Gut Diversity Could Yield Better Treatments for Sickle Cell Disease

Hassan Brim, PhD

A better understanding on gut microbiota could result in an improvement in pain therapies for patients with sickle cell disease (SCD).

A team, led by Hassan Brim, PhD, Department of Pathology, Department of Medicine, Cancer Center, Microbiology and Center for Sickle Cell Disease, Howard University College of Medicine, characterized the gut microbiome in patients with sickle cell disease.

For children with vaso-occlusive crises, antibiotic prophylaxis is often prescribed to reduce hospitalizations and mortality. However, antibiotic administration for patients younger than 5 years can often alter gut microbiome diversity and composition because of both antibiotic effects and subclinical bowel ischemia caused by the sickle cell disease.

“The gut microbiome is the most consequential microbiome in our body,” the authors wrote. “Multiple studies highlighted its central role in many systemic processes that can affect some of the pathophysiological features of SCD.”

Advancements in technology have made exploring gut microbiota structure and identifying its composition a possibility.

The Study

Patients with sickle cell disease are at an increased risk of tissue injuries, permeability, and bacterial translocation due to recurrent hypoxia-reperfusion injuries.

However, a better understanding on gut microbiome could have a significant impact on disease course.

The investigators collected stool and saliva samples from both health controls (n = 14) and patients with sickle cell disease (n = 14) between 22-57 years. The team used Next Generation Sequencing (NGS) to analyze the bacterial composition of amplified 16S rDNA.

They also established differential bacterial groups at many taxonomy levels using pairwise group analyses and established bacterial group abundance and differentials using DeSeq software.

Bacterial Families

A major dysbiosis stood out for patients with sickle cell disease, where the Firmicutes/Bacteroidetes ratio was lower. This could be an important indicator of gut microbiota homeostasis, where the stool ratio for the control group was 1.00004, compared to the ratio for the sickle cell group of 0.65801 (P = 0.0212).

The abundance analysis of the stool samples revealed that the 2 groups were significantly different for 10 out of the 24 bacterial classes and the DeSeq analysis showed that 4 of the 10 classes were more prevalent in patients with sickle cell disease, including Saccharribacteria, Negativicutes, Actinobacteria, and Bacteroidia.

Bacilli, Deltaproteobacteria, Entisphaeria, Spirochaetia, Methanobacteria and Opitutae were less abundant in patients with sickle cell disease.

The differences at the class level translated into differences in 11 of 31 bacterial Orders more abundant in the sickle cell disease group and hodospirillales, Candidatus Saccharibacteria, Bifidobacteriales and Selenomonadales, while Pasteurellales, Desulfovribrionales, Bacillales, Victivallales, Spirochaetales, Methanobacteriales and Opitutales were more abundant in the controls.

Acetobacteraceae, Acidaminococcaceae, Candidatus Saccharibacteria, Peptostreptococcaceae, Bifidobacteriaceae, Veillonellaceae, Actinomycetaceae, Clostridiales, Bacteroidacbactereae and Fusobacteriaceae were also families more abundant in patients with sickle cell disease.

Overall, the dysbiosis translated into 420 different operational taxonomic units (OTUs).

“A major dysbiosis was observed in SCD patients for bacteria that are known strong pro-inflammatory triggers,” the authors wrote. “We have generated a descriptive analysis of the gut microbiome in adults with SCD which suggests a major dysbiosis at higher taxonomy levels.”

The study, “The gut microbiome in sickle cell disease: Characterization and potential implications,” was published online in PLOS One.