Skip to main content
Top
Published in: Journal of Translational Medicine 1/2019

Open Access 01-12-2019 | Research

Intestinal injury and gut permeability in sickle cell disease

Authors: Dibyendu Dutta, Barbara Methe, Salomon Amar, Alison Morris, Seah H. Lim

Published in: Journal of Translational Medicine | Issue 1/2019

Login to get access

Abstract

Background

Due to recurrent hypoxia-reperfusion injury induced by vaso-occlusive crises (VOC), patients with sickle cell disease (SCD) may have intestinal injury and increased permeability. These may explain the qualitative and quantitative neutrophil abnormalities observed in these patients.

Methods

Serum intestinal fatty-acid binding protein (iFABP), lipopolysaccharides (LPS), and CD62L were measured by ELISA. Multicolor flow cytometry was used to measure circulating aged neutrophils.

Results

Compared to controls, SCD individuals had higher iFABP (median: 1.38 ng/ml vs 0.81 ng/ml; p = 0.04) and LPS (median: 2.15 μg/ml vs 0.69 μg/ml; p = 0.03), indicating intestinal injury and increased intestinal bacterial translocation into the systemic circulation. They also had higher soluble CD62L (median: 1.38 μg/ml vs 1.11 μg/ml; p = 0.04). Among SCD individuals, soluble CD62L correlated positively with circulating aged neutrophils (R = 0.7, p = 0.03) and LPS (R = 0.66, p = 0.027). Surprisingly, serum iFABP in SCD correlated negatively with both LPS (R = − 0.7, p = 0.02) and soluble CD62L (R = − 0.56, p = 0.08).

