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• W2146074997 abstract "The gut microbiotas of zebrafish and mice share six bacterial divisions, although the specific bacteria within these divisions differ. To test how factors specific to host gut habitat shape microbial community structure, we performed reciprocal transplantations of these microbiotas into germ-free zebrafish and mouse recipients. The results reveal that communities are assembled in predictable ways. The transplanted community resembles its community of origin in terms of the lineages present, but the relative abundance of the lineages changes to resemble the normal gut microbial community composition of the recipient host. Thus, differences in community structure between zebrafish and mice arise in part from distinct selective pressures imposed within the gut habitat of each host. Nonetheless, vertebrate responses to microbial colonization of the gut are ancient: Functional genomic studies disclosed shared host responses to their compositionally distinct microbial communities and distinct microbial species that elicit conserved responses. The gut microbiotas of zebrafish and mice share six bacterial divisions, although the specific bacteria within these divisions differ. To test how factors specific to host gut habitat shape microbial community structure, we performed reciprocal transplantations of these microbiotas into germ-free zebrafish and mouse recipients. The results reveal that communities are assembled in predictable ways. The transplanted community resembles its community of origin in terms of the lineages present, but the relative abundance of the lineages changes to resemble the normal gut microbial community composition of the recipient host. Thus, differences in community structure between zebrafish and mice arise in part from distinct selective pressures imposed within the gut habitat of each host. Nonetheless, vertebrate responses to microbial colonization of the gut are ancient: Functional genomic studies disclosed shared host responses to their compositionally distinct microbial communities and distinct microbial species that elicit conserved responses. Animal evolution has occurred, and is occurring, in a world dominated by microorganisms. As animals evolved to occupy different habitats (addresses) and niches (professions) in our biosphere, they have forged strategic alliances with microorganisms on their body surfaces. The genomes of microbes within these consortia encode physiologic traits that are not represented in host genomes: Microbial-microbial and host-microbial mutualism endows the resulting “super-organisms” with a fitness advantage (Ley et al., 2006bLey R.E. Peterson D.A. Gordon J.I. Ecological and evolutionary forces shaping microbial diversity in the human intestine.Cell. 2006; 124: 837-848Abstract Full Text Full Text PDF PubMed Scopus (2018) Google Scholar). The majority of these microbes are present in digestive tract communities where, among other things, they contribute to the harvest of dietary nutrients that would otherwise be inaccessible (Bäckhed et al., 2004Bäckhed F. Ding H. Wang T. Hooper L.V. Koh G.Y. Nagy A. Semenkovich C.F. Gordon J.I. The gut microbiota as an environmental factor that regulates fat storage.Proc. Natl. Acad. Sci. USA. 2004; 101: 15718-15723Crossref PubMed Scopus (3733) Google Scholar, Sonnenburg et al., 2005Sonnenburg J.L. Xu J. Leip D.D. Chen C.H. Westover B.P. Weatherford J. Buhler J.D. Gordon J.I. Glycan foraging in vivo by an intestine-adapted bacterial symbiont.Science. 2005; 307: 1955-1959Crossref PubMed Scopus (718) Google Scholar), as well as to the education of the host's immune system (Cebra, 1999Cebra J.J. Influences of microbiota on intestinal immune system development.Am. J. Clin. Nutr. 1999; 69: 1046S-1051SPubMed Google Scholar). The advent of massively parallel DNA sequencers provides an opportunity to define the gene content of these indigenous microbial communities with increased speed and economy. These “microbiome” sequencing projects promise to provide a more comprehensive view of the genetic landscape of animal-microbial alliances and testable hypotheses about the contributions of microbial communities to animal biology. The results should allow a number of fundamental questions to be addressed. Is there an identifiable core