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Comparative evaluation of establishing a human gut microbial community within rodent models.

ABSTRACT: The structure of the human gut microbial community is determined by host genetics and environmental factors, where alterations in its structure have been associated with the onset of different diseases. Establishing a defined human gut microbial community within inbred rodent models provides a means to study microbial-related pathologies, however, an in-depth comparison of the established human gut microbiota in the different models is lacking. We compared the efficiency of establishing the bacterial component of a defined human microbial community within germ-free (GF) rats, GF mice, and antibiotic-treated specific pathogen-free mice. Remarkable differences were observed between the different rodent models. While the majority of abundant human-donor bacterial phylotypes were established in the GF rats, only a subset was present in the GF mice. Despite the fact that members of the phylum Bacteriodetes were well established in all rodent models, mice enriched for phylotypes related to species of Bacteroides. In contrary to the efficiency of Clostridiales to populate the GF rat in relative proportions to that of the human-donor, members of Clostridia cluster IV only poorly colonize the mouse gut. Thus, the genetic background of the different recipient rodent systems (that is, rats and mice) strongly influences the nature of the populating human gut microbiota, determining each model's biological suitability.

SUBMITTER: Wos-Oxley M

PROVIDER: S-EPMC3427216 | biostudies-literature | 2012 May-Jun

REPOSITORIES: biostudies-literature

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Comparative evaluation of establishing a human gut microbial community within rodent models.

Wos-Oxley Melissa M Bleich André A Oxley Andrew P A AP Kahl Silke S Janus Lydia M LM Smoczek Anna A Nahrstedt Hannes H Pils Marina C MC Taudien Stefan S Platzer Matthias M Hedrich Hans-Jürgen HJ Medina Eva E Pieper Dietmar H DH

Gut microbes 20120501 3

The structure of the human gut microbial community is determined by host genetics and environmental factors, where alterations in its structure have been associated with the onset of different diseases. Establishing a defined human gut microbial community within inbred rodent models provides a means to study microbial-related pathologies, however, an in-depth comparison of the established human gut microbiota in the different models is lacking. We compared the efficiency of establishing the bact ...[more]

PMID: 22572831

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Project description:BackgroundThe gut microbiota (GM) constitutes a critical factor in the maintenance of physiological homeostasis. Numerous studies have empirically demonstrated that the GM is closely associated with the onset and progression of osteoporosis (OP). Nevertheless, the characteristics of the GM and its metabolites related to different forms of OP are poorly understood. In the present study, we examined the changes in the GM and its metabolites associated with various types of OP as well as the correlations among them.MethodsWe simultaneously established rat postmenopausal, disuse-induced, and glucocorticoid-induced OP models. We used micro-CT and histological analyses to observe bone microstructure, three-point bending tests to measure bone strength, and enzyme-linked immunosorbent assay (ELISA) to evaluate the biochemical markers of bone turnover in the three rat OP models and the control. We applied 16s rDNA to analyze GM abundance and employed untargeted metabolomics to identify fecal metabolites in all four treatment groups. We implemented multi-omics methods to explore the relationships among OP, the GM, and its metabolites.ResultsThe 16S rDNA sequencing revealed that both the abundance and alterations of the GM significantly differed among the OP groups. In the postmenopausal OP model, the bacterial genera g__Bacteroidetes_unclassified, g__Firmicutes_unclassified, and g__Eggerthella had changed. In the disuse-induced and glucocorticoid-induced OP models, g__Akkermansia and g__Rothia changed, respectively. Untargeted metabolomics disclosed that the GM-derived metabolites significantly differed among the OP types. However, a Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that it was mainly metabolites implicated in lipid and amino acid metabolism that were altered in all cases. An association analysis indicated that the histidine metabolism intermediate 4-(β-acetylaminoethyl) imidazole was common to all OP forms and was strongly correlated with all bone metabolism-related bacterial genera. Hence, 4-(β-acetylaminoethyl) imidazole might play a vital role in OP onset and progression.ConclusionsThe present work revealed the alterations in the GM and its metabolites that are associated with OP. It also disclosed the changes in the GM that are characteristic of each type of OP. Future research should endeavor to determine the causal and regulatory effects of the GM and the metabolites typical of each form of OP.

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Comparative evaluation of establishing a human gut microbial community within rodent models.

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Comparative evaluation of establishing a human gut microbial community within rodent models.

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