Presentation Title

Manipulation of the Gut Microbiome: Influencing alcohol-induced neuroinflammation

Presenter Information

Greg HavtonFollow

Faculty Mentor

Daryl Davies, Lisa Asatryan, Rachel Reyes

Start Date

23-11-2019 8:00 AM

End Date

23-11-2019 8:45 AM

Location

103

Session

poster 1

Type of Presentation

Poster

Subject Area

biological_agricultural_sciences

Abstract

Alcohol Use Disorder (AUD) is responsible for 5.9% of all global deaths and is characterized by CNS intoxication symptoms, impaired brain activity, poor motor coordination, and behavioral changes due to alcohol’s effect. Persistent exposure to alcohol can also affect immune response and enteric microbiome compositions. Circulating endotoxins and increased inflammatory cytokines secreted by toll-like receptors (TLR) have been observed in alcoholics and within animal models of alcohol exposure. Ethanol can promote signaling on astrocyte membranes through TLRs. These receptors activate a transcription factor for production of pro-inflammatory cytokines called NF-κβ, chemokines, and reactive oxygen species. It is important to investigate additional mechanisms for new potential AUD treatments to identify novel targets. Therefore, we are investigating the role of the microbiome on alcohol-induced behaviors and neuroinflammation.

In this study, we treated mice to disrupt the microbiome composition using non-absorbable, broad-spectrum antibiotics as a cocktail (Bacitracin, Neomycin, Vancomycin, and Pimaricin). Three experimental groups and one control were used in a “Drinking in the Dark” Module to test this hypothesis over a four week period. After treatment, immunohistochemistry and microscopy were used to look at the dentate gyrus, radiatum layer of the hippocampus, to look at glial fibrillary acidic protein (GFAP)-labeled astrocytes.

Antibiotic treatment corresponded with an increase in alcohol consumption, which also marked a decrease in GFAP+ astrocyte density compared to controls. The disruption in the microbiome with increased alcohol consumption and subsequent reduction in astrocytic-protection supports maintaining a healthy microbiome. With this, observations have suggested the microbiome as a potential target against the detrimental effects of alcohol abuse on the brain.

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Nov 23rd, 8:00 AM Nov 23rd, 8:45 AM

Manipulation of the Gut Microbiome: Influencing alcohol-induced neuroinflammation

103

Alcohol Use Disorder (AUD) is responsible for 5.9% of all global deaths and is characterized by CNS intoxication symptoms, impaired brain activity, poor motor coordination, and behavioral changes due to alcohol’s effect. Persistent exposure to alcohol can also affect immune response and enteric microbiome compositions. Circulating endotoxins and increased inflammatory cytokines secreted by toll-like receptors (TLR) have been observed in alcoholics and within animal models of alcohol exposure. Ethanol can promote signaling on astrocyte membranes through TLRs. These receptors activate a transcription factor for production of pro-inflammatory cytokines called NF-κβ, chemokines, and reactive oxygen species. It is important to investigate additional mechanisms for new potential AUD treatments to identify novel targets. Therefore, we are investigating the role of the microbiome on alcohol-induced behaviors and neuroinflammation.

In this study, we treated mice to disrupt the microbiome composition using non-absorbable, broad-spectrum antibiotics as a cocktail (Bacitracin, Neomycin, Vancomycin, and Pimaricin). Three experimental groups and one control were used in a “Drinking in the Dark” Module to test this hypothesis over a four week period. After treatment, immunohistochemistry and microscopy were used to look at the dentate gyrus, radiatum layer of the hippocampus, to look at glial fibrillary acidic protein (GFAP)-labeled astrocytes.

Antibiotic treatment corresponded with an increase in alcohol consumption, which also marked a decrease in GFAP+ astrocyte density compared to controls. The disruption in the microbiome with increased alcohol consumption and subsequent reduction in astrocytic-protection supports maintaining a healthy microbiome. With this, observations have suggested the microbiome as a potential target against the detrimental effects of alcohol abuse on the brain.