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  1. AU="Spencer, Sean P"
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  1. Article ; Online: Resisting weight gain with prebiotic fibre.

    Carter, Matthew M / Spencer, Sean P

    Nature metabolism

    2024  Volume 6, Issue 3, Page(s) 389–391

    MeSH term(s) Humans ; Prebiotics ; Weight Gain
    Chemical Substances Prebiotics
    Language English
    Publishing date 2024-02-22
    Publishing country Germany
    Document type Journal Article
    ISSN 2522-5812
    ISSN (online) 2522-5812
    DOI 10.1038/s42255-024-00998-w
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  2. Article: Metagenomic Immunoglobulin Sequencing (MIG-Seq) Exposes Patterns of IgA Antibody Binding in the Healthy Human Gut Microbiome.

    Olm, Matthew R / Spencer, Sean P / Silva, Evelyn Lemus / Sonnenburg, Justin L

    bioRxiv : the preprint server for biology

    2023  

    Abstract: IgA, the most highly produced human antibody, is continually secreted into the gut to shape the intestinal microbiota. Methodological limitations have critically hindered defining which microbial strains are targeted by IgA and why. Here, we develop a ... ...

    Abstract IgA, the most highly produced human antibody, is continually secreted into the gut to shape the intestinal microbiota. Methodological limitations have critically hindered defining which microbial strains are targeted by IgA and why. Here, we develop a new technique, Metagenomic Immunoglobulin Sequencing (MIG-Seq), and use it to determine IgA coating levels for thousands of gut microbiome strains in healthy humans. We find that microbes associated with both health and disease have higher levels of coating, and that microbial genes are highly predictive of IgA binding levels, with mucus degradation genes especially correlated with high binding. We find a significant reduction in replication rates among microbes bound by IgA, and demonstrate that IgA binding is more correlated with host immune status than traditional microbial abundance measures. This study introduces a powerful technique for assessing strain-level IgA binding in human stool, paving the way for deeper understanding of IgA-based host microbe interactions.
    Language English
    Publishing date 2023-11-21
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.11.21.568153
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  3. Article ; Online: When Gut Microbiota Creep into Fat, the Fat Creeps Back.

    Spencer, Sean P / Sonnenburg, Justin L

    Cell

    2020  Volume 183, Issue 3, Page(s) 589–591

    Abstract: Ha and colleagues describe a previously unappreciated diversity of microbes in the mesenteric adipose tissue (MAT) surrounding the GI tract. Viable bacteria that are mislocalized from the gut microbiota and metabolically adapted to the MAT contribute to ... ...

    Abstract Ha and colleagues describe a previously unappreciated diversity of microbes in the mesenteric adipose tissue (MAT) surrounding the GI tract. Viable bacteria that are mislocalized from the gut microbiota and metabolically adapted to the MAT contribute to the "creeping fat" of Crohn's disease.
    MeSH term(s) Adaptation, Physiological ; Adipose Tissue ; Crohn Disease ; Gastrointestinal Microbiome ; Humans ; Mesentery
    Language English
    Publishing date 2020-10-30
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2020.10.008
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  4. Article ; Online: Colons or semi-colons: punctuating the regional variation of intestinal microbial-immune interactions.

    Culver, Rebecca N / Spencer, Sean P / Huang, Kerwyn Casey

    Nature reviews. Gastroenterology & hepatology

    2020  Volume 17, Issue 6, Page(s) 319–320

    MeSH term(s) Colon ; Humans ; Intestines ; Microbial Interactions
    Language English
    Publishing date 2020-04-22
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Comment
    ZDB-ID 2493722-8
    ISSN 1759-5053 ; 1759-5045
    ISSN (online) 1759-5053
    ISSN 1759-5045
    DOI 10.1038/s41575-020-0302-z
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  5. Article ; Online: Pursuing Human-Relevant Gut Microbiota-Immune Interactions.

    Spencer, Sean P / Fragiadakis, Gabriela K / Sonnenburg, Justin L

    Immunity

    2019  Volume 51, Issue 2, Page(s) 225–239

    Abstract: The gut microbiota is a complex and plastic network of diverse organisms intricately connected with human physiology. Recent advances in profiling approaches of both the microbiota and the immune system now enable a deeper exploration of immunity- ... ...

    Abstract The gut microbiota is a complex and plastic network of diverse organisms intricately connected with human physiology. Recent advances in profiling approaches of both the microbiota and the immune system now enable a deeper exploration of immunity-microbiota connections. An important next step is to elucidate a human-relevant "map" of microbial-immune wiring while focusing on animal studies to probe a prioritized subset of interactions. Here, we provide an overview of this field's current status and discuss two approaches for establishing priorities for detailed investigation: (1) longitudinal intervention studies in humans probing the dynamics of both the microbiota and the immune system and (2) the study of traditional populations to assess lost features of human microbial identity whose absence may be contributing to the rise of immunological disorders. These human-centered approaches offer a judicious path forward to understand the impact of the microbiota in immune development and function.
    MeSH term(s) Animals ; Gastrointestinal Microbiome/immunology ; Homeostasis ; Host-Pathogen Interactions ; Humans ; Immune System ; Immunity ; Patient-Centered Care
    Language English
    Publishing date 2019-08-26
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
    ZDB-ID 1217235-2
    ISSN 1097-4180 ; 1074-7613
    ISSN (online) 1097-4180
    ISSN 1074-7613
    DOI 10.1016/j.immuni.2019.08.002
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  6. Article ; Online: Ultra-deep sequencing of Hadza hunter-gatherers recovers vanishing gut microbes

