Intestinal Microbial Products From Alcohol-Fed Mice Contribute to Intestinal Permeability and Peripheral Immune Activation.
ADP-ribosyl Cyclase 1
/ immunology
Animals
Bacteria, Anaerobic
/ metabolism
Binge Drinking
/ metabolism
CD4 Antigens
/ immunology
Central Nervous System Depressants
/ pharmacology
Electric Impedance
Epithelial Cells
/ drug effects
Ethanol
/ pharmacology
Female
Gastrointestinal Microbiome
Immune System
/ drug effects
Intestinal Absorption
/ drug effects
Intestinal Mucosa
/ drug effects
Intestines
/ drug effects
Male
Mice
Mice, Inbred C57BL
Monocytes
/ drug effects
Permeability
/ drug effects
Alcohol
Dysbiosis
Immune Activation
Intestinal Permeability
Microbial Products
Journal
Alcoholism, clinical and experimental research
ISSN: 1530-0277
Titre abrégé: Alcohol Clin Exp Res
Pays: England
ID NLM: 7707242
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
03
05
2019
accepted:
08
08
2019
pubmed:
14
8
2019
medline:
29
9
2020
entrez:
14
8
2019
Statut:
ppublish
Résumé
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. 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. Microbial products from male and female alcohol-fed mice significantly decreased TEER (mean percentage change from baseline alcohol-fed 0.86 Ω/cm Collectively, these data suggest that microbial products contribute to immune activation and intestinal permeability associated with alcohol dysbiosis. Further, utilization of these ex vivo microbial product assays will allow us to rapidly assess the impact of microbial products on intestinal permeability and immune activation and to identify probiotic therapies to ameliorate these defects.
Sections du résumé
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/cm
CONCLUSIONS
Collectively, these data suggest that microbial products contribute to immune activation and intestinal permeability associated with alcohol dysbiosis. Further, utilization of these ex vivo microbial product assays will allow us to rapidly assess the impact of microbial products on intestinal permeability and immune activation and to identify probiotic therapies to ameliorate these defects.
Identifiants
pubmed: 31407808
doi: 10.1111/acer.14176
pmc: PMC6867691
mid: NIHMS1045971
doi:
Substances chimiques
CD4 Antigens
0
Central Nervous System Depressants
0
Ethanol
3K9958V90M
ADP-ribosyl Cyclase 1
EC 3.2.2.6
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2122-2133Subventions
Organisme : NIAAA NIH HHS
ID : K99 AA026336
Pays : United States
Organisme : NIAAA NIH HHS
ID : P60 AA009803
Pays : United States
Organisme : NIAAA NIH HHS
ID : R00 AA026336
Pays : United States
Organisme : NIGMS NIH HHS
ID : U54 GM104940
Pays : United States
Informations de copyright
© 2019 by the Research Society on Alcoholism.
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