Human Alcohol-Microbiota Mice have Increased Susceptibility to Bacterial Pneumonia
Kelly C. Cunningham,
Deandra R. Smith,
Daniel N. Villageliú,
Christi M. Ellis,
Amanda E. Ramer-Tait,
Jeffrey D. Price,
Todd A. Wyatt,
Daren L. Knoell,
Mystera M. Samuelson,
Patricia E. Molina,
David A. Welsh,
Derrick R. Samuelson
Affiliations
Kelly C. Cunningham
Department of Internal Medicine-Pulmonary Division, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA
Deandra R. Smith
Department of Pharmacy Practice and Science, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198, USA
Daniel N. Villageliú
Department of Internal Medicine-Pulmonary Division, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA
Christi M. Ellis
Department of Internal Medicine-Pulmonary Division, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA
Amanda E. Ramer-Tait
Department of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, NE 68588, USA
Jeffrey D. Price
Department of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, NE 68588, USA
Todd A. Wyatt
Department of Internal Medicine-Pulmonary Division, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA
Daren L. Knoell
Department of Internal Medicine-Pulmonary Division, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA
Mystera M. Samuelson
Department of Environmental, Agricultural and Occupational Health, College of Public Health, University of Nebraska Medical Center, Omaha, NE 68198, USA
Patricia E. Molina
Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
David A. Welsh
Department of Internal Medicine, Section of Pulmonary/Critical Care & Allergy/Immunology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
Derrick R. Samuelson
Department of Internal Medicine-Pulmonary Division, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA
Preclinical studies have shown that chronic alcohol abuse leads to alterations in the gastrointestinal microbiota that are associated with behavior changes, physiological alterations, and immunological effects. However, such studies have been limited in their ability to evaluate the direct effects of alcohol-associated dysbiosis. To address this, we developed a humanized alcohol-microbiota mouse model to systematically evaluate the immunological effects of chronic alcohol abuse mediated by intestinal dysbiosis. Germ-free mice were colonized with human fecal microbiota from individuals with high and low Alcohol Use Disorders Identification Test (AUDIT) scores and bred to produce human alcohol-associated microbiota or human control-microbiota F1 progenies. F1 offspring colonized with fecal microbiota from individuals with high AUDIT scores had increased susceptibility to Klebsiella pneumoniae and Streptococcus pneumoniae pneumonia, as determined by increased mortality rates, pulmonary bacterial burden, and post-infection lung damage. These findings highlight the importance of considering both the direct effects of alcohol and alcohol-induced dysbiosis when investigating the mechanisms behind alcohol-related disorders and treatment strategies.
