Abstract / Summary
The DOHaD theory was originally proposed to explain the link between fetal development and risk for non-communicable disease - NCD. With advancements in human microbiome research, this theory has been extended to consider postnatal development of the infant gut microbiome and how this contributes to NCD trajectories. C. difficile transiently colonizes the gut microbiota of up to 50% of infants without causing symptoms, but has been associated with disease in the longterm. We reviewed and summarized the current literature to identify prenatal, birth and postnatal factors contributing to C. difficile colonization , and subsequent changes in host biology and NCD outcomes. Many early-life factors promote C. difficile colonization, including prenatal overweight, cesarean birth, hospitalization, antibiotic exposure, formula feeding, histamine-2 receptor antagonist treatment, household pets and smoking, and daycare attendance. Whereas, prenatal milk consumption and having siblings seem to protect against colonization. When C. difficile is present in the gut, associated changes to gut microbiota and metabolites are reported in observational studies. Clinical trial evidence suggests that preceding changes like a reduction in Bifidobacterium species, could promote C. difficile colonization. C. difficile colonization during infancy increases the risk for NCD, including obesity and many atopic diseases (asthma, eczema, food and peanut sensitization). Furthermore, its colonization and abundance was found to be a statistical mediator of these health outcomes, pointing to a potential mediating role for C. difficile in NCD onset. Evidence from the current literature supports the inclusion of C. difficile colonization during infancy as an important biomarker in the developmental origins of disease.