Search Results (419)

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

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

Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder associated with gut microbiota dysbiosis and impaired intestinal barrier function. Probiotic interventions have shown potential in alleviating intestinal inflammation and restoring microbial balance. This study explores the protective effects of Lacticaseibacillus paracasei (L. paracasei) E10 in mice. L. paracasei E10 demonstrated strong gastrointestinal transit tolerance, high mucosal adhesion, and probiotic properties such as hydrophobicity and aggregation ability (p < 0.05). The oral administration of L. paracasei E10 significantly alleviated colitis symptoms by reducing the disease activity index, preserving colonic architecture, increasing goblet cell density, and upregulating tight junction proteins, thereby enhancing intestinal barrier integrity. 16S rRNA sequencing revealed that L. paracasei E10 supplementation enriched microbial diversity, increased the abundance of Muribaculaceae, and modulated the Firmicutes/Bacteroidetes ratio, contributing to gut homeostasis. These findings indicate that L. paracasei E10 is a potential candidate for IBD management. Full article

Background and Objectives: Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder with diverse subtypes. Recent evidence has suggested a link between vitamin D deficiency and IBS; however, the associations between vitamin D levels, IBS subtypes, and hematological–biochemical parameters remain unclear. The aim of this research was to investigate the associations between vitamin D status, IBS subtypes, and sex, along with their relationships with biochemical and hematological parameters. Materials and Methods: This retrospective study included 240 patients diagnosed with IBS according to the Rome IV criteria at Van Yüzüncü Yıl University Medical Faculty Hospital. The patients were classified as diarrhea-predominant (IBS-D), constipation-predominant (IBS-C), or mixed-type (IBS-M). The patients’ serum vitamin D levels and hematological (hemoglobin, white blood cell and platelet counts, and mean corpuscular volume) and biochemical (ferritin, iron, calcium, magnesium, and vitamin B12 levels) parameters were evaluated at baseline and after vitamin D supplementation. Sex-related differences were assessed. Results: Baseline vitamin D levels were low in all IBS subtypes, with no significant differences between the groups. Vitamin D supplementation resulted in a significant increase in serum vitamin D levels across all subtypes (p = 0.001). No significant correlations were identified between vitamin D levels and hematological or biochemical parameters. Sex differences in vitamin D levels were only significant in the IBS-M group, both at baseline and post-treatment (p < 0.05). Conclusions: Vitamin D deficiency is prevalent among all IBS subtypes and significantly improves with supplementation, independently of the subtype. Although no associations were found between vitamin D levels and laboratory parameters, the observed sex differences in patients with IBS-M highlight the need for further research into potential sex-related pathophysiological mechanisms. These findings support the integration of routine vitamin D assessment and supplementation into the clinical management of IBS, especially in patients with the IBS-M subtype and female sex, to potentially improve patient outcomes. Full article

Background: The gut microbiome is a key modulator of the gut–brain axis and may contribute to the pathophysiology of both gastrointestinal and systemic disorders. This study aimed to evaluate gut microbiota composition and tryptophan/phenylalanine metabolism in women with unclassified irritable bowel syndrome (IBS-U), with or without coexisting chronic fatigue syndrome (CFS). Methods: Eighty women were enrolled and divided into two groups: IBS-U without CFS (Group I, n = 40) and IBS-U with coexisting CFS (Group II, n = 40). Microbial composition and diversity were assessed using the GA-map™ Dysbiosis Test, including the dysbiosis index (DI) and Shannon Diversity Index (SDI). Hydrogen and methane levels were measured in breath samples. Urinary concentrations of selected microbial and neuroactive metabolites—homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), kynurenic acid (KYNA), xanthurenic acid (XA), quinolinic acid (QA), hydroxyphenylacetic acid (HPA), and 3-indoxyl sulfate (3-IS)—were quantified using LC-MS/MS. Fatigue severity was assessed using the Chalder Fatigue Questionnaire (CFQ-11) and the fatigue severity scale (FSS). Results: Compared to Group I, patients with IBS-CFS showed significantly greater microbial diversity, higher breath methane levels, and elevated urinary concentrations of QA, XA, 3-IS, and HVA, alongside lower concentrations of 5-HIAA and KYN. Fatigue severity was positively correlated with urinary XA and QA levels. Conclusions: Women with IBS and coexisting CFS exhibit distinct gut microbiota and tryptophan metabolite profiles compared to those without fatigue. The observed metabolite–symptom associations, particularly involving neuroactive kynurenine derivatives, warrant further investigation. These preliminary findings should be interpreted as hypothesis-generating and require validation through high-resolution microbiome analyses, functional pathway profiling, and longitudinal or interventional studies to clarify causality and clinical significance. Full article

