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A pig model of the human gastrointestinal tract.

ABSTRACT: Easy access to next generation sequencing has enabled the rapid analysis of complex microbial populations. To take full advantage of these technologies, animal models enabling the manipulation of human microbiomes and the study of the impact of such perturbations on the host are needed. To this aim we are developing experimentally tractable and clinically relevant pig models of the human adult and infant gastro-intestinal tract. The intestine of germ-free piglets was populated with human adult or infant fecal microbial populations, and the piglets were maintained on solid or milk diet, respectively. Amplicons of 16S rRNA V6 region were deep-sequenced to monitor to what extent the transplanted human microbiomes changed in the pig. Within 24 h of transfer of human fecal microbiome to pigs, bacterial microbiomes rich in Proteobacteria emerged. These populations evolved toward a more diverse composition rich in Bacteroidetes and Firmicutes. In the experiment where infant microbiome was used, the phylogenetic composition of the transplanted bacterial population converged toward that of the human inoculum. A majority of sequences belonged to a relatively small number of operational taxonomic units, whereas at the other end of the abundance spectrum, a large number of rare and transient OTUs were detected. Analysis of fecal and colonic microbiomes originating from the same animal indicate that feces closely replicate the colonic microbiome. We conclude that the pig intestine can be colonized with human fecal microbiomes to generate a realistic model of the human GI tract.

SUBMITTER: Zhang Q

PROVIDER: S-EPMC3669164 | biostudies-literature | 2013 May-Jun

REPOSITORIES: biostudies-literature

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A pig model of the human gastrointestinal tract.

Zhang Quanshun Q Widmer Giovanni G Tzipori Saul S

Gut microbes 20130402 3

Easy access to next generation sequencing has enabled the rapid analysis of complex microbial populations. To take full advantage of these technologies, animal models enabling the manipulation of human microbiomes and the study of the impact of such perturbations on the host are needed. To this aim we are developing experimentally tractable and clinically relevant pig models of the human adult and infant gastro-intestinal tract. The intestine of germ-free piglets was populated with human adult o ...[more]

PMID: 23549377

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Project description:BackgroundThe expression of taste receptors (TASRs) and their signalling molecules in the gastrointestinal (GI) epithelial cells, including enteroendocrine cells (EECs), suggests they participate in chemosensing mechanisms influencing GI physiology via the release of endocrine messengers. TASRs mediate gustatory signalling by interacting with different transducers, including ?-gustducin (G?gust) and ?-transducin (G?tran) G protein subunits. This study tested whether G?tran and G?gust immunoreactive (-IR) cells are affected by a short-term (3 days) and long-term (30 days) high protein (Hp) diet in the pig GI tract.ResultIn the stomach, G?gust and G?tran-IR cells contained serotonin (5-HT) and ghrelin (GHR), while in the small and large intestine, G?gust and G?tran-IR colocalized with 5-HT-, cholecystokinin (CCK)- and peptide YY (PYY)-IR. There was a significant increase in the density of G?tran-IR cells in the pyloric mucosa in both short- and long-term Hp diet groups (Hp3 and Hp30) vs. the control group (Ctr) (P<0.05), while the increase of G?gust-IR cells in the pyloric mucosa was significant in Hp30 group vs. Ctr and vs. Hp3 (P<0.05); these cells included G?tran / 5HT-IR and G?tran / GHR-IR cells (P<0.05 and P<0.001 vs. Ctr, respectively) as well as G?gust /5-HT-IR or G?gust / GHR-IR cells (P<0.05 and P<0.01 vs. Ctr, respectively). In the small intestine, we recorded a significant increase in G?tran-IR cells in the duodenal crypts and a significant increase of G?gust-IR cells in the jejunal crypts in Hp3 group compared to HP30 (P<0.05). With regard to the number of G?tran-G?gust IR cells colocalized with CCK or 5-HT, there was only a significant increase of G?tran / CCK-IR cells in Hp3 group compared to Ctr (P = 0.01).ConclusionThis study showed an upregulation of selected subpopulations of G?gust / G?tran-IR cells in distinct regions of the pig GI tract by short- and long-term Hp diet lending support to TASR-mediated effects in metabolic homeostasis and satiety mechanisms.

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A pig model of the human gastrointestinal tract.

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A pig model of the human gastrointestinal tract.

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