5 results on '"Gibbons, Sean"'
Search Results
2. The short-chain fatty acid receptor, FFA2, contributes to gestational glucose homeostasis.
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Fuller, Miles, Priyadarshini, Medha, Gibbons, Sean M., Angueira, Anthony R., Brodsky, Michael, Hayes, M. Geoffrey, Kovatcheva-Datchary, Petia, Bäckhed, Fredrik, Gilbert, Jack A., Lowe Jr., William L., and Layden, Brian T.
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FATTY acids , *HOMEOSTASIS , *CARBOXYLIC acids , *PHYSIOLOGICAL control systems , *GLUCOSE - Abstract
The structure of the human GI microbiota can change during pregnancy, which may influence gestational metabolism; however, a mechanism of action remains unclear. Here we observed that in wildtype (WT) mice the relative abundance of Actinobacteria and Bacteroidetes increased during pregnancy. Along with these changes, short chain fatty acids (SCFAs), which are mainly produced through gut microbiota fermentation, significantly changed in both the cecum and peripheral blood throughout gestation in these mice. SCFAs are recognized by G protein coupled receptors (GPCRs) such as FFA2, and we have previously demonstrated that the Ffar2 expression is higher in pancreatic islets during pregnancy. Using female Ffar2-/- mice, we explored the physiological relevance of signaling through this GPCR and found that Ffar2-deficient female mice developed fasting hyperglycemia and impaired glucose tolerance in the setting of impaired insulin secretion as compared to WT mice during, but not prior to, pregnancy. Insulin tolerance tests were similar in Ffar2-/- and WT mice before and during pregnancy. Next, we examined the role of FFA2 in gestational ß cell mass, observing that Ffar2-/- mice had diminished gestational expansion of ß cells during pregnancy. Interestingly, mouse genotype had no significant impact on the composition of the gut microbiome, but did affect the observed SCFA profiles, suggesting a functional difference in the microbiota. Together, these results suggest a potential link between increased Ffar2 expression in islets and the alteration of circulating SCFA levels, possibly explaining how changes in the gut microbiome contribute to gestational glucose homeostasis. [ABSTRACT FROM AUTHOR]
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- 2015
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3. Non-responder phenotype reveals apparent microbiome-wide antibiotic tolerance in the murine gut.
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Diener, Christian, Hoge, Anna C. H., Kearney, Sean M., Kusebauch, Ulrike, Patwardhan, Sushmita, Moritz, Robert L., Erdman, Susan E., and Gibbons, Sean M.
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GUT microbiome , *BACTERIAL diversity , *PHENOTYPES , *CEFOPERAZONE , *ANTIBIOTICS - Abstract
Broad spectrum antibiotics cause both transient and lasting damage to the ecology of the gut microbiome. Antibiotic-induced loss of gut bacterial diversity has been linked to susceptibility to enteric infections. Prior work on subtherapeutic antibiotic treatment in humans and non-human animals has suggested that entire gut communities may exhibit tolerance phenotypes. In this study, we validate the existence of these community tolerance phenotypes in the murine gut and explore how antibiotic treatment duration or a diet enriched in antimicrobial phytochemicals might influence the frequency of this phenotype. Almost a third of mice exhibited whole-community tolerance to a high dose of the β-lactam antibiotic cefoperazone, independent of antibiotic treatment duration or dietary phytochemical amendment. We observed few compositional differences between non-responder microbiota during antibiotic treatment and the untreated control microbiota. However, gene expression was vastly different between non-responder microbiota and controls during treatment, with non-responder communities showing an upregulation of antimicrobial tolerance genes, like efflux transporters, and a down-regulation of central metabolism. Future work should focus on what specific host- or microbiome-associated factors are responsible for tipping communities between responder and non-responder phenotypes so that we might learn to harness this phenomenon to protect our microbiota from routine antibiotic treatment. Diener, Hoge et al. show that a third of mice exhibit tolerance to a high dose of the β-lactam antibiotic cefoperazone, independent of antibiotic treatment duration or dietary phytochemical amendment. They find that non-responder microbiota upregulates antimicrobial tolerance genes and downregulates central metabolism without altering community composition or diversity, providing insights into the mechanisms of community-wide antibiotic tolerance. [ABSTRACT FROM AUTHOR]
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- 2021
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4. Longitudinal analysis reveals transition barriers between dominant ecological states in the gut microbiome.
