Stabilization of the murine gut microbiome following weaning

Abstract

Ecologists hypothesize that community structure and stability affect productivity, sensitivity to invasion and extinction, and resilience and resistance to perturbations. Viewed in the context of the gut microbiome, the stability of the gut community is important for understanding the effects of antibiotics, diet change and other perturbations on host health and colonization resistance. Here we describe the dynamics of a self-contained community, the murine gut microbiome. Using 16S rRNA gene sequencing of fecal samples collected daily from individual mice, we characterized the community membership and structure to determine whether there were significant changes in the gut community during the first year of life. Based on analysis of molecular variance, we observed two community states. The first was observed in the 10 days following weaning and the second was observed by 15 days following weaning. Interestingly, these two states had the same bacterial populations, but those populations had different relative abundances in the two states. By calculating the root mean squared distances between samples collected in the early and late states for each mouse, we observed that the late state was more stable than the early state. This increase in stability was not correlated with increased taxonomic richness, taxonomic diversity, or phylogenetic diversity. In the absence of an experimentally induced perturbation, the second community state was relatively constant through 364 days post weaning. These results suggest a high degree of stability in the microbiome once the community reached the second state.

Figure 1. Weights of mice over the first 364 d post weaning (dpw). For each litter two male mice were co-housed and two female mice were co-housed. In addition, two males and two females from the second litter were each individually housed. The vertical bars along the bottom indicate samples that were used for the microbiome analysis described in the current study.

Figure 2. Temporal variation of the community structure of the murine gut microbiome for all 12 mice together as well as those from two female and one male animal over the first 364 dpw as represented in NMDS plots using the Θ_YC distance metric. The stress for this representation was 0.15. Samples collected between 0 and 9 dpw are in blue, those from 11 to 140 dpw are in green, those from 141–150 dpw are in red, and samples from 364 dpw are in black. Larger characters are closer in the unrepresented axis and smaller characters are further into the unrepresented axis. Animated versions of the NMDS plots for each animal and all points together are available as supplementary data.

Figure 3. Average Θ_YC distances between days for the same animal (self-comparison) and between different animals (other-comparison) for 0 to 9 dpw (blue) and 141 and 151 (red) dpw. Error bars represent the 95% confidence interval.

Figure 4. Relative difference in root mean squared θ_YC distances to the early (0–9 dpw) and late (141–150 dpw) samples for each animal. Rectangles with “NC” indicate that the samples were not characterized and those with “ND” indicate those samples that had fewer than 1,900 sequences.

Figure 5. Relative percentage of secretory IgA as total protein in the feces of each animal over the first 150 dpw. Rectangles with “NC” indicate that the samples were not characterized and the sample with “ND” did not yield useable data.