{"doi":"10.1038/ismej.2013.89","title":"A metabolomic view of how the human gut microbiota impacts the host metabolome using humanized and gnotobiotic mice","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>Defining the functional status of host-associated microbial ecosystems has proven challenging owing to the vast number of predicted genes within the microbiome and relatively poor understanding of community dynamics and community–host interaction. Metabolomic approaches, in which a large number of small molecule metabolites can be defined in a biological sample, offer a promising avenue to ‘fingerprint’ microbiota functional status. Here, we examined the effects of the human gut microbiota on the fecal and urinary metabolome of a humanized (HUM) mouse using an optimized ultra performance liquid chromatography–mass spectrometry-based method. Differences between HUM and conventional mouse urine and fecal metabolomic profiles support host-specific aspects of the microbiota’s metabolomic contribution, consistent with distinct microbial compositions. Comparison of microbiota composition and metabolome of mice humanized with different human donors revealed that the vast majority of metabolomic features observed in donor samples are produced in the corresponding HUM mice, and individual-specific features suggest ‘personalized’ aspects of functionality can be reconstituted in mice. Feeding the mice a defined, custom diet resulted in modification of the metabolite signatures, illustrating that host diet provides an avenue for altering gut microbiota functionality, which in turn can be monitored via metabolomics. Using a defined model microbiota consisting of one or two species, we show that simplified communities can drive major changes in the host metabolomic profile. Our results demonstrate that metabolomics constitutes a powerful avenue for functional characterization of the intestinal microbiota and its interaction with the host.</jats:p>","journal":"The ISME Journal","year":2013,"id":14457,"datarank":10.300379207518763,"base_score":5.886104031450156,"endowment":5.886104031450156,"self_citation_contribution":0.8829156047175235,"citation_network_contribution":9.41746360280124,"self_endowment_contribution":0.8829156047175235,"citer_contribution":9.41746360280124,"corpus_percentile":null,"corpus_rank":null,"citation_count":359,"citer_count":200,"citers_with_citation_signal":200,"citers_with_endowment":200,"datacite_reuse_total":12,"is_dataset":false,"is_dataset_confidence":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":114111,"name":"P C Kashyap","orcid":null,"position":1,"is_corresponding":false},{"id":114112,"name":"T A Nelson","orcid":null,"position":2,"is_corresponding":false},{"id":114113,"name":"P A Aronov","orcid":null,"position":3,"is_corresponding":false},{"id":114114,"name":"M S Donia","orcid":null,"position":4,"is_corresponding":false},{"id":114115,"name":"A Spormann","orcid":null,"position":5,"is_corresponding":false},{"id":114116,"name":"M A Fischbach","orcid":null,"position":6,"is_corresponding":false},{"id":114117,"name":"J L Sonnenburg","orcid":null,"position":7,"is_corresponding":false},{"id":114110,"name":"A Marcobal","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":5.886104031450156,"endowment":5.886104031450156,"datacite_reuse_total":12,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"23739052","pmcid":"PMC3965317","openalex_id":"https://openalex.org/W2093500216","authors":[],"funders":[{"funder_name":"NIH HHS","grant_id":"DP2-OD006515","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"R01-DK085025","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"R01 DK085025","title":null},{"funder_name":"NIH HHS","grant_id":"DP2 OD006515","title":null},{"funder_name":"National Institutes of Health","grant_id":"1DP2OD006515-01","title":"Discovery of gut microbiota-targeted small molecules: new tools and therapeutics"},{"funder_name":"National Institutes of Health","grant_id":"5R01DK085025-10","title":"Impact of Diet on Intestinal Microbiota-Host Dynamics"}],"total_grants":6,"fwci":13.4603,"citation_percentile":0.99288417,"influential_citations":6,"citation_trend":[{"year":2013,"count":6},{"year":2014,"count":15},{"year":2015,"count":32},{"year":2016,"count":37},{"year":2017,"count":25},{"year":2018,"count":27},{"year":2019,"count":40},{"year":2020,"count":36},{"year":2021,"count":32},{"year":2022,"count":26},{"year":2023,"count":20},{"year":2024,"count":40},{"year":2025,"count":15},{"year":2026,"count":7}],"oa_status":"bronze","license":"OUP Standard Publication Reuse","oa_locations":[{"url":"https://www.nature.com/articles/ismej201389.pdf","host_type":"journal"},{"url":"https://www.nature.com/articles/ismej201389.pdf","host_type":"BRONZE"},{"url":"https://www.nature.com/articles/ismej201389.pdf","host_type":"publisher"},{"url":"http://www.nature.com/articles/ismej201389.pdf","host_type":"publisher"},{"url":"http://www.nature.com/articles/ismej201389","host_type":"publisher"},{"url":"https://academic.oup.com/ismej/article-pdf/7/10/1933/56426884/41396_2013_article_bfismej201389.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1038/ismej.2013.89","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/23739052","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3965317","host_type":"repository"},{"url":"https://dx.doi.org/10.1038/ismej.2013.89","host_type":""}],"fields_of_study":["Gut microbiota and health","Metabolomics and Mass Spectrometry Studies","Diet and metabolism studies","Biology","Medicine","Environmental Science","0301 basic medicine","0303 health sciences","03 medical and health sciences","Animals","Bacteria","Bacterial Physiological Phenomena","Biodiversity","Diet","Feces","Germ-Free Life","Humans","Intestinal Mucosa","Intestines","Metabolome","Metabolomics","Mice","Mice, Inbred C57BL","Microbiota","RNA, Ribosomal, 16S","Urine"],"mesh_terms":["Animals","Bacteria","Diet","Feces","Germ-Free Life","Humans","Intestinal Mucosa","Intestines","Mice, Inbred C57BL","RNA, Ribosomal, 16S","Urine","Bacterial Physiological Phenomena","Biodiversity","Mice","Metabolomics","Metabolome","Microbiota"],"keywords":["Metabolome","Metabolomics","Biology","Hum","Microbiome","Gut flora","Host (biology)","Metabolite","Computational biology","Human microbiome","Dysbiosis","Genetics","Bioinformatics","Biochemistry","Bacteria","Microbiota","Biodiversity","Urine","Bacterial Physiological Phenomena","Diet","Intestines","Mice, Inbred C57BL","Feces","Mice","RNA, 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