Biology subjects

Kaakoush, N. O.

Publications and source records attributed to Kaakoush, N. O..

4 recordsLinked to original sources

bioRxiv2024

Long-read metagenomics empowers precise tracking of bacterial strains and their genomic changes after fecal microbiota transplantation

Fecal microbiota transplantation (FMT) has revolutionized the treatment of recurrent Clostridioides difficile infection (rCDI) and is being evaluated across other diseases. Accurate tracking of bacterial strains that stably engraft in recipients is critical for understanding the determinants of strain engraftment, evaluating their correlation with clinical outcomes, and guiding the development of therapeutic bacterial consortia. While short-read sequencing has advanced FMT research, it faces challenges in strain-level de novo metagenomic assembly. In this study, we described a novel framework, LongTrack, which uses long-read metagenomic assemblies and rigorous informatics tailored for FMT strain tracking. We highlighted LongTracks advantage over short-read approaches especially when multiple strains co-exist in the same sample. We showed LongTrack uncovered hundreds of engrafted strains across six FMT cases of rCDI and inflammatory bowel disease patients. Furthermore, long reads also allowed us to assess the genomic and epigenomic stability of engrafted strains during the 5-year follow-ups, revealing structural variations that may be associated with strain adaptation in a new host environment. Combined, our study advocates the use of long-read metagenomics and LongTrack to enhance strain tracking in future FMT studies, paving the way for the development of more effective defined biotherapeutic as an alternative to FMT.

microbiology↗

bioRxiv2024

Impact of maternal obesogenic diet on maternal and offspring microbiome development

Pregnancy can alter gut microbiota composition, but how an obesogenic diet impacts maternal gut microbiota, and the extent to which this influences offspring microbiome can be obscured by confounding factors. This study examined changes in gut microbiota composition across pre-pregnancy, gestation and lactation in rat dams fed either a high-fat, high-sugar Cafeteria (Caf) diet or Chow. Microbiome development was assessed in their offspring weaned onto chow. Caf diet consumption during pregnancy increased weight gain and adiposity, and compromised subsequent maternal nursing behaviour. - and {beta} diversity measures in Caf-fed dams showed a different trajectory across the progression of pregnancy, with no change in Bacteroidetes and Firmicutes abundance compared with Chow dams. Offspring born to Caf dams exhibited greater adiposity and plasma leptin at weaning and 14 weeks of age than those born to Chow dams. Maternal Caf diet induced clear differences in {beta} diversity in weanlings but not diversity. SourceTracker analysis revealed similarities in the gut microbiota of Chow weanlings and maternal gut microbiota in lactation, whereas the microbiota of Caf weanlings was similar to the maternal gut microbiota during gestation. Maternal Caf diet exerted only marginal effects on gut microbiota composition in 14-week-old offspring.

developmental biology↗

bioRxiv2020

Strain population structure varies widely across bacterial species and predicts strain colonization in unrelated individuals

The population structure of strains within a bacterial species is poorly defined, despite the functional importance of strain variation in the human gut microbiota on health. Here we analyzed >1000 sequenced bacterial strains from the fecal microbiota of 47 individuals from two countries and combined them with >150,000 bacterial genomes from NCBI to quantify the strain population size of different bacterial species, as well as the frequency of finding the same strain colonized in unrelated individuals who had no opportunities for direct microbial strain transmission. Strain population sizes ranged from tens to over one-hundred thousand per species. Prevalent strains in common gut microbiota species with small population sizes were the most likely to be harbored in two or more unrelated individuals. The finite strain population size of certain species creates the opportunity to comprehensively sequence the entirety of these species prevalent strains and associate their presence in different individuals with health outcomes.

microbiology↗

bioRxiv2019

Defined microbiota transplant restores Th17/RORtγ+ regulatory T cell balance in mice colonized with inflammatory bowel disease microbiotas

The building evidence for the contribution of microbiota to human disease has spurred an effort to develop therapies that target the gut microbiota. This is particularly evident in inflammatory bowel diseases, where clinical trials of fecal microbiota transplant have shown some efficacy. To aid the development of novel microbiota-targeted therapies and to better understand the biology underpinning such treatments, we have used gnotobiotic mice to model microbiota manipulations in the context of microbiotas from humans with inflammatory bowel disease. Mice colonized with IBD donor-derived microbiotas exhibit a stereotypical set of phenotypes, characterized by abundant mucosal Th17 cells and a deficit in the tolerogenic ROR{gamma}t+ Treg cell subset. Transplanting healthy donor-derived microbiota into mice colonized with human IBD microbiotas lead to induction of ROR{gamma}t+ Treg cells, which was associated with an increase in the density of the microbiotas following transplant. Microbiota transplant reduced gut Th17 cells in mice colonized with a microbiota from a donor with Crohns disease. By culturing strains from this microbiota and screening them in vivo, we identified a specific strain that potently induces Th17 cells. Microbiota transplants reduced the relative abundance of this strain in the gut microbiota, correlated with a reduction in Th17 cells.

immunology↗