Advances in metagenomics have allowed a detailed study of the gut microbiome, and its role in human health and disease. Infants born prematurely possess a fragile gut microbial ecosystem that is vulnerable to perturbation. Alterations in the developing gut microbiome in preterm infants are linked to life-threatening diseases such as necrotizing enterocolitis (NEC) and late-onset sepsis; and may impact future risk of asthma, atopy, obesity, and psychosocial disease. In this mini-review, we summarize recent literature on the origins and patterns of development of the preterm gut microbiome in the perinatal period. The host-microbiome-environmental factors that portend development of dysbiotic intestinal microbial patterns associated with NEC and sepsis are reviewed. Strategies to manipulate the microbiome and mitigate dysbiosis, including the use of probiotics and prebiotics will also be discussed. Finally, we explore the challenges and future directions of gut microbiome research in preterm infants.

Bacterial infections are common in the etiology of human diseases owing to the ubiquity of bacteria. Such infections promote the development of periodontal disease, bacterial pneumonia, typhoid, acute gastroenteritis, and diarrhea in susceptible hosts. These diseases may be resolved using antibiotics/antimicrobial therapy in some hosts. However, other hosts may be unable to eliminate the bacteria, allowing them to persist for long durations and significantly increasing the carrier's risk of developing cancer over time. Indeed, infectious pathogens are modifiable cancer risk factors, and through this comprehensive review, we highlight the complex relationship between bacterial infections and the development of several cancer types. For this review, searches were performed on the PubMed, Embase, and Web of Science databases encompassing the entirety of 2022. Based on our investigation, we found several critical associations, of which some are causative: Porphyromonas gingivalis and Fusobacterium nucleatum are associated with periodontal disease, Salmonella spp., Clostridium perfringens, Escherichia coli, Campylobacter spp., and Shigella are associated with gastroenteritis. Helicobacter pylori infection is implicated in the etiology of gastric cancer, and persistent Chlamydia infections present a risk factor for the development of cervical carcinoma, especially in patients with the human papillomavirus (HPV) coinfection. Salmonella typhi infections are linked with gallbladder cancer, and Chlamydia pneumoniae infection is implicated in lung cancer, etc. This knowledge helps identify the adaptation strategies used by bacteria to evade antibiotic/antimicrobial therapy. The article also sheds light on the role of antibiotics in cancer treatment, the consequences of their use, and strategies for limiting antibiotic resistance. Finally, the dual role of bacteria in cancer development as well as in cancer therapy is briefly discussed, as this is an area that may help to facilitate the development of novel microbe-based therapeutics as a means of securing improved outcomes.

Bronchopulmonary dysplasia (BPD) is a debilitating disease in premature infants resulting from lung injury that disrupts alveolar and pulmonary vascular development. Despite the use of lung-protective ventilation and targeted oxygen therapy, BPD rates have not significantly changed over the last decade. Recent evidence suggests that sepsis and conditions initiating the systemic inflammatory response syndrome in preterm infants are key risk factors for BPD. However, the mechanisms by which sepsis-associated systemic inflammation and microbial dissemination program aberrant lung development are not fully understood. Progress has been made within the last 5 years with the inception of animal models allowing mechanistic investigations into neonatal acute lung injury and alveolar remodeling attributable to endotoxemia and necrotizing enterocolitis. These recent studies begin to unravel the pathophysiology of early endothelial immune activation via pattern recognition receptors such as Toll-like receptor 4 and disruption of critical lung developmental processes such as angiogenesis, extracellular matrix deposition, and ultimately alveologenesis. Here we review scientific evidence from preclinical models of neonatal sepsis-induced lung injury to new data emerging from clinical literature.