5595849 THE GUT MICROBIOME AND HYDROXYUREA EFFECT ON SICKLE CELL DISEASE CHILDREN FROM ANGOLA

Abstract

Background: Sickle cell disease (SCD) is an inherited hematological disorder and a serious global health problem, affecting between 20 and 25 million people worldwide [1]. In the Sub-Saharan Africa, where it is more prevalent, it contributes up to 90% of under-5 mortality [2]. Although hydroxyurea (HU) is the leading treatment for these patients, its effects on the gut microbiome have not yet been explored. Some studies reported that gastroenteritis events were less frequent in SCA children taking HU and it also significantly improved the survival from pneumococcal infections [3,4]. HU may have a protective effect, not only by improving several hematological parameters but also by lowering the risk of some bacterial infections. Aims: In this context, the aim of this study was to investigate this association by characterizing the gut microbiome of an Angolan SCA pediatric population before and after 6 months of HU treatment and comparing with a control group of healthy siblings. Results: A total of 113 fecal samples were obtained and sequenced by NGS for the 16S rRNA gene (V3-V4 regions), which corresponded to 40 children in the control and before HU groups and 33 after HU, aged between 4-12 years old. Our findings revealed that these three groups exhibit some notable differences, especially within Lachnospiraceae and Ruminococcaceae family. After HU treatment there was an increase of several beneficial bacteria, such as: Blautia coccoides (p=0.009), Blautia luti (p<0.001), Blautia faecis (p=0.008), Bifidobacterium longum (p=0.011), Dorea formicigenerans (p<0.001), Dorea massiliensis (p=0.003), Eubacterium halii (p=0.004), Elusimicrobium spp (p=0.032), Ruminococcus callidus (p=0.037), Ruminococcus faecis (p=0.012), Roseburia spp (p=0.050) and Subdoligranulum variabile (p=0.009). Most of those OTUs are SCFAs producing species, having butyrate or propionate as end-products of bacterial metabolism, both exhibiting anti-inflammatory properties. Moreover, children before HU had higher abundance of bacteria considered pathogenic, like E. coli (p=0.001), Clostridiun_g24 (p=0.039) and H. influenzae (p=0.050). Conclusion: Overall, this study provides the first evidence of the HU effect on the gut microbiome and provides a rationale for further research for developing treatments to reduce gut microbiota-driven inflammation, which may attenuate the dysbiosis and chronic symptoms experienced by these patients. This work was supported by FCT/Aga Khan (project nº330842553) and FCT/MCTES (UIDB/05608/2020 and UIDP/05608/2020) –H&TRC.