microbiota and microbiome associated with a given host species? How are a microbiota and its microbiome selected, and how do they evolve within and between hosts? What are the functional correlates of diversity in the membership of a microbiota and in the genetic composition of its microbiome? Answers to these questions also require model organisms to assess how communities are assembled, to determine how different members impact community function and host biology, and to ascertain the extent of redundancy or modularity within a microbiota. One approach for generating such models is to use gnotobiotics—the ability to raise animals under germ-free (GF) conditions—to colonize them at varying points in their life cycle with a single microbe or more complex collections, and to then observe the effects of host habitat on microbial community structure and function and of the community on the host. Methods for raising and propagating rodents under GF conditions have been available for 50 years (see Wostmann, 1981Wostmann B.S. The germfree animal in nutritional studies.Annu. Rev. Nutr. 1981; 1: 257-279Crossref PubMed Scopus (117) Google Scholar), although genomic and allied computational methods for comprehensively assessing microbial community composition, gene content, and host-microbial structure/function relationships have only been deployed in the last five years (e.g., Hooper and Gordon, 2001Hooper L.V. Gordon J.I. Commensal host-bacterial relationships in the gut.Science. 2001; 292: 1115-1118Crossref PubMed Scopus (1649) Google Scholar, Ley et al., 2005Ley R.E. Bäckhed F. Turnbaugh P. Lozupone C.A. Knight R.D. Gordon J.I. Obesity alters gut microbial ecology.Proc. Natl. Acad. Sci. USA. 2005; 102: 11070-11075Crossref PubMed Scopus (3777) Google Scholar). Recently, we developed techniques for rearing the zebrafish (Danio rerio) under GF conditions (Rawls et al., 2004Rawls J.F. Samuel B.S. Gordon J.I. Gnotobiotic zebrafish reveal evolutionarily conserved responses to the gut microbiota.Proc. Natl. Acad. Sci. USA. 2004; 101: 4596-4601Crossref PubMed Scopus (615) Google Scholar). In principle, this model organism provides a number of attractive and distinctive features for analyzing host-microbial mutualism. Zebrafish remain transparent until adulthood, creating an opportunity to visualize microbes in their native gut habitats in real time. A deep draft reference genome sequence of D. rerio is available (http://www.sanger.ac.uk/Projects/D_rerio/). In addition, forward genetic tests and chemical screens can be conducted (Patton and Zon, 2001Patton E.E. Zon L.I. The art and design of genetic screens: zebrafish.Nat. Rev. Genet. 2001; 2: 956-966Crossref PubMed Scopus (340) Google Scholar, Peterson and Fishman, 2004Peterson R.T. Fishman M.C. Discovery and use of small molecules for probing biological processes in zebrafish.Methods Cell Biol. 2004; 76: 569-591Crossref PubMed Scopus (47) Google Scholar) to characterize zebrafish signaling pathways regulated by microbial consortia and/or their component members. A preliminary functional genomic study of the effects of colonizing GF zebrafish with an unfractionated microbiota harvested from adult conventionally raised (CONV-R) zebrafish revealed 59 genes whose responses were similar to those observed when GF mice were colonized with an adult mouse gut microbiota (Rawls et al., 2004Rawls J.F. Samuel B.S. Gordon J.I. Gnotobiotic zebrafish reveal evolutionarily conserved responses to the gut microbiota.Proc. Natl. Acad. Sci. USA. 2004; 101: 4596-4601Crossref PubMed Scopus (615) Google Scholar). These genes encode products affecting processes ranging from nutrient metabolism to innate immunity and gut epithelial cell turnover (Rawls et al., 2004Rawls J.F. Samuel B.S. Gordon J.I. Gnotobiotic zebrafish reveal evolutionarily conserved responses to the gut microbiota.Proc. Natl. Acad. Sci. USA. 2004; 101: 4596-4601Crossref PubMed Scopus (615) Google Scholar). The experiments did not distinguish whether the host responses were evolutionarily conserved and thus present in the last common ancestor of fish and mammals, or if they had been independently derived in mammals and fish. However, the fact that numerous homologous genes and shared cellular changes comprised the “common” response favors the notion of evolutionary conservation over convergence. It was also