Human Alcohol-Microbiota Mice have Increased Susceptibility to Bacterial Pneumonia

Area of Science:

• Microbiology and Immunology
• Gastroenterology
• Toxicology

Background:

• Chronic alcohol abuse is linked to gastrointestinal microbiota alterations, impacting behavior, physiology, and immunity.
• Previous studies faced limitations in assessing direct effects of alcohol-associated gut dysbiosis.
• Understanding alcohol's impact on the gut microbiome is crucial for addressing alcohol-related disorders.

Purpose of the Study:

• To systematically evaluate the immunological effects of chronic alcohol abuse mediated by intestinal dysbiosis.
• To develop and utilize a humanized alcohol-microbiota mouse model for this investigation.

Main Methods:

• Germ-free mice were colonized with human fecal microbiota from individuals with high and low Alcohol Use Disorders Identification Test (AUDIT) scores.
• Fecal microbiota transplantation generated human alcohol-associated microbiota and human control-microbiota F1 progenies.
• Assessed susceptibility to *Klebsiella pneumoniae* and *Streptococcus pneumoniae* pneumonia in F1 offspring.

Main Results:

• F1 offspring with microbiota from high AUDIT individuals showed increased mortality rates from pneumonia.
• Pulmonary bacterial burden and post-infection lung damage were significantly higher in these mice.
• Alcohol-induced gut dysbiosis exacerbates susceptibility to bacterial pneumonia.

Conclusions:

• Alcohol-induced gut dysbiosis plays a critical role in the immunological consequences of chronic alcohol abuse.
• The humanized alcohol-microbiota mouse model effectively demonstrates the link between dysbiosis and increased infection susceptibility.
• Investigating alcohol-related disorders requires consideration of both direct alcohol effects and alcohol-induced dysbiosis for effective treatment strategies.