Conclusions

Since LPS translocation across the intestinal barrier may be due to increases in the intestinal bacterial density, gut permeability, or both, the negative correlations between iFABP and LPS, and CD62L raise the possibility that any damage-associated molecular patterns induced by intestinal injury may modulate the degree of bacterial translocation. Our results provide the first evidence of the presence of intestinal injury and increased gut permeability in SCD.
Literature
1.
go back to reference Gage TP, Gagnier JM. Ischemic colitis complicating sickle cell crisis. Gastroenterol. 1983;84:171–4. Gage TP, Gagnier JM. Ischemic colitis complicating sickle cell crisis. Gastroenterol. 1983;84:171–4.
2.
go back to reference Karim A, Ahmed S, Rossoff LJ, Siddiqui R, Fuchs A, Multz AS. Fulminant ischaemic colitis with atypical clinical features complicating sickle cell disease. Postgrad Med J. 2002;78:370–2.CrossRef Karim A, Ahmed S, Rossoff LJ, Siddiqui R, Fuchs A, Multz AS. Fulminant ischaemic colitis with atypical clinical features complicating sickle cell disease. Postgrad Med J. 2002;78:370–2.CrossRef
3.
go back to reference Green BT, Branch MS. Ischemic colitis in a young adult during sickle cell crisis: case report and review. Gastrointest Endosc. 2003;57:605–7.CrossRef Green BT, Branch MS. Ischemic colitis in a young adult during sickle cell crisis: case report and review. Gastrointest Endosc. 2003;57:605–7.CrossRef
4.
go back to reference de Chadarevian JP, Balarezo FS, Heggere M, Dampier C. Splenic arteries and veins in pediatric sickle cell disease. Pediatr Dev Pathol. 2001;4:538–44.CrossRef de Chadarevian JP, Balarezo FS, Heggere M, Dampier C. Splenic arteries and veins in pediatric sickle cell disease. Pediatr Dev Pathol. 2001;4:538–44.CrossRef
5.
go back to reference Lim SH, Morris A, Li K, Fitch AC, Fast L, Goldberg L, Quesenberry M, Sprinz P, Methé B. Intestinal microbiome analysis revealed dysbiosis in sickle cell disease. Am J Hematol. 2018;93:E91–3.CrossRef Lim SH, Morris A, Li K, Fitch AC, Fast L, Goldberg L, Quesenberry M, Sprinz P, Methé B. Intestinal microbiome analysis revealed dysbiosis in sickle cell disease. Am J Hematol. 2018;93:E91–3.CrossRef
6.
go back to reference Brim H, Vilmenay K, Atefi N, Abdul A, Daremipouran M, Lee EL, Gillevet PM, O’Neal P, Ashktorab H. Gut microbiome analysis reveals major dysbiosis in sickle cell diseases patients with a prevalence of Veillonella strains. Gastroenterol. 2017;152(Suppl. 1):S631.CrossRef Brim H, Vilmenay K, Atefi N, Abdul A, Daremipouran M, Lee EL, Gillevet PM, O’Neal P, Ashktorab H. Gut microbiome analysis reveals major dysbiosis in sickle cell diseases patients with a prevalence of Veillonella strains. Gastroenterol. 2017;152(Suppl. 1):S631.CrossRef
7.
go back to reference Moreno-Indias I, Torres M, Montserrat JM, Sanchez-Alcoholado L, Cardona F, Tinahones FJ, Gozal D, Poroyko VA, Navajas D, Queipo-Ortuño MI, Farré R. Intermittent hypoxia alters gut microbiota diversity in a mouse model of sleep apnoea. Eur Respir J. 2015;45:1055–65.CrossRef Moreno-Indias I, Torres M, Montserrat JM, Sanchez-Alcoholado L, Cardona F, Tinahones FJ, Gozal D, Poroyko VA, Navajas D, Queipo-Ortuño MI, Farré R. Intermittent hypoxia alters gut microbiota diversity in a mouse model of sleep apnoea. Eur Respir J. 2015;45:1055–65.CrossRef
8.
go back to reference Ahmed J, Kumar A, Jafri F, Batool S, Knoll B, Lim SH. Lower incidence of hospital-onset Clostridium difficile infection in sickle cell disease. N Engl J Med. 2019;380(9):887–8.CrossRef Ahmed J, Kumar A, Jafri F, Batool S, Knoll B, Lim SH. Lower incidence of hospital-onset Clostridium difficile infection in sickle cell disease. N Engl J Med. 2019;380(9):887–8.CrossRef
9.
go back to reference Lard LR, Mul FP, de Haas M, Roos D, Duits AJ. Neutrophil activation in sickle cell disease. J Leukoc Biol. 1999;66:411–5.CrossRef Lard LR, Mul FP, de Haas M, Roos D, Duits AJ. Neutrophil activation in sickle cell disease. J Leukoc Biol. 1999;66:411–5.CrossRef
10.
go back to reference Anyaegbu CC, Okpala IE, Akren’Ova YA, Salimonu LS. Peripheral blood neutrophil count and candidacidal activity correlate with the clinical severity of sickle cell anaemia (SCA). Eur J Haematol. 1998;60:267–8.CrossRef Anyaegbu CC, Okpala IE, Akren’Ova YA, Salimonu LS. Peripheral blood neutrophil count and candidacidal activity correlate with the clinical severity of sickle cell anaemia (SCA). Eur J Haematol. 1998;60:267–8.CrossRef
11.
go back to reference Lum AF, Wun T, Staunton D, Simon SI. Inflammatory potential of neutrophils detected in sickle cell disease. Am J Hematol. 2004;76:126–33.CrossRef Lum AF, Wun T, Staunton D, Simon SI. Inflammatory potential of neutrophils detected in sickle cell disease. Am J Hematol. 2004;76:126–33.CrossRef
12.
go back to reference Turhan A, Weiss LA, Mohandas N, Coller BS, Frenette PS. Primary role for adherent leukocytes in sickle cell vascular occlusion: a new paradigm. Proc Natl Acad Sci USA. 2002;99:3047–51.CrossRef Turhan A, Weiss LA, Mohandas N, Coller BS, Frenette PS. Primary role for adherent leukocytes in sickle cell vascular occlusion: a new paradigm. Proc Natl Acad Sci USA. 2002;99:3047–51.CrossRef
13.
go back to reference Zhang D, Chen G, Manwani D, Mortha A, Xu C, Faith JJ, Burk RD, Kunisaki Y, Jang JE, Scheiermann C, Merad M, Frenette PS. Neutrophil ageing is regulated by the microbiome. Nature. 2015;525:528–32.CrossRef Zhang D, Chen G, Manwani D, Mortha A, Xu C, Faith JJ, Burk RD, Kunisaki Y, Jang JE, Scheiermann C, Merad M, Frenette PS. Neutrophil ageing is regulated by the microbiome. Nature. 2015;525:528–32.CrossRef
14.
go back to reference Tartey S, Takeuchi O. Pathogen recognition and Toll-like receptor targeted therapeutics in innate immune cells. Int Rev Immunol. 2017;36:57–73.CrossRef Tartey S, Takeuchi O. Pathogen recognition and Toll-like receptor targeted therapeutics in innate immune cells. Int Rev Immunol. 2017;36:57–73.CrossRef
15.
go back to reference Wiens M, Korzhev M, Krasko A, Thakur NL, Perović-Ottstadt S, Breter HJ, Ushijima H, Diehl-Seifert B, Müller IM, Müller WE. Innate immune defense of the sponge Suberites domuncula against bacteria involves a MyD88-dependent signaling pathway Induction of a perforin-like molecule. J Biol Chem. 2005;280:27949–59.CrossRef Wiens M, Korzhev M, Krasko A, Thakur NL, Perović-Ottstadt S, Breter HJ, Ushijima H, Diehl-Seifert B, Müller IM, Müller WE. Innate immune defense of the sponge Suberites domuncula against bacteria involves a MyD88-dependent signaling pathway Induction of a perforin-like molecule. J Biol Chem. 2005;280:27949–59.CrossRef
16.
go back to reference Lim SH, Fast L, Morris A. Sickle cell vaso-occlusive crisis: it’s a gut feeling. J Transl Med. 2016;14:334.CrossRef Lim SH, Fast L, Morris A. Sickle cell vaso-occlusive crisis: it’s a gut feeling. J Transl Med. 2016;14:334.CrossRef
Metadata
Title
Intestinal injury and gut permeability in sickle cell disease
Authors
Dibyendu Dutta
Barbara Methe
Salomon Amar
Alison Morris
Seah H. Lim
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2019
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-019-1938-8

Other articles of this Issue 1/2019

Journal of Translational Medicine 1/2019 Go to the issue