Dissertation/ Thesis
Προβολή σε EDS

Host genetics shapes crypt niche colonisation by keystone gut bacteria, influencing metabolic health

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: Host genetics shapes crypt niche colonisation by keystone gut bacteria, influencing metabolic health
Συγγραφείς: Morillo Sanz Dias, Felipe
Thesis Advisors: Baud, Amelie
Πηγή: TDX (Tesis Doctorals en Xarxa)
Στοιχεία εκδότη: Universitat Pompeu Fabra, 2026.
Έτος έκδοσης: 2026
Φυσική περιγραφή: 360 p.
Θεματικοί όροι: Microbioma, Microbiome, Microbiota, Rata, Rat, Budell, Gut, Intestino, Bacteris, Bacteria, Bacterias, Bioinformàtica, Bioinformatics, Bioinformática, Heretabilitat, Heritability, 383,656, Genètica, Genetics, Genética, Inferència causal, Causal inference, Inferencia causal, Efectes poligènics, Polygenic effects, Efectos poligénicos, Gremis de co-abundància, Co-abundance guilds, Gremios de coabundancia, Xarxa, Network, Redes, Diversity, Diversidad, Anàlisi de la mediació, Mediation analysis, Análisis de mediación, Aleatorització mendeliana, Mendelian randomization, Aleatorización mendeliana, Efectes genètics agregats, Aggregate genetic effects, Efectos genéticos agregados, Cec, Caecum, Intestino ciego, Genètica de poblacions, Population genetics, Genética de poblaciones, Genètica quantitativa, Quantitative genetics, Genética cuantitativa
Περιγραφή: Se adoptó un diseño “polygenic-first” para inferencia causal del microbioma cecal en ratas HS, combinando metagenómica shallow-shotgun y modelos lineales mixtos para identificar efectos poligénicos del hospedador sobre rasgos del microbioma. Un pipeline reproducible optimizado para shallow-shotgun superó a 16S en la detección de estos efectos, destacando Bacteroides y Prevotella, su gremio compartido y la β-diversidad. Enriquecimientos genómicos sugirieron adaptaciones al nicho de las criptas y motivaron la selección de genes candidatos del hospedador. Un conjunto de SNP centinelas, mediante validación cruzada, explicó efectos poligénicos a nivel de género y sirvió como instrumento en mediación y aleatorización Mendeliana, dando lugar a un modelo de ecuaciones estructurales que vinculó bacterias clave, estructura comunitaria y metabolismo. Los efectos directos de estos géneros sobre la glucosa en ayunas fueron de signo opuesto y se compensaron por efectos indirectos mediados por rasgos comunitarios, apoyando intervenciones de ingeniería de nicho guiadas por genotipo.
Description (Translated): A “polygenic-first” design for causal inference was adopted to study the caecal microbiome of HS rats, combining shallow-shotgun metagenomics with linear-mixed models to map host polygenic effects on multi-level microbiome traits. A reproducible, shallow shotgun-optimised pipeline yielded better results for detecting such effects than 16S, with heritable signals concentrating in Bacteroides and Prevotella, their shared guild, and β-diversity. Then, genome-resolved enrichments suggested potential adaptations to the crypt niche, leading to a hypothesis-driven selection of host genes. A cross-validated set of sentinel SNPs for these candidate genes explained genus-level polygenic effects and served as instruments in mediation and Mendelian randomisation analyses, contributing to a structural equation model that linked keystone bacteria, community structure, and host metabolism. The effects of these genera on fasting glucose levels had opposite signs and were balanced by indirect effects routed through community traits, suggesting that genotype-aware, niche-engineering interventions could better modulate glycaemia and other health-related traits.
Universitat Pompeu Fabra. Doctorat en Biomedicina
Τύπος εγγράφου: Dissertation/Thesis
Περιγραφή αρχείου: application/pdf
Γλώσσα: English
Σύνδεσμος πρόσβασης: https://hdl.handle.net/10803/696724
Rights: L'accés als continguts d'aquesta tesi queda condicionat a l'acceptació de les condicions d'ús establertes per la següent llicència Creative Commons: http://creativecommons.org/licenses/by-nc-nd/4.0/
Αριθμός Καταχώρησης: edstdx.10803.696724
Βάση Δεδομένων: TDX
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  Data: Host genetics shapes crypt niche colonisation by keystone gut bacteria, influencing metabolic health
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  Data: Baud, Amelie
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  Data: TDX (Tesis Doctorals en Xarxa)
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  Data: Universitat Pompeu Fabra, 2026.
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  Data: 360 p.
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– Name: Abstract
  Label: Description
  Group: Ab
  Data: Se adoptó un diseño “polygenic-first” para inferencia causal del microbioma cecal en ratas HS, combinando metagenómica shallow-shotgun y modelos lineales mixtos para identificar efectos poligénicos del hospedador sobre rasgos del microbioma. Un pipeline reproducible optimizado para shallow-shotgun superó a 16S en la detección de estos efectos, destacando Bacteroides y Prevotella, su gremio compartido y la β-diversidad. Enriquecimientos genómicos sugirieron adaptaciones al nicho de las criptas y motivaron la selección de genes candidatos del hospedador. Un conjunto de SNP centinelas, mediante validación cruzada, explicó efectos poligénicos a nivel de género y sirvió como instrumento en mediación y aleatorización Mendeliana, dando lugar a un modelo de ecuaciones estructurales que vinculó bacterias clave, estructura comunitaria y metabolismo. Los efectos directos de estos géneros sobre la glucosa en ayunas fueron de signo opuesto y se compensaron por efectos indirectos mediados por rasgos comunitarios, apoyando intervenciones de ingeniería de nicho guiadas por genotipo.
– Name: Abstract
  Label: Description (Translated)
  Group: Ab
  Data: A “polygenic-first” design for causal inference was adopted to study the caecal microbiome of HS rats, combining shallow-shotgun metagenomics with linear-mixed models to map host polygenic effects on multi-level microbiome traits. A reproducible, shallow shotgun-optimised pipeline yielded better results for detecting such effects than 16S, with heritable signals concentrating in Bacteroides and Prevotella, their shared guild, and β-diversity. Then, genome-resolved enrichments suggested potential adaptations to the crypt niche, leading to a hypothesis-driven selection of host genes. A cross-validated set of sentinel SNPs for these candidate genes explained genus-level polygenic effects and served as instruments in mediation and Mendelian randomisation analyses, contributing to a structural equation model that linked keystone bacteria, community structure, and host metabolism. The effects of these genera on fasting glucose levels had opposite signs and were balanced by indirect effects routed through community traits, suggesting that genotype-aware, niche-engineering interventions could better modulate glycaemia and other health-related traits.<br />Universitat Pompeu Fabra. Doctorat en Biomedicina
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  Data: <link linkTarget="URL" linkTerm="https://hdl.handle.net/10803/696724" linkWindow="_blank">https://hdl.handle.net/10803/696724</link>
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  Data: L'accés als continguts d'aquesta tesi queda condicionat a l'acceptació de les condicions d'ús establertes per la següent llicència Creative Commons: http://creativecommons.org/licenses/by-nc-nd/4.0/
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      – Text: English
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        PageCount: 360
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    Titles:
      – TitleFull: Host genetics shapes crypt niche colonisation by keystone gut bacteria, influencing metabolic health
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            – D: 28
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              Type: published
              Y: 2026
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