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. 2021 Aug 25;16(8):e0255956.
doi: 10.1371/journal.pone.0255956. eCollection 2021.

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

Hassan Brim  1 , James Taylor  1 , Muneer Abbas  1 , Kimberly Vilmenay  1 , Mohammad Daremipouran  1 , Sudhir Varma  2 , Edward Lee  1 , Betty Pace  3 , Waogwende L Song-Naba  4 , Kalpna Gupta  4   5   6 , Sergei Nekhai  1 , Patricia O'Neil  7 , Hassan Ashktorab  1
Affiliations

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

Hassan Brim et al. PLoS One. .

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.

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Conflict of interest statement

With regard to Dr. Sudhir Varma, the owner of HiThru Analytics, his main role in this study was to perform 16S rDNA Next Generation Sequencing data analysis and figures generation. This does not alter our adherence PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1
Differential bacterial Classes (A), Orders (B) and Families (C) between SCD subjects and healthy controls’ stool samples.
Fig 2
Fig 2. Differential OTUs between SCD subjects and healthy controls’ stool samples.
Fig 3
Fig 3
Differential bacterial Classes (A), Orders (B) and Families (C) between SCD subjects and healthy controls’ saliva samples.
Fig 4
Fig 4. Differential OTUs between SCD subjects and healthy controls’ saliva samples.
Fig 5
Fig 5
Differential bacterial Classes (A), Orders (B) and Families (C) between SS and AA Townes mice stool samples.
Fig 6
Fig 6. Differential OTUs between SS and AA townes mice stool samples.
See this image and copyright information in PMC

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