Abstract

Abstract Background Background: Despite its established clinical efficacy, the immunological effects of exclusive enteral nutrition (EEN) in Crohn’s disease (CD) are yet to be elucidated. This study investigated the impact of EEN on circulating peripheral blood mononuclear cells (PBMCs) and how any effects observed varied according to clinical response to treatment. Methods Methods: Children with active CD received EEN for eight weeks as their sole induction treatment. Blood and faecal samples were collected prior to EEN and upon EEN completion. PBMCs were isolated, stained and analysed using flow cytometry. Differences in PBMCs types were compared during EEN. Faecal calprotectin was measured with ELISA. Absence of gluten immunogenic peptide (GIP) in faeces was used as a proxy marker of EEN compliance. Results Results: Nine participants were recruited (Table 1), three of whom initiated azathioprine during their course of EEN. Following treatment with EEN a decrease in the relative number and frequency of circulating effector memory CD8+ T cells re-expressing CD45RA (TEMRA) was observed with a corresponding increase in the frequency of circulating central and effector memory CD8+ T cells (Fig. 1). When we excluded participants that commenced thiopurines during their course of EEN a decrease in the relative number of circulating TEMRA CD8+ T cells persisted and a decrease in naïve CD8+ T cells in the blood was also observed. Participants who demonstrated a decrease in faecal calprotectin 50% following treatment with EEN (n= 5) also demonstrated an increase in the frequency of circulating central memory CD8+ T cells. When focussing on participants (n=7) within our cohort who demonstrated a high-level of compliance (undetected GIP in faeces) during EEN, we again observed a decrease in number of TEMRA CD8+ T cells in blood alongside an increase in the frequency of circulating central and effector memory CD8+ T cells. Conclusion Conclusion: We observed significant changes in CD8+ T cell populations in the peripheral blood of children following treatment with EEN. These changes were observed irrespective of background immunomodulator use and persisted in participants which achieved >50% decrease in FC or demonstrated compliance to EEN. Our observed changes in CD8+ T cell populations, particularly the consistent increases in circulating effector and memory CD8+ T cells, are likely a consequence of the actions of EEN in decreasing the diversity and composition of the gut bacteria, therefore reducing the recruitment of effector/memory cells from the blood into the intestine.

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