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The adult human gut microbiota is dominated by two divisions of Bacteria, the Bacteroidetes and the Firmicutes. Assembly of this community begins at birth through processes that remain largely undefined. In this report, we examine the adaptations of Bacteroides thetaiotaomicron, a prominent member of the adult distal intestinal microbiota, during the suckling and weaning periods. Germ-free NMRI mice were colonized at birth from their gnotobiotic mothers, who harbored this anaerobic Gram-negative saccharolytic bacterium. B. thetaiotaomicron was then harvested from the ceca of these hosts during the suckling period (postnatal day 17) and after weaning (postnatal day 30). Whole genome transcriptional profiles were obtained at these two time points using custom B. thetaiotaomicron GeneChips. Transcriptome-based in silico reconstructions of bacterial metabolism and gas chromatography-mass spectrometry and biochemical assays of carbohydrate utilization in vivo indicated that in the suckling gut B. thetaiotaomicron prefers host-derived polysaccharides, as well as mono- and oligosaccharides present in mother's milk. After weaning, B. thetaiotaomicron expands its metabolism to exploit abundant, plant-derived dietary polysaccharides. The bacterium's responses to postnatal alterations in its nutrient landscape involve expression of gene clusters encoding environmental sensors, outer membrane proteins involved in binding and import of glycans, and glycoside hydrolases. These expression changes are interpreted in light of a phylogenetic analysis that revealed unique expansions of related polysaccharide utilization loci in three human alimentary tract-associated Bacteroidetes, expansions that likely reflect the evolutionary adaptations of these species to different nutrient niches. The adult human gut microbiota is dominated by two divisions of Bacteria, the Bacteroidetes and the Firmicutes. Assembly of this community begins at birth through processes that remain largely undefined. In this report, we examine the adaptations of Bacteroides thetaiotaomicron, a prominent member of the adult distal intestinal microbiota, during the suckling and weaning periods. Germ-free NMRI mice were colonized at birth from their gnotobiotic mothers, who harbored this anaerobic Gram-negative saccharolytic bacterium. B. thetaiotaomicron was then harvested from the ceca of these hosts during the suckling period (postnatal day 17) and after weaning (postnatal day 30). Whole genome transcriptional profiles were obtained at these two time points using custom B. thetaiotaomicron GeneChips. Transcriptome-based in silico reconstructions of bacterial metabolism and gas chromatography-mass spectrometry and biochemical assays of carbohydrate utilization in vivo indicated that in the suckling gut B. thetaiotaomicron prefers host-derived polysaccharides, as well as mono- and oligosaccharides present in mother's milk. After weaning, B. thetaiotaomicron expands its metabolism to exploit abundant, plant-derived dietary polysaccharides. The bacterium's responses to postnatal alterations in its nutrient landscape involve expression of gene clusters encoding environmental sensors, outer membrane proteins involved in binding and import of glycans, and glycoside hydrolases. These expression changes are interpreted in light of a phylogenetic analysis that revealed unique expansions of related polysaccharide utilization loci in three human alimentary tract-associated Bacteroidetes, expansions that likely reflect the evolutionary adaptations of these species to different nutrient niches. Our adult gut is colonized with a community of 10-100 trillion microbes. This microbiota, and its collective genome (microbiome), provide us with important physiological attributes that are not encoded in our own human genome, including the ability to break down otherwise indigestible nutrients that are delivered to the distal gut, such as dietary plant polysaccharides (1Sonnenburg J.L. Xu J. Leip D.D. Chen C.H. Westover B.P. Weatherford J. Buhler J.D. Gordon J.I. Science. 2005; 307: 1955-1959Crossref PubMed Scopus (795) Google Scholar, 2Gill S.R. Pop M. Deboy R.T. Eckburg P.B. Turnbaugh P.J. Samuel B.S. Gordon J.I. Relman D.A. Fraser-Liggett C.M. Nelson K.E. Science. 2006; 312: 1355-1359Crossref PubMed Scopus (3137) Google Scholar). A recent comprehensive 16 S rRNA-based enumeration study of the distal intestinal microbiota of a small number of healthy adult humans demonstrated that >99% of detected phylogenetic types (phylotypes) belong to two of the 70 bacterial divisions (superkingdoms) currently known in nature: the Bacteroidetes and the Firmicutes (3Eckburg P.B. Bik E.M. Bernstein C.N. Purdom E. Dethlefsen L. Sargent M. Gill S.R. Nelson K.E. Relman D.A. Science. 