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21 pages, 432 KiB  
Review
Interplay Between Depression and Inflammatory Bowel Disease: Shared Pathogenetic Mechanisms and Reciprocal Therapeutic Impacts—A Comprehensive Review
by Amalia Di Petrillo, Agnese Favale, Sara Onali, Amit Kumar, Giuseppe Abbracciavento and Massimo Claudio Fantini
J. Clin. Med. 2025, 14(15), 5522; https://doi.org/10.3390/jcm14155522 - 5 Aug 2025
Abstract
Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract. Although the aetiology of IBD remains largely unknown, several studies suggest that an individual’s genetic susceptibility, external environmental factors, intestinal microbial flora, and immune responses are all factors involved in [...] Read more.
Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract. Although the aetiology of IBD remains largely unknown, several studies suggest that an individual’s genetic susceptibility, external environmental factors, intestinal microbial flora, and immune responses are all factors involved in and functionally linked to the pathogenesis of IBD. Beyond the gastrointestinal manifestations, IBD patients frequently suffer from psychiatric comorbidities, particularly depression and anxiety. It remains unclear whether these disorders arise solely from reduced quality of life or whether they share overlapping biological mechanisms with IBD. This review aims to explore the bidirectional relationship between IBD and depressive disorders (DDs), with a focus on four key shared mechanisms: immune dysregulation, genetic susceptibility, alterations in gut microbiota composition, and dysfunction of the hypothalamic–pituitary–adrenal (HPA) axis. By examining recent literature, we highlight how these interconnected systems may contribute to both intestinal inflammation and mood disturbances. Furthermore, we discuss the reciprocal pharmacologic interactions between IBD and DDs: treatments for IBD, such as TNF-alpha and integrin inhibitors, have demonstrated effects on mood and anxiety symptoms, while certain antidepressants appear to exert independent anti-inflammatory properties, potentially reducing the risk or severity of IBD. Overall, this review underscores the need for a multidisciplinary approach to the care of IBD patients, integrating psychological and gastroenterological assessment. A better understanding of the shared pathophysiology may help refine therapeutic strategies and support the development of personalized, gut–brain-targeted interventions. Full article
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23 pages, 4178 KiB  
Article
Taxonomic Biomarkers of Gut Microbiota with Potential Clinical Utility in Mexican Adults with Obesity and Depressive and Anxiety Symptoms
by María Alejandra Samudio-Cruz, Daniel Cerqueda-García, Elizabeth Cabrera-Ruiz, Alexandra Luna-Angulo, Samuel Canizales-Quinteros, Carlos Landa-Solis, Gabriela Angélica Martínez-Nava, Paul Carrillo-Mora, Edgar Rangel-López, Juan Ríos-Martínez, Blanca López-Contreras, Jesús Fernando Valencia-León and Laura Sánchez-Chapul
Microorganisms 2025, 13(8), 1828; https://doi.org/10.3390/microorganisms13081828 - 5 Aug 2025
Abstract
While the gut microbiota of obese children in Mexico has been studied, its relationship with depressive and anxiety symptoms in obese adults remains unexplored. The aim of this study was to describe the gut microbiota profile of Mexican adults with obesity and its [...] Read more.
