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

Lasha Gogokhia | Kate Buhrke | Rickesha Bell | Brenden Hoffman | D Garrett Brown | Christin Hanke-Gogokhia | Nadim J Ajami | Matthew C Wong | Arevik Ghazaryan | John F Valentine | Nathan Porter | Eric Martens | Ryan O'Connell | Vinita Jacob | Ellen Scherl | Carl Crawford | W Zac Stephens | Sherwood R Casjens | Randy S Longman | June L Round
Cell host & microbe | 2019

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.

Pubmed ID: 30763538

Research resources used in this publication

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Associated grants

  • Agency: NCCIH NIH HHS, United States
    Id: DP2 AT008746
  • Agency: NIH HHS, United States
    Id: P40 OD010995
  • Agency: NHLBI NIH HHS, United States
    Id: R00 HL102228
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM114817
  • Agency: NHGRI NIH HHS, United States
    Id: T32 HG008962
  • Agency: Wellcome Trust, United Kingdom
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK114252
  • Agency: NIGMS NIH HHS, United States
    Id: DP2 GM111099
  • Agency: NIAID NIH HHS, United States
    Id: N01AI95375

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GenBank (tool)

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NIH genetic sequence database that provides annotated collection of all publicly available DNA sequences for almost 280 000 formally described species (Jan 2014) .These sequences are obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects, including whole-genome shotgun (WGS) and environmental sampling projects. Most submissions are made using web-based BankIt or standalone Sequin programs, and GenBank staff assigns accession numbers upon data receipt. It is part of International Nucleotide Sequence Database Collaboration and daily data exchange with European Nucleotide Archive (ENA) and DNA Data Bank of Japan (DDBJ) ensures worldwide coverage. GenBank is accessible through NCBI Entrez retrieval system, which integrates data from major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information, and biomedical journal literature via PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of GenBank database are available by FTP.

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GraphPad Prism (tool)

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Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.

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Fisher BioReagents (tool)

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USeq (tool)

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ClinicalTrials.gov (tool)

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Registry and results database of federally and privately supported clinical trials conducted in United States and around world. Provides information about purpose of trial, who may participate, locations, and phone numbers for more details. This information should be used in conjunction with advice from health care professionals.Offers information for locating federally and privately supported clinical trials for wide range of diseases and conditions. Research study in human volunteers to answer specific health questions. Interventional trials determine whether experimental treatments or new ways of using known therapies are safe and effective under controlled environments. Observational trials address health issues in large groups of people or populations in natural settings. ClinicalTrials.gov contains trials sponsored by National Institutes of Health, other federal agencies, and private industry. Studies listed in database are conducted in all 50 States and in 178 countries.

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