Human Alcohol-Microbiota Mice have Increased Susceptibility to Bacterial Pneumonia

Author:

Cunningham Kelly C.1,Smith Deandra R.2,Villageliú Daniel N.1,Ellis Christi M.1,Ramer-Tait Amanda E.34ORCID,Price Jeffrey D.34,Wyatt Todd A.156,Knoell Daren L.12ORCID,Samuelson Mystera M.57ORCID,Molina Patricia E.8ORCID,Welsh David A.9,Samuelson Derrick R.14ORCID

Affiliation:

1. Department of Internal Medicine-Pulmonary Division, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA

2. Department of Pharmacy Practice and Science, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198, USA

3. Department of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, NE 68588, USA

4. Nebraska Food for Health Center, University of Nebraska-Lincoln, Lincoln, NE 68588, USA

5. Department of Environmental, Agricultural and Occupational Health, College of Public Health, University of Nebraska Medical Center, Omaha, NE 68198, USA

6. Department of Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68198, USA

7. Animal Behavior Core, University of Nebraska Medical Center, Omaha, NE 68198, USA

8. Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA

9. Department of Internal Medicine, Section of Pulmonary/Critical Care & Allergy/Immunology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA

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 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.

Funder

National Institutes of Health

Publisher

MDPI AG

Subject

General Medicine

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