While the gut microbiota of obese children in Mexico has been studied, its relationship with depressive and anxiety symptoms in obese adults remains unexplored. The aim of this study was to describe the gut microbiota profile of Mexican adults with obesity and its association with depression and anxiety. We sequenced the V3-V4 region of the 16S rRNA gene from stool samples of obese adults categorized into four groups: control (OCG), with depressive symptoms (OD), with anxiety symptoms (OAx), or with both (ODAx). Alpha diversity was assessed using t-tests, beta diversity was assessed with PERMANOVA, and taxonomic differences was assessed with LEfSe. Associations between bacterial genera and clinical variables were analyzed using the Maaslin2 library. Bacteroidota was the most prevalent phylum, and Prevotella was the dominant enterotype across all groups. Although overall diversity did not differ significantly, 30 distinct taxonomic biomarkers were identified among groups as follows: 4 in OCG (Firmicutes), 5 in OD (Firmicutes, Bacteroidota), 13 in OAx (Firmicutes, Bacteroidetes, Fusobacteroidota, Proteobacteria), and 8 in ODAx (Firmicutes). This is the first study to identify distinct gut microbiota profiles in obese Mexican adults with depressive and anxiety symptoms. These findings suggest important microbial biomarkers for improving the diagnosis and treatment of mental health conditions in obesity. Full article
(This article belongs to the Special Issue Gut Microbiota: Influences and Impacts on Human Health)
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20 pages, 4612 KiB  
Article
Effect of a Gluten-Free Diet on the Intestinal Microbiota of Women with Celiac Disease
by M. Mar Morcillo Serrano, Paloma Reche-Sainz, Daniel González-Reguero, Marina Robas-Mora, Rocío de la Iglesia, Natalia Úbeda, Elena Alonso-Aperte, Javier Arranz-Herrero and Pedro A. Jiménez-Gómez
Antibiotics 2025, 14(8), 785; https://doi.org/10.3390/antibiotics14080785 - 2 Aug 2025
Viewed by 204
Abstract
Background/Objectives: Celiac disease (CD) is an autoimmune disorder characterized by small intestinal enteropathy triggered by gluten ingestion, often associated with gut dysbiosis. The most effective treatment is strict adherence to a gluten-free diet (GFD), which alleviates symptoms. This study uniquely integrates taxonomic, [...] Read more.
Background/Objectives: Celiac disease (CD) is an autoimmune disorder characterized by small intestinal enteropathy triggered by gluten ingestion, often associated with gut dysbiosis. The most effective treatment is strict adherence to a gluten-free diet (GFD), which alleviates symptoms. This study uniquely integrates taxonomic, functional, and resistance profiling to evaluate the gut microbiota of women with CD on a GFD. Methods: To evaluate the long-term impact of a GFD, this study analyzed the gut microbiota of 10 women with CD on a GFD for over a year compared to 10 healthy controls with unrestricted diets. Taxonomic diversity (16S rRNA gene sequencing and the analysis of α and β-diversity), metabolic functionality (Biolog EcoPlates®), and antibiotic resistance profiles (Cenoantibiogram) were assessed. Results: Metagenomic analysis revealed no significant differences in taxonomic diversity but highlighted variations in the abundance of specific bacterial genera. Women with CD showed increased proportions of Bacteroides, Streptococcus, and Clostridium, associated with inflammation, but also elevated levels of beneficial genera such as Roseburia, Oxalobacter, and Paraprevotella. Despite no significant differences in metabolic diversity, higher minimum inhibitory concentrations (MICs) in women in the healthy control group suggest that dietary substrates in unrestricted diets may promote the proliferation of fast-growing bacteria capable of rapidly developing and disseminating antibiotic resistance mechanisms. Conclusions: These findings indicate that prolonged adherence to a GFD in CD supports remission of gut dysbiosis, enhances microbiota functionality, and may reduce the risk of antibiotic resistance, emphasizing the importance of dietary management in CD. Full article
(This article belongs to the Special Issue Antibiotic Resistance: A One-Health Approach, 2nd Edition)
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11 pages, 827 KiB  
Study Protocol
The Effect of Faecal Microbiota Transplantation on Cognitive Function in Cognitively Healthy Adults with Irritable Bowel Syndrome: Protocol for a Randomised, Placebo-Controlled, Double-Blinded Pilot Study
by Sara Alaeddin, Yanna Ko, Genevieve Z. Steiner-Lim, Slade O. Jensen, Tara L. Roberts and Vincent Ho
Methods Protoc. 2025, 8(4), 83; https://doi.org/10.3390/mps8040083 (registering DOI) - 1 Aug 2025
Viewed by 257
Abstract
Faecal microbiota transplantation (FMT) is an emerging therapy for gastrointestinal and neurological disorders, acting via the microbiota–gut–brain axis. Altering gut microbial composition may influence cognitive function, but this has not been tested in cognitively healthy adults. This randomised, double-blinded, placebo-controlled pilot trial investigates [...] Read more.
