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

Authors

Hassan Brim, The Center For Sickle Cell Disease
James Taylor, The Center For Sickle Cell Disease
Muneer Abbas, The Center For Sickle Cell Disease
Kimberly Vilmenay, The Center For Sickle Cell Disease
Mohammad Daremipouran, The Center For Sickle Cell Disease
Sudhir Varma, HiThru Analytics
Edward Lee, The Center For Sickle Cell Disease
Betty Pace, Augusta State University
Waogwende L. Song-Naba, University of Minnesota Twin Cities
Kalpna Gupta, University of Minnesota Twin Cities
Sergei Nekhai, The Center For Sickle Cell Disease
Patricia O’Neil, Food and Drug Administration
Hassan Ashktorab, The Center For Sickle Cell Disease

Document Type

Article

Publication Date

8-1-2021

Abstract

Background Sickle Cell Disease (SCD) is an inherited blood disorder that leads to hemolytic anemia, pain, organ damage and early mortality. It is characterized by polymerized deoxygenated hemoglobin, rigid sickle red blood cells and vaso-occlusive crises (VOC). Recurrent hypoxia-reperfusion injury in the gut of SCD patients could increase tissue injury, permeability, and bacterial translocation. In this context, the gut microbiome, a major player in health and disease, might have significant impact. This study sought to characterize the gut microbiome in SCD. Methods Stool and saliva samples were collected from healthy controls (n = 14) and SCD subjects (n = 14). Stool samples were also collected from humanized SCD murine models including Berk, Townes and corresponding control mice. Amplified 16S rDNA was used for bacterial composition analysis using Next Generation Sequencing (NGS). Pairwise group analyses established differential bacterial groups at many taxonomy levels. Bacterial group abundance and differentials were established using DeSeq software. Results A major dysbiosis was observed in SCD patients. The Firmicutes/Bacteroidetes ratio was lower in these patients. The following bacterial families were more abundant in SCD patients: Acetobacteraceae, Acidaminococcaceae, Candidatus Saccharibacteria, Peptostreptococcaceae, Bifidobacteriaceae, Veillonellaceae, Actinomycetaceae, Clostridiales, Bacteroidacbactereae and Fusobacteriaceae. This dysbiosis translated into 420 different operational taxonomic units (OTUs). Townes SCD mice also displayed gut microbiome dysbiosis as seen in human SCD. Conclusion A major dysbiosis was observed in SCD patients for bacteria that are known strong pro-inflammatory triggers. The Townes mouse showed dysbiosis as well and might serve as a good model to study gut microbiome modulation and its impact on SCD pathophysiology.

Recommended Citation

Brim, Hassan; Taylor, James; Abbas, Muneer; Vilmenay, Kimberly; Daremipouran, Mohammad; Varma, Sudhir; Lee, Edward; Pace, Betty; Song-Naba, Waogwende L.; Gupta, Kalpna; Nekhai, Sergei; O’Neil, Patricia; and Ashktorab, Hassan, "The gut microbiome in sickle cell disease: Characterization and potential implications" (2021). The Center For Sickle Cell Disease Faculty Publications. 3.
https://dh.howard.edu/sicklecell_fac/3