 12(10):e1005907. doi: 10.1371/journal.ppat.1005907.