Faecal cytokine levels of preterm infants coupled with microbiome profiles represent a potential non-invasive method to predict severity of necrotizing enterocolitis

Abstract

Objectives: Necrotizing enterocolitis (NEC) is a life-threatening disease, and the most common gastrointestinal emergency in premature infants. Accurate early diagnosis is challenging. Modified Bells staging is routinely used to guide diagnosis, but early diagnostic signs are non-specific, potentially leading to unobserved disease progression, which is problematic given the often rapid deterioration observed. We investigated faecal cytokine levels, coupled with gut microbiota profiles, as a non-invasive method to discover specific NEC-associated signatures that can be applied as potential diagnostic markers. Study design: Premature babies born below 32 weeks of gestation were admitted to the 2-site neonatal intensive care unit (NICU) of Imperial College hospitals (St. Marys or Queen Charlottes & Chelsea) between January 2011 and December 2012. Faecal samples from diapers were collected consecutively during the NICU stay. Results: Evaluation of microbiota profiles revealed only minor differences. However, at later time points, significant changes in microbiota structure were observed for Firmicutes, with Enterococcus being the least abundant in Bell stage 2/3 NEC. Faecal cytokine levels were similar to those found in previous studies evaluating systemic cytokine concentrations in NEC settings, but measurement in faeces represents a non-invasive method to evaluate the early onset of the disease. For IL-1α, IL-5 and IL-10, a significantly rising gradient of levels were observed from healthy to NEC1 to NEC2/3. Conclusions: Differences in certain faecal cytokine profiles in patients with NEC indicate their potential use as diagnostic biomarkers to facilitate earlier diagnosis. Additionally, associations between microbial and cytokine profiles, contribute to improving knowledge about NEC pathogenesis.

Fecal cytokine profile in preterm infants in the diagnosis of necrotizing enterocolitis: pilot study results

“…Zenner и соавт. получили данные о повышении уровня большого спектра фекальных цитокинов в группах новорожденных с НЭК I стадии и НЭК II-III стадии по сравнению с группой контроля (IL-2, IL-4, IL-6, IL-10, IL-12, IFN-g) [14]. Наибольшее значение для диагностики НЭК II-III стадии имели IL-4, IL-6 и IL-10 в образцах, собранных за 5-10 дней до манифестации НЭК.…”

“…C. Zenner и соавт. отмечают повышение уровня IL-10 в образцах кала, собранных за 5-10 дней до манифестации НЭК [14]. Y. Seo и соавт.…”

“…: показатели фекального IL-8 были значительно выше у детей с НЭК, чем у детей с инфекционным процессом другой локализации [18]. Однако, по данным C. Zenner и соавт., возможно проведение дифференциальной диагностики между НЭК I стадии и НЭК II-III стадии по уровню фекальных IL-1a, IL-10 и IL-5 [14].…”

“…Тем не менее ряд авторов признают неоспоримое преимущество цитокинового профиля кала как маркера повреждения кишечной стенки и активации местного воспалительного ответа в виде не только очевидной органоспецифичности, но и возможности неинвазивной диагностики различных воспалительных заболеваний кишечника [10,12,14].…”