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

• Published in: PloS one Vol. 16; no. 8; p. e0255956
• Main Authors: 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, Ashktorab, Hassan
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 25-08-2021; Public Library of Science (PLoS)
• Subjects: Adult; African Americans; Analysis; Anemia; Anemia, Sickle Cell - epidemiology; Anemia, Sickle Cell - microbiology; Animal models; Animals; Antibiotics; Bacteria; Bacteria - isolation & purification; Bar codes; Biology and Life Sciences; Blood; Blood cells; Cancer; Care and treatment; Case-Control Studies; Computer and Information Sciences; Data processing; Deoxygenation; Diagnosis; Differentials; Digestive system; Dysbacteriosis; Dysbiosis; Dysbiosis - complications; Dysbiosis - microbiology; Erythrocytes; Female; Gastrointestinal Microbiome; Health aspects; Hematology; Hemoglobin; Hemolytic anemia; Hospitalization; Humans; Hypoxia; Identification and classification; Inflammation; Intestinal microflora; Male; Medical schools; Medicine; Medicine and Health Sciences; Mice; Microbiomes; Microbiota; Microbiota (Symbiotic organisms); Middle Aged; Mutation; Next-generation sequencing; Nosocomial infections; Observations; Oncology; Pain; Pathology; Permeability; Prevention; Reperfusion; Reperfusion injury; Research and Analysis Methods; Risk factors; rRNA 16S; Saliva; Sickle cell anemia; Sickle cell disease; Taxonomy; Translocation; Young Adult; United States; Minneapolis Minnesota; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0255956

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.
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.
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.
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.