Zonulin: A Potential Marker of Intestine Injury in Newborns

Abstract

Introduction Zonulin (ZO), a new diagnostic biomarker of intestinal permeability, was tested in newborns presenting symptoms of infection and/or inflammation of the gut or being at risk of intestinal pathology. Material and Methods Serum ZO was assessed in 81 newborns diagnosed with sepsis, necrotizing enterocolitis (NEC), rotavirus infection, and gastroschisis, also in extremely low gestational age babies, and in controls (healthy newborns). ZO concentration was compared to C-reactive protein (CRP) and procalcitonin (PCT) values, leucocyte and platelet count, basic demographic data, and the value of the Neonatal Therapeutic Intervention Scoring System (NTISS). Results Median values of ZO were markedly higher in groups with rotavirus infection and gastroschisis (36.0 (1-3Q: 26.0–43.2) and 20.3 (1-3Q: 17.7–28.2) ng/ml, resp.) versus controls (3.5 (1-3Q: 2.7–4.8) ng/ml). Its concentration in the NEC group was twice as high as in controls but did not reach statistical significance. ZO levels were not related to NTISS, CRP, and PCT. Conclusions Zonulin is a promising biomarker of intestinal condition, markedly elevated in rotavirus infections. Its role in defining the severity of necrotizing enterocolitis and the risk for perforation is not well described and needs further evaluation. An increase in zonulin may not be parallel to the release of inflammatory markers, and low CRP should not exclude an injury to neonatal intestine.

Analysis of Faecal Zonulin and Calprotectin Concentrations in Healthy Children During the First Two Years of Life. An Observational Prospective Cohort Study

“…We have not found other literature giving data on zonulin concentrations in children's stool up to two years old (only zonulin concentrations in children's blood have been given). Tarko et al [35] found significantly higher zonulin blood concentrations in children with abdominal wall defects and rotavirus infection. In another study, blood zonulin levels in children born before 28 weeks of pregnancy were lower compared to a control group (note that the zonulin levels were not given) [36].…”

“…(3) The need to use interview data from the mothers of children, which might have resulted in errors especially related to the assessment of the effects of antibiotic therapy. (4) No formal sample size calculations were employed for this analysis because the cohort size was defined as a continuation of a former study in which the sample size was based on numbers sufficient according to previously published studies [35,42,44,45].…”

Immunogenicity of rotavirus vaccine (RotarixTM) in infants with environmental enteric dysfunction

“…Elevated levels of zonulin in serum has been found to be associated with rotavirus infection in infants in Poland [ 35 ]. Further, it has been demonstrated that Dendritic Cells (DC) open the tight junctions between epithelial cells, send dendrites directly in the lumen for antigen sampling [ 36 – 38 ], suggesting that increased permeablility evidenced by high levels of Zonulin facilitates sending DC processes in lumen for antigen upatake.…”

Tight junction structure, function, and assessment in the critically ill: a systematic review

“…Five studies investigated TJs in infants with necrotizing enterocolitis (NEC). Urinary claudin-2 [ 43 ] and -3 [ 44 ] and plasma zonulin [ 45 ] are elevated in this setting and correlate temporally with episodes of NEC. Tissue levels of claudin-2 are also altered in NEC, with increased staining in the colon [ 46 ] and decreased staining in the intestine [ 43 ].…”