Constipation, a widespread gastrointestinal disorder, imposes significant burdens on healthcare systems the and global health-related quality of life, yet current options remain suboptimal due to limited mechanistic understanding and efficacy limitations. Given the pivotal significance of the interactions between the gut microbiota and the host on governing bowel movement, we employed a multi-modal approach integrating animal experiments, ELISA, histopathology, qRT-PCR, GC-MS, and 16S rRNA metagenomics to evaluate the functional potential of Lactobacillus rhamnosus LRa05 against loperamide-induced constipation in mice. LRa05 treatment markedly alleviated constipation symptoms, as evidenced by reduced first black stool expulsion time, increased fecal moisture, and enhanced intestinal motility. Mechanistic investigations revealed that LRa05 balanced gastrointestinal regulatory peptides. It also downregulated aquaporin (AQP4/AQP8) mRNA levels and activated the SCF/C-Kit signaling pathway. These effects contributed to the restoration of intestinal peristalsis. Furthermore, LRa05 rebalanced gut microbiota composition by enriching beneficial, including Alloprevotella and Lachnospiraceae NK4A136, key SCFA producers. Thus, LRa05 could boost short chain fatty acid (SCFA) production, which is vital for stimulating intestinal motility, improving mucosal function, and relieving constipation. These findings demonstrated that LRa05 could mitigate constipation through a multi-target mechanism: regulating motility-related gene transcription, restructuring the microbial community, balancing gastrointestinal peptides, repairing the colonic mucosa, and promoting SCFAs for fecal hydration. Our study positions LRa05 as a promising probiotic candidate for constipation management. Full article

The gut-brain axis (GBA) represents an operant acting in a two-direction communication system between the gastrointestinal tract and the central nervous system, mediated by the enteric nervous system (ENS), vagus nerve, immune pathways, and endocrine signaling. In recent years, evidence has highlighted the pivotal role of the gut microbiota in modulating this axis, forming the microbiota-gut-brain axis (MGBA). Our review synthesizes current knowledge on the anatomical and functional substrates of gut-brain communication, focusing on interoceptive signaling, the roles of intrinsic primary afferent neurons (IPANs) and enteroendocrine cells (EECs) and the influence of microbial metabolites, including short-chain fatty acids (SCFAs), bile acids, and indoles. These agents modulate neurotransmission, epithelial barrier function, and neuroimmune interactions. The vagus nerve serves as a primary pathway for afferent sensory signaling from the gut influenced indirectly by the ENS and microbiota. Dysbiosis has been associated with altered gut-brain signaling and implicated in the pathophysiology of disorders ranging from irritable bowel syndrome to mood disorders and neurodegeneration. Microbial modulation of host gene expression via epigenetic mechanisms, including microRNAs, adds another layer of complexity. The gut has a crucial role as an active sensory and signaling organ capable of influencing higher-order brain functions. Understanding the MGBA has significant implications for new therapeutic interventions targeting the microbiome to manage neurogastroenterological and even neuropsychiatric conditions. Full article

Background: Intestinal epithelial barrier (IEB) dysfunction is related to multiple gastrointestinal disorders, notably inflammatory bowel disease (IBD). Betulinic acid (BA), a compound derived from birch bark, has demonstrated potential therapeutic benefits in IBD. Nevertheless, the impact of BA on IEB function has not been fully elucidated. Methods: The current study aimed to explore the potential underlying mechanisms of BA in dextran sodium sulfate (DSS)-induced IBD in mice and co-culture models involving Caco-2/HT29-MTX-E12 cell monolayers or mouse intestinal organoids (IOs) in conjunction with macrophages stimulated by lipopolysaccharide (LPS). Results: In vivo, BA treatment significantly improved body weight and colon length, alleviated disease activity index (DAI) scores, and reduced colonic histopathological injury in IBD mice. In vitro, BA reduced the flux of FITC-dextran; increased the TEER; and decreased the production of IL-6, IL-1β, and TNF-α while increasing IL-10 mRNA levels. Additionally, BA enhanced IEB formation by upregulating ZO-1, occludin (OCLN), and claudin-1 (CLDN1). Molecular docking studies revealed significant docking scores and interactions between BA and PPAR-γ. Moreover, BA significantly upregulated PPAR-γ protein expression, decreased NF-κB and MLC2 phosphorylation, and reduced MLCK protein expression. However, this effect was reversed by GW9662, an effective PPAR-γ antagonist. Conclusions: The findings reveal that BA mitigates IBD by safeguarding the intestinal barrier against dysfunction. This effect may be attributed to its ability to suppress inflammation and enhance the expression of tight junction proteins by modulating the PPAR-γ/NF-κB signaling pathway. Full article

