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Gazzaniga, Francesca

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Gazzaniga

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Francesca

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Gazzaniga, Francesca

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2019 - 20202

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Author's Publications: search.filters.isAuthorOfPublication.e0a8a729-4583-4148-b8ea-bb3faff5ac32

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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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    Microbiota-Targeted Maternal Antibodies Protect Neonates From Enteric Infection
    (Springer Science and Business Media LLC, 2020-01-23) Zheng, Wen; Zhao, Wenjing; Wu, Meng; Song, Xinyang; Caro, Florence; Sun, Ximei; Gazzaniga, Francesca; Stefanetti, Giuseppe; Oh, Sungwhan; Mekalanos, John; Kasper, Dennis
    Although maternal antibodies protect newborns from infection, little is known about how protective antibodies are induced without prior pathogen exposure. Here we show that neonatal mice lacking the capacity to produce IgG are protected by maternal natural IgG antibodies to the enteric pathogen enterotoxigenic Escherichia coli (ETEC) when antibodies are delivered either trans-placentally or through milk. By challenging pups fostered on either maternal antibody¬–sufficient or –deficient dams, we found that milk-derived IgG was critical for protection against ETEC-induced disease. Pups utilize the neonatal Fc receptor (FcRn) to transfer IgG from milk into serum, and this IgG provides protection against systemic and mucosal E. coli infection. The maternal commensal microbiota can induce antibodies that recognize antigens expressed by ETEC and other Enterobacteriaceae species. Induction of maternal antibodies against a commensal Pantoea species confers ETEC protection in pups. The surprising role of the microbiota in eliciting protective antibodies to a specific neonatal pathogen represents an important host defense mechanism against neonatal infection.