unclear whether these common host responses were elicited by the same or different bacterial signals in each host or by signals from the whole community versus from specific bacteria. A recent comprehensive 16S rRNA sequence-based survey of the adult mouse gut disclosed that, as in humans, >99% of the bacterial phylogenetic types (phylotypes) belong to two divisions—the Firmicutes and Bacteroidetes (Ley et al., 2005Ley R.E. Bäckhed F. Turnbaugh P. Lozupone C.A. Knight R.D. Gordon J.I. Obesity alters gut microbial ecology.Proc. Natl. Acad. Sci. USA. 2005; 102: 11070-11075Crossref PubMed Scopus (3777) Google Scholar). In contrast, limited surveys of different fish species indicate that their gut communities are dominated by the Proteobacteria (Cahill, 1990Cahill M.M. Bacterial flora of fishes: a review.Microb. Ecol. 1990; 19: 21-41Crossref PubMed Scopus (431) Google Scholar, Huber et al., 2004Huber I. Spanggaard B. Appel K.F. Rossen L. Nielsen T. Gram L. Phylogenetic analysis and in situ identification of the intestinal microbial community of rainbow trout (Oncorhynchus mykiss, Walbaum).J. Appl. Microbiol. 2004; 96: 117-132Crossref PubMed Scopus (187) Google Scholar, Rawls et al., 2004Rawls J.F. Samuel B.S. Gordon J.I. Gnotobiotic zebrafish reveal evolutionarily conserved responses to the gut microbiota.Proc. Natl. Acad. Sci. USA. 2004; 101: 4596-4601Crossref PubMed Scopus (615) Google Scholar, Bates et al., 2006Bates J.M. Mittge E. Kuhlman J. Baden K.N. Cheesman S.E. Guillemin K. Distinct signals from the microbiota promote different aspects of zebrafish gut differentiation.Dev. Biol. 2006; 297: 374-386Crossref PubMed Scopus (374) Google Scholar, Romero and Navarrete, 2006Romero J. Navarrete P. 16S rDNA-based analysis of dominant bacterial populations associated with early life stages of coho salmon (Oncorhynchus kisutch).Microb. Ecol. 2006; 51: 422-430Crossref PubMed Scopus (141) Google Scholar). Fish and mammals live in very different environments, so it is possible that differences in their gut microbiotas arise from “legacy effects” (e.g., local environmental microbial community composition or inheritance of a microbiota from a parent). Furthermore, legacy effects might combine with “gut habitat effects” (e.g., distinct selective pressures arising from differences in anatomy, physiology, immunologic “climate,” or nutrient milieu) to shape the different community structures of fish and mammals. In the present study, we have performed reciprocal microbiota transplantations in GF zebrafish and mice. We provide evidence that gut habitat shapes microbial community structure and that both animal species respond in remarkably similar ways to components of one another's microbiota. Our previous survey of the gut microbiota of adult CONV-R zebrafish was limited to 176 bacterial 16S rRNA gene sequences (Rawls et al., 2004Rawls J.F. Samuel B.S. Gordon J.I. Gnotobiotic zebrafish reveal evolutionarily conserved responses to the gut microbiota.Proc. Natl. Acad. Sci. USA. 2004; 101: 4596-4601Crossref PubMed Scopus (615) Google Scholar). Therefore, we performed a more comprehensive analysis of intestinal contents pooled from 18 adult male and female C32 zebrafish (comprised of two independent pools, each containing material from 9 animals). A total of 1456 bacterial 16S rRNA sequences formed the final analyzed dataset: 616 from pool 1 and 840 from pool 2 (libraries JFR0503 and JFR0504, respectively, in Table S1 available with this article online). Phylogenetic analysis revealed 198 “species-level” phylotypes defined by 99% pairwise sequence identity. These phylotypes represented a total of 11 bacterial divisions and were dominated by the Proteobacteria (82% ± 22.9% [SD] of all clones averaged across both libraries) and the Fusobacteria (11% ± 15.2%; Figure 1, Figure 2). The Firmicutes, Bacteroidetes, Verrucomicrobia, Actinobacteria, TM7, Planctomycetes, TM6, Nitrospira, and OP10 divisions were minor components (3.2%–0.6%). Six of the eleven bacterial divisions found in adult zebrafish are also found in mice (Ley et al., 2005Ley R.E. Bäckhed F. Turnbaugh P. Lozupone C.A. Knight R.D. Gordon J.I. Obesity alters gut microbial ecology.Proc. Natl. Acad. Sci. USA. 2005; 102: 11070-11075Crossref PubMed Scopus (3777) Google Scholar); five of these are also shared by the adult human microbiota (Eckburg et al., 2005Eckburg P.B. Bik E.M. Bernstein C.N. Purdom E. Dethlefsen L. Sargent M. Gill S.R. Nelson K.E. Relman D.A. Diversity of the human intestinal microbial flora.Science. 