Faculty Bibliography

This review highlights major advances in neurogastroenterology since Rome IV, offering a condensed summary of a comprehensive document to appear in the forthcoming Rome V book. Prepared by an international team of experts, it emphasizes pivotal studies that have deepened understanding of the physiological and pathophysiological mechanisms underlying disorders of gut-brain interaction (DGBI). These disorders are inherently complex and multifactorial, shaped by interactions among neuronal, epithelial, immune, smooth muscle, interstitial, and microbial populations. The review outlines cutting-edge technologies advancing the field and explores key themes, including brain-gut interactions, neurobiology, and neuroplasticity of the enteric nervous system, neuroimmune function, microbiome influences, and abnormalities of the gut-brain axis in DGBI. Risk factors for DGBI are considered, with serotonergic signaling presented as a conceptual framework for linking symptomatology and pathophysiology. Finally, we discuss how these scientific advances can translate into novel therapeutic strategies to improve patient care.

INTRODUCTION/BACKGROUND:Many children with abdominal pain-associated disorders of gut-brain interaction (AP-DGBI) have meal-related symptoms. The aim of the current study was to determine if meal-related symptoms defined specific mutually exclusive subgroups (classes) and, if so, whether these relate to other pathophysiologic factors. METHODS:Between 2020 and 2022, 289 children with AP-DGBI completed questionnaires evaluating gastrointestinal symptoms, psychosocial variables (e.g., somatization), and health-related quality of life (HRQoL). Latent class analysis (LCA) evaluated symptom patterns using 10 gastrointestinal symptoms, while univariable latent class regression (LCR) analyzed associations with covariates. KEY RESULTS/RESULTS:Three latent classes emerged: Class 1 (characterized by low meal- and stool-related symptom burden, 35.0%), Class 2 (exhibiting meal-related symptoms, 32.2%), and Class 3 (manifesting meal- and stool-related symptoms, 32.8%). Compared to Class 1, odds of belonging to Class 2 were significantly associated with increasing age, female sex, and lower HRQoL in physical and school functioning. Compared to Class 1, odds of belonging to Class 3 were similarly associated with increasing age, female sex, somatization, and with reduced HRQoL in physical, social, and psychosocial domains. There were no group differences with respect to depression, social stress, or anxiety. CONCLUSIONS AND INFERENCES/CONCLUSIONS:In youth with AP-DGBI, three distinct phenotypic groups are identified. Two of these distinct groups experience meal-related symptoms: one with associated bowel symptoms and the other without. These two meal-related symptom groups are associated with increasing age, female sex, somatization, and reduced HRQoL (particularly physical). These findings underscore the distinctness and importance of identifying the drivers of meal-related symptoms in children with AP-DGBI.

Addressing endemic stunting remains a primary United Nations development goal. One potential contributor to global linear growth failure is environmental enteric dysfunction (EED). However, it has proven challenging to address with interventions focused on water, sanitation and hygiene. Initial theories of EED placed primacy on recurrent enteric exposures; however, it appears that these exposures are inadequate to explain the phenotype and sequelae. Children in EED endemic regions are at high risk of having inadequate nutrition, and strong associations can be found between malnutrition and stunting. In this review, we summarize the clinical, translational and mechanistic evidence linking intake of animal source foods as a source of protein and micro-nutrients and, in their absence, essential amino acid (EAA) deficiency with stunted growth and features of EED such as altered immune behaviour. EAA deficiency has been linked to growth failure through several mechanistic pathways including intestinal inflammation, barrier disruption and chondral plate closure, and amino acid supplementation has shown clinical efficacy. By better understanding this linkage, we will be able to better study not only EED but also pathways in which dietary sources mechanistically alter systemic signalling in metabolism and immune function. This article is part of the theme issue 'Biological, biomedical and environmental drivers of stunting'.

BACKGROUND & AIMS/OBJECTIVE:Adverse experiences during early life can disrupt gut-brain axis development, but the mechanisms linking early life stress (ELS) to long-term gastrointestinal (GI) dysmotility and pain remain unclear. METHODS:We used a maternal separation (MS) mouse model of ELS and assessed visceral pain sensitivity, intestinal motility, and enteric nervous system (ENS) composition. Two large human pediatric population cohorts were also analyzed for associations between early life stress and DGBI risk. RESULTS:MS in mice led to visceral hypersensitivity, sex-specific motility defects, and altered ENS composition, including increased serotonergic innervation and changes in subtype-specific neuronal proportions. Degarelix-mediated suppression of gonadal hormones reversed MS-induced visceral pain and motility defects, implicating sex hormones in long-term gut changes. MS led to enhanced sympathetic innervation of the ENS and chemical sympathectomy restored normal motility, suggesting sympathetic overactivity in ELS-related gut dysfunction. In humans, significant associations between maternal mental health problems and pediatric disorders of gut-brain interaction (DGBI) were observed in both cohorts, mirroring preclinical findings. CONCLUSION/CONCLUSIONS:These results identify ELS-driven changes in enteric, sensory, and sympathetic pathways as contributors to DGBI risk and offer insight into potential therapeutic targets.