Search

Background: The human gut microbiota is inoculated at birth and undergoes a process of assembly and diversification during the first few years of life. Studies in mice and humans have revealed associations between the early-life gut microbiome and future susceptibility to immune and metabolic diseases. To resolve microbe and host contributing factors to early-life development and to disease states requires experimental platforms that support reproducible, longitudinal, and high-content analyses. Results: Here, we deployed a continuous single-stage chemostat culture model of the human distal gut to study gut microbiota from 18- to 24-month-old children integrating both culture-dependent and -independent methods. Chemostat cultures recapitulated multiple aspects of the fecal microbial ecosystem enabling investigation of relationships between bacterial strains and metabolic function, as well as a resource from which we isolated and curated a diverse library of early life bacterial strains. Conclusions: We report the reproducible, longitudinal dynamics of early-life bacterial communities cultured in an advanced model of the human gut providing an experimental approach and a characterized bacterial resource to support future investigations of the human gut microbiota in early childhood. [ABSTRACT FROM AUTHOR]

Abstract Background The human gut microbiota is inoculated at birth and undergoes a process of assembly and diversification during the first few years of life. Studies in mice and humans have revealed associations between the early-life gut microbiome and future susceptibility to immune and metabolic diseases. To resolve microbe and host contributing factors to early-life development and to disease states requires experimental platforms that support reproducible, longitudinal, and high-content analyses. Results Here, we deployed a continuous single-stage chemostat culture model of the human distal gut to study gut microbiota from 18- to 24-month-old children integrating both culture-dependent and -independent methods. Chemostat cultures recapitulated multiple aspects of the fecal microbial ecosystem enabling investigation of relationships between bacterial strains and metabolic function, as well as a resource from which we isolated and curated a diverse library of early life bacterial strains. Conclusions We report the reproducible, longitudinal dynamics of early-life bacterial communities cultured in an advanced model of the human gut providing an experimental approach and a characterized bacterial resource to support future investigations of the human gut microbiota in early childhood.

The Oligo-Mouse-Microbiota (OMM12) is a recently developed synthetic bacterial community for functional microbiome research in mouse models (Brugiroux et al., 2016). To date, the OMM12 model has been established in several germ-free mouse facilities world-wide and is employed to address a growing variety of research questions related to infection biology, mucosal immunology, microbial ecology and host-microbiome metabolic cross-talk. The OMM12 consists of 12 sequenced and publically available strains isolated from mice, representing five bacterial phyla that are naturally abundant in the murine gastrointestinal tract (Lagkouvardos et al., 2016). Under germ-free conditions, the OMM12 colonizes mice stably over multiple generations. Here, we investigated whether stably colonized OMM12 mouse lines could be reproducibly established in different animal facilities. Germ-free C57Bl/6J mice were inoculated with a frozen mixture of the OMM12 strains. Within 2 weeks after application, the OMM12 community reached the same stable composition in all facilities, as determined by fecal microbiome analysis. We show that a second application of the OMM12 strains after 72 h leads to a more stable community composition than a single application. The availability of such protocols for reliable de novo generation of gnotobiotic rodents will certainly contribute to increasing experimental reproducibility in biomedical research. [ABSTRACT FROM AUTHOR]