    Carter, Matthew M. / Olm, Matthew R. / Merrill, Bryan D. / Dahan, Dylan / Tripathi, Surya / Spencer, Sean P. / Yu, Feiqiao B. / Jain, Sunit / Neff, Norma / Jha, Aashish R. / Sonnenburg, Erica D. / Sonnenburg, Justin L.

    Cell. 2023 July, v. 186, no. 14 p.3111-3124.e13

    2023  

    Abstract: The gut microbiome modulates immune and metabolic health. Human microbiome data are biased toward industrialized populations, limiting our understanding of non-industrialized microbiomes. Here, we performed ultra-deep metagenomic sequencing on 351 fecal ... ...

    Abstract The gut microbiome modulates immune and metabolic health. Human microbiome data are biased toward industrialized populations, limiting our understanding of non-industrialized microbiomes. Here, we performed ultra-deep metagenomic sequencing on 351 fecal samples from the Hadza hunter-gatherers of Tanzania and comparative populations in Nepal and California. We recovered 91,662 genomes of bacteria, archaea, bacteriophages, and eukaryotes, 44% of which are absent from existing unified datasets. We identified 124 gut-resident species vanishing in industrialized populations and highlighted distinct aspects of the Hadza gut microbiome related to in situ replication rates, signatures of selection, and strain sharing. Industrialized gut microbes were found to be enriched in genes associated with oxidative stress, possibly a result of microbiome adaptation to inflammatory processes. This unparalleled view of the Hadza gut microbiome provides a valuable resource, expands our understanding of microbes capable of colonizing the human gut, and clarifies the extensive perturbation induced by the industrialized lifestyle.
    Keywords Archaea ; data collection ; digestive system ; eukaryotic cells ; genome ; humans ; industrialization ; intestinal microorganisms ; lifestyle ; metagenomics ; microbiome ; oxidative stress ; California ; Nepal ; Tanzania ; human gut microbiome ; metagenomic assembly ; metagenomic metaanalysis ; Treponema succinifaciens ; strain sharing ; hunter-gatherer
    Language English
    Dates of publication 2023-07
    Size p. 3111-3124.e13.
    Publishing place Elsevier Inc.
    Document type Article ; Online
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2023.05.046
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  7. Article ; Online: Ultra-deep sequencing of Hadza hunter-gatherers recovers vanishing gut microbes.

    Carter, Matthew M / Olm, Matthew R / Merrill, Bryan D / Dahan, Dylan / Tripathi, Surya / Spencer, Sean P / Yu, Feiqiao B / Jain, Sunit / Neff, Norma / Jha, Aashish R / Sonnenburg, Erica D / Sonnenburg, Justin L

    Cell

    2023  Volume 186, Issue 14, Page(s) 3111–3124.e13

    Abstract: The gut microbiome modulates immune and metabolic health. Human microbiome data are biased toward industrialized populations, limiting our understanding of non-industrialized microbiomes. Here, we performed ultra-deep metagenomic sequencing on 351 fecal ... ...

    Abstract The gut microbiome modulates immune and metabolic health. Human microbiome data are biased toward industrialized populations, limiting our understanding of non-industrialized microbiomes. Here, we performed ultra-deep metagenomic sequencing on 351 fecal samples from the Hadza hunter-gatherers of Tanzania and comparative populations in Nepal and California. We recovered 91,662 genomes of bacteria, archaea, bacteriophages, and eukaryotes, 44% of which are absent from existing unified datasets. We identified 124 gut-resident species vanishing in industrialized populations and highlighted distinct aspects of the Hadza gut microbiome related to in situ replication rates, signatures of selection, and strain sharing. Industrialized gut microbes were found to be enriched in genes associated with oxidative stress, possibly a result of microbiome adaptation to inflammatory processes. This unparalleled view of the Hadza gut microbiome provides a valuable resource, expands our understanding of microbes capable of colonizing the human gut, and clarifies the extensive perturbation induced by the industrialized lifestyle.
    MeSH term(s) Humans ; Gastrointestinal Microbiome/genetics ; Microbiota ; Metagenome ; Eukaryota ; High-Throughput Nucleotide Sequencing ; Metagenomics
    Language English
    Publishing date 2023-06-21
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2023.05.046
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  8. Article ; Online: No strict requirement for eosinophils for bone marrow plasma cell survival.

    Bortnick, Alexandra / Chernova, Irene / Spencer, Sean P / Allman, David

    European journal of immunology

    2018  Volume 48, Issue 5, Page(s) 815–821

    Abstract: Lasting antibody responses are maintained by long-lived plasma cells, which are thought to lodge in the BM in specialized survival niches. Eosinophils have been reported to function as a critical component of the BM survival niche where they are thought ... ...

