Intestinal pathophysiological and microbial changes in sickle cell disease: Potential targets for therapeutic intervention

Abstract

Summary There is a large therapeutic gap in the treatment of sickle cell disease (SCD). Recent studies demonstrated the presence of pathophysiological and microbial changes in the intestine of patients with SCD. The intestinal microbes have also been found to regulate neutrophil ageing and possible basal activation of circulating neutrophils. Both aged and activated neutrophils are pivotal for the pathogenesis of vaso‐occlusive crisis in SCD. In this paper, we will provide an overview of the intestinal pathophysiological and microbial changes in SCD. Based on these changes, we will propose therapeutic approaches that could be investigated for treating SCD.

The gut microbiome in sickle cell disease: Characterization and potential implications

“…The cross talk between the microbiota and the immune system, and more specifically the neutrophils within innate immunity, adjusts the magnitude of neutrophil-mediated inflammation on challenge while preventing neutrophil responses against commensals and allowing opportunistic pathogens to flourish [ 43 ]. More specifically to the context of SCD, the gut microbiota is reported to affect neutrophil ageing activation processes that play major roles in vaso-occlusive crises in these patients [ 44 ]. Studies correlating gut microbiota composition and specific immune signatures are needed to further shed light on these correlations.…”

Rifaximin on intestinally‐related pathologic changes in sickle cell disease

“…Although sickling is a prerequisite for the development of VOC, the dissociation between the number of sickled erythrocytes observed on the peripheral blood smear and symptoms of VOC suggests that, in addition to sickled erythrocytes, certain co-factors are needed for the pathogenesis of VOC. 1 Many clinical and laboratory observations have implicated neutrophils as one of the co-factors. These observations include higher baseline white cell counts (WBCs) S1 , and higher risks for stroke S2 , acute chest syndrome S3 , and premature death S4 in those with a WBC >15 × 10 9 /L.…”

Vaso-occlusive crisis in sickle cell disease: a vicious cycle of secondary events

“…Phases 2/3 are not always followed by Phase 4. Instead, these phases may feedback into Phase 1 to create a vicious cycle of VOC that we previously proposed [ 7 ]. Examples supporting this notion are seen in the prolonged hospital length-of-stay (LOS) beyond the average of five days for an episode of VOC [ 8 ] in many patients, the development of worsening symptoms, and the onset of acute chest syndrome during hospital stay.…”