2005; 308: 1635-1638Crossref PubMed Scopus (5278) Google Scholar, 4Ley R.E. Peterson D.A. Gordon J.I. Cell. 2006; 124: 837-848Abstract Full Text Full Text PDF PubMed Scopus (2190) Google Scholar). Within each division there is great diversity at the species and subspecies levels. Moreover, these shallow lineages show considerable variation between individual humans (3Eckburg P.B. Bik E.M. Bernstein C.N. Purdom E. Dethlefsen L. Sargent M. Gill S.R. Nelson K.E. Relman D.A. Science. 2005; 308: 1635-1638Crossref PubMed Scopus (5278) Google Scholar, 4Ley R.E. Peterson D.A. Gordon J.I. Cell. 2006; 124: 837-848Abstract Full Text Full Text PDF PubMed Scopus (2190) Google Scholar). The mechanisms controlling assembly of our microbiotas remain ill defined. This issue can be framed as follows. What is the effect of the microbial community that is available to colonize a host at the time of birth (the legacy effect)? What is the effect of the gut environment itself on shaping the available community, and is the gut selecting for properties that are common or unique to members of bacterial divisions (the host effect)? Recent reciprocal transplantation experiments have emphasized the importance of host habitat: when the gut microbiota of a conventionally raised mouse is introduced into a germ-free zebrafish recipient, and vice versa, the recipient gut acts as a biological filter to amplify members of the donor community that most closely resemble its normal (native) species. (5Rawls J.F. Mahowald M. Ley R.E. Gordon J.I. Cell. 2006; 127: 423-433Abstract Full Text Full Text PDF PubMed Scopus (660) Google Scholar). Our gut-associated Firmicutes and Bacteroidetes have not been identified outside of the intestinal habitat. Thus, they are likely acquired by transmission from our mothers or other family members soon after birth. This notion is supported by several observations. Studies using C57Bl/6J mice revealed that offspring inherit microbiotas similar to those of their mothers (6Ley R.E. Backhed F. Turnbaugh P. Lozupone C.A. Knight R.D. Gordon J.I. Proc. Natl. Acad. Sci. U. S. A. 2005; 102: 11070-11075Crossref PubMed Scopus (4137) Google Scholar). The effect of kinship was evident across generations: C57Bl/6J mothers who are sisters have gut microbiotas that are similar to one another and to those of their offspring (6Ley R.E. Backhed F. Turnbaugh P. Lozupone C.A. Knight R.D. Gordon J.I. Proc. Natl. Acad. Sci. U. S. A. 2005; 102: 11070-11075Crossref PubMed Scopus (4137) Google Scholar). Culture-based studies of humans indicate that infants, who are germ-free in utero, also acquire their initial microbiota from the vaginal and fecal microbiota of their mothers (7Gronlund M.M. Lehtonen O.P. Eerola E. Kero P. J. Pediatr. Gastroenterol. Nutr. 1999; 28: 19-25Crossref PubMed Scopus (689) Google Scholar, 8Mandar R. Mikelsaar M. Biol. Neonate. 1996; 69: 30-35Crossref PubMed Scopus (130) Google Scholar). The extent to which host genotype influences the composition of the postnatally acquired microbiota is unclear. 16 S rRNA fingerprinting studies of a small number of adult monozygotic twin pairs indicated their fecal microbiotas were more similar to one another than to their marital partners. However, the same trend was true for dizygotic twins, underscoring the importance of a shared mother (9Zoetendal E.G. Akkermans A.D.L. Vliet W.M.A.-V. Visser J.A.G.M.D. Vos W.M.D. Microbial Ecology Health Disease. 2001; 13: 129-134Crossref Scopus (443) Google Scholar). Although many studies have been carried out to decipher the composition of the fecal microbiota during the postnatal period, the majority have used culture-based methods and hence are subject to sampling bias and to limited sensitivity (10Pace N.R. Science. 