Intestinal Integrity Biomarkers in Early Antiretroviral-Treated Perinatally HIV-1–Infected Infants

Abstract

Intestinal fatty acid binding protein (iFABP) levels did not differ between human immunodeficiency virus type 1 (HIV-1)- infected infants and uninfected infants exposed to HIV-1, but those who breastfed had substantially lower levels. Zonulin levels increased from 3 to 5.3 months of age with perinatal acquisition of HIV-1 despite early antiretroviral treatment. Biomarkers of intestinal integrity (ie, iFABP and zonulin) were compared in 56 HIV-1-positive African infants who received early antiretroviral treatment and 53 HIV-1-exposed but uninfected (HEU) controls. Despite heightened inflammation and immune activation in HIV-positive infants, iFABP and zonulin levels at 3 months of age were not different from those in HEU infants and largely were not correlated with inflammatory and immune activation biomarkers. However, zonulin levels increased and became significantly higher in HIV-positive infants as compared to HEU infants by 5 months of age, despite viral suppression due to antiretroviral treatment. These findings have implications for intestinal integrity biomarker profiling in perinatal HIV-1 infection.

Interleukin‐10 and Zonulin Are Associated With Postoperative Delayed Gastric Emptying in Critically Ill Surgical Pediatric Patients: A Prospective Pilot Study

“…The correlation between delayed gastric emptying and elevated levels of IL‐10 is consistent with previous literature on IL‐10 and GI homeostasis, including gut barrier integrity and GI motility 33‐36 . An inverse relationship between IL‐10 and zonulin has also been previously reported, though not in critically ill patients 30,37 . Few studies have examined zonulin and gastric emptying or the relationship between IL‐10, zonulin, and gastric emptying, and results vary among existing studies 6,32,38,39 .…”

“…Pediatric studies examining zonulin levels have not included critically ill patients and have focused on patients with chronic inflammatory conditions. [28][29][30] In addition to differences in the study population, our study examined zonulin at 2 time points, allowing for an assessment of zonulin under 2 conditions for the same patient, and found a decrease in zonulin postoperatively. Downregulation of zonulin has been reported and found to be associated with beneficial physiologic changes to the epithelial barrier.…”

“…[33][34][35][36] An inverse relationship between IL-10 and zonulin has also been previously reported, though not in critically ill patients. 30,37 Few studies have examined zonulin and gastric emptying or the relationship between IL-10, zonulin, and gastric emptying, and results vary among existing studies. 6,32,38,39 In nonsurgical critically ill adults, delayed gastric emptying was associated with markers of loss of gut barrier integrity and elevated levels of zonulin, but there was no correlation with IL-10.…”

“…Both studies examined zonulin only at 1 time point. Pediatric studies examining zonulin levels have not included critically ill patients and have focused on patients with chronic inflammatory conditions 28‐30 . In addition to differences in the study population, our study examined zonulin at 2 time points, allowing for an assessment of zonulin under 2 conditions for the same patient, and found a decrease in zonulin postoperatively.…”

Immune Activation, Inflammation, and Non-AIDS Co-Morbidities in HIV-Infected Patients under Long-Term ART

“…HIV infection, associated with high levels of pro-inflammatory cytokines, causes chronic immune activation, enhanced by HIV-induced gut disruption and dysbiosis [127,129]. Moreover, Persaud et al has demonstrated that IL-6 correlates with intestinal fatty acid binding protein-2 (IFABP2), a biomarker of intestinal damage, suggesting an association between inflammation and intestinal integrity [130]. Indeed, gut immunity and alterations are not fully restored by effective ART, leading to microbial translocation.…”