Faecal microbiota transplantation (FMT) is an emerging therapy for gastrointestinal and neurological disorders, acting via the microbiota–gut–brain axis. Altering gut microbial composition may influence cognitive function, but this has not been tested in cognitively healthy adults. This randomised, double-blinded, placebo-controlled pilot trial investigates whether FMT is feasible and improves cognition in adults with irritable bowel syndrome (IBS). Participants receive a single dose of FMT or placebo via rectal retention enema. Cognitive performance is the primary outcome, assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB). Secondary outcomes include IBS symptom severity and mood. Tertiary outcomes include microbiome composition and plasma biomarkers related to inflammation, short-chain fatty acids, and tryptophan metabolism. Outcomes are assessed at baseline and at one, three, six, and twelve months following treatment. We hypothesise that FMT will lead to greater improvements in cognitive performance than placebo, with benefits extending beyond practice effects, emerging at one month and persisting in the long term. The findings will contribute to evaluating the safety and efficacy of FMT and enhance our understanding of gut–brain interactions. Full article
(This article belongs to the Section Public Health Research)
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33 pages, 799 KiB  
Review
The Ten Dietary Commandments for Patients with Irritable Bowel Syndrome: A Narrative Review with Pragmatic Indications
by Nicola Siragusa, Gloria Baldassari, Lorenzo Ferrario, Laura Passera, Beatrice Rota, Francesco Pavan, Fabrizio Santagata, Mario Capasso, Claudio Londoni, Guido Manfredi, Danilo Consalvo, Giovanni Lasagni, Luca Pozzi, Vincenza Lombardo, Federica Mascaretti, Alice Scricciolo, Leda Roncoroni, Luca Elli, Maurizio Vecchi and Andrea Costantino
Nutrients 2025, 17(15), 2496; https://doi.org/10.3390/nu17152496 - 30 Jul 2025
Viewed by 548
Abstract
Irritable bowel syndrome (IBS) is a gut–brain axis chronic disorder, characterized by recurrent abdominal pain and altered bowel habits in the absence of organic pathology. Nutrition plays a central role in symptom management, yet no single dietary strategy has demonstrated universal effectiveness. This [...] Read more.
Irritable bowel syndrome (IBS) is a gut–brain axis chronic disorder, characterized by recurrent abdominal pain and altered bowel habits in the absence of organic pathology. Nutrition plays a central role in symptom management, yet no single dietary strategy has demonstrated universal effectiveness. This narrative review critically evaluates current nutritional approaches to IBS. The low-Fermentable Oligo-, Di-, Mono-saccharides and Polyols (FODMAP) diet is the most extensively studied and provides short-term symptom relief, but its long-term effects on microbiota diversity remain concerning. The Mediterranean diet, due to its anti-inflammatory and prebiotic properties, offers a sustainable, microbiota-friendly option; however, it has specific limitations in the context of IBS, particularly due to the adverse effects of certain FODMAP-rich foods. A gluten-free diet may benefit individuals with suspected non-celiac gluten sensitivity, although improvements are often attributed to fructan restriction and placebo and nocebo effects. Lactose-free diets are effective in patients with documented lactose intolerance, while a high-soluble-fiber diet is beneficial for constipation-predominant IBS. IgG-based elimination diets are emerging but remain controversial and require further validation. In this review, we present the 10 dietary commandments for IBS, pragmatic and easily retained recommendations. It advocates a personalized, flexible, and multidisciplinary management approach, avoiding rigidity and standardized protocols, with the aim of optimizing adherence, symptom mitigation, and health-related quality of life. Future research should aim to evaluate, in real-world clinical settings, the impact and applicability of the 10 dietary commandments for IBS in terms of symptom improvement and quality of life Full article
(This article belongs to the Special Issue Dietary Interventions for Functional Gastrointestinal Disorders)
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21 pages, 1343 KiB  
Review
Autobrewery Syndrome and Endogenous Ethanol Production in Patients with MASLD: A Perspective from Chronic Liver Disease
by Silvia Andaloro, Valeria De Gaetano, Ferdinando Cardone, Gianluca Ianiro, Lucia Cerrito, Maria Pallozzi, Leonardo Stella, Antonio Gasbarrini and Francesca Romana Ponziani
Int. J. Mol. Sci. 2025, 26(15), 7345; https://doi.org/10.3390/ijms26157345 - 30 Jul 2025
Viewed by 351
Abstract
Autobrewery syndrome is a rare condition characterized by the endogenous fermentation of carbohydrates by gut microbiota, which exceeds the liver’s detoxification capacity and leads to signs and symptoms of acute alcohol intoxication. This condition has significant clinical, social, and legal implications. Beyond the [...] Read more.
