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Gregory, Katherine

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Gregory

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Katherine

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Gregory, Katherine
Author's Publications: search.filters.isAuthorOfPublication.c266271c-feb6-4891-b1a9-52c2968fd427

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    A Complex Human-Gut Microbiome Cultured in an Anaerobic Intestine-on-a-Chip
    (‎Nature Research, 2019-07) Jalili-Firoozinezhad, Sasan; Gazzaniga, Francesca; Calamari, Elizabeth; Camacho, Diogo; Fadel, Cicely; Bein, Amir; Swenor, Ben; Nestor, Bret; Cronce, Michael; Levy, Oren; Gregory, Katherine; Breault, David; Cabral, Joaquim; Novak, Richard; Kasper, Dennis; Tovaglieri, Alessio; Ingber, Donald
    The diverse bacterial populations that comprise the commensal microbiome of the human intestine play a central role in health and disease. A method that sustains complex microbial communities in direct contact with living human intestinal cells and their overlying mucus layer in vitro would thus enable the investigation of host–microbiome interactions. Here, we show the extended coculture of living human intestinal epithelium with stable communities of aerobic and anaerobic human gut microbiota, using a microfluidic intestine-on-a-chip that permits the control and real-time assessment of physiologically relevant oxygen gradients. When compared to aerobic coculture conditions, the establishment of a transluminal hypoxia gradient in the chip increased intestinal barrier function and sustained a physiologically relevant level of microbial diversity, consisting of over 200 unique operational taxonomic units from 11 different genera and an abundance of obligate anaerobic bacteria, with ratios of Firmicutes and Bacteroidetes similar to those observed in human faeces. The intestine-on-a-chip may serve as a discovery tool for the development of microbiome-related therapeutics, probiotics and nutraceuticals.
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    Longitudinal Analysis of the Premature Infant Intestinal Microbiome Prior to Necrotizing Enterocolitis: A Case-Control Study
    (Public Library of Science, 2015) Zhou, Yanjiao; Shan, Gururaj; Sodergren, Erica; Weinstock, George; Walker, W.; Gregory, Katherine
    Necrotizing enterocolitis (NEC) is an inflammatory disease of the newborn bowel, primarily affecting premature infants. Early intestinal colonization has been implicated in the pathogenesis of NEC. The objective of this prospective case-control study was to evaluate differences in the intestinal microbiota between infants who developed NEC and unaffected controls prior to disease onset. We conducted longitudinal analysis of the 16S rRNA genes of 312 samples obtained from 12 NEC cases and 26 age-matched controls with a median frequency of 7 samples per subject and median sampling interval of 3 days. We found that the microbiome undergoes dynamic development during the first two months of life with day of life being the major factor contributing to the colonization process. Depending on when the infant was diagnosed with NEC (i.e. early vs. late onset), the pattern of microbial progression was different for cases and controls. The difference in the microbiota was most overt in early onset NEC cases and controls. In proximity to NEC onset, the abundances of Clostridium sensu stricto from Clostridia class were significantly higher in early onset NEC subjects comparing to controls. In late onset NEC, Escherichia/Shigella among Gammaproteobacteria, showed an increasing pattern prior to disease onset, and was significantly higher in cases than controls six days before NEC onset. Cronobacter from Gammaproteobacteria was also significantly higher in late onset NEC cases than controls 1-3 days prior to NEC onset. Thus, the specific infectious agent associated with NEC may vary by the age of infant at disease onset. We found that intravenously administered antibiotics may have an impact on the microbial diversity present in fecal material. Longitudinal analysis at multiple time points was an important strategy utilized in this study, allowing us to appreciate the dynamics of the premature infant intestinal microbiome while approaching NEC at various points.
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    Influence of maternal breast milk ingestion on acquisition of the intestinal microbiome in preterm infants
    (BioMed Central, 2016) Gregory, Katherine; Samuel, Buck S.; Houghteling, Pearl; Shan, Guru; Ausubel, Frederick; Sadreyev, Ruslan; Walker, W.
    Background: The initial acquisition and early development of the intestinal microbiome during infancy are important to human health across the lifespan. Mode of birth, antibiotic administration, environment of care, and nutrition have all been shown to play a role in the assembly of the intestinal microbiome during early life. For preterm infants, who are disproportionately at risk of inflammatory intestinal disease (i.e., necrotizing enterocolitis), a unique set of clinical factors influence the establishment of the microbiome. The purpose of this study was to establish the influence of nutritional exposures on the intestinal microbiome in a cohort of preterm infants early in life. Results: Principal component analysis of 199 samples from 30 preterm infants (<32 weeks) over the first 60 days following birth showed that the intestinal microbiome was influenced by postnatal time (p < 0.001, R 2 = 0.13), birth weight (p < 0.001, R 2 = 0.08), and nutrition (p < 0.001, R 2 = 0.21). Infants who were fed breast milk had a greater initial bacterial diversity and a more gradual acquisition of diversity compared to infants who were fed infant formula. The microbiome of infants fed breast milk were more similar regardless of birth weight (p = 0.049), in contrast to the microbiome of infants fed infant formula, which clustered differently based on birth weight (p < 0.001). By adjusting for differences in gut maturity, an ordered succession of microbial phylotypes was observed in breast milk-fed infants, which appeared to be disrupted in those fed infant formula. Supplementation with pasteurized donor human milk was partially successful in promoting a microbiome more similar to breast milk-fed infants and moderating rapid increases in bacterial diversity. Conclusions: The preterm infant intestinal microbiome is influenced by postnatal time, birth weight, gestational age, and nutrition. Feeding with breast milk appears to mask the influence of birth weight, suggesting a protective effect against gut immaturity in the preterm infant. These findings suggest not only a microbial mechanism underpinning the body of evidence showing that breast milk promotes intestinal health in the preterm infant but also a dynamic interplay of host and dietary factors that facilitate the colonization of and enrichment for specific microbes during establishment of the preterm infant microbiota. Electronic supplementary material The online version of this article (doi:10.1186/s40168-016-0214-x) contains supplementary material, which is available to authorized users.