Abstract Body

Microbiome Assessment and Associated Clinical Outcomes in Preterms

Neonatal gut microbiota colonization plays an important role in promoting health on the short and long term. Early microbial functions include priming of the immune system and growth regulation. Long-term consequences of a disturbed colonization include an increased risk for allergy, asthma, and inflammatory and auto-immune diseases, and impaired neurocognitive outcome. Preterm infants, who by definition suffer from incomplete gut tissue and immune system maturation, are at increased risk for an aberrant microbial colonization by many factors, including prolonged exposure to antibiotics. Dysbiosis is considered a key risk factor for necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) in this population. Since the major prognostic factors for NEC and LOS include early diagnosis and treatment, an urgent but yet unmet need exists for early, preferably preclinical and noninvasive, diagnostic biomarkers. Microbial and metabolic alterations are expected to occur before NEC and LOS onset, and could therefore hypothetically serve as a target for biomarker development and for early therapeutic, and possibly even preventive, strategies. This would provide clinicians with a window of opportunity to initiate therapy before clinical symptoms appear, probably reducing mortality rates.

In this presentation, data from an ongoing nationwide cohort study will be presented, including infants < 30 weeks of gestational age, with the aim to predict NEC and LOS onset in preclinical stage, using fecal biomarkers. For this study, over 25.000 fecal samples from 3000 infants in 9 neonatal intensive care units in the Netehrlands and Belgium, have been collected and analyzed by LC-MS, electronic-nose-technology and molecular techniques to describe microbiota composition. Furthermore, an overview is given on observed associations between gut microbiota colonization in preterm infants and short and long term health outcomes, including beneficial and negative factors influencing outcome. Novel techniques to describe the microbiome and microbial functions will be discussed.

Abstract Body

The health of preterm infants is associated with the structure and function of the gut microbiome. Studies have observed a change in gut microbiome (dysbiosis) in preterm infants who develop necrotising enterocolitis (NEC) or late onset sepsis (LOS) in comparison to preterm infants who do not. Key taxa have been identified as associated with ill health (klebsiella, proteobacteria ) or good health (bifidobacteria, lactobacilli) defned as lack of these key neonatal diseases. Most data is from observational studies, where only association can be shown, but probiotic studies with mechanistic work offer insights into how these effects may be modulated, as does data from mechanistic work embedded in other enteral intervention studies in preterm infants.

In term infants breast fed infants have a different microbiome than formula fed infants. In preterm infants many factors impact the microbiome including type and amount of mothers own milk (MOM) received, antibiotics received, probiotic exposure, day of postnatal life and the neonatal intensive care unit in which the infant is cared for.

The microbiome may exert beneficial health effects via multiple mechanisms, many of which are very poorly understood especially in the preterm infant. These include competetive exclusion of pathogenic bacteria, production of metabolites that impact host physiology (such as vitamins or short chain fatty acids) or metabolites that act as substrate for other gut bacteria (bifidogenic effects). Certain taxa exhibit direct effect on gut enterocytes and tight junctions, and impact on enterocyte transcriptome. These mechanisms are impacted by host responses at both the intestinal luminal level and within the systemic circulation. Additionally some impacts are co-dependent on other factors contained in breast milk, such as human milk oligosaccharides that support the growth of specific species such as bifidobacterium. Adverse short term health effects include the dysbiosis that precedes NEC or LOS, as well as prolongation to time taken to establish full feeds and impacting on length of stay. Manipulation of the preterm microbiome with deliberately administered probiotics is possible, and an impact has been shown on both functional taxonomy and metabolic function of the microbiome.

Longer term health impacts are potentially driven by metabolic programming of the infant impacting on the likelihood of developing metabolic syndrome in later life. Other diseases have been shown in adulthood to be associated with changes in the microbiome, such as Parkinsons disease, but direct links to the preterm microbiome are currently lacking.