Autobrewery syndrome is a rare condition characterized by the endogenous fermentation of carbohydrates by gut microbiota, which exceeds the liver’s detoxification capacity and leads to signs and symptoms of acute alcohol intoxication. This condition has significant clinical, social, and legal implications. Beyond the acute effects, the role of excessive endogenous ethanol production in the progression of chronic diseases—particularly liver disease—is still under investigation. In this review, we aim to describe the key clinical features of autobrewery syndrome, identify the main microbial pathogens involved, and explore the potential impact of endogenous ethanol production on the development and progression of chronic liver disease. Although robust data and standardized treatment protocols are currently lacking, we discuss the general principles of management and outline possible therapeutic strategies and future perspectives. Full article
(This article belongs to the Special Issue Gut Microbiota in Human Disease and Health)
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25 pages, 1301 KiB  
Review
Going with the Flow: Sensorimotor Integration Along the Zebrafish GI Tract
by Millie E. Rogers, Lidia Garcia-Pradas, Simone A. Thom, Roberto A. Vazquez and Julia E. Dallman
Cells 2025, 14(15), 1170; https://doi.org/10.3390/cells14151170 - 30 Jul 2025
Viewed by 476
Abstract
Sensorimotor integration along the gastrointestinal (GI) tract is crucial for normal gut function yet remains poorly understood in the context of neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD). The genetic tractability of zebrafish allows investigators to generate molecularly defined models that [...] Read more.
Sensorimotor integration along the gastrointestinal (GI) tract is crucial for normal gut function yet remains poorly understood in the context of neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD). The genetic tractability of zebrafish allows investigators to generate molecularly defined models that provide a means of studying the functional circuits of digestion in vivo. Optical transparency during development allows for the use of optogenetics and calcium imaging to elucidate the mechanisms underlying GI-related symptoms associated with ASD. The array of commonly reported symptoms implicates altered sensorimotor integration at various points along the GI tract, from the pharynx to the anus. We will examine the reflex arcs that facilitate swallowing, nutrient-sensing, absorption, peristalsis, and evacuation. The high level of conservation of these processes across vertebrates also enables us to explore potential therapeutic avenues to mitigate GI distress in ASD and other NDDs. Full article
(This article belongs to the Special Issue Modeling Developmental Processes and Disorders in Zebrafish)
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20 pages, 770 KiB  
Review
Histamine Metabolism in IBD: Towards Precision Nutrition
by Dimitra Kanta, Eleftherios Katsamakas, Anna Maia Berg Gudiksen and Mahsa Jalili
Nutrients 2025, 17(15), 2473; https://doi.org/10.3390/nu17152473 - 29 Jul 2025
Viewed by 397
Abstract
Patients with Inflammatory Bowel Disease (IBD) exhibit a dysregulated immune response that may be further exacerbated by bioactive compounds, such as histamine. Current dietary guidelines for IBD primarily focus on symptom management and flare-up prevention, yet targeted nutritional strategies addressing histamine metabolism remain [...] Read more.
