Microbiome signatures of progression toward celiac disease onset in at-risk children in a longitudinal prospective cohort study
Other than exposure to gluten and genetic compatibility, the gut microbiome has been suggested to be involved in celiac disease (CD) pathogenesis by mediating interactions between gluten/environmental factors and the host immune system. However, to establish disease progression markers, it is essent...
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| creator | Leonard, Maureen M. Valitutti, Francesco Karathia, Hiren Pujolassos, Meritxell Kenyon, Victoria Fanelli, Brian Troisi, Jacopo Subramanian, Poorani Camhi, Stephanie Colucci, Angelo Serena, Gloria Cucchiara, Salvatore Trovato, Chiara Maria Malamisura, Basilio Francavilla, Ruggiero Elli, Luca Hasan, Nur A. Zomorrodi, Ali R. Colwell, Rita Fasano, Alessio |
| description | Other than exposure to gluten and genetic compatibility, the gut microbiome has been suggested to be involved in celiac disease (CD) pathogenesis by mediating interactions between gluten/environmental factors and the host immune system. However, to establish disease progression markers, it is essential to assess alterations in the gut microbiota before disease onset. Here, a prospective metagenomic analysis of the gut microbiota of infants at risk of CD was done to track shifts in the microbiota before CD development. We performed cross-sectional and longitudinal analyses of gut microbiota, functional pathways, and metabolites, starting from 18 mo before CD onset, in 10 infants who developed CD and 10 matched nonaffected infants. Cross-sectional analysis at CD onset identified altered abundance of six microbial strains and several metabolites between cases and controls but no change in microbial species or pathway abundance. Conversely, results of longitudinal analysis revealed several microbial species/strains/pathways/metabolites occurring in increased abundance and detected before CD onset. These had previously been linked to autoimmune and inflammatory conditions (e.g., Dialister invisus, Parabacteroides sp., Lachnospiraceae, tryptophan metabolism, and metabolites serine and threonine). Others occurred in decreased abundance before CD onset and are known to have anti-inflammatory effects (e.g., Streptococcus thermophilus, Faecalibacterium prausnitzii, and Clostridium clostridioforme). Additionally, we uncovered previously unreported microbes/pathways/metabolites (e.g., Porphyromonas sp., high mannose–type N-glycan biosynthesis, and serine) that point to CD-specific biomarkers. Our study establishes a road map for prospective longitudinal study designs to better understand the role of gut microbiota in disease pathogenesis and therapeutic targets to reestablish tolerance and/or prevent autoimmunity. |
| doi_str_mv | 10.1073/pnas.2020322118 |
| format | Article |
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However, to establish disease progression markers, it is essential to assess alterations in the gut microbiota before disease onset. Here, a prospective metagenomic analysis of the gut microbiota of infants at risk of CD was done to track shifts in the microbiota before CD development. We performed cross-sectional and longitudinal analyses of gut microbiota, functional pathways, and metabolites, starting from 18 mo before CD onset, in 10 infants who developed CD and 10 matched nonaffected infants. Cross-sectional analysis at CD onset identified altered abundance of six microbial strains and several metabolites between cases and controls but no change in microbial species or pathway abundance. Conversely, results of longitudinal analysis revealed several microbial species/strains/pathways/metabolites occurring in increased abundance and detected before CD onset. These had previously been linked to autoimmune and inflammatory conditions (e.g., Dialister invisus, Parabacteroides sp., Lachnospiraceae, tryptophan metabolism, and metabolites serine and threonine). Others occurred in decreased abundance before CD onset and are known to have anti-inflammatory effects (e.g., Streptococcus thermophilus, Faecalibacterium prausnitzii, and Clostridium clostridioforme). Additionally, we uncovered previously unreported microbes/pathways/metabolites (e.g., Porphyromonas sp., high mannose–type N-glycan biosynthesis, and serine) that point to CD-specific biomarkers. Our study establishes a road map for prospective longitudinal study designs to better understand the role of gut microbiota in disease pathogenesis and therapeutic targets to reestablish tolerance and/or prevent autoimmunity.