1997; 276: 734-740Crossref PubMed Scopus (1976) Google Scholar, 11Hugenholtz P. Goebel B.M. Pace N.R. J. PubMed Google Scholar). there are the of a comprehensive 16 S rRNA enumeration of gut microbial during the postnatal period, in related or we not there is of to a community, or there is a period of by of members of the Culture-based enumeration studies have that reflect host legacy are identified the and are by PubMed Scopus Google Scholar, R. S. PubMed Scopus Google Scholar, J. Pediatr. PubMed Scopus Google Scholar, Google Scholar). However, prominent that are members of the adult microbiota have been identified as as postnatal day in delivered J. Pediatr. PubMed Scopus Google Scholar, M. K.E. L. J. Sci. 1996; PubMed Scopus Google that species in this In the present we the of members of the adult microbiota are to during the suckling period that they can to of after the from a of mother's to one in plant-derived polysaccharides. this we Bacteroides thetaiotaomicron, a Gram-negative that of and of Bacteroidetes in the most comprehensive 16 S rRNA enumeration of the adult human microbiota to (3Eckburg P.B. Bik E.M. Bernstein C.N. Purdom E. Dethlefsen L. Sargent M. Gill S.R. Nelson K.E. Relman D.A. Science. 2005; 308: 1635-1638Crossref PubMed Scopus (5278) Google Scholar). of B. to in the adult gut is its of to the and metabolism of plant and other dietary polysaccharides in our J. J. S. Gordon J.I. Science. PubMed Scopus Google Scholar). The B. thetaiotaomicron genome is to glycoside and polysaccharide to break down polysaccharides that we on our own our the B. thetaiotaomicron and we have used postnatal day clusters of glycoside polysaccharide polysaccharide used postnatal day clusters of glycoside polysaccharide polysaccharide at a comprehensive The B. thetaiotaomicron genome also of two proteins that of of are outer membrane in to binding polysaccharides, they likely in of these into the J. J. 1996; PubMed Scopus Google Scholar). are to be proteins with that to with the outer membrane J. PubMed Scopus Google Scholar). B. thetaiotaomicron also of environmental and that and members of that of the in a into a J. J. S. Gordon J.I. Science. PubMed Scopus Google Scholar). of the proteins are used by B. thetaiotaomicron to polysaccharides and involved their metabolism J.L. Gordon J.I. Proc. Natl. Acad. Sci. U. S. A. 2006; PubMed Scopus Google Scholar). encoding and are to one another in the B. thetaiotaomicron genome of loci and are of gene clusters encoding involved in carbohydrate metabolism of J. J. S. Gordon J.I. Science. PubMed Scopus Google Scholar). of the clusters that glycoside also and This that the polysaccharide and in these clusters are to for and of on their Our of the adaptations of B. thetaiotaomicron to the suckling period in a gnotobiotic mouse this the importance of host polysaccharides in B. thetaiotaomicron during the suckling period and the of these polysaccharide utilization clusters to their of B. of the mice used by the Studies to the were in gnotobiotic Gordon J.I. Nutr. PubMed Scopus Google a light on at and to and In a one and two NMRI mice were with of of B. thetaiotaomicron in J.L. Gordon J.I. Proc. Natl. Acad. Sci. U. S. A. 2006; PubMed Scopus Google Scholar). were at postnatal day and The of were to that there were The of bacterial of the and was on and time assays J.L. Gordon J.I. Proc. Natl. Acad. Sci. U. S. A. 2006; PubMed Scopus Google Scholar, B.S. Gordon J.I. Proc. Natl. Acad. Sci. U. S. A. 2006; PubMed Scopus Google Scholar). Whole of B. thetaiotaomicron in from mice were in After in each was and for at to from the and the was for to The were to a bacterial The were from ceca by from their distal and in The were in of to from mice were in of of at from mice were with of and the were by (6Ley R.E. Backhed F. Turnbaugh P. Lozupone C.A. Knight R.D. Gordon J.I. Proc. Natl. Acad. Sci. U. S. A. 2005; 102: 11070-11075Crossref PubMed Scopus (4137) Google Scholar). was and for to custom B. thetaiotaomicron to (1Sonnenburg J.L. Xu J. Leip D.D. Chen C.H. Westover B.P. Weatherford J. Buhler J.D. Gordon J.I. Science. 2005; 307: 1955-1959Crossref PubMed Scopus (795) Google Scholar). of the used in this study are available from the number was used for initial for that were between and ceca were present for the the for a was and a of on analysis of analysis of the R. Proc. Natl. Acad. Sci. U. S. A. 2001; PubMed Scopus Google Scholar). these were using of R. Proc. Natl. Acad. Sci. U. S. A. 2001; PubMed Scopus Google Scholar, Science. 1997; PubMed Scopus Google Scholar). was used to expression at with or vice were also the to related to polysaccharide metabolism and R. C.A. R. J. P. M. S. J. P. 2006; PubMed Scopus Google to known and of B. thetaiotaomicron during in of B. thetaiotaomicron, in of and was introduced into the of a of the same The were then at with at of at or was to a of of the were and after carbohydrate and in were by for at and the were for to B. thetaiotaomicron as (1Sonnenburg J.L. Xu J. Leip D.D. Chen C.H. Westover B.P. Weatherford J. Buhler J.D. Gordon J.I. Science. 