Patients with Inflammatory Bowel Disease (IBD) exhibit a dysregulated immune response that may be further exacerbated by bioactive compounds, such as histamine. Current dietary guidelines for IBD primarily focus on symptom management and flare-up prevention, yet targeted nutritional strategies addressing histamine metabolism remain largely unexplored. This narrative review aims to summarize the existing literature on the complex interplay between IBD and histamine metabolism and propose a novel dietary framework for managing IBD progression in patients with histamine intolerance (HIT). Relevant studies were identified through a comprehensive literature search of PubMed/MEDLINE, Google Scholar, ScienceDirect, Scopus, and Web of Science. The proposed low-histamine diet (LHD) aims to reduce the overall histamine burden in the body through two primary strategies: (1) minimizing exogenous intake by limiting high-histamine and histamine-releasing foods and (2) reducing endogenous histamine production by modulating gut microbiota composition, specifically targeting histamine-producing bacteria. In parallel, identifying individuals who are histamine-intolerant and understanding the role of histamine-degrading enzymes, such as diamine oxidase (DAO) and histamine-N-methyltransferase (HNMT), are emerging as important areas of focus. Despite growing interest in the role of histamine and mast cell activation in gut inflammation, no clinical trials have investigated the effects of a low-histamine diet in IBD populations. Therefore, future research should prioritize the implementation of LHD interventions in IBD patients to evaluate their generalizability and clinical applicability. Full article
(This article belongs to the Special Issue Precise Nutrition Therapy to Inflammatory Bowel Diseases)
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34 pages, 1059 KiB  
Review
Autism Spectrum Disorder: From Experimental Models to Probiotic Application with a Special Focus on Lactiplantibacillus plantarum
by Giusi Sabatini, Ilenia Boccadoro, Roberta Prete, Natalia Battista and Aldo Corsetti
Nutrients 2025, 17(15), 2470; https://doi.org/10.3390/nu17152470 - 29 Jul 2025
Viewed by 433
Abstract
Background/Objectives: Autism spectrum disorder (ASD) encompasses several neurodevelopmental disorders, whose onset is correlated to genetic and environmental factors. Although the etiopathogenesis is not entirely clear, the involvement of inflammatory processes, the endocannabinoid system, and alterations in the permeability and composition of the intestinal [...] Read more.
Background/Objectives: Autism spectrum disorder (ASD) encompasses several neurodevelopmental disorders, whose onset is correlated to genetic and environmental factors. Although the etiopathogenesis is not entirely clear, the involvement of inflammatory processes, the endocannabinoid system, and alterations in the permeability and composition of the intestinal microbiota are known to occur. Methods: This review systematically explores the literature available to date on the most widely used murine models for the study of ASD, the main biomarkers investigated for the diagnosis of ASD, and the therapeutic potential of probiotics, with a particular focus on the use of strains of Lactiplantibacillus (Lpb.) plantarum in in vivo models and clinical trials for ASD. Results: Several studies have demonstrated that targeting multifactorial biomarkers in animal models and patients contributes to a more comprehensive understanding of the complex mechanisms underlying ASD. Moreover, accumulating evidence supports the beneficial effect of probiotics, including Lpb. plantarum, as a promising alternative therapeutic strategy, capable of modulating gut–brain axis communication. Conclusions: Probiotic supplementation, particularly with selected Lpb. plantarum strains, is emerging as a potential complementary approach for ameliorating ASD-related gastrointestinal and behavioral symptoms. However, further large-scale clinical studies are essential to validate their efficacy and determine optimal treatment protocols and dietary strategies. Full article
(This article belongs to the Special Issue The Effect of Nutrition Interventions on Neuropsychiatric Diseases)
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24 pages, 1753 KiB  
Review
A Review of Probiotic Supplementation and Its Impact on the Health and Well-Being of Domestic Cats
by Bhagavathi Sundaram Sivamaruthi, Periyanaina Kesika, Chaiyavat Chaiyasut, Pranom Fukngoen and Natarajan Sisubalan
Vet. Sci. 2025, 12(8), 703; https://doi.org/10.3390/vetsci12080703 - 28 Jul 2025
Viewed by 510
Abstract
Probiotic supplementation in domestic cats has emerged as a promising non-pharmaceutical strategy to enhance gut health, immune function, and overall well-being. This review critically examines the current literature on probiotic use in feline health, highlighting evidence from studies involving both healthy and diseased [...] Read more.
