Gut microbiota and metabolites have been implicated in driving chronic pain in sickle cell disease (SCD), according to a study published in bioRvix. 

The resulting multisystemic damage caused by deformed erythrocytes is the main contributor to SCD pain. Some scientists hypothesize that gut microbiota and metabolites may likewise play a role in driving pain; this is based on the idea that inflammatory metabolic products may influence the environments in which intestinal microbiota reside. In addition, the standard practice of administering penicillin from birth to 6 years of age as prophylaxis against pneumococcal sepsis furnish further evidence that patients with SCD may have altered gut bacteria. 

Recent studies demonstrate that patients with SCD have differences in the number and type of bacteria in their fecal material compared with healthy individuals. This indicates that gut dysbiosis is a feature of SCD; it does not, however, address the question regarding its role in driving SCD pain. 

To investigate this issue further, the authors of the study conducted studies on transgenic SCD mice. The research team manipulated the gut microbiota of both SCD and wild-type mice via fecal material transplant. They found that fecal content excreted by SCD mice induced chronic pain when administered orally to wild-type mice, indicating that gut microbiome plays a role in driving pain in SCD. 

Read more about SCD etiology 

Further studies involving transgenic sickle cell mice revealed bilirubin to be a possible metabolite that drives SCD pain via the altering of vagus nerve activity. The research team also discovered that chronic SCD pain can be alleviated via the administration of Akkermansia mucinophila probiotic, thus implicating this gut bacteria in driving sickle cell pain. 

“In summary, these studies highlight the gut microbiome as a novel intervention site for chronic sickle cell disease pain management,” the authors concluded. 


Sadler KE, Atkinson SN, Ehlers VL, et al. Gut microbiota and metabolites drive chronic sickle cell disease painbioRxiv. Published online April 28, 2023. doi:10.1101/2023.04.25.538342