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Levy, Roie, Magis, Andrew T., Earls, John C., Manor, Ohad, Wilmanski, Tomasz, Lovejoy, Jennifer, Gibbons, Sean M., Omenn, Gilbert S., Hood, Leroy, and Price, Nathan D.
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GUT microbiome , *OMEGA-6 fatty acids , *PREVOTELLA , *BACTEROIDES , *CLINICAL chemistry - Abstract
The Pioneer 100 Wellness Project involved quantitatively profiling 108 participants' molecular physiology over time, including genomes, gut microbiomes, blood metabolomes, blood proteomes, clinical chemistries, and data from wearable devices. Here, we present a longitudinal analysis focused specifically around the Pioneer 100 gut microbiomes. We distinguished a subpopulation of individuals with reduced gut diversity, elevated relative abundance of the genus Prevotella, and reduced levels of the genus Bacteroides. We found that the relative abundances of Bacteroides and Prevotella were significantly correlated with certain serum metabolites, including omega-6 fatty acids. Primary dimensions in distance-based redundancy analysis of clinical chemistries explained 18.5% of the variance in bacterial community composition, and revealed a Bacteroides/Prevotella dichotomy aligned with inflammation and dietary markers. Finally, longitudinal analysis of gut microbiome dynamics within individuals showed that direct transitions between Bacteroides-dominated and Prevotella-dominated communities were rare, suggesting the presence of a barrier between these states. One implication is that interventions seeking to transition between Bacteroides- and Prevotella-dominated communities will need to identify permissible paths through ecological state-space that circumvent this apparent barrier. [ABSTRACT FROM AUTHOR]
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- 2020
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5. Elevated rates of horizontal gene transfer in the industrialized human microbiome.
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Groussin, Mathieu, Poyet, Mathilde, Sistiaga, Ainara, Kearney, Sean M., Moniz, Katya, Noel, Mary, Hooker, Jeff, Gibbons, Sean M., Segurel, Laure, Froment, Alain, Mohamed, Rihlat Said, Fezeu, Alain, Juimo, Vanessa A., Lafosse, Sophie, Tabe, Francis E., Girard, Catherine, Iqaluk, Deborah, Nguyen, Le Thanh Tu, Shapiro, B. Jesse, and Lehtimäki, Jenni
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HORIZONTAL gene transfer , *HUMAN microbiota , *BACTERIAL genomes , *GUT microbiome , *CITY dwellers , *GENES , *BACTERIAL population - Abstract
Industrialization has impacted the human gut ecosystem, resulting in altered microbiome composition and diversity. Whether bacterial genomes may also adapt to the industrialization of their host populations remains largely unexplored. Here, we investigate the extent to which the rates and targets of horizontal gene transfer (HGT) vary across thousands of bacterial strains from 15 human populations spanning a range of industrialization. We show that HGTs have accumulated in the microbiome over recent host generations and that HGT occurs at high frequency within individuals. Comparison across human populations reveals that industrialized lifestyles are associated with higher HGT rates and that the functions of HGTs are related to the level of host industrialization. Our results suggest that gut bacteria continuously acquire new functionality based on host lifestyle and that high rates of HGT may be a recent development in human history linked to industrialization. [Display omitted] • Thousands of gut bacterial genomes from worldwide human populations were sequenced • HGT occurs at high frequency in the gut microbiome of individual persons • HGT occurs more frequently in the microbiome of industrialized and urban populations • Transferred gene functions in the microbiome reflect the lifestyle of the host A worldwide microbiome analysis from 15 populations along the industrialization gradient reveals that horizontal gene transfer occurs on short timescales and that microbiomes continuously acquire new functionality based on host lifestyle. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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