Probiotic supplementation in domestic cats has emerged as a promising non-pharmaceutical strategy to enhance gut health, immune function, and overall well-being. This review critically examines the current literature on probiotic use in feline health, highlighting evidence from studies involving both healthy and diseased cats. Probiotic strains such as Lactobacillus, Bifidobacterium, Bacillus, Enterococcus, and Saccharomyces have demonstrated beneficial effects, including the modulation of the gut microbiota, a reduction in inflammation, and an improvement in gastrointestinal symptoms. Mechanistically, probiotics exert effects through microbial competition, the enhancement of epithelial barrier function, and immune modulation via cytokine and antimicrobial peptide regulation. Despite promising outcomes, limitations such as short study durations, small sample sizes, and narrow breed diversity constrain generalizability. Future research should prioritize long-term, multi-omics-integrated studies to elucidate mechanisms and optimize clinical application. Overall, probiotics offer a safe, functional dietary tool for improving feline health and may complement conventional veterinary care. Full article
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15 pages, 664 KiB  
Article
Real-World Safety of Vedolizumab in Inflammatory Bowel Disease: A Retrospective Cohort Study Supported by FAERS Signal Analysis
by Bojana Milašinović, Sandra Vezmar Kovačević, Srđan Marković, Marija Jovanović, Tamara Knežević Ivanovski, Đorđe Kralj, Petar Svorcan, Branislava Miljković and Katarina Vučićević
Pharmaceuticals 2025, 18(8), 1127; https://doi.org/10.3390/ph18081127 - 28 Jul 2025
Viewed by 394
Abstract
Background/Objectives: Vedolizumab is a gut-selective anti-integrin monoclonal antibody approved for the treatment of inflammatory bowel disease (IBD). While clinical trials have demonstrated a favorable safety profile, real-world studies are essential for identifying rare adverse events (AEs) and evaluating post-marketing safety. This study [...] Read more.
Background/Objectives: Vedolizumab is a gut-selective anti-integrin monoclonal antibody approved for the treatment of inflammatory bowel disease (IBD). While clinical trials have demonstrated a favorable safety profile, real-world studies are essential for identifying rare adverse events (AEs) and evaluating post-marketing safety. This study assessed vedolizumab’s safety in a real-world cohort and supported the detection of potential safety signals. Methods: A retrospective chart review was conducted on adult IBD patients treated with vedolizumab at a tertiary center in the Republic of Serbia between October 2021 and August 2022. Data included demographics, AEs, and newly reported extraintestinal manifestations (EIMs). Exposure-adjusted incidence rates were calculated per 100 patient-years (PYs). Disproportionality analysis using the FDA Adverse Event Reporting System (FAERS) was performed to identify safety signals, employing reporting odds ratios (RORs) and proportional reporting ratios (PRRs) for AEs also observed in the cohort. Prior IBD therapies and reasons for discontinuation were evaluated. Results: A total of 107 patients (42.1% Crohn’s disease, 57.9% ulcerative colitis) were included, with a median vedolizumab exposure of 605 days. There were 92 AEs (56.51/100 PYs), most frequently infections (23.95/100 PYs), gastrointestinal disorders (4.30/100 PYs), and skin disorders (4.30/100 PYs). The most frequently reported preferred terms (PTs) included COVID-19, COVID-19 pneumonia, nephrolithiasis, and nasopharyngitis. Arthralgia (12.90/100 PYs) was the most frequent newly reported EIM. No discontinuations due to vedolizumab AEs occurred. FAERS analysis revealed potential signals for events not listed in prescribing information but observed in the cohort: nephrolithiasis, abdominal pain, diarrhea, malaise, cholangitis, gastrointestinal infection, blood pressure decreased, weight decreased, female genital tract fistula, respiratory symptom, and appendicectomy. Most patients had received three prior therapies, often stopping one due to AEs. Conclusions: Vedolizumab demonstrated a favorable safety profile in the IBD cohort. However, FAERS-identified signals, such as nephrolithiasis, gastrointestinal infections, and decreased blood pressure, warrant further investigation in larger, more diverse populations. Full article
(This article belongs to the Special Issue Therapeutic Drug Monitoring and Adverse Drug Reactions: 2nd Edition)
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17 pages, 564 KiB  
Review
Gut Feelings: Linking Dysbiosis to Depression—A Narrative Literature Review
by Anca C. Bibolar, Vlad I. Nechita, Florin C. Lung, Bianca D. Crecan-Suciu and Ramona L. Păunescu
Medicina 2025, 61(8), 1360; https://doi.org/10.3390/medicina61081360 - 27 Jul 2025
Viewed by 834
Abstract
The balance between physiological, psychological, and environmental factors often shapes human experience. In recent years, research has drawn attention to the gut microbiota as a significant contributor to brain function and emotional regulation. This narrative review examines how changes in gut microbiota may [...] Read more.
