Exploring the Mediterranean Diet as A Promising Approach for Alleviating Chronic Pain in Sickle Cell Disease

Abstract Sickle cell disease (SCD) affects more than 100,000 people in the United States and causes a significant burden to affected individuals, their families, and national healthcare systems. Pain is the hallmark symptom of SCD, and such pain is frequently poorly managed and adversely affects coping and psychological well-being as well as health-related quality of life. In a mouse model of SCD our team showed that the gut microbiome plays a prominent role in pain. The composition of gut microbial communities and their metabolic function is dynamic and modifiable, making it a prime therapeutic target for reducing pain in SCD. A Mediterranean diet (MedDiet) has anti-inflammatory, antioxidant, and pain-relieving benefits, with positive effects on the gut microbiome in non-SCD populations. While diet is thus viewed as critical for managing SCD and its severity, there is a shocking lack of studies examining diet as an approach to managing SCD symptoms including pain. In this R21, we propose to conduct a randomized crossover study of a 4-week MedDiet compared to usual diet (control) among 24 adults with SCD and chronic pain (30 will be recruited). The aim of the feeding study is to explore the effect of a MedDiet compared to usual diet in altering the gut microbiota and microbial metabolites and reducing chronic pain. We will collect blood and stool samples throughout. We will also apply a reverse translational approach: transplanting fecal samples from the human participants before and after the MedDiet intervention to sex concordant SCD mice. The goal of this aim is to investigate the role of diet-induced changes in gut microbiota in altering the metabolic profile and sensitivity to pain by evaluating fecal microbiota transplant of human samples to SCD mice. We will apply an interdisciplinary approach with a high probability of success due to our team of highly productive investigators, who bring expertise in hematology, pain management, nutrition, basic pain neurobiology, pharmacology, microbiome research in both human and mouse models, and clinical care in SCD management. In the future, we anticipate further testing and broadly disseminating evidence of the effectiveness of a MedDiet for mitigating chronic pain in SCD and understanding its underlying mechanisms for a high national public health impact.