Brandow Amanda M, Atkinson Samantha N, Manjarres Zulmary, Ehlers Vanessa L, Pratt McKenna L, Mehta Iti, Mudunuri Sruthi, Kappagantu Aishwarya, Shiers Stephanie I, Mazhar Khadijah, Simms Mackenzie A, Alhendi Sahar, Sheshadri Anagha, Cervantes Anna M, Reese Jeffrey C, Tavares-Ferreira Diana, Sankaranarayanan Ishwarya, Schaub Mandee K, Waltz Tyler B, Hayward Michael, Rodríguez García Dianise M, Dussor Gregory, Salzman Nita H, Palmer Kelli L, Stucky Cheryl L, Price Theodore J, Sadler Katelyn E
Department of Pediatrics, Division of Hematology/Oncology, Bone Marrow Transplantation, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Center for Microbiome Research, Medical College of Wisconsin, Milwaukee, WI 53226, USA; Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Cell Host Microbe. 2025 Sep 16. doi: 10.1016/j.chom.2025.08.012.
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.
患有镰状细胞病（SCD）的个体遭受着病因不明的使人衰弱的慢性疼痛。最近的16S核糖体RNA基因测序研究揭示了SCD患者的肠道菌群失调。然而，尚不清楚这些肠道微生物变化是否会导致SCD慢性疼痛。通过使用转基因SCD小鼠，我们确定，从健康对照进行粪便微生物群移植后，SCD慢性疼痛得到缓解，具体是通过增加益生菌嗜黏蛋白阿克曼氏菌的相对丰度来实现的。相反，SCD肠道微生物群的移植通过胆红素-迷走神经TRPM2信号传导在野生型受体中诱发了持续性疼痛。来自SCD个体的生物标本以及对人结节神经节组织的空间转录组分析确定了其他细菌种类和神经元表达的转录本，这些应作为新型SCD镇痛靶点进行探索。