The balance between physiological, psychological, and environmental factors often shapes human experience. In recent years, research has drawn attention to the gut microbiota as a significant contributor to brain function and emotional regulation. This narrative review examines how changes in gut microbiota may relate to depression. We selected studies that explore the link between intestinal dysbiosis and mood, focusing on mechanisms such as inflammation, vagus nerve signaling, HPA axis activation, gut permeability, and neurotransmitter balance. Most of the available data come from animal models, but findings from human studies suggest similar patterns. Findings are somewhat difficult to compare due to differences in measurement procedures and patient groups. However, several microbial shifts have been observed in people with depressive symptoms, and trials with probiotics or fecal microbiota transplant show potential. These results remain limited. We argue that these interventions deserve more attention, especially in cases of treatment-resistant or inflammation-driven depression. Understanding how the gut and brain interact could help define clearer subtypes of depression and guide new treatment approaches. Full article
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12 pages, 415 KiB  
Article
Anxiety Moderates the Relationship Between Stress and Pain in IBS Patients: A Prospective Diary Study
by Sanda Pletikosić Tončić, Marko Tončić and Sanja Bradić
Gastrointest. Disord. 2025, 7(3), 50; https://doi.org/10.3390/gidisord7030050 - 26 Jul 2025
Viewed by 336
Abstract
Background/Objectives: Irritable bowel syndrome (IBS) is a common disorder of brain–gut interaction characterized by abdominal pain and altered bowel habits. While stress and anxiety are known to exacerbate IBS symptoms, less is understood about how these factors interact on a daily timescale. This [...] Read more.
Background/Objectives: Irritable bowel syndrome (IBS) is a common disorder of brain–gut interaction characterized by abdominal pain and altered bowel habits. While stress and anxiety are known to exacerbate IBS symptoms, less is understood about how these factors interact on a daily timescale. This study aimed to clarify the relationship between daily stress and abdominal pain in IBS and to examine whether trait anxiety moderates this association. Methods: Forty-nine IBS patients completed daily assessments of stress and abdominal pain over a 14-day period. Participants rated abdominal pain three times daily and reported daily stress levels across seven life domains each evening. Trait anxiety was assessed at baseline using the STAI-T. Results: Hierarchical linear modeling was used to analyze within-person and between-person effects. An increase in between-person stress was associated with increased probability of abdominal pain among individuals with low-to-moderate trait anxiety, while this was not observed in patients with high trait anxiety. Even though within-person (day-to-day) stress variations had an impact on pain probability, the effects of between-person variations were multiple times greater. Conclusions: These findings suggest that the interplay between stress and anxiety in IBS might not be uniform. High trait anxiety may, under certain conditions, attenuate rather than amplify the link between stress and pain, possibly pointing to a more dynamic relationship. Full article
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15 pages, 2863 KiB  
Review
Gut–Brain Interactions in Neuronal Ceroid Lipofuscinoses: A Systematic Review Beyond the Brain in Paediatric Dementias
by Stefania Della Vecchia, Maria Marchese, Alessandro Simonati and Filippo Maria Santorelli
Int. J. Mol. Sci. 2025, 26(15), 7192; https://doi.org/10.3390/ijms26157192 - 25 Jul 2025
Viewed by 203
Abstract
Neuronal ceroid lipofuscinoses (NCLs) are paediatric neurodegenerative disorders that primarily affect the central nervous system (CNS). The high prevalence of gastrointestinal (GI) symptoms has prompted researchers and clinicians to move beyond an exclusively “brain-centric” perspective. At the molecular level, mutations in CLN genes [...] Read more.
