Lee Sonny T. M.

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Lee
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Sonny T. M.
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  • Article
    Tracking microbial colonization in fecal microbiota transplantation experiments via genome-resolved metagenomics
    (BioMed Central, 2017-05-04) Lee, Sonny T. M. ; Kahn, Stacy A. ; Delmont, Tom O. ; Shaiber, Alon ; Esen, Ozcan C. ; Hubert, Nathaniel A. ; Morrison, Hilary G. ; Antonopoulos, Dionysios A. ; Rubin, David T. ; Eren, A. Murat
    Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection and shows promise for treating other medical conditions associated with intestinal dysbioses. However, we lack a sufficient understanding of which microbial populations successfully colonize the recipient gut, and the widely used approaches to study the microbial ecology of FMT experiments fail to provide enough resolution to identify populations that are likely responsible for FMT-derived benefits. We used shotgun metagenomics together with assembly and binning strategies to reconstruct metagenome-assembled genomes (MAGs) from fecal samples of a single FMT donor. We then used metagenomic mapping to track the occurrence and distribution patterns of donor MAGs in two FMT recipients. Our analyses revealed that 22% of the 92 highly complete bacterial MAGs that we identified from the donor successfully colonized and remained abundant in two recipients for at least 8 weeks. Most MAGs with a high colonization rate belonged to the order Bacteroidales. The vast majority of those that lacked evidence of colonization belonged to the order Clostridiales, and colonization success was negatively correlated with the number of genes related to sporulation. Our analysis of 151 publicly available gut metagenomes showed that the donor MAGs that colonized both recipients were prevalent, and the ones that colonized neither were rare across the participants of the Human Microbiome Project. Although our dataset showed a link between taxonomy and the colonization ability of a given MAG, we also identified MAGs that belong to the same taxon with different colonization properties, highlighting the importance of an appropriate level of resolution to explore the functional basis of colonization and to identify targets for cultivation, hypothesis generation, and testing in model systems. The analytical strategy adopted in our study can provide genomic insights into bacterial populations that may be critical to the efficacy of FMT due to their success in gut colonization and metabolic properties, and guide cultivation efforts to investigate mechanistic underpinnings of this procedure beyond associations.
  • 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.