Researchers from UT Dallas and the Medical College of Wisconsin (MCW) have identified the role of gut bacteria in sickle cell disease–related pain, focusing on Akkermansia muciniphila a bacterium often reduced in patients. In their study, chronic pain in mice with sickle cell disease was alleviated through fecal transplants from healthy mice, providing strong evidence that microbiome composition can influence pain. Sickle cell disease, a genetic disorder causing misshapen red blood cells that block blood flow, often leads to acute pain episodes, and notably, over 50% of patients also suffer from chronic pain.

Sadler explained that acute and chronic pain in sickle cell disease arise from different mechanisms, with the gut microbiome increasingly recognized as a key driver of chronic pain, as seen in conditions like fibromyalgia. The team’s research identified Akkermansia muciniphila a probiotic supplement available over the counter as a potential therapeutic target, since it produces short-chain fatty acids critical for easing pain. Transplanting this bacterium into sickle cell mice nearly eliminated their chronic pain, while transferring gut bacteria from sickle cell mice to healthy mice induced pain symptoms such as touch and cold sensitivity, despite the absence of the genetic disorder.

Sadler noted that altering the gut microbiome can stimulate intestinal nerve endings that relay signals to the central nervous system, leading to central sensitization a heightened sensitivity driven by changes in the brain or spinal cord. Since the gut microbiome naturally shifts with diet, age, lifestyle, medications, and environment, probiotics like Akkermansia may help manage these changes, though their long-term use might require rotation as gut bacteria adapt. The study, led by Dr. Amanda Brandow, professor of pediatrics and pediatric hematologist at MCW, reflects a long-standing collaboration between Brandow and Sadler since 2017.

Brandow emphasized that chronic sickle cell pain severely impacts patients quality of life, and these findings offer promising preclinical evidence to support future clinical trials using probiotics or fecal microbiota transplantation as novel treatments. Sadler added that developing a therapy targeting chronic pain could be life-changing especially since current options are limited gene therapy is costly, requires chemotherapy, and focuses mainly on acute rather than chronic pain. She noted that this approach represents an unexplored, potentially affordable alternative for patients who often face barriers to accessing effective pain management.

Source: https://news.utdallas.edu/health-medicine/chronic-sickle-cell-pain-study-2025/