Trigodet Florian

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Trigodet
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Florian
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  • Article
    Metabolic independence drives gut microbial colonization and resilience in health and disease
    (BioMed Central, 2023-04-17) Watson, Andrea R. ; Füssel, Jessika ; Veseli, Iva ; DeLongchamp, Johanna Zaal ; Silva, Marisela ; Trigodet, Florian ; Lolans, Karen ; Shaiber, Alon ; Fogarty, Emily ; Runde, Joseph M. ; Quince, Christopher ; Yu, Michael K. ; Söylev, Arda ; Morrison, Hilary G. ; Lee, Sonny T. M. ; Kao, Dina ; Rubin, David T. ; Jabri, Bana ; Louie, Thomas ; Eren, A. Murat
    Changes in microbial community composition as a function of human health and disease states have sparked remarkable interest in the human gut microbiome. However, establishing reproducible insights into the determinants of microbial succession in disease has been a formidable challenge.Here we use fecal microbiota transplantation (FMT) as an in natura experimental model to investigate the association between metabolic independence and resilience in stressed gut environments. Our genome-resolved metagenomics survey suggests that FMT serves as an environmental filter that favors populations with higher metabolic independence, the genomes of which encode complete metabolic modules to synthesize critical metabolites, including amino acids, nucleotides, and vitamins. Interestingly, we observe higher completion of the same biosynthetic pathways in microbes enriched in IBD patients.These observations suggest a general mechanism that underlies changes in diversity in perturbed gut environments and reveal taxon-independent markers of "dysbiosis" that may explain why widespread yet typically low-abundance members of healthy gut microbiomes can dominate under inflammatory conditions without any causal association with disease.
  • Article
    Bile acid fitness determinants of a Bacteroides fragilis isolate from a human pouchitis patient
    (American Society for Microbiology, 2023-12-08) Fiebi, Aretha ; Schnizlein, Matthew K. ; Pena-Rivera, Selymar ; Trigodet, Florian ; Dubey, Abhishek Anil ; Hennessy, Miette K. ; Basu, Anindita ; Pott, Sebastian ; Dalal, Sushila R. ; Rubin, David ; Sogin, Mitchell L. ; Eren, A. Murat ; Chang, Eugene B. ; Crosson, Sean
    Bacteroides fragilis comprises 1%–5% of the gut microbiota in healthy humans but can expand to >50% of the population in ulcerative colitis (UC) patients experiencing inflammation. The mechanisms underlying such microbial blooms are poorly understood, but the gut of UC patients has physicochemical features that differ from healthy patients and likely impact microbial physiology. For example, levels of the secondary bile acid deoxycholate (DC) are highly reduced in the ileoanal J-pouch of UC colectomy patients. We isolated a B. fragilis strain from a UC patient with pouch inflammation (i.e., pouchitis) and developed it as a genetic model system to identify genes and pathways that are regulated by DC and that impact B. fragilis fitness in DC and crude bile. Treatment of B. fragilis with a physiologically relevant concentration of DC reduced cell growth and remodeled transcription of one-quarter of the genome. DC strongly induced expression of chaperones and select transcriptional regulators and efflux systems, and down-regulated protein synthesis genes. Using a barcoded collection of ≈50,000 unique insertional mutants, we further defined B. fragilis genes that contribute to fitness in media containing DC or crude bile. Genes impacting cell envelope functions including cardiolipin synthesis, cell surface glycosylation, and systems implicated in sodium-dependent bioenergetics were major bile acid fitness factors. As expected, there was limited overlap between transcriptionally regulated genes and genes that impacted fitness in bile when disrupted. Our study provides a genome-scale view of a B. fragilis bile response and genetic determinants of its fitness in DC and crude bile.