New research suggests that the gut microbiome plays a critical role in sickle cell disease (SCD). Researchers at Albert Einstein College of Medicine and Montefiore Health System, led by Paul Frenette, M.D., demonstrated that neutrophils, a type of white blood cell, become activated by gut microbes and stick to sickled red blood cells, causing vessel blockages.
Sickle cell disease is most common among individuals from sub-saharan Africa, the Caribbean, and South and Central America. There are around 100,000 cases in the United States, with the majority occurring among African American populations. SCD is a genetic disorder that produces abnormal hemoglobin, causing red blood cells to be sickle-shaped. The abnormally shaped red cells result in blood clots which cause pain and organ damage.
In 2002, Frenette reported that these blood clots often form when sickled red cells stick to neutrophils. In their current study, published in Nature, Frenette showed that activated, pro-inflammatory neutrophils interact with sickled red cells. Because neutrophils become activated in response to microbes, Frenette reasoned that sickled red cells might stick to neutrophils that were activated by the resident microbiome.
To test this idea, the team treated SCD mice with antibiotics to deplete their microbiome. They found a reduction in the activated neutrophils that cause clots, as well as a reduction in SCD-associated liver damage. They also found that children taking penicillin daily (SCD patients are at an increased risk for infections) had fewer activated, pro-inflammatory neutrophils than children not taking penicillin.
These findings suggest that antibiotics could help prevent the pain, blood clots, and eventual organ damage associated with SCD. This is good news for people with SCD, because such therapies could greatly improve their quality of life.
