Clostridioides difficile infection and gut dysbiosis: Interpreting the interplay in adults and neonates

Clostridioides difficile infections (CDI) are associated with high morbidity and mortality with symptoms ranging from mild diarrhea to fulminant colitis. Studies have shown that individuals with CDI have remarkable reduction in richness and diversity of species.
There is depletion of Bacteroidetes, Firmicutes, and Actinobacteria phyla which are responsible for maintaining gut homeostasis and inhibits germination of C. difficile and increase in Proteobacteria population. Similarly, in infants with CDI, there is depletion of Bacteroidetes, Firmicutes and Bifidobacteria, and increase in population of pathogenic organisms, such as Staphylococcus aureus, Escherichia coli, Enterococcus, Shigella spp., Citrobacter spp., and Klebsiella spp. Usually, the abundance of Ruminococcus, absence of receptors for clostridial toxin, immature immune system and presence of neutralizing antibodies describe the absence of clinical symptoms in infants.
Considering that C. difficile projects differently in individuals and is mostly asymptomatic in infants suggests that a specific type of microenvironment is required for C. difficile to produce its symptoms, and this environment is usually seen in adults with gut dysbiosis.
Microbiota dysbiosis also leads to biochemical and immunological alterations, that in turn increases the colonization capacity and supports germination and growth of C. difficile, which in turn release inflammatory enterotoxins, responsible for the clinical manifestations. Several factors (prolonged hospitalization, antibiotic treatment, elderly, multimorbidity, immunosuppression, gastric acid suppression, gastric surgery) that contribute to gut dysbiosis increase the susceptibility of individuals to CDI.
Although antibiotic is the mainstay therapy for CDI, adjunctive therapies comprising probiotics, prebiotics, synbiotics, postbiotics or fecal microbiota transplantation do play a significant role in restoring the homeostasis of gut microbiota. Studies have shown that probiotics in combination with prebiotics reduce the incidence of CDI by 50 % in susceptible individuals. Thus, adjunctive therapies targeting microbiota seems to play a pivotal role in therapeutic arsenal for CDI.

Clinical Catch:

• Probiotics in combination with prebiotics reduce the incidence of CDI by 50 % in high-risk individuals.
• Adjunctive therapies targeting microbiota seems to play a pivotal role in therapeutic arsenal for CDI.

Source: Vasilescu IM, Chifiriuc MC, Pircalabioru GG, et al. Gut Dysbiosis and Clostridioides difficile Infection in Neonates and Adults. Front Microbiol. 2022;12:651081. Published 2022 Jan 20. doi:10.3389/fmicb.2021.651081.

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