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Study of Factors Influencing the Dynamics of Colonisation and Decolonisation of the Digestive Tract by Clostridioides Difficile in Infants

Sponsor: Fondation Hôpital Saint-Joseph

Summary

Clostridioides difficile (formerly C. difficile) is a bacterium found in the form of spores (a resistant form) to which patients may be exposed in a hospital environment. Once ingested, the spore can germinate in the digestive tract in its vegetative form (active form of the bacterium) and then takes on the appearance of a Gram-positive bacillus that colonizes the digestive microbiota. This preliminary stage of digestive colonization by the bacterium is facilitated by certain factors, in particular exposure to antibiotics, which disrupt the composition of the digestive microbiota (dysbiosis) and thus facilitate the establishment of C. difficile following the removal of the barrier effect of the digestive microbiota. Certain strains (known as "toxinogenic") are then able to produce the main virulence factors (toxins A (TcdA) and B (TcdB)), thereby causing the main clinical signs of digestive infection, particularly in patients with risk factors for C. difficile infection (elderly people, progressive cancer, immunodepression, etc.).The treatment of CDI is mainly based on the oral administration of anti-Clostridioides difficile antibiotics such as Fidaxomicin (FDX) or Vancomycin (VAN) for a period of 10 days, according to the European recommendations of the ESCMID and the American recommendations of the IDSA. Despite effective treatment, CDI is characterized by a high recurrence rate of up to 25% of cases, with multiple recurrences that can be particularly debilitating for patients. The effect of disruption of the gut microbiota (dysbiosis) following exposure to antibiotics can be explained by several non-exclusive hypotheses, such as the disappearance of protective bacterial species in the gut microbiota or, conversely, the appearance of bacterial species that favor the colonization of C. difficile. Hospitalization, and more generally healthcare, has often been identified as a risk factor for CDI.Indeed, C. difficile is found ubiquitously in the environment and contaminates food products. It is still difficult to assess the frequency of contamination through the ingestion of contaminated food and the potential colonization of the host. Only the composition of the gut microbiota appears to be an interesting avenue to explore, especially since it changes significantly during the first year of life as important events occur, including dietary diversification with the introduction of the first solid foods.

Official title: Study of Factors Influencing the Dynamicsof Colonisation and Decolonisation of the Digestive Tract by Clostridioides Difficile in Infants

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