Nutrition has an indirect effect on the gastrointestinal function of the host and thereby on health, mainly by influencing the composition and activity of the human gut microbiota. The aim of this PhD project was to investigate the effect of nutrition as a factor affecting the intestinal microbiome-host relationship in critically ill children and whether it has an impact on clinical disease severity.

The balance between requirement and delivery of energy and macronutrients was assessed in a cohort of 124 critically ill children. Then an integrated approach of metataxonomics and metabolomics analysis was undertaken to examine how feeding during critical illness affects the gut-host relationship. Collection of faecal samples was required for the assessment of faecal calprotectin, gut microbiota and their metabolites while serum samples were used for the analysis of inflammatory cytokines, and intestinal injury biomarkers.

Overall this project has recorded a cross-link between feed, gut homeostasis with systemic inflammation and host metabolism. Within the feed delivered, fat delivery was often above requirements compared to protein and carbohydrate. In addition, both protein deficit and higher delivery of fat were associated with elevation in the levels of pro-inflammatory cytokines. The results also showed that abnormalities in gut health biomarkers were associated with elevation in inflammatory cytokines. Finally this study also recorded a profound loss of diversity in the faecal microbiome of critically ill children. This was associated with the loss of key commensal species and increased levels of opportunistic pathogens. Consequently resulted in reduced functionality of the gut microbiome manifested by reduced production of SCFAs and abnormalities in BAs metabolism. The current study showed for the first time that energy underfeeding appeared to influence the microbial composition of critically ill children.

In conclusion this work provided an insight about the potential contribution of nutrition as a factor to improve the disease state in critically ill children, if targeted to modulate gut microbiome and host response to critical illness.