Early dysbiosis in Crohn’s disease, delayed dysbiosis in ulcerative colitis

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An international team has advanced a hypothesis on the etiology of chronic inflammatory bowel diseases (CIBD): neonatal intestinal dysbiosis is thought to induce the development of Crohn’s disease, while ulcerative colitis is thought to be correlated with day-to-day disruptions of the microbiota.

 

Crohn’s disease and ulcerative colitis begin during or shortly after adolescence, and could result from aberrant immune responses linked to intestinal dysbiosis, in subjects with a genetic predisposition. Patients suffering from CIBD present with modifications of their microbial populations: in particular,  reduced  diversity and depletion of Faecalibacterium prausnitzii (with anti-inflammatory properties), as well as an excess of Proteobacteria in Crohn’s disease.

Diseases linked to the Western lifestyle

Despite their similarities, the two CIBD present characteristics that lead us to believe they have different etiologies. In this context, an international research team proposed a hypothesis based on an epidemiological observation: exposure of naive subjects to an environment that favors the development of intestinal diseases (Western lifestyle) leads to the rapid onset of cases of ulcerative colitis, while the first cases of Crohn’s disease take years to appear.

Dysbioses with distinct timelines?

The researchers consider that the risk of developing Crohn’s disease is elicited by early impairments of the intestinal microbiota. Perinatal dysbiosis following delivery by cesarean section, bathing too often or antibiotic therapy, are thought to prepare the ground for the disease by disrupting the development of the infant’s immune system. Conversely, ulcerative colitis is thought to be an inflammatory response linked to an ongoing dysbiosis, triggered by environmental factors such as diet, antibiotic therapy, quitting smoking, pollution…

A meta-analysis used to confirm the hypothesis

A meta-analysis provided support for the researchers’ hypothesis in showing a significant association between cesarean section, excessive hygiene in infants, the use of antibiotics and Crohn’s disease, while no correlation could be established between these risk factors and ulcerative colitis. However, the observation needs to be confirmed. It could be supported by prospective studies in children adopted from non-westernized countries, or in couples living in an environment that predisposes to CIBD. If the hypothesis is correct, both groups should develop more cases of ulcerative colitis than of Crohn’s disease.

 

Sources:

L. Beaugerie, E. Langhol, N. Nyboe-Andersen, et al. Differences in epidemiological features between ulcerative colitis and Crohn’s disease: The early life-programmed versus late dysbiosis hypothesis. Medical Hypotheses 115 (2018) 19–21.