The effect of nutrient deprivation on early life small intestinal mucosal microbiome and host proteome

Nutrition plays a vital role in shaping the intestinal microbiome. However, many hospitalized children undergo periods of fasting during medical treatment. Changes to the small intestinal microbiota in early life in the setting of enteral deprivation has not been well described.The aim of this study is to investigate the impact of enteral deprivation on the small intestinal mucosal microbiome and to identify factors that shape this interaction in infancy.Intestinal biopsies were collected from proximal (fed) and distal (unfed) small bowel at the time of ostomy closure in children with a small intestinal stoma. Mucosal and luminal microbiome comparisons were performed including beta diversity and differential abundance and correlations with clinical factors were analyzed. Host proteomics were compared between fed and unfed samples and correlated with microbiome parameters. Finally, microbial results were validated in another cohort of pediatric patients.Samples from 13 children (median age 84 days) were collected. Mucosal microbiome communities in the fed and unfed segments were strikingly similar (paired UniFrac distance (beta diversity)), while luminal effluent differed significantly from fed samples (PERMANOVA, p=0.003). Multivariate analysis revealed patient as the strongest predictor of UniFrac distance. Environmental variables did not influence the intra-patient microbial dissimilarity. Host proteomics were similar intra-patient (paired fed-unfed Euclidian distance) and showed a correlation with UniFrac distance (Spearman rho=0.71, p<0.001). Specific proteins and functional clusters were significantly different between paired samples, including lipid metabolism and intra-cellular trafficking, while no difference was seen in innate immune proteins. The microbiome results were validated in a different cohort with similar characteristics.We found the host to be the most dominant factor in the structure of the early life small intestinal mucosal microbiome. Nutrient deprivation was associated with specific changes in host proteome. Further research is needed to better understand this host-microbe-nutrition interaction.