The microbiota plays a crucial role in pediatric health by shaping immune development and influencing infection susceptibility. In infants and children, an immature microbiota may compromise immune defense, increasing the risk of bacterial infections. This review evaluates clinical trials on the microbiota’s role in neonatal and pediatric bacterial infections, including sepsis, infections in pediatric cancer patients, and Clostridioides difficile-associated dysbiosis. We summarized original research articles published from 2000 to May 2024 on the microbiota and bacterial infections in neonates and children. A balanced microbiota is essential for infection prevention, particularly in premature infants and immunocompromised children. Studies of microbiome signatures in the gut, oral cavity, and nasopharynx have highlighted how microbiota composition influences infection risk, treatment response, and adverse effects from antibiotics and chemotherapy. Disruptions from antibiotic exposure, chemotherapy, and hematopoietic stem cell transplantation frequently lead to dysbiosis, characterized by depletion of commensal bacteria and overgrowth of pathobionts, including antibiotic-resistant strains such as C. difficile. Conversely, microbiota-restorative interventions, such as probiotics and fecal microbiota transplantation, show promise in reducing bacterial infections by enhancing microbial resilience. The microbiota plays a critical role in predicting and potentially treating bacterial infections in children. While antibiotics remain essential, their widespread use has significant consequences for microbiota health. Striking a balance between effective infection control and microbiota preservation is crucial, particularly in vulnerable pediatric populations. Implementing judicious antibiotic use and exploring microbiota-based therapies may mitigate long-term microbiota disruptions, ultimately improving infection outcomes and overall pediatric health.
