Elevated urinary 3‐indoxyl sulfate in sickle cell disease

Intestinal pathophysiological abnormalities in steady state and after vaso‐occlusive crisis in murine sickle cell disease

“…As patients with SCD showed elevated levels of urinary 3idoxyl sulphate without increased abundance of intestinal Clostridiales, 16 we postulated that SCD is associated with increased intestinal microbial density. To obtain direct confirmation, we next measured the bacterial 16S rRNA gene copy number in stool pellets from the mice.…”

Very low incidence of <i>Clostridioides difficile</i> infection in pediatric sickle cell disease patients

“…8,12,13 However, the low rates of CDI in both pediatric and adult SCD patients are consistent with the theory that SCD microbiome -likely due to changes in intestinal metabolome is potentially protective against C. difficile disease. 10,14,15 It is hypothesized that hypoxia-reperfusion injury in SCD alters intestinal microbiota and use of opioids impairs intestinal motility, both leading to bacterial overgrowth and subsequently increased concentrations of intestinal butyrate which inhibits the proliferation of C. difficile. 14 The bacterial overgrowth due to opioids may also play a role in reducing the risks for hospital-onset CDI by creating a tight microbial biofilm which depletes spatial opportunity for the colonization and proliferation of C. difficile.…”

“…10,14,15 It is hypothesized that hypoxia-reperfusion injury in SCD alters intestinal microbiota and use of opioids impairs intestinal motility, both leading to bacterial overgrowth and subsequently increased concentrations of intestinal butyrate which inhibits the proliferation of C. difficile. 14 The bacterial overgrowth due to opioids may also play a role in reducing the risks for hospital-onset CDI by creating a tight microbial biofilm which depletes spatial opportunity for the colonization and proliferation of C. difficile. 14 Another potential hypothesis is hemoglobin S induced right shift of the oxygen-hemoglobin dissociation curve leading to increased oxygen availability which may inhibit the proliferation of C. difficile.…”

“…14 The bacterial overgrowth due to opioids may also play a role in reducing the risks for hospital-onset CDI by creating a tight microbial biofilm which depletes spatial opportunity for the colonization and proliferation of C. difficile. 14 Another potential hypothesis is hemoglobin S induced right shift of the oxygen-hemoglobin dissociation curve leading to increased oxygen availability which may inhibit the proliferation of C. difficile. 8 One study limitation was our inability to review charts for all non-SCD patients identified as having C. difficile infection.…”

Intestinal pathophysiological and microbial changes in sickle cell disease: Potential targets for therapeutic intervention

“…Although direct evidence showing a similar increase in the intestinal microbial density in SCD patients is lacking, two observations would support the similarity. Our group has found that SCD patients had higher urinary 3‐indoxyl sulphate (3‐IS) (Dutta et al , ). Intestinal 3‐IS is a metabolite of tryptophan generated by indole‐producing microbes and it promotes the proliferation of intestinal Clostridiales (Farowski et al , ).…”