Neuronal ceroid lipofuscinoses (NCLs) are paediatric neurodegenerative disorders that primarily affect the central nervous system (CNS). The high prevalence of gastrointestinal (GI) symptoms has prompted researchers and clinicians to move beyond an exclusively “brain-centric” perspective. At the molecular level, mutations in CLN genes lead to lysosomal dysfunction and impaired autophagy, resulting in intracellular accumulation of storage material that disrupts both central and enteric neuronal homeostasis. To systematically examine current clinical and preclinical knowledge on gut involvement in NCLs, with a focus on recent findings related to the enteric nervous system and gut microbiota. We conducted a systematic review following the PRISMA guidelines using PubMed as the sole database. Both clinical (human) and preclinical (animal) studies were included. A total of 18 studies met the inclusion criteria, focusing on gastrointestinal dysfunction, nervous system involvement, and gut microbiota. We found that the nature of GI symptoms was multifactorial in NCLs, involving not only the CNS but also the autonomic and enteric nervous systems, which were affected early by lysosomal deposits and enteric neuron degeneration. Of note, preclinical studies showed that gene therapy could improve not only CNS manifestations but also GI ones, which may have beneficial implications for patient care. While the role of the ENS seems to be clearer, that of gut microbiota needs to be further clarified. Current evidence from preclinical models highlighted alterations in the composition of the microbiota and suggested a possible influence on the progression and modulation of neurological symptoms. However, these results need to be confirmed by further studies demonstrating the causality of this relationship. GI involvement is a key feature of NCLs, with early impact on the enteric nervous system and possible links to gut microbiota. Although preclinical findings—particularly on gene therapy—are encouraging due to their dual impact on both CNS and GI manifestations, the causal role of the gut microbiota remains to be fully elucidated. In this context, the development of sensitive and specific outcome measures to assess GI symptoms in clinical trials is crucial for evaluating the efficacy of future therapeutic interventions. Full article
(This article belongs to the Section Molecular Neurobiology)
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12 pages, 1475 KiB  
Article
The Prevalence and Clinical Significance of Toe Walking in Autism Spectrum Disorder: A Cross-Sectional Study in an Italian Pediatric Sample
by Carola Costanza, Beatrice Gallai, Michele Sorrentino, Martina Gnazzo, Giulia Pisanò, Lucia Parisi, Eva Germanò, Agata Maltese, Maria Esposito, Michele Roccella and Marco Carotenuto
Medicina 2025, 61(8), 1346; https://doi.org/10.3390/medicina61081346 - 25 Jul 2025
Viewed by 366
Abstract
Background and Objectives: Toe walking (TW) is frequently observed in children with Autism Spectrum Disorder (ASD), yet its clinical significance and association with comorbid conditions remain poorly understood. This study aimed to examine the prevalence of TW in a large Italian cohort [...] Read more.
Background and Objectives: Toe walking (TW) is frequently observed in children with Autism Spectrum Disorder (ASD), yet its clinical significance and association with comorbid conditions remain poorly understood. This study aimed to examine the prevalence of TW in a large Italian cohort of children with ASD and to explore its association with ASD severity, sleep disturbances, feeding behaviors, and gastrointestinal symptoms. Materials and Methods: A total of 289 children with ASD and 289 typically developing controls (TDC), matched for age and sex, were evaluated in a multicentric observational study. TW was assessed during neurodevelopmental evaluations. Sleep quality was assessed using the Sleep Disturbance Scale for Children (SDSC), feeding behaviors via the Brief Autism Mealtime Behavior Inventory (BAMBI), and gastrointestinal symptoms through clinical reporting. Statistical analyses included Chi-square tests, Mann–Whitney U tests, Spearman correlations, and logistic regressions. Results: TW was significantly more prevalent in the ASD group (27.3%) than in TDC (5.5%, p < 0.0001). Within the ASD group, TW occurred in 50.5% of children with Level 3 severity but was absent in Levels 1 and 2 (p < 0.0001). Males exhibited TW more frequently than females. Children with TW had higher SDSC scores (ρ = 0.33, p < 0.0001), though no subscale independently predicted TW. Constipation was reported in 100% of children with Level 3 ASD and was strongly correlated with SDSC total scores (ρ = 0.58, p < 0.0001). The Disorders of Arousal (DA) subscale emerged as an independent predictor of constipation (β = 0.184, p = 0.019). Conclusions: TW in ASD appears to be a marker of greater neurodevelopmental severity and is associated with sleep disturbances and gastrointestinal dysfunction. These findings support the hypothesis that TW may reflect broader dysfunctions involving the gut–brain axis, sensory processing, and motor control. The routine clinical assessment of TW should include the evaluation of sleep and somatic symptoms to better understand the multisystemic nature of ASD phenotypes. Full article
(This article belongs to the Section Pediatrics)
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