</description><identifier>ISSN: 0027-8424</identifier><identifier>ISSN: 1091-6490</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.2020322118</identifier><identifier>PMID: 34253606</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Abundance ; Autoimmune diseases ; Autoimmunity ; Biological Sciences ; Biomarkers ; Biomarkers - metabolism ; Biosynthesis ; Celiac disease ; Celiac Disease - metabolism ; Celiac Disease - microbiology ; Child, Preschool ; Cohort analysis ; Cross-Sectional Studies ; Environmental factors ; Female ; Gastrointestinal Microbiome - genetics ; Gluten ; Glycan ; Host Microbial Interactions ; Humans ; Immune system ; Immunological tolerance ; Infant ; Infants ; Inflammation ; Intestinal microflora ; Longitudinal Studies ; Male ; Mannose ; Metabolic Networks and Pathways ; Metabolites ; Metabolome ; Metagenomics ; Microbiomes ; Microbiota ; Microorganisms ; Pathogenesis ; Prospective Studies ; Serine ; Therapeutic targets ; Threonine ; Tryptophan</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2021-07, Vol.118 (29), p.1-12</ispartof><rights>Copyright © 2021 the Author(s). Published by PNAS.</rights><rights>Copyright National Academy of Sciences Jul 20, 2021</rights><rights>Copyright © 2021 the Author(s). Published by PNAS. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4248-f9c5f0cd51c90690c1953d3d0f30b3f9522463d84da91003c5e0cc68d8c7d2a3</citedby><cites>FETCH-LOGICAL-c4248-f9c5f0cd51c90690c1953d3d0f30b3f9522463d84da91003c5e0cc68d8c7d2a3</cites><orcidid>0000-0002-1473-2240 ; 0000-0002-2134-0261 ; 0000-0003-3869-1815 ; 0000-0002-0873-0759 ; 0000-0001-7152-7254 ; 0000-0003-2962-7379 ; 0000-0003-3607-6552 ; 0000-0002-2939-9698 ; 0000-0001-5432-1502</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/27052545$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/27052545$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27901,27902,53766,53768,57992,58225</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34253606$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Leonard, Maureen M.</creatorcontrib><creatorcontrib>Valitutti, Francesco</creatorcontrib><creatorcontrib>Karathia, Hiren</creatorcontrib><creatorcontrib>Pujolassos, Meritxell</creatorcontrib><creatorcontrib>Kenyon, Victoria</creatorcontrib><creatorcontrib>Fanelli, Brian</creatorcontrib><creatorcontrib>Troisi, Jacopo</creatorcontrib><creatorcontrib>Subramanian, Poorani</creatorcontrib><creatorcontrib>Camhi, Stephanie</creatorcontrib><creatorcontrib>Colucci, Angelo</creatorcontrib><creatorcontrib>Serena, Gloria</creatorcontrib><creatorcontrib>Cucchiara, Salvatore</creatorcontrib><creatorcontrib>Trovato, Chiara Maria</creatorcontrib><creatorcontrib>Malamisura, Basilio</creatorcontrib><creatorcontrib>Francavilla, Ruggiero</creatorcontrib><creatorcontrib>Elli, Luca</creatorcontrib><creatorcontrib>Hasan, Nur A.</creatorcontrib><creatorcontrib>Zomorrodi, Ali R.</creatorcontrib><creatorcontrib>Colwell, Rita</creatorcontrib><creatorcontrib>Fasano, Alessio</creatorcontrib><creatorcontrib>The CD-GEMM Team</creatorcontrib><creatorcontrib>CD-GEMM Team</creatorcontrib><creatorcontrib>The CD-GEMM Team</creatorcontrib><title>Microbiome signatures of progression toward celiac disease onset in at-risk children in a longitudinal prospective cohort study</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Other than exposure to gluten and genetic compatibility, the gut microbiome has been suggested to be involved in celiac disease (CD) pathogenesis by mediating interactions between gluten/environmental factors and the host immune system. However, to establish disease progression markers, it is essential to assess alterations in the gut microbiota before disease onset. Here, a prospective metagenomic analysis of the gut microbiota of infants at risk of CD was done to track shifts in the microbiota before CD development. We