Gut microbial colonisation in premature neonates predicts neonatal sepsis

Abstract

Background Neonatal sepsis due to intestinal bacterial translocation is a major cause of morbidity and mortality. Understanding microbial colonisation of the gut in prematurity may predict risk of sepsis to guide future strategies to manipulate the microbiome. Methods Prospective longitudinal study of premature infants. Stool samples were obtained weekly. DNA was extracted and the V6 hypervariable region of 16S rRNA was amplified followed by high throughput pyrosequencing, comparing subjects with and without sepsis. Results Six neonates were 24–27 weeks gestation at birth and had 18 samples analysed. Two subjects had no sepsis during the study period, two developed late-onset culture-positive sepsis and two had culture-negative systemic inflammation. 324 350 sequences were obtained. The meconium was not sterile and had predominance of Lactobacillus, Staphylococcus and Enterobacteriales. Overall, infants who developed sepsis began life with low microbial diversity, and acquired a predominance of Staphylococcus, while healthy infants had more diversity and predominance of Clostridium, Klebsiella and Veillonella. Conclusions In very low birth weight infants, the authors found that meconium is not sterile and is less diverse from birth in infants who will develop late-onset sepsis. Empiric, prolonged antibiotics profoundly decrease microbial diversity and promote a microbiota that is associated not only with neonatal sepsis, but the predominant pathogen previously identified in the microbiome. Our data suggest that there may be a ‘healthy microbiome’ present in extremely premature neonates that may ameliorate risk of sepsis. More research is needed to determine whether altered antibiotics, probiotics or other novel therapies can re-establish a healthy microbiome in neonates.

The developing human preterm neonatal immune system: A case for more research in this area

“…For example, in small series the intestinal microbial flora appeared distinct in preterm infants who develop sepsis, suggesting a potentially acquired predisposition [75]. Feeding human breast milk to premature infants reduces the incidence of necrotizing enterocolitis and favorably impacts their health in a number of other ways [76], whereas broad-spectrum antibiotic exposure was associated with a higher incidence of necrotizing enterocolitis [77; 78; 79].…”

Role of Guidelines on Length of Therapy in Chorioamnionitis and Neonatal Sepsis

“…18 Prolonged use of antibiotics in neonates can affect the bacterial balance of the intestinal microbiome, increasing the risk of subsequent infection with resistant bacteria, invasive candidiasis, and affecting early immune programming. 19,20 In addition, treatment with antibiotics in the neonatal period is an independent risk factor for wheezing requiring inhaled corticosteroids. 21 In preterm infants, prolonged antibiotics is associated with increased mortality and necrotizing enterocolitis.…”

Klebsiella pneumoniae in Breast Milk-A Cause of Sepsis in Neonate

“…The results obtained from the recent studies suggest the occurrence of bacteria in the digestive tract also during the intrauterine life. The presence of the bacterium was detected in the fetal meconium and probably on the skin and, also in the colostrum and breast milk immediately after birth [8]. Currently, it is believed that breast milk is an important source of probiotic bacteria, which colonize the digestive tract immediately after birth.…”