Exploring the early-life gut microbiome: The impact of preterm birth, breastfeeding and maternal factors on infant health and development

The gut microbiome (GM) has garnered significant interest due to its associations with a wide range of diseases and long-lasting effects on health extending beyond the gastrointestinal tract. In infancy, the GM is established in the period immediately after birth and undergoes rapid maturation. Early establishment of a diverse and stable GM plays a crucial role in gut health and immune system development. This process is destabilised in preterm infants, potentially leading to adverse outcomes such as gut inflammation, necrotising enterocolitis (NEC), sepsis, and allergies A myriad of factors are known to influence the early life GM. Breastfeeding guides GM maturation by delivering beneficial bacteria like bifidobacteria and lactobacilli, along with human milk oligosaccharides (HMOs) that selectively promote the growth of these bacteria. Bacteriophages are an often overlooked component that is key in regulating gut bacterial populations and contributes to microbial diversity and stability. Recent evidence suggests that even maternal neurological conditions can be transmitted to her child via GM modulations. This might explain the recent findings that maternal stress can alter the composition of the human milk microbiome, potentially impacting the infant's GN and development. During this PhD project, we explored the preterm gut virome, revealing distinct developmental patterns in preterm infants' microbiota and finding evidence of strong early-life bacteriophage similarity between twins. We found significant virome compositional alterations associated with clinical factors like bronchopulmonary dysplasia (BPD) and antibiotic treatments, emphasising the importance of considering the virome in managing prematurity complications. To study whether maternal pre-pregnancy body mass index (BMI) affects human milk composition and how this impacts infant gut microbiota and metabolism, the MAINHEALTH observational birth cohort was designed. We found that milk metabolome, milk microbiome, and infant GM correlate strongly with infant growth trajectories. However, they mature independently and correlate with distinct clinical and anthropometric factors. This could inform personalised nutrition and probiotics treatments to improve infant health. Finally, we investigated the relationship between postpartum maternal stress and human milk microbiome composition, finding significant alterations in the milk microbiome of stressed mothers. These findings provide the foundations for further research into the causality and physiological impact of stressinduced changes in milk microbiota to uncover its role in the intergenerational transmission of stress.