Identifying differences in the gut microbiome among people with sickle cell disease, sickle cell trait and healthy control

Dr Balamurugan Ramadass, Additional Professor, Department of Biochemistry, AIIMS, Bhubaneswar;Dr Ranjeet Murthy, RMRC - ICMR, BhubaneswarTo investigate the differences in gut microbiome composition among individuals with sickle cell disease, sickle cell trait, and healthy controls. Sickle cell disease (SCD) results from a mutation in the beta-globin gene, leading to abnormal hemoglobin S, which causes red blood cells to assume a sickle shape under low oxygen conditions. Vaso-occlusive crises (VOCs) are painful episodes caused by blood vessel obstruction, leading to inflammation and organ damage. The gut microbiome may influence inflammation and immune responses, potentially affecting SCD severity and VOC frequency. Limited comparative studies exist on gut microbiome profiles across SCD, sickle cell trait, and healthy individuals, highlighting the need for this research. Stool samples were collected from participants, and DNA was extracted for 16S rRNA gene analysis using Oxford Nanopore technology. Taxonomic classification and operational taxonomic unit (OTU) clustering were performed to analyze microbial diversity. Bacteroides fragilis and Romboutsia spp. were enriched in the SCD group (SS), while Streptococcus spp. were more abundant in healthy controls (AA). Core microbiota analysis revealed distinct abundance patterns among the groups, with specific taxa showing significant differences. Alpha diversity metrics indicated lower observed OTUs in SS compared to AA. Beta diversity analysis demonstrated distinct microbial community structures between SS and AS groups, with 19 taxa identified as key contributors to these differences. Differential abundance analysis highlighted specific taxa enriched or depleted in each group, correlating certain bacteria with VOC frequency in SS patients. The study suggests that gut microbiome composition varies significantly among individuals with SCD, sickle cell trait, and healthy controls, potentially influencing disease severity and VOC episodes. Findings indicate a need for larger studies to confirm these results and explore the gut microbiome's role in SCD treatment and management. The research underscores the potential of the gut microbiome as a biomarker for SCD severity and a target for therapeutic interventions, such as probiotics and dietary modifications.