Background: A low-FODMAP diet is considered as a potential supportive treatment approach in some gastrointestinal disorders. The aim of this study was to systematically review the literature for randomized controlled trials assessing the efficacy of the low-FODMAP diet on the severity of gastrointestinal symptoms and quality of life in patients with gastrointestinal disorders. Methods: This review was conducted in accordance with CASP tool and PRISMA guidelines. A comprehensive search of the PubMed, Scopus, and Web of Science databases resulted in the identification of fourteen randomized controlled trials. Results: Ten studies examined the effect of the low-FODMAP diet in patients with irritable bowel syndrome (IBS), three with inflammatory bowel disease (IBD), and one with symptomatic proton pump inhibitor (PPI) refractory gastroesophageal reflux disease (GERD). All interventions compared the low-FODMAP diet with another diet and lasted from 3 to 12 weeks. Most studies on IBS showed significant improvements in abdominal pain, bloating, and quality of life compared to control diets. In IBD, improvements were mainly observed in functional gastrointestinal symptoms, while no clear benefit was demonstrated in GERD. Heterogeneity in study designs, intervention durations, comparator diets, and outcome measures limited the ability to conduct a meta-analysis. Conclusions: Although a low-FODMAP diet may reduce symptoms in selected individuals, it is not universally necessary. Importantly, the diet’s restrictive nature and potential long-term effects—such as nutritional deficiencies and alterations in gut microbiota—highlight the need for clinical supervision by dietitians with expertise in gastrointestinal disorders. Furthermore, in some cases, symptom improvement may be achievable through less restrictive changes, such as improving food hygiene and reducing intake of processed or high-sugar foods. Further high-quality randomized controlled trials with standardized endpoints and longer follow-up are needed to clarify the efficacy and safety of the low-FODMAP diet across various gastrointestinal conditions. Full article

The gut serves as the main site for nutrient digestion and absorption. Simultaneously, it functions as the body’s largest immune organ, playing a dual role in sustaining physiological equilibrium and offering immunological defense against intestinal ailments. Maintaining the structural and functional integrity of the intestine is paramount for ensuring animal health and productivity. Puerarin, a naturally derived isoflavonoid from the Pueraria species, exhibits multifaceted bioactivities, such as antioxidant, anti-inflammatory, antimicrobial, and immunomodulatory properties. Emerging evidence highlights puerarin’s capacity to enhance gut health in farm animals through four pivotal mechanisms: (1) optimization of intestinal morphology via crypt-villus architecture remodeling, (2) augmentation of systemic and mucosal antioxidant defenses through Nrf2/ARE pathway activation, and (3) reinforcement of intestinal barrier function by regulating tight junction proteins (e.g., ZO-1, occludin), mucin secretion, intestinal mucosal immune barrier, the composition of microbiota, and the derived beneficial metabolites; (4) regulating the function of the intestinal nervous system via reshaping the distribution of intestinal neurons and neurotransmitter secretion function. This review synthesizes current knowledge on puerarin’s protective effects on intestinal physiology in farm animals, systematically elucidates its underlying molecular targets (including TLR4/NF-κB, MAPK, and PI3K/Akt signaling pathways), and critically evaluates its translational potential in mitigating enteric disorders such as post-weaning diarrhea and inflammatory bowel disease in agricultural practices. Full article

Irritable bowel syndrome (IBS) is a widespread functional gastrointestinal disorder characterised by chronic abdominal discomfort and altered bowel habits. Despite its high impact on life quality and healthcare systems, the initial pathophysiology of IBS is not yet fully understood. The present narrative review aims to synthesise and integrate recent evidence regarding the multifactorial nature of IBS, focusing on the interplay between gut–brain interactions, microbiota, and immune responses, without proposing a novel model but rather reinforcing and updating existing conceptual frameworks. A comprehensive literature search of relevant studies published in English during the past two decades was conducted using Pub-Med, Scopus, and Google Scholar. The selected articles were thoroughly evaluated to provide a complete overview of IBS-related research. The review demonstrates that IBS is not only a multifactorial condition involving gut–brain axis dysregulation, altered gut motility, visceral hypersensitivity, and microbiome disturbances, but also a crucial psