Host and microbial factors influencing the gut microbial community structure

Abstract

Gut microbial colonization begins at birth and dynamic ecological succession occurs before establishment of a stable, resilient adult community structure. Colonization outcomes in early life have long-term effects on host health. Understanding factors governing neonatal gut community structure development and adult structure modulation will allow therapeutic manipulation of the gut community for disease prevention/treatment. Submetagenomic analysis was done to identify microbial factors potentially triggering community stability in neonate piglets. Piglet faecal microbiota was fractionated before and after key points in community development using suppression subtractive hybridization. Analysis of immunoglobulin A bound to gut microbes showed that distinct groups are bound, potentially influencing colonization outcomes. Comparisons using pyrosequencing showed that colon and cecum microbiota of mice on a standard diet were similar at higher taxonomic levels, with minor differences at finer scale reflecting spatial location. Changes in host nutrient intake were found to generically drive community shift in 2 independent mouse genotypes - low energy density (LED) diet samples showed significantly higher relative abundances of mucin-degrading Verrucomicrobiae and Bacteroidia. Ability to use host secretions as an alternative energy source is predicted to confer selective advantage under reduced host nutrient intake. To track host secretion uptake, mice were intravenously injected with 13C and 15N-labeled threonine. Isotope incorporation by bacteria was tracked with nanoscale secondary ion mass spectrometry. Greater uptake was seen in LED diet mice, indicating increased importance of host secretions to bacterial nutrition relative to host-ingested nutrients. Different populations showed differential uptake, suggesting varied ability to utilise host secretions. This is expected to influence population fitness and drive community shift under host nutrient intake limitation.