2005; 307: 1955-1959Crossref PubMed Scopus (795) Google Scholar). of chromatography-mass spectrometry analysis of was carried out as in J.L. Xu J. Leip D.D. Chen C.H. Westover B.P. Weatherford J. Buhler J.D. Gordon J.I. Science. 2005; 307: 1955-1959Crossref PubMed Scopus (795) Google biochemical assays were on that been and in of and of this were and was by at for by on and of a and was by another of the for at the on and of of the were at The of and were in the and were in using well methods A Google Scholar). The are to the of the of of encoding and were identified in the genome of B. thetaiotaomicron J. J. S. Gordon J.I. Science. PubMed Scopus Google Bacteroides S. B. B. A. L. J. A. A. E. J. B. J. Science. 2005; 307: PubMed Scopus Google B. A. S. M. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google and J. 2005; PubMed Scopus Google by individual each genome using of and as J. 1997; PubMed Scopus Google Scholar). 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Buhler J.D. Gordon J.I. Science. 2005; 307: 1955-1959Crossref PubMed Scopus (795) Google Scholar). In of B. thetaiotaomicron at and into B. thetaiotaomicron to the of suckling and we genome transcriptional of the using of its (1Sonnenburg J.L. Xu J. Leip D.D. Chen C.H. Westover B.P. Weatherford J. Buhler J.D. Gordon J.I. Science. 2005; 307: 1955-1959Crossref PubMed Scopus (795) Google Scholar). was from and then from three to from each was to or from harvested from individual that been to from three different and of from were used as for of each of the was to a B. thetaiotaomicron of the using analysis of R. Proc. Natl. Acad. Sci. U. S. 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P. 2006; PubMed Scopus Google revealed that of involved in of or are in with the and that involved in the metabolism of as well as involved in metabolism of these us to that the ceca of mice B. thetaiotaomicron and host-derived and these nutrients as B. thetaiotaomicron on in the B. thetaiotaomicron in mice a different gut environment to that in from the of mother's and of a in plant-derived polysaccharides and are of three types of and and of and S. S. Sci. Full Text Full Text PDF PubMed Scopus Google Scholar). with the composition of plant and the in the by our mice are and (1Sonnenburg J.L. Xu J. Leip D.D. Chen C.H. Westover B.P. Weatherford J. Buhler J.D. Gordon J.I. Science. 2005; 307: 1955-1959Crossref PubMed Scopus (795) Google Scholar). and gas chromatography-mass spectrometry analysis of the of mice revealed that and are more in with of the and identified as in our analysis expression in the ceca of mice and This is for to in from plant polysaccharides and this is by the of and in silico of B. thetaiotaomicron metabolism revealed that in for and utilization are at in the ceca of with suckling the that plant are by B. also that in the B. thetaiotaomicron expression of one of its polysaccharide The two and two that are for at B. thetaiotaomicron expression of two and in a as well as to import and that can the and These to of that Bacteroides species expression of their loci in to changes in (1Sonnenburg J.L. Xu J. Leip D.D. Chen C.H. Westover B.P. Weatherford J. Buhler J.D. Gordon J.I. Science. 2005; 307: 1955-1959Crossref PubMed Scopus (795) Google Scholar, J.L. Gordon J.I. Proc. Natl. Acad. Sci. U. S. A. 2006; PubMed Scopus Google Scholar, B. M.M. Science. 2005; 307: PubMed Scopus Google Scholar). into expression of B. thetaiotaomicron polysaccharide utilization in the ceca of and mice the that the its to with available polysaccharide in the our analysis of the B. thetaiotaomicron genome revealed that encoding and to and J. J. S. Gordon J.I. Science. PubMed Scopus Google Scholar). these clusters encoding and These us to that these utilization that the for and polysaccharide J. J. S. Gordon J.I. Science. PubMed Scopus Google Scholar). this is in the same utilization expression when their polysaccharide species These loci also provide into the for and the of the of B. thetaiotaomicron in a gut this we our of B. thetaiotaomicron expression in the ceca of or mice for the of or encoded by that were to to identified such loci of these loci are in the other loci encoding proteins and are at of the loci pairs a encoding outer membrane with R. 2005; 13: Full Text Full Text PDF PubMed Scopus Google Scholar). This using a R. 2005; 13: Full Text Full Text PDF PubMed Scopus Google to the of the This to with and gene expression through of S. A. 2006; PubMed Scopus Google Scholar). on their with E. these B. thetaiotaomicron the loci likely have polysaccharide as well as the and expression of these and the that they to their polysaccharide species also identified other loci not