Animal Models for Microbiome Research Advancing Basic and Translational Science: Proceedings of a Workshop (2018) / Chapter Skim
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4 Modeling Human Microbiota in Animal Systems
4 Modeling Human Microbiota in Animal Systems
Pages 17-28
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From page 17... ...
The six speakers were Federico Rey, assistant professor of bacteriology at the University of Wisconsin–Madison; Patrice Cani, a researcher from the Belgian Fund for Scientific Research and a group leader at the Université de Louvain Drug Research Institute; Wendy Garrett, professor of immunology and infectious diseases at the Harvard T.H. Chan School of Public Health; Richard Blumberg, professor of medicine at Harvard Medical School and co-director of the Harvard Digestive Diseases Center; Nancy Moran, the Leslie Surginer Endowed Professor in the Department of Integrative Biology at The University of Texas; and Tracy Bale, professor of neuroscience in the School of Veterinary Medicine and Department of Psychiatry at the Perelman School of Medicine, University of Pennsylvania.
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From page 18... ...
coli. One conclusion from these studies, said Rey, is that the microbial choline utilization pathway may limit choline availability during pregnancy and affect fetal brain development.
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From page 19... ...
from adipocytes causes mice to develop spontaneous obesity (Geurts et al., 2015) ; thus germ-free mice that received microbes from the genetically modified obese mice gained both weight and fat mass, while their adipose tissue displayed metabolic changes similar to those observed in the donor mice.
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From page 20... ...
nucleatum greatly expanded the number of multiple types of myeloid immune cells at the earliest stages of colorectal tumor development. To determine if these results had any bearing on what was happening in human colorectal cancer, Garrett and her collaborators examined RNAseq data generated as part of The Cancer Genome Atlas program and found the same signatures in humans that they saw in mice.
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From page 21... ...
So-called invariant NKT cells recognize host and microbial lipid antigens presented by the molecule CD1d and play a critical role in the early immune response as orchestrators of downstream events. Invariant NKT cells, said Blumberg, are important regulators of bacterial commensalism, whether it involves a pathogen, such as Pseudomonas aeruginosa, or a commensal organism, such as E
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From page 22... ...
. Furthermore, they showed that germ-free mice are highly susceptible to oxazolone-induced colitis associated with triggers that activate invariant NKT cells, and that this susceptibility is eliminated if the mice are exposed to what he called microbial programming during the first couple of weeks of their lives.
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From page 23... ...
THE INTERFACE BETWEEN MICROBES AND NEUROSCIENCE: TWO CASE STUDIES Bee Microbiome When Moran began working with Apis mellifera, the Western or European honeybee, about 6 years ago, her goal was to use this species to study different aspects of how its distinct microbiome comes together, how the microbes within that microbiome interact, and how those interactions affect the behavior of bees. The honeybee gut microbiota comprises nine bacterial species that form dense, spatially organized communities in the hindguts of adult workers (Kwong and Moran, 2016)
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From page 24... ...
She also noted that her group developed methods to grow the nine species of bacteria in the honeybee gut microbiome as pure cultures in the laboratory and to introduce fluorescence or luminescence genes that enable them to monitor microbiome composition. Inoculating the bees is simply a matter of feeding a sucrose solution or pollen laced with one or more of the bacterial species.
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From page 25... ...
. In one learning experiment, Moran and her colleagues, using the plasmid system they created to introduce genes into honeybee microbiome species, studied the effect on bee behavior of adding L-dOPA, a precursor to dopamine, into bee gut bacteria.
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From page 26... ...
To answer that question, Bale and her colleagues looked at whether maternal stress during early pregnancy in mice changed the vaginal microbiome in a manner that persisted until the time of birth. In fact, early stress changes both the bacterial and the viral composition of the vaginal microbiome that persists through at least two days after birth (Jasarevic et al., 2015b)
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From page 27... ...
To get at causality, she and her colleagues performed a difficult set of experiments in which they delivered the pups via cesarean section and inoculated them with vaginal lavages from stressed and control mothers, a procedure that appears to reproduce the bacterial load and diversity of the vaginal microbiome in the gut of the offspring. It also reproduces the elevated stress response in post-pubertal males delivered vaginally from mothers exposed to stress.
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From page 28... ...
These differences, though not by themselves, manifesting as disease or a behavioral disorder, are establishing how the male and female gut and brain respond to the environment later in life. For example, exposing these animals to a week of chronic stress lowers gut permeability in the males but not females born of mothers who experienced stress during early pregnancy.
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