Gut microbiota and metabolites drive chronic sickle cell disease pain in mice. Cell Host Microbe 2025 Oct 08;33(10):1703-1714.e8
Date
09/18/2025Pubmed ID
40961935Pubmed Central ID
PMC12448112DOI
10.1016/j.chom.2025.08.012Scopus ID
2-s2.0-105017711904 (requires institutional sign-in at Scopus site) 6 CitationsAbstract
Individuals with sickle cell disease (SCD) suffer from debilitating chronic pain that does not have a clear etiology. Recent 16S ribosomal RNA gene sequencing studies revealed gut dysbiosis in individuals with SCD. It is unclear, however, whether these intestinal microbial changes contribute to chronic SCD pain. Using transgenic SCD mice, we determined that chronic SCD pain is alleviated following fecal microbiota transplantation from healthy controls, specifically by increasing the relative abundance of probiotic Akkermansia muciniphila. Reciprocally, transplantation of the SCD gut microbiome induced persistent pain in wild-type recipients via bilirubin-vagus nerve TRPM2 signaling. Biospecimens from individuals with SCD and spatial transcriptomic analysis of human nodose ganglia tissue identified additional bacterial species and neuronally expressed transcripts that should be explored as novel SCD analgesic targets.
Author List
Brandow AM, Atkinson SN, Manjarres Z, Ehlers VL, Pratt ML, Mehta I, Mudunuri S, Kappagantu A, Shiers SI, Mazhar K, Simms MA, Alhendi S, Sheshadri A, Cervantes AM, Reese JC, Tavares-Ferreira D, Sankaranarayanan I, Schaub MK, Waltz TB, Hayward M, Rodríguez García DM, Dussor G, Salzman NH, Palmer KL, Stucky CL, Price TJ, Sadler KEAuthors
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 PhD, MD Center Director 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
MESH terms used to index this publication - Major topics in bold
Anemia, Sickle CellAnimals
Chronic Pain
Disease Models, Animal
Dysbiosis
Fecal Microbiota Transplantation
Female
Gastrointestinal Microbiome
Humans
Male
Mice
Mice, Transgenic
Probiotics
TRPM Cation Channels
Verrucomicrobia