2005; 308: 1635-1638Crossref PubMed Scopus (4888) Google Scholar; Figure 1A). However, zebrafish community members within these shared divisions are distinct from those in mice and humans at more shallow phylogenetic resolution (Figures 1B–1D). The composition of the mouse gut microbiota is affected by host genotype, as well as by legacy (it is inherited from the mother; Ley et al., 2005Ley R.E. Bäckhed F. Turnbaugh P. Lozupone C.A. Knight R.D. Gordon J.I. Obesity alters gut microbial ecology.Proc. Natl. Acad. Sci. USA. 2005; 102: 11070-11075Crossref PubMed Scopus (3777) Google Scholar). To determine whether the observed differences between zebrafish and mouse microbiotas reflect host genome-encoded variations in their gut habitats versus differences in the local microbial consortium available for colonization, we colonized (1) adult GF mice with an unfractionated gut microbiota harvested from CONV-R adult zebrafish (yielding “Z-mice”) and (2) GF zebrafish larvae with a gut microbiota from CONV-R adult mice (“M-zebrafish”). By comparing the composition of the community introduced into the GF host (“input community”) with the community that established itself in the host (Z-mouse or M-zebrafish “output community”), we sought to determine whether gut microbial ecology is primarily influenced by legacy effects (the input community structure would persist in the new host) versus gut habitat effects (the representation changes when certain taxa are selected). We introduced the pooled intestinal contents of 18 CONV-R adult zebrafish belonging to the C32 inbred strain (pools 1 and 2 above) into adult GF mice belonging to the NMRI inbred strain (n = 6, Table S1, Figure S1). The resulting Z-mice were housed in gnotobiotic isolators and sacrificed 14 days after colonization (i.e., after several cycles of replacement of the intestinal epithelium and its overlying mucus layer). Their cecal contents were harvested and provided community DNA for 16S rRNA sequence-based enumerations. The cecum was selected for this analysis because it is a well-defined anatomic structure located at the junction of the small intestine and colon, and its luminal contents can be readily and reliably recovered. It also harbors a very dense microbial population in CONV-R mice (1011–1012 organisms/ml luminal contents) that has been comprehensively surveyed (Ley et al., 2005Ley R.E. Bäckhed F. Turnbaugh P. Lozupone C.A. Knight R.D. Gordon J.I. Obesity alters gut microbial ecology.Proc. Natl. Acad. Sci. USA. 2005; 102: 11070-11075Crossref PubMed Scopus (3777) Google Scholar). In addition to the 1456 16S rRNA sequences representing 198 phylotypes from the input zebrafish community (libraries JFR0503 and JFR0504; see above), we obtained a total of 1836 sequences representing 179 phylotypes from the Z-mouse cecal community (libraries JFR0507–12; Figures S1 and S2). Only 12% of the phylotypes found in the Z-mouse community, representing 39% of all sequences, were detected in the input zebrafish community. The dominant division in the input zebrafish community (Proteobacteria) persisted but shrank in abundance in the Z-mouse community (82% ± 22.9% in the input versus 41.7% ± 8.9% in the output; Figure 2). The Z-mouse community only contained members of the γ- and β-Proteobacteria subdivisions, whereas the input zebrafish community had also included δ- and α-Proteobacteria. In addition, members of the Bacteroidetes detected in the input zebrafish community were not observed in the Z-mouse community. The Z-mouse community showed a striking amplification of the Firmicutes (1% ± 1.1% of the input, 54.3% ± 6.5% of the Z-mouse output; Figure 2); this amplification included members of Bacilli as well as Clostridia classes. By comparing communities at multiple thresholds for pairwise percent identity among 16S rRNA gene sequences (%ID), we determined that divergence between the input zebrafish and output Z-mouse communities occurred at 89%ID and higher (Figure 3). This implies that genera represented within the zebrafish and Z-mouse gut microbiotas are different but represent the same major lineages. The analysis also demonstrated that the phylotypes that bloomed in the mouse cecum were minor constituents of the input zebrafish digestive tract community. Despite the difference in genus/species representation, the richness and diversity of the input zebrafish and Z-mouse gut communities remained similar through the shift in microbial community composition (Figure S2 and Table S1). When a similar analysis was applied to the input mouse and M-mouse communities obtained from a mouse-into-mouse microbiota transplant experiment (Bäckhed et al., 2004Bäckhed F. Ding H. Wang T. Hooper L.V. Koh G.Y. Nagy A. Semenkovich C.F. Gordon J.I. The gut microbiota as an environmental factor that regulates fat storage.Proc. Natl. Acad. Sci. USA. 2004; 101: 15718-15723Crossref PubMed Scopus (3733) Google Scholar), we found that a high degree of similarity was maintained at levels as great as 97%ID (Figure 3). Based on these results, we concluded that (1) the difference in composition of the input zebrafish and output Z-mouse communities is not likely to be due to the microbiota transplantation procedure per se and (2) the adult mouse cecum is able to support a complex foreign microbial consortium by shaping its composition. We performed the reciprocal experiment by colonizing recently hatched (3 days post-fertilization [dpf]) GF C32 zebrafish with the pooled cecal contents of three CONV-R adult female mice (libraries JFR0505 and JFR0506 in Table S1) and conducting surveys of the recipients' digestive tract communities 3 or 7 days later (libraries JFR0513-18 in Table S1; Figure S1). As in the previous experiment, the dominant bacterial division in the input mouse community (Firmicutes) persisted in the output M-zebrafish community (87.3% ± 2.2% of input, 64.9% ± 41.7% of output; Figure 2). However, only members of Bacilli, the dominant Firmicute class in the zebrafish but not the normal mouse gut microbiota, were retained; other prominent members of the Firmicutes found in the input mouse library (i.e., Clostridia and Mollicutes) were no longer detected in the M-zebrafish gut. Bacteroidetes (9.8% ± 3.3% of input community) were also undetected. Proteobacteria, a minor member of the input mouse community, were amplified markedly in the M-zebrafish gut (2.2% ± 0.6% of input, 35.1% ± 41.7% of output; Figure 2). In addition to their drastic compositional differences, we also found that the output M-zebrafish community was less rich and less diverse than the input mouse community (Table S1 and Figure S2), indicating that only a small subset of the mouse gut microbial consortium was able to establish and/or thrive in the larval M-zebrafish gut. In contrast to the reciprocal zebrafish-into-mouse experiment where the contents of the adult fish gut were gavaged directly into the stomachs of recipient GF mice, our mouse-into-zebrafish gut microbiota transplantation involved introduction of mouse cecal contents into gnotobiotic zebrafish medium (GZM) containing 3dpf fish. Therefore, environmental factors could operate to select a subset of the input mouse community prior to entry in the recipient fish gut. The similarities between input mouse and M-zebrafish communities were high, from 86%ID to 91%ID, above which the communities diverged in composition (Figure 3), i.e., different genera were representative of the same deeper phylogenetic lineages. Indeed, there was no overlap between phylotypes with threshold pairwise ≥99%ID in the datasets obtained from the input mouse and M-zebrafish communities. This was due, in part, to the limited degree of coverage (73% for the input community according to Good's method; Good, 1953Good I.J. The population frequencies of species and the estimation of population parameters.Biometrika. 1953; 40: 237-264Crossref Google Scholar). Phylotypes that were detected only in the M-zebrafish community were identifiable in the input mouse community using PCR and phylotype-specific primers (e.g., Staphylococcus; data not shown). Compared to the reciprocal zebrafish-into-mouse transplantation experiment, the input mouse and output M-zebrafish communities diverged at a higher %ID cut-off (Figure 3), indicating that they were more similar at a higher taxonomic level than the zebrafish/Z-mouse communities. Part of the drop in similarity could be attributed to the experimental manipulation since a similar analysis of a zebrafish-into-zebrafish transplant (Rawls