of these two loci and two loci and glycoside to and one to a These that B. thetaiotaomicron polysaccharide utilization loci that be by environmental or in with loci of and of and plant-derived polysaccharides that B. thetaiotaomicron to different species with and on studies that and are for the ability of B. thetaiotaomicron to is to that at of the pairs in the genome of this are to its ability to and other polysaccharides. The of gene pairs in polysaccharide utilization loci with mechanisms and of loci in the most common through which these loci be the evolutionary of pairs in members of the Bacteroidetes, we a the of pairs encoded by the of three species with the human alimentary pairs from B. pairs from B. pairs from B. and pairs from The two Bacteroides species are normal members of the human P. is a member of the microbiota and mechanisms to in a habitat. The of our analysis that many similar pairs are between B. thetaiotaomicron and B. is the B. thetaiotaomicron present in the utilization this is most similar to pairs from B. in in these B. pairs are of loci also encoding in and in that they similar as the related B. thetaiotaomicron and J. 1997; PubMed Scopus Google Scholar). is to that the of related pairs between these two Bacteroides species that their polysaccharide utilization loci or similar in the distal gut and of However, in to the related pairs shared between B. thetaiotaomicron and B. the that each bacterial species also expansions of pairs that not have closely related in the other species of this from one related of which belong to B. thetaiotaomicron A in similar unique expansions of in B. in these of and of are to this species and in These that each Bacteroides species and its own of that in using nutrient that not be to other members of the identified a of B. thetaiotaomicron and to which expression changes between the suckling and belong to pairs in which are of the expression at with expression at and these changes in expression the we that two closely related pairs of were to different in vivo was at by and in another was at and Thus, these two closely related proteins have unique and are in to the of different they have the ability to to similar have been during genome that they be the of different environmental in to different nutrient Our analysis of gene expression in revealed that of the that were in vivo at to the of by their of Moreover, of the glycoside in the two and were also in after to this Thus, B. thetaiotaomicron loci encoding and that show expression during the suckling period to be to the of more carbohydrate in and host this we have used gnotobiotic mice to the transcriptional and adaptations of B. thetaiotaomicron to the suckling and distal Although their gut not of the present with a microbiota, our provide a for experiments the of more of gut microbes. show that during the suckling period, B. thetaiotaomicron on the host for in to from mother's milk. The ability of B. thetaiotaomicron to host-derived polysaccharides those in the importance of in shaping the of the The ability of the to and in the gut a in this that can a member of the adult microbial community as dietary polysaccharides are A of the responses of B. thetaiotaomicron to nutrient in the gut is of encoding involved in polysaccharide the that B. thetaiotaomicron is a from expression of its polysaccharide utilization in to host and However, a of the polysaccharide utilization of B. thetaiotaomicron in our gnotobiotic of postnatal gut is likely that to other host microbial or expression of other of its The of the polysaccharide utilization loci in is similar to the which involved in binding and J. 1997; PubMed Scopus Google and and J. 1996; PubMed Scopus Google of this by is on of during J. 2001; PubMed Scopus Google Scholar). is to be a and is to the and proteins that are of the loci we This that B. thetaiotaomicron at three different mechanisms to polysaccharide utilization on the similar of polysaccharide utilization loci encoding transcriptional and the expression of these loci in the of their encoded can be of the biochemical of the polysaccharide species that are by these as well as they are the and a with to with This also a and two a and a Thus, this be in and or a notion with the that is in suckling and adult mice a In the polysaccharide utilization loci identified in this can as points and for and biochemical studies to the of a gut to alterations in nutrient by changes in host and and for and Samuel for many during the of these and for with with
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