Abstract
BackgroundGut microbial communities of mammals are thought to show stable differences between individuals. This means that the properties imparted by the gut microbiota become a unique and constant characteristic of the host. Manipulation of the microbiota has been proposed as a useful tool in health care, but a greater understanding of mechanisms which lead to community stability is required. Here we have examined the impact of host immunoregulatory phenotype on community dynamics.Methods and FindingsDenaturing gradient gel electrophoresis was used to analyse the faecal bacterial community of BALB/c and C57BL/6 mice and C57BL/6 mice deficient for either type I interferon (IFN) signalling (IRF9 KO mice) or type I and type II IFN signalling (STAT1 KO mice). Temporal variation was found in all mouse strains. A measure of the ability for a community structure characteristic of the host to be maintained over time, the individuality index, varied between mouse strains and available data from pigs and human models. IRF9 KO mice had significantly higher temporal variation, and lower individuality, than other mouse strains. Examination of the intestinal mucosa of the IRF9 KO mice revealed an increased presence of T-cells and neutrophils in the absence of inflammation.SignificanceThe high temporal variation observed in the gut microbiota of inbred laboratory mice has implications for their use as experimental models for the human gut microbiota. The distinct IRF9 and STAT1 phenotypes suggest a role for IRF9 in immune regulation within the gut mucosa and that further study of interferon responsive genes is necessary to understand host-gut microbe relationships.
Highlights
The gastro-intestinal tract of mammals is colonised with a diverse range of micro-organisms
We examined mice that differ in their capacity to regulate immune responses measuring both the constancy of community structure in individual mouse gut communities and the differences in community structure between mice, to derive a measure of the relative importance of sustained and transient differences in gut community between animals that we refer to as the individuality index
The gut microbiota of adult mice had relatively low constancy of composition We monitored temporal variation in the composition of the gut microbiota of healthy mice that were housed under controlled conditions
Summary
The gastro-intestinal tract of mammals is colonised with a diverse range of micro-organisms. In recent years evidence has accumulated to support the idea that the community structure of the gut microbiota is a major contributor to the phenotype of the host animal. This evidence comprises three distinct streams: Firstly, available gut community dynamics studies have shown high temporal constancy within, and distinct composition between, adult individuals [1,2,3]. Gnotobiotic animal studies show that molecules of microbial origin are essential for host developmental pathways [13] and that different microbial strains can engender distinct host responses [14] These observations suggest important roles for the gut community in health, defining a healthy gut community is difficult. We have examined the impact of host immunoregulatory phenotype on community dynamics
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