et al., 2004Rawls J.F. Samuel B.S. Gordon J.I. Gnotobiotic zebrafish reveal evolutionarily conserved responses to the gut microbiota.Proc. Natl. Acad. Sci. USA. 2004; 101: 4596-4601Crossref PubMed Scopus (615) Google Scholar) revealed a drop in similarity at a comparable %ID (Figure 3). The similarity indices described above are derived from phylotype abundances at different phylotype thresholds (%IDs). However, an implicit assumption underlying such an analysis is that all phylotypes are treated equally regardless of lineage, even though they may represent similar or very unrelated lineages (Lozupone and Knight, 2005Lozupone C. Knight R. UniFrac: a new phylogenetic method for comparing microbial communities.Appl. Environ. Microbiol. 2005; 71: 8228-8235Crossref PubMed Scopus (4578) Google Scholar). Another way to compare communities is the UniFrac analysis: In this method, the abundance of each lineage is weighted, such that the abundance of lineages is considered as well as which lineages are present (Lozupone and Knight, 2005Lozupone C. Knight R. UniFrac: a new phylogenetic method for comparing microbial communities.Appl. Environ. Microbiol. 2005; 71: 8228-8235Crossref PubMed Scopus (4578) Google Scholar). The UniFrac approach circumvents the problem of having to decide at what %ID level to define the phylotype units that we call “different” (the cut-off is likely to vary according to lineage). UniFrac analysis revealed that replicate Z-mouse datasets are most similar to the input zebrafish datasets with respect to detected lineages (Figure 2). However, the abundance of the Firmicutes in Z-mice expanded to resemble the division's abundance in CONV-R mice, indicating that the input community, although derived from a zebrafish, has been shaped to resemble a native mouse community. Similarly, the M-zebrafish communities are most similar to the mouse input communities by UniFrac, but the Proteobacteria in M-zebrafish expanded to resemble a CONV-R zebrafish community, indicating that the input mouse community has been shaped to resemble a native zebrafish microbiota (Figure 2). Together, the results from our reciprocal microbiota transplantation experiments disclose that (1) gut habitat sculpts community composition in a consistent fashion, regardless of the input, and (2) stochastic effects are minimal (One notable exception was that γ-Proteobacteria in M-zebrafish [Escherichia, Shigella, and Proteus spp.] were more abundant in one experimental replicate [69.8% ± 20.5%] compared to the other [0.5% ± 0.6%]). The amplified taxa in both sets of transplantation experiments represented dominant divisions in the native gut microbiota of the respective host: Firmicutes in the case of teleostification (zebrafish-into-mouse), Proteobacteria in the case of murinization (mouse-into-zebrafish). While the studies described above indicated that the composition of the gut microbiota is sensitive to host habitat, we did not know whether the host response was sensitive to microbial community composition. Therefore, we conducted a GeneChip-based functional genomic analysis of gene expression in the distal small intestines (ileums) of mice that had been subjected to zebrafish-into-mouse (Z-mice) and mouse-into-mouse (M-mice) microbiota transplantations. All animals (n = 3–5/treatment group) were sacrificed 14 days after inoculation, RNA was prepared from the ileum of each mouse, and the cRNA target generated from each RNA sample was hybridized to an Affymetrix 430 v2 mouse GeneChip. Ingenuity Pathways Analysis software (IPA; see Supplemental Data) was then used to compare host responses to these different microbial communities. IPA software was utilized for genes that exhibited a ≥1.5-fold change (increased or decreased) in their expression compared to GF controls (false discovery rate <1%). Despite the different bacterial compositions of the two input communities, their impact on the mouse was remarkably similar (Figure 4). The number of IPA-annotated mouse genes whose expression changed in response to the two microbiotas was comparable: 500 in response to the native mouse microbiota (Table S7) and 525 in response to the zebrafish microbiota (Table S8 and Figure 4A). Approximately half of the genes (225) were responsive to both microbial communities (Table S10): 217 (96.4%) were regulated in the same