performed cross-sectional and longitudinal analyses of gut microbiota, functional pathways, and metabolites, starting from 18 mo before CD onset, in 10 infants who developed CD and 10 matched nonaffected infants. Cross-sectional analysis at CD onset identified altered abundance of six microbial strains and several metabolites between cases and controls but no change in microbial species or pathway abundance. Conversely, results of longitudinal analysis revealed several microbial species/strains/pathways/metabolites occurring in increased abundance and detected before CD onset. These had previously been linked to autoimmune and inflammatory conditions (e.g., Dialister invisus, Parabacteroides sp., Lachnospiraceae, tryptophan metabolism, and metabolites serine and threonine). Others occurred in decreased abundance before CD onset and are known to have anti-inflammatory effects (e.g., Streptococcus thermophilus, Faecalibacterium prausnitzii, and Clostridium clostridioforme). Additionally, we uncovered previously unreported microbes/pathways/metabolites (e.g., Porphyromonas sp., high mannose–type N-glycan biosynthesis, and serine) that point to CD-specific biomarkers. Our study establishes a road map for prospective longitudinal study designs to better understand the role of gut microbiota in disease pathogenesis and therapeutic targets to reestablish tolerance and/or prevent autoimmunity.</description><subject>Abundance</subject><subject>Autoimmune diseases</subject><subject>Autoimmunity</subject><subject>Biological Sciences</subject><subject>Biomarkers</subject><subject>Biomarkers - metabolism</subject><subject>Biosynthesis</subject><subject>Celiac disease</subject><subject>Celiac Disease - metabolism</subject><subject>Celiac Disease - microbiology</subject><subject>Child, Preschool</subject><subject>Cohort analysis</subject><subject>Cross-Sectional Studies</subject><subject>Environmental factors</subject><subject>Female</subject><subject>Gastrointestinal Microbiome - genetics</subject><subject>Gluten</subject><subject>Glycan</subject><subject>Host Microbial Interactions</subject><subject>Humans</subject><subject>Immune system</subject><subject>Immunological tolerance</subject><subject>Infant</subject><subject>Infants</subject><subject>Inflammation</subject><subject>Intestinal microflora</subject><subject>Longitudinal Studies</subject><subject>Male</subject><subject>Mannose</subject><subject>Metabolic Networks and Pathways</subject><subject>Metabolites</subject><subject>Metabolome</subject><subject>Metagenomics</subject><subject>Microbiomes</subject><subject>Microbiota</subject><subject>Microorganisms</subject><subject>Pathogenesis</subject><subject>Prospective Studies</subject><subject>Serine</subject><subject>Therapeutic 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signatures of progression toward celiac disease onset in at-risk children in a longitudinal prospective cohort study</title><author>Leonard, Maureen M. ; Valitutti, Francesco ; Karathia, Hiren ; Pujolassos, Meritxell ; Kenyon, Victoria ; Fanelli, Brian ; Troisi, Jacopo ; Subramanian, Poorani ; Camhi, Stephanie ; Colucci, Angelo ; Serena, Gloria ; Cucchiara, Salvatore ; Trovato, Chiara Maria ; Malamisura, Basilio ; Francavilla, Ruggiero ; Elli, Luca ; Hasan, Nur A. ; Zomorrodi, Ali R. ; Colwell, Rita ; Fasano, Alessio</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4248-f9c5f0cd51c90690c1953d3d0f30b3f9522463d84da91003c5e0cc68d8c7d2a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Abundance</topic><topic>Autoimmune diseases</topic><topic>Autoimmunity</topic><topic>Biological Sciences</topic><topic>Biomarkers</topic><topic>Biomarkers - 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A</addtitle><date>2021-07-20</date><risdate>2021</risdate><volume>118</volume><issue>29</issue><spage>1</spage><epage>12</epage><pages>1-12</pages><issn>0027-8424</issn><issn>1091-6490</issn><eissn>1091-6490</eissn><abstract>Other than exposure to gluten and genetic compatibility, the gut microbiome has been suggested to be involved in celiac disease (CD) pathogenesis by mediating interactions between gluten/environmental factors and the host immune system. However, to establish disease progression markers, it