Abstract
The incidence and prevalence rate of chronic inflammatory disorders is on the rise in the pediatric population. Recent research indicates the crucial role of interactions between the altered intestinal microbiome and the immune system in the pathogenesis of several chronic inflammatory disorders in children, such as inflammatory bowel disease (IBD) and autoimmune diseases, such as type 1 diabetes mellitus (T1DM) and celiac disease (CeD). Here, we review recent knowledge concerning the pathogenic mechanisms underlying these disorders, and summarize the facts suggesting that the initiation and progression of IBD, T1DM, and CeD can be partially attributed to disturbances in the patterns of composition and abundance of the gut microbiota. The standard available therapies for chronic inflammatory disorders in children largely aim to treat symptoms. Although constant efforts are being made to maximize the quality of life for children in the long-term, sustained improvements are still difficult to achieve. Additional challenges are the changing physiology associated with growth and development of children, a population that is particularly susceptible to medication-related adverse effects. In this review, we explore new promising therapeutic approaches aimed at modulation of either gut microbiota or the activity of the immune system to induce a long-lasting remission of chronic inflammatory disorders. Recent preclinical studies and clinical trials have evaluated new approaches, for instance the adoptive transfer of immune cells, with genetically engineered regulatory T cells expressing antigen-specific chimeric antigen receptors. These approaches have revolutionized cancer treatments and have the potential for the protection of high-risk children from developing autoimmune diseases and effective management of inflammatory disorders. The review also focuses on the findings of studies that indicate that the responses to a variety of immunotherapies can be enhanced by strategic manipulation of gut microbiota, thus emphasizing on the importance of proper interaction between the gut microbiota and immune system for sustained health benefits and improvement of the quality of life of pediatric patients.
Highlights
The role of the immune system is to efficiently target diverse pathogens, such as viruses and bacteria, to keep cancer cells in check and avoid reactions against its own tissues and organs [1, 2]
Analysis of the microbiome in pediatric inflammatory bowel disease (IBD) patients revealed increased IgG binding by invasive strains, such as Burkholderia cepacia, Flavonifractor plautii and Rumminococcus sp., while IgG binding of noninvasive Pseudomonas protogens was reduced [370]
Several pathogens, including S. enterica, Shigella flexneri, Yersinia enterocolitica, and V. cholerae may participate in IBD pathogenesis because they produce mucin-degrading enzymes [379,380,381,382], and they may break down the intestinal mucosal barrier that reduces the contact between microorganisms and the epithelial cell surface
Summary
The role of the immune system is to efficiently target diverse pathogens, such as viruses and bacteria, to keep cancer cells in check and avoid reactions against its own tissues and organs [1, 2]. During inflammation in response to foreign antigens, the immune cells of the tissue, such as macrophages and dendritic cells, release cytokines [e.g. interleukin-1 (IL-1) and tumor necrosis factor-a (TNF-a)] that stimulate the infiltration of circulating leukocytes [7, 8]. Neutrophils are the first leukocytes that enter the local injury site They destroy the antigen by phagocytosis and release granules rich in enzymes, reactive oxygen species, and cytokines, such as IL-1, IL-6, and TNF-a [10, 11]. Lymphocytes, including different types of T and B cells, are the line of defense. They play a crucial role in inflammation by secreting cytokines, producing antibodies and immune complexes [12, 13]. The production of inflammatory cytokines, growth factors, and enzymes during inflammation may lead to tissue damage and secondary repair processes [4]
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