    Abstract Lasting antibody responses are maintained by long-lived plasma cells, which are thought to lodge in the BM in specialized survival niches. Eosinophils have been reported to function as a critical component of the BM survival niche where they are thought to provide pro-survival signals to nearby plasma cells. Recent study shows that many BM plasma cells are recently generated and chiefly short-lived cells, raising the possibility that rare plasma cell-eosinophil interactions are a rate-limiting step needed to establish lasting humoral immunity. To address these issues, we examined the impact of eosinophil depletion on short- and long-lived BM plasma cells in the context of antibody responses induced by both T-cell dependent and T-cell independent antigens. Surprisingly, our results failed to support a role for eosinophils in either plasma cell generation or survival. These studies included examination of plasma cell frequencies in mice lacking eosinophils either after antibody-mediated depletion, or due to mutation of the GATA1 locus.
    MeSH term(s) Animals ; Antibodies/immunology ; Antibody Formation/immunology ; Bone Marrow/immunology ; Bone Marrow Cells/immunology ; Eosinophils/immunology ; Female ; GATA1 Transcription Factor/genetics ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Plasma Cells/cytology ; Plasma Cells/immunology ; T-Lymphocytes/immunology ; Tumor Necrosis Factor Ligand Superfamily Member 13/metabolism
    Chemical Substances Antibodies ; GATA1 Transcription Factor ; Gata1 protein, mouse ; Tnfsf13 protein, mouse ; Tumor Necrosis Factor Ligand Superfamily Member 13
    Language English
    Publishing date 2018-03-23
    Publishing country Germany
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 120108-6
    ISSN 1521-4141 ; 0014-2980
    ISSN (online) 1521-4141
    ISSN 0014-2980
    DOI 10.1002/eji.201747229
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  9. Article ; Online: Dietary and commensal derived nutrients: shaping mucosal and systemic immunity.

    Spencer, Sean P / Belkaid, Yasmine

    Current opinion in immunology

    2012  Volume 24, Issue 4, Page(s) 379–384

    Abstract: The intestine serves as the primary site of nutrient absorption in the body while also harboring the highest burden of commensal microflora and representing a major portal of pathogen exposure. As such, the immune network of the intestine relies on both ... ...

    Abstract The intestine serves as the primary site of nutrient absorption in the body while also harboring the highest burden of commensal microflora and representing a major portal of pathogen exposure. As such, the immune network of the intestine relies on both dietary and commensal derived signals to guide appropriate function. Recent advances highlight the role of dietary derived nutrients and commensal derived metabolites in shaping gastrointestinal immunity. In particular, vitamin A has been shown to have dominant and pleiotropic effects in the intestine. In addition, dietary derived AHR ligands and commensal derived metabolites are now emerging as important players in mucosal immunity. Thus nutrition, commensal microflora and the mucosal immune system are all intimately connected.
    MeSH term(s) Animals ; Diet ; Humans ; Immunity, Mucosal/immunology ; Intestinal Mucosa/immunology ; Nutritional Physiological Phenomena/immunology
    Language English
    Publishing date 2012-07-31
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Review
    ZDB-ID 1035767-1
    ISSN 1879-0372 ; 0952-7915
    ISSN (online) 1879-0372
    ISSN 0952-7915
    DOI 10.1016/j.coi.2012.07.006
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  10. Article: Dietary and commensal derived nutrients: shaping mucosal and systemic immunity

    Spencer, Sean P / Belkaid, Yasmine

    Current Opinion in Immunology. 2012 Aug., v. 24, no. 4

    2012  

    Abstract: The intestine serves as the primary site of nutrient absorption in the body while also harboring the highest burden of commensal microflora and representing a major portal of pathogen exposure. As such, the immune network of the intestine relies on both ... ...

    Abstract The intestine serves as the primary site of nutrient absorption in the body while also harboring the highest burden of commensal microflora and representing a major portal of pathogen exposure. As such, the immune network of the intestine relies on both dietary and commensal derived signals to guide appropriate function. Recent advances highlight the role of dietary derived nutrients and commensal derived metabolites in shaping gastrointestinal immunity. In particular, vitamin A has been shown to have dominant and pleiotropic effects in the intestine. In addition, dietary derived AHR ligands and commensal derived metabolites are now emerging as important players in mucosal immunity. Thus nutrition, commensal microflora and the mucosal immune system are all intimately connected.
    Keywords absorption ; immune system ; intestines ; metabolites ; microorganisms ; mucosal immunity ; nutrients ; nutrition ; pathogens ; pleiotropy ; vitamin A
    Language English
    Dates of publication 2012-08
    Size p. 379-384.
    Publishing place Elsevier Ltd
    Document type Article
    ZDB-ID 1035767-1
    ISSN 1879-0372 ; 0952-7915
    ISSN (online) 1879-0372
    ISSN 0952-7915
    DOI 10.1016/j.coi.2012.07.006
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