is essential to assess alterations in the gut microbiota before disease onset. Here, a prospective metagenomic analysis of the gut microbiota of infants at risk of CD was done to track shifts in the microbiota before CD development. We performed cross-sectional and longitudinal analyses of gut microbiota, functional pathways, and metabolites, starting from 18 mo before CD onset, in 10 infants who developed CD and 10 matched nonaffected infants. Cross-sectional analysis at CD onset identified altered abundance of six microbial strains and several metabolites between cases and controls but no change in microbial species or pathway abundance. Conversely, results of longitudinal analysis revealed several microbial species/strains/pathways/metabolites occurring in increased abundance and detected before CD onset. These had previously been linked to autoimmune and inflammatory conditions (e.g., Dialister invisus, Parabacteroides sp., Lachnospiraceae, tryptophan metabolism, and metabolites serine and threonine). Others occurred in decreased abundance before CD onset and are known to have anti-inflammatory effects (e.g., Streptococcus thermophilus, Faecalibacterium prausnitzii, and Clostridium clostridioforme). Additionally, we uncovered previously unreported microbes/pathways/metabolites (e.g., Porphyromonas sp., high mannose–type N-glycan biosynthesis, and serine) that point to CD-specific biomarkers. Our study establishes a road map for prospective longitudinal study designs to better understand the role of gut microbiota in disease pathogenesis and therapeutic targets to reestablish tolerance and/or prevent autoimmunity.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>34253606</pmid><doi>10.1073/pnas.2020322118</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-1473-2240</orcidid><orcidid>https://orcid.org/0000-0002-2134-0261</orcidid><orcidid>https://orcid.org/0000-0003-3869-1815</orcidid><orcidid>https://orcid.org/0000-0002-0873-0759</orcidid><orcidid>https://orcid.org/0000-0001-7152-7254</orcidid><orcidid>https://orcid.org/0000-0003-2962-7379</orcidid><orcidid>https://orcid.org/0000-0003-3607-6552</orcidid><orcidid>https://orcid.org/0000-0002-2939-9698</orcidid><orcidid>https://orcid.org/0000-0001-5432-1502</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Proceedings of the National Academy of Sciences - PNAS, 2021-07, Vol.118 (29), p.1-12 |
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| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8307711 |
| source | Jstor Complete Legacy; MEDLINE; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Abundance Autoimmune diseases Autoimmunity Biological Sciences Biomarkers Biomarkers - metabolism Biosynthesis Celiac disease Celiac Disease - metabolism Celiac Disease - microbiology Child, Preschool Cohort analysis Cross-Sectional Studies Environmental factors Female Gastrointestinal Microbiome - genetics Gluten Glycan Host Microbial Interactions Humans Immune system Immunological tolerance Infant Infants Inflammation Intestinal microflora Longitudinal Studies Male Mannose Metabolic Networks and Pathways Metabolites Metabolome Metagenomics Microbiomes Microbiota Microorganisms Pathogenesis Prospective Studies Serine Therapeutic targets Threonine Tryptophan |
| title | Microbiome signatures of progression toward celiac disease onset in at-risk children in a longitudinal prospective cohort study |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-31T19%3A11%3A04IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-jstor_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Microbiome%20signatures%20of%20progression%20toward%20celiac%20disease%20onset%20in%20at-risk%20children%20in%20a%20longitudinal%20prospective%20cohort%20study&rft.jtitle=Proceedings%20of%20the%20National%20Academy%20of%20Sciences%20-%20PNAS&rft.au=Leonard,%20Maureen%20M.&rft.aucorp=The%20CD-GEMM%20Team&rft.date=2021-07-20&rft.volume=118&rft.issue=29&rft.spage=1&rft.epage=12&rft.pages=1-12&rft.issn=0027-8424&rft.eissn=1091-6490&rft_id=info:doi/10.1073/pnas.2020322118&rft_dat=%3Cjstor_pubme%3E27052545%3C/jstor_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2555178227&rft_id=info:pmid/34253606&rft_jstor_id=27052545&rfr_iscdi=true |