Human Alcohol-Microbiota Mice have Increased Susceptibility to Bacterial Pneumonia

Authors

Kelly C. Cunningham, University of Nebraska Medical CenterFollow
Deandra R. Smith, University of Nebraska Medical CenterFollow
Daniel Villageliú, University of Nebraska Medical CenterFollow
Christi M. Ellis, University of Nebraska Medical Center
Amanda E. Ramer-Tait, University of Nebraska - LincolnFollow
Jeffrey D. Price, University of Nebraska-Lincoln
Todd A. Wyatt, University of Nebraska Medical Center, Nebraska-Western Iowa Health Care SystemFollow
Daren L. Knoell, University of Nebraska Medical CenterFollow
Patricia E. Molina, Louisiana State University Health Sciences Center
David A. Welsh, Louisiana State University Health Sciences Center
Derrick R. Samuelson, University of Nebraska Medical CenterFollow

Document Type

Article

Date of this Version

9-13-2023

Citation

Cunningham, K.C.; Smith, D.R.; Villageliú, D.N.; Ellis, C.M.; Ramer-Tait, A.E.; Price, J.D.;Wyatt, T.A.; Knoell, D.L.; Samuelson, M.M.; Molina, P.E.; et al. Human Alcohol-Microbiota Mice have Increased Susceptibility to Bacterial Pneumonia. Cells 2023, 12, 2267. https://doi.org/10.3390/ cells12182267

Comments

Open access.

Abstract

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 alcoholmicrobiota 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.