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

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.

[1]  Liping Xiao,et al.  Depletion of Intestinal Microbiome Partially Rescues Bone Loss in Sickle Cell Disease Male Mice , 2019, Scientific Reports.

[2]  B. Methé,et al.  Effects of rifaximin on circulating aged neutrophils in sickle cell disease , 2019, American journal of hematology.

[3]  B. Methé,et al.  Intestinal injury and gut permeability in sickle cell disease , 2019, Journal of Translational Medicine.

[4]  J. Dahlerup,et al.  Fecal Microbiota Transplantation Is Superior to Fidaxomicin for Treatment of Recurrent Clostridium difficile Infection. , 2019, Gastroenterology.

[5]  B. Methé,et al.  Elevated urinary 3‐indoxyl sulfate in sickle cell disease , 2019, American journal of hematology.

[6]  Seah H. Lim,et al.  Low Incidence of Hospital-Onset Clostridium difficile Infection in Sickle Cell Disease. , 2019, The New England journal of medicine.

[7]  M. Llinás,et al.  Identifying the Components of Acidosis in Patients With Severe Plasmodium falciparum Malaria Using Metabolomics , 2018, The Journal of infectious diseases.

[8]  David A. Williams,et al.  Flipping the Switch: Initial Results of Genetic Targeting of the Fetal to Adult Globin Switch in Sickle Cell Patients , 2018, Blood.

[9]  B. Methé,et al.  Invasive non-typhoidal Salmonella in sickle cell disease in Africa: is increased gut permeability the missing link? , 2018, Journal of Translational Medicine.

[10]  P. Oefner,et al.  Assessment of urinary 3-indoxyl sulfate as a marker for gut microbiota diversity and abundance of Clostridiales , 2018, Gut microbes.

[11]  Scott T. Miller,et al.  A Phase 3 Trial of l‐Glutamine in Sickle Cell Disease , 2018, The New England journal of medicine.

[12]  M. Fanucchi,et al.  Applicability of and potential barriers preventing allogeneic stem cell transplant in sickle cell patients treated outside a sickle cell program , 2018, American journal of hematology.

[13]  B. Methé,et al.  Intestinal microbiome analysis revealed dysbiosis in sickle cell disease , 2018, American journal of hematology.

[14]  H. T. Park,et al.  Akkermansia muciniphila-derived extracellular vesicles influence gut permeability through the regulation of tight junctions , 2018, Experimental & Molecular Medicine.

[15]  L. Wood,et al.  Short-chain fatty acids, prebiotics, synbiotics, and systemic inflammation: a systematic review and meta-analysis. , 2017, The American journal of clinical nutrition.

[16]  Edward L. Lee,et al.  GUT Microbiome Analysis Reveals Major Dysbiosis in Sickle Cell Diseases Patients with a Prevalence of Veillonella Strains , 2017 .

[17]  G. Veres,et al.  Gene Therapy in a Patient with Sickle Cell Disease: Brief Report , 2017, The New England journal of medicine.

[18]  K. Ataga,et al.  Crizanlizumab for the Prevention of Pain Crises in Sickle Cell Disease , 2017, The New England journal of medicine.

[19]  A. Sher,et al.  Sensing of the microbiota by NOD1 in mesenchymal stromal cells regulates murine hematopoiesis. , 2017, Blood.

[20]  Osamu Takeuchi,et al.  Pathogen recognition and Toll-like receptor targeted therapeutics in innate immune cells , 2017, International reviews of immunology.

[21]  Stephen P. Dearth,et al.  Composition of the gut microbiota modulates the severity of malaria , 2016, Proceedings of the National Academy of Sciences.

[22]  J. Faith,et al.  Neutrophil ageing is regulated by the microbiome , 2015, Nature.

[23]  H. Tilg,et al.  Intestinal permeability – a new target for disease prevention and therapy , 2014, BMC Gastroenterology.

[24]  A. Gorbach,et al.  Microvascular oxygen consumption during sickle cell pain crisis. , 2014, Blood.

[25]  Joseph A Hill United States Life Tables , 2013 .

[26]  M. Pimentel,et al.  Gastrointestinal bacterial overgrowth: pathogenesis and clinical significance , 2013, Therapeutic advances in chronic disease.

[27]  C. Haywood,et al.  Mortality Rates and Age at Death from Sickle Cell Disease: U.S., 1979–2005 , 2013, Public health reports.

[28]  Anand P. Patil,et al.  Global epidemiology of sickle haemoglobin in neonates: a contemporary geostatistical model-based map and population estimates , 2013, The Lancet.

[29]  C. Steiner,et al.  Acute care utilization and rehospitalizations for sickle cell disease. , 2010, JAMA.

[30]  C. Leevy,et al.  Rifaximin treatment in hepatic encephalopathy. , 2010, The New England journal of medicine.

[31]  E. Arias,et al.  United States life tables, 2005. , 2010, National vital statistics reports : from the Centers for Disease Control and Prevention, National Center for Health Statistics, National Vital Statistics System.

[32]  M. Telen,et al.  Cardiopulmonary complications leading to premature deaths in adult patients with sickle cell disease , 2009, American journal of hematology.

[33]  Ian R. Holzman,et al.  Butyrate enhances the intestinal barrier by facilitating tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers. , 2009, The Journal of nutrition.

[34]  D. Golan,et al.  Adherent leukocytes capture sickle erythrocytes in an in vitro flow model of vaso‐occlusion , 2007, American journal of hematology.

[35]  P. Arbogast,et al.  Medical care utilization and mortality in sickle cell disease: A population‐based study , 2005, American journal of hematology.

[36]  H. Ushijima,et al.  Innate Immune Defense of the Sponge Suberites domuncula against Bacteria Involves a MyD88-dependent Signaling Pathway , 2005, Journal of Biological Chemistry.

[37]  M. Sorror,et al.  Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. , 2005, Blood.

[38]  S. Simon,et al.  Inflammatory potential of neutrophils detected in sickle cell disease , 2004, American journal of hematology.

[39]  S. Dulchavsky,et al.  Enterocyte apoptosis and barrier function are modulated by SIgA after exposure to bacteria and hypoxia/reoxygenation. , 2003, Surgery.

[40]  P. Oliveira,et al.  Neutrophil activation by heme: implications for inflammatory processes. , 2002, Blood.

[41]  A. Duits,et al.  Neutrophil activation in sickle cell disease , 1999, Journal of leukocyte biology.

[42]  Scott T. Miller,et al.  Silent cerebral infarcts in sickle cell anemia: a risk factor analysis. The Cooperative Study of Sickle Cell Disease. , 1999, Pediatrics.

[43]  M L Terrin,et al.  Hydroxyurea and Sickle Cell Anemia Clinical Utility of a Myelosuppressive “Switching” Agent , 1996, Medicine.

[44]  O. Castro,et al.  The acute chest syndrome in sickle cell disease: incidence and risk factors. The Cooperative Study of Sickle Cell Disease. , 1994, Blood.

[45]  O. Platt,et al.  Mortality in sickle cell disease. Life expectancy and risk factors for early death. , 1994, The New England journal of medicine.

[46]  O. Agbai Anti-sickling effect of dietary thiocyanate in prophylactic control of sickle cell anemia. , 1986, Journal of the National Medical Association.

[47]  J. Davies,et al.  Gene Therapy in a Patient with Sickle Cell Disease. , 2017, The New England journal of medicine.