Gut microbiota and metabolites drive chronic sickle cell disease pain. bioRxiv 2023 Apr 28
Date
05/10/2023Pubmed ID
37163080Pubmed Central ID
PMC10168372DOI
10.1101/2023.04.25.538342Abstract
Pain is a debilitating symptom and leading reason for hospitalization of individuals with sickle cell disease. Chronic sickle cell pain is poorly managed because the biological basis is not fully understood. Using transgenic sickle cell mice and fecal material transplant, we determined that the gut microbiome drives persistent sickle cell pain. In parallel patient and mouse analyses, we identified bilirubin as one metabolite that induces sickle cell pain by altering vagus nerve activity. Furthermore, we determined that decreased abundance of the gut bacteria Akkermansia mucinophila is a critical driver of chronic sickle cell pain. These experiments demonstrate that the sickle cell gut microbiome drives chronic widespread pain and identify bacterial species and metabolites that should be targeted for chronic sickle cell disease pain management.
Author List
Sadler KE, Atkinson SN, Ehlers VL, Waltz TB, Hayward M, Rodríguez García DM, Salzman NH, Stucky CL, Brandow AMAuthors
Samantha N. Atkinson PhD Bioinformatics Analyst III in the Microbiology and Immunology department at Medical College of WisconsinAmanda Brandow DO Professor in the Pediatrics department at Medical College of Wisconsin
Nita H. Salzman MD, PhD Director, Professor in the Pediatrics department at Medical College of Wisconsin
Cheryl L. Stucky PhD Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin
