source: Haematologica

year: 2020

authors: Philip Lee, Arpan A. Sinha, Vijaya L. Soma, Carlos Cruz, Tao Wang, Olga Aroniadis, Betsy C. Herold, Paul S. Frenette, David L. Goldman, and Deepa Manwani

Despite advances in the survival of pediatric patients with sickle cell disease (SCD), affected individuals continue to experience progressive end-organ damage, recurrent painful vaso-occlusive episodes (VOEs) and a shortened lifespan, highlighting the need for additional therapies. Recent animal and human studies suggest that antibiotic exposure may actually ameliorate the severity of SCD by altering the gastrointestinal microbiome. Specifically, depletion of intestinal microbiota by administration of broad-spectrum antibiotics significantly reduces the number of circulating pro-inflammatory, aged neutrophils and improves inflammation-related organ damage or endotoxin-induced septic shock in mouse models of SCD.

Further, routine administration of penicillin propylaxis to SCD patients up to 5 years of age has also been associated with a reduced percentage and absolute number of aged neutrophils. A recent murine study showed the dependence of stress-induced VOEs and inflammation on the gut microbiota, mediated by aged neutrophil expansion. These observations suggest that in addition to infection prevention, there may be a role for extended antibiotic “prophylaxis” to reduce SCD severity by modulating the gut microbiome to decrease inflammation.

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