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Expansion of Bacteriophages Is Linked to Aggravated Intestinal Inflammation and Colitis.

TitleExpansion of Bacteriophages Is Linked to Aggravated Intestinal Inflammation and Colitis.
Publication TypeJournal Article
Year of Publication2019
AuthorsGogokhia L, Buhrke K, Bell R, Hoffman B, D Brown G, Hanke-Gogokhia C, Ajami NJ, Wong MC, Ghazaryan A, Valentine JF, Porter N, Martens E, O'Connell R, Jacob V, Scherl E, Crawford C, W Stephens Z, Casjens SR, Longman RS, Round JL
JournalCell Host Microbe
Volume25
Issue2
Pagination285-299.e8
Date Published2019 02 13
ISSN1934-6069
KeywordsAnimals, Bacteria, Bacteriophages, CD4-Positive T-Lymphocytes, Colitis, Ulcerative, Colorectal Neoplasms, Disease Models, Animal, Fecal Microbiota Transplantation, Gastrointestinal Microbiome, Humans, Interferon-gamma, Intestinal Mucosa, Mice, Mice, Inbred C57BL, Mice, Knockout, Pilot Projects, Prospective Studies, Specific Pathogen-Free Organisms
Abstract

Bacteriophages are the most abundant members of the microbiota and have the potential to shape gut bacterial communities. Changes to bacteriophage composition are associated with disease, but how phages impact mammalian health remains unclear. We noted an induction of host immunity when experimentally treating bacterially driven cancer, leading us to test whether bacteriophages alter immune responses. Treating germ-free mice with bacteriophages leads to immune cell expansion in the gut. Lactobacillus, Escherichia, and Bacteroides bacteriophages and phage DNA stimulated IFN-γ via the nucleotide-sensing receptor TLR9. The resultant immune responses were both phage and bacteria specific. Additionally, increasing bacteriophage levels exacerbated colitis via TLR9 and IFN-γ. Similarly, ulcerative colitis (UC) patients responsive to fecal microbiota transplantation (FMT) have reduced phages compared to non-responders, and mucosal IFN-γ positively correlates with bacteriophage levels. Bacteriophages from active UC patients induced more IFN-γ compared to healthy individuals. Collectively, these results indicate that bacteriophages can alter mucosal immunity to impact mammalian health.

DOI10.1016/j.chom.2019.01.008
Alternate JournalCell Host Microbe
PubMed ID30763538
Grant List / / Wellcome Trust / United Kingdom
DP2 GM111099 / GM / NIGMS NIH HHS / United States
R00 HL102228 / HL / NHLBI NIH HHS / United States
R01 GM114817 / GM / NIGMS NIH HHS / United States
R01 DK114252 / DK / NIDDK NIH HHS / United States
DP2 AT008746 / AT / NCCIH NIH HHS / United States