Histone deacetylase inhibition by gut microbe-generated short chain fatty acids entrains intestinal epithelial circadian rhythms

Gastroenterology. 2022 Aug 4:S0016-5085(22)00827-7. doi: 10.1053/j.gastro.2022.07.051. Online ahead of print. ABSTRACT BACKGROUND & AIMS: The circadian clock orchestrates ∼24-hour oscillations of gastrointestinal epithelial structure and function that drive diurnal rhythms in gut microbiota. Here, we use experimental and computational approaches in intestinal organoids to reveal reciprocal effects of gut microbial metabolites on epithelial timekeeping by […]

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Leveraging metabolic modeling to identify functional metabolic alterations associated with COVID-19 disease severity

Metabolomics. 2022 Jul 11;18(7):51. doi: 10.1007/s11306-022-01904-9. ABSTRACT OBJECTIVE: Since the COVID-19 pandemic began in early 2020, SARS-CoV2 has claimed more than six million lives world-wide, with over 510 million cases to date. To reduce healthcare burden, we must investigate how to prevent non-acute disease from progressing to severe infection requiring hospitalization. METHODS: To achieve this […]

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Fecal sphingolipids predict parenteral nutrition associated cholestasis in the neonatal intensive care unit

JPEN J Parenter Enteral Nutr. 2022 Mar 13. doi: 10.1002/jpen.2374. Online ahead of print. ABSTRACT BACKGROUND: Parenteral nutrition associated cholestasis (PNAC) in the neonatal intensive care unit (NICU) causes significant morbidity and associated healthcare costs. Laboratory detection of PNAC currently relies on elevated serum conjugated bilirubin levels in the aftermath of impaired bile flow. Here, […]

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Comparative analyses of parasites with a comprehensive database of genome-scale metabolic models

PLoS Comput Biol. 2022 Feb 23;18(2):e1009870. doi: 10.1371/journal.pcbi.1009870. eCollection 2022 Feb. ABSTRACT Protozoan parasites cause diverse diseases with large global impacts. Research on the pathogenesis and biology of these organisms is limited by economic and experimental constraints. Accordingly, studies of one parasite are frequently extrapolated to infer knowledge about another parasite, across and within genera. […]

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Comparative analyses of parasites with a comprehensive database of geno-scale metabolic models

PLoS Comput Biol. 2022 Feb 23;18(2):e1009870. doi: 10.1371/journal.pcbi.1009870. Online ahead of print. ABSTRACT Protozoan parasites cause diverse diseases with large global impacts. Research on the pathogenesis and biology of these organisms is limited by economic and experimental constraints. Accordingly, studies of one parasite are frequently extrapolated to infer knowledge about another parasite, across and within […]

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Quantifying cumulative phenotypic and genomic evidence for procedural generation of metabolic network reconstructions

PLoS Comput Biol. 2022 Feb 7;18(2):e1009341. doi: 10.1371/journal.pcbi.1009341. Online ahead of print. ABSTRACT Genome-scale metabolic network reconstructions (GENREs) are valuable tools for understanding microbial metabolism. The process of automatically generating GENREs includes identifying metabolic reactions supported by sufficient genomic evidence to generate a draft metabolic network. The draft GENRE is then gapfilled with additional reactions […]

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Computational approaches to understanding Clostridioides difficile metabolism and virulence

Curr Opin Microbiol. 2022 Feb;65:108-115. doi: 10.1016/j.mib.2021.11.002. Epub 2021 Nov 25. ABSTRACT The progress of infection by Clostridioides difficile is strongly influenced by metabolic cues it encounters as it colonizes the gastrointestinal tract. Both colonization and regulation of virulence have a multi-factorial interaction between host, microbiome, and gene expression cascades. While these connections with metabolism […]

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An updated genome-scale metabolic network reconstruction of Pseudomonas aeruginosa PA14 to characterize mucin-driven shifts in bacterial metabolism

NPJ Syst Biol Appl. 2021 Oct 8;7(1):37. doi: 10.1038/s41540-021-00198-2. ABSTRACT Mucins are present in mucosal membranes throughout the body and play a key role in the microbe clearance and infection prevention. Understanding the metabolic responses of pathogens to mucins will further enable the development of protective approaches against infections. We update the genome-scale metabolic network […]

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Novel Drivers of Virulence in Clostridioides difficile Identified via Context-Specific Metabolic Network Analysis

mSystems. 2021 Oct 26;6(5):e0091921. doi: 10.1128/mSystems.00919-21. Epub 2021 Oct 5. ABSTRACT The pathogen Clostridioides difficile causes toxin-mediated diarrhea and is the leading cause of hospital-acquired infection in the United States. Due to growing antibiotic resistance and recurrent infection, targeting C. difficile metabolism presents a new approach to combat this infection. Genome-scale metabolic network reconstructions (GENREs) […]

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Perinatal Outcomes of Asynchronous Influenza Vaccination, Ceará, Brazil, 2013-2018

Emerg Infect Dis. 2021;27(9):2409-2420. doi: 10.3201/eid2709.203791. ABSTRACT In Ceará, Brazil, seasonal influenza transmission begins before national annual vaccination campaigns commence. To assess the perinatal consequences of this misalignment, we tracked severe acute respiratory infection (SARI), influenza, and influenza immunizations during 2013-2018. Among 3,297 SARI cases, 145 (4.4%) occurred in pregnant women. Statewide vaccination coverage was […]

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