The association of prematurity and medical conditions with the gut microbiome of mammals

Abstract

Rapid development in the microbiome field has accelerated the identification of association between the microbiome and the host. Early-life microbial seeding has been suggested to impact health later in life, and a breakdown in the development of the host:microbiome relationship is thought to contribute to disease development. This thesis encompasses three studies, centred around the impact of nutritional supplementation on the gut microbiome of preterm lambs, infants born moderate-late preterm (MLPT) and adults diagnosed with nonalcoholic fatty liver disease (NAFLD). The first study hypothesised that the microbial composition differs along the gastrointestinal tract in preterm lambs that were subject to a short-term, early-life nutritional supplementation with either branched-chain amino acids or a complex carbohydrate, maltodextrin. My results indicated that, combining data from term and preterm lambs, the anatomical site explained 54% (q-value=0.0004) of the variance in microbial beta diversity but that there was no significant effect of early-life nutritional supplementation on the microbial diversities of preterm lambs. However, prematurity per se explained 5.7% (q-value=0.024) of the variance in microbial beta diversity that was observed between the preterm and term-born lambs indicating that, in a tightly controlled experimental context, preterm birth itself alters the gut microbiome. Consistent with this study in lambs, in a cohort study of MLPT infants enrolled in a clinical trial of nutritional management, nutrition type had no effect on the acquisition and establishment of the gut microbiota over the first 10 days after birth. However, the maternal and perinatal environment (maternal socioeconomic status, antibiotic use, gestational age and delivery mode) did have a significant impact on the microbiome (q-value<0.05). By 4-months corrected age, the impact of these factors on the microbiome was largely superseded by the impact of infants’ environmental exposure (e.g. hospital of birth and length of hospital stay) and types of milk feeding. The third study focused on adults with NAFLD and hypothesised that their gut microbiome would change after four weeks of very-low-calorie diets (VLCD) followed by supplementation with prebiotic inulin with prior short-term metronidazole. My results showed a noticeable shift of Firmicutes/Bacteroidetes (p=0.002) ratio towards that of non-obese individuals, with reduced levels of Roseburia, Streptococcus, and Dialister after VLCD treatment. However, low compliance in the faecal sample collection at later time points precluded further microbiome analysis. Overall, the impact of nutritional supplementation on the gut microbiome is subtle in early life, when the microbial population is vulnerable towards other perinatal factors (e.g. prematurity). By contrast, changes in dietary habits later in life do perturb the established microbiome structure. The mechanism(s) that explain the relationship between the plasticity of the microbiome and developmental stage remain to be determined.