Advances in Understanding the Human Gut Microbiota and Its Implication in Pediatric Celiac Disease—A Narrative Review

Abstract

Celiac disease (CD) is a multifactorial disorder, defined by a complex interplay of genetic and environmental factors. Both genetic predisposition and dietary exposure to gluten are essential factors in triggering CD. However, there is proof that their presence is necessary, but not sufficient, for disease development. Through gut microbiota modulation, several additional environmental factors have shown their potential role as co-factors in CD pathogenesis. The aim of this review is to illustrate the possible mechanisms that stand behind the gut microbiota’s involvement in CD pathogenesis. Furthermore, we discuss microbiota manipulation’s potential role as both a preventative and therapeutic option. The available literature provides evidence that even before CD onset, factors including cesarean birth and formula feeding, as well as intestinal infection exposure, amplify the risk of CD in genetically predisposed individuals, due to their influence on the intestinal microbiome composition. Active CD was associated with elevated levels of several Gram-negative bacterial genera, including Bacteroides, Escherichia, and Prevotella, while beneficial bacteria such as lactobacilli and bifidobacteria were less abundant. Viral and fungal dysbiosis has also been described in CD, evidencing specific taxa alteration. A gluten-free diet (GFD) may improve the clinical symptoms and duodenal histopathology, but the persistence of intestinal dysbiosis in CD children under a GFD urges the need for additional therapy. Probiotics, prebiotics, and fecal microbial transplant have demonstrated their efficacy in restoring gut microbiota eubiosis in adult CD patients; however, their efficacy and safety as adjunctive therapies to a GFD in pediatric patients needs further investigation.

Exploring a Complex Interplay: Kidney–Gut Axis in Pediatric Chronic Kidney Disease

“…This disorder is characterized by a microbial imbalance, with increased amounts of certain genera of Gram-negative bacteria, like Bacteroides , Escherichia , and Prevotella , and decreasing concentrations of good bacteria, such as lactobacilli and bifidobacteria . Moreover, individuals with celiac disease also exhibit dysbiosis involving viruses and fungi [ 74 ].…”

Unraveling chronic kidney disease in children: a surprising manifestation of celiac disease

“…The introduction of screening for CD has enabled the diagnosis of certain cases even in the absence of typical digestive symptoms ( 7 ). According to recent studies ( 8 , 9 ), the occurrence of CD is twice as common in children compared to adults, and 1.5 times higher to women than men. Although small intestinal biopsy remains the “gold standard” in the diagnosis of CD, current serological tests, such as tissue transglutaminase, endomysial gliadin and de-amidated peptide antibodies, have become more important in the diagnosis of the disease ( 5 ).…”

Clinical Perspectives of Gut Microbiota in Patients with Chronic Kidney Disease and End-Stage Kidney Disease: Where Do We Stand?

“…GM is constantly evolving and displaying a wide diversity within the same person and in comparison, to others [ 3 ]. GM connects with vital organs, including the brain, bone marrow, cardiovascular system (CVS), kidney, body’s immune system, and the central nervous system, and has been seen as a potential cause for a variety of diseases in the aforementioned organs [ 4 , 5 , 6 , 7 , 8 , 9 , 10 ]. GM activates immune cells derived from bone marrow, resulting in a low-grade inflammatory reaction that affects the brain and kidneys via circulation [ 11 ].…”