Intestinal Microbial Products From Alcohol‐Fed Mice Contribute to Intestinal Permeability and Peripheral Immune Activation

Background Alcohol use causes significant disruption of intestinal microbial communities, yet exactly how these dysbiotic communities interact with the host is unclear. We sought to understand the role of microbial products associated with alcohol dysbiosis in mice on intestinal permeability and imm...

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Published in:Alcoholism, clinical and experimental research clinical and experimental research, 2019-10, Vol.43 (10), p.2122-2133
Main Authors: Samuelson, Derrick R., Gu, Min, Shellito, Judd E., Molina, Patricia E., Taylor, Christopher M., Luo, Meng, Welsh, David A.
Format: Article
Language:English
Subjects:
Activation
Activation analysis
Alcohol
Alcohol use
Alcohols
Anaerobic conditions
Anaerobic microorganisms
CD38 antigen
CD4 antigen
CD8 antigen
Disruption
Dysbacteriosis
Dysbiosis
Flow cytometry
Immune Activation
Intestinal Permeability
Intestine
Leukocytes (mononuclear)
Lymphocytes
Lymphocytes T
Microbial activity
Microbial Products
Microbiota
Peripheral blood mononuclear cells
Permeability
Probiotics
Stimulation
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Summary:Background Alcohol use causes significant disruption of intestinal microbial communities, yet exactly how these dysbiotic communities interact with the host is unclear. We sought to understand the role of microbial products associated with alcohol dysbiosis in mice on intestinal permeability and immune activation in an in vitro model system. Methods Microbiota samples from binge‐on‐chronic alcohol‐fed and pair‐fed male and female mice were cultured in Gifu Anaerobic Broth for 24 hours under anaerobic conditions. Live/whole organisms were removed, and microbial products were collected and added to human peripheral blood mononuclear cells (PBMCs) or polarized C2BBe1 intestinal epithelial monolayers. Following stimulation, transepithelial electrical resistance (TEER) was measured using a volt/ohm meter and immune activation of PBMC was assessed via flow cytometry. Results Microbial products from male and female alcohol‐fed mice significantly decreased TEER (mean percentage change from baseline alcohol‐fed 0.86 Ω/cm2 vs. pair‐fed 1.10 Ω/cm2) compared to microbial products from control mice. Following ex vivo stimulation, immune activation of PBMC was assessed via flow cytometry. We found that microbial products from alcohol‐fed mice significantly increased the percentage of CD38+ CD4+ (mean alcohol‐fed 17.32% ± 0.683% standard deviation (SD) vs. mean pair‐fed 14.2% ± 1.21% SD, p 
ISSN:0145-6008
1530-0277
DOI:10.1111/acer.14176