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

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-? 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-?. Similarly, ulcerative colitis (UC) patients responsive to fecal microbiota transplantation (FMT) have reduced phages compared to non-responders, and mucosal IFN-? positively correlates with bacteriophage levels. Bacteriophages from active UC patients induced more IFN-? compared to healthy individuals. Collectively, these results indicate that bacteriophages can alter mucosal immunity to impact mammalian health.

SUBMITTER: Gogokhia L

PROVIDER: S-EPMC6885004 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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

Gogokhia Lasha L Buhrke Kate K Bell Rickesha R Hoffman Brenden B Brown D Garrett DG Hanke-Gogokhia Christin C Ajami Nadim J NJ Wong Matthew C MC Ghazaryan Arevik A Valentine John F JF Porter Nathan N Martens Eric E O'Connell Ryan R Jacob Vinita V Scherl Ellen E Crawford Carl C Stephens W Zac WZ Casjens Sherwood R SR Longman Randy S RS Round June L JL

Cell host & microbe 20190201 2

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. Lactobac ...[more]

PMID: 30763538

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Project description:New findingsWhat is the central question of this study? What is the role of mas-related G protein-coupled receptor X2 (MRGPRX2/Mrgprb2) in ulcerative colitis in relation to the intestinal flora, intestinal barrier and immune response? What is the main finding and its importance? Knockout of mouse Mrgprb2 aggravates dextran sulfate sodium (DSS)-induced colitis, which is associated with altered gut microbiota and immune response and disruption of the intestinal barrier. MRGPRB2 may have a protective effect on DSS-induced colitis.AbstractUlcerative colitis (UC) is a chronic immune-related disease, and changes in the intestinal microbiota and damage to the intestinal barrier contribute to its pathogenesis. Mast cells (MCs) are widely distributed in the gastrointestinal tract and are thought to be related to the pathogenesis of UC. Human mas-related G protein-coupled receptor X2 (MRGPRX2) and its mouse homologue, Mrgprb2, are selectively expressed on MCs to recruit immune cells and modulate host defence against microbial infection. To investigate the role of Mrgprb2 in UC in mice, we compared the differences between Mrgprb2 knockout (b2KO) male mice and wild-type (WT) male mice with dextran sulfate sodium (DSS)-induced colitis in the severity of clinical symptoms, inflammatory cell infiltration, degree of intestinal barrier damage and composition of the intestinal flora. The results showed that weight loss, disease activity index score, colon shortening and colonic pathological damage were significantly increased in b2KO mice while MC activation, cytokine and chemokine secretion, and inflammatory cell infiltration were decreased. In addition, the abundance and diversity of the intestinal microbiota were reduced in b2KO mice. B2KO mice also exhibited a reduction of probiotics such as norank_f_Muribaculaceae and Lactobacillus and increase of harmful bacteria like Escherichia-Shigella. Intestinal mucosal barrier damage of b2KO mice was more severe than that of WT mice due to the attenuated expression of mucin-2 and occludin. These results demonstrated that MRGPRB2 may have a protective effect on DSS-induced colitis by altering the intestinal flora, participating in barrier repair and recruiting inflammatory cells to eliminate pathogens.

Dataset Information

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

Publications

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

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