direction. Among the two sets of responsive genes, there was shared enrichment of IPA-annotated metabolic pathways involved in (1) biosynthesis and metabolism of fatty acids (sources of energy as well as substrates for synthesis of more complex cellular lipids in an intestinal epithelium that undergoes continuous and rapid renewal); (2) metabolism of essential amino acids (valine, isoleucine, and lysine); (3) metabolism of amino acids that contain the essential trace element selenium (selenocystine/selenomethioinine) and are incorporated into the active sites of selenoproteins such as glutathione peroxidase; (4) metabolism of butyrate (a product of polysaccharide fermentation that is a key energy source for the gut epithelium); and (5) biosynthesis of bile acids needed for absorption of lipids and other hydrophobic nutrients (Figure 4B and Table S12). Both communities altered expression of a similar set of genes involved in insulin-like growth factor-1 (Igf-1), vascular endothelial growth factor (Vegf), B cell receptor, and interleukin-6 (Il-6) signaling pathways (Figure 4C and Table S13). These results are intriguing: Previous mouse-into-mouse and zebrafish-into-zebrafish transplantations revealed that the microbiota-directed increase in proliferative activity of gut epithelial lineage progenitors is a shared host response (Rawls et al., 2004Rawls J.F. Samuel B.S. Gordon J.I. Gnotobiotic zebrafish reveal evolutionarily conserved responses to the gut microbiota.Proc. Natl. Acad. Sci. USA. 2004; 101: 4596-4601Crossref PubMed Scopus (615) Google Scholar). The underlying mechanisms are not known. However, we recently found that components of Igf-1, Vegf, B cell receptor, and Il-6 signaling pathways were significantly enriched in mouse small intestinal epithelial progenitors (Giannakis et al., 2006Giannakis M. Stappenbeck T.S. Mills J.C. Leip D.G. Lovett M. Clifton S.W. Ippolito J.E. Glasscock J.I. Arumugam M. Brent M.R. Gordon J.I. Molecular properties of adult mouse gastric and intestinal epithelial progenitors in their niches.J. Biol. Chem. 2006; 281: 11292-11300Crossref PubMed Scopus (151) Google Scholar). Thus, it is tempting to speculate that these pathways may be involved in mediating the microbiota's effect on mouse intestinal epithelial renewal. Taken together, these results reveal a commonality in the transcriptional responses of the mouse to two microbial communities with shared divisions represented by different lineages at a finer phylogenetic resolution (Figure 1). This common response to a microbiota may reflect as yet unappreciated shared functional properties expressed by the two compositionally distinct communities and/or a core response, evolved by the mouse gut to distinct microbial communities. Analysis of zebrafish 3 days after colonization with either a zebrafish or a mouse microbiota at 3dpf also demonstrated shared features of the host response to both microbial communities. To quantify these responses, we selected biomarkers identified from our comparisons of 6dpf GF, CONV-R, and Z-zebrafish (Rawls et al., 2004Rawls J.F. Samuel B.S. Gordon J.I. Gnotobiotic zebrafish reveal evolutionarily conserved responses to the gut microbiota.Proc. Natl. Acad. Sci. USA. 2004; 101: 4596-4601Crossref PubMed Scopus (615) Google Scholar). Quantitative real-time RT-PCR (qRT-PCR) of biomarkers of lipid metabolism, including fasting-induced adipose factor (fiaf; circulating inhibitor of lipoprotein lipase, Bäckhed et al., 2004Bäckhed F. Ding H. Wang T. Hooper L.V. Koh G.Y. Nagy A. Semenkovich C.F. Gordon J.I. The gut microbiota as an environmental factor that regulates fat storage.Proc. Natl. Acad. Sci. USA. 2004; 101: 15718-15723Crossref PubMed Scopus (3733) Google Scholar), carnitine palmitoyltransferase 1a (cpt1a), and the trifunctional enzyme hydroxyacylCoA dehydrogenase/3-ketoacylCoA thiolase/enoyl CoA hyd" @default.
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• W2146074997 date "2006-10-01" @default.
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• W2146074997 title "Reciprocal Gut Microbiota Transplants from Zebrafish and Mice to Germ-free Recipients Reveal Host Habitat Selection" @default.
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• W2146074997 doi "https://doi.org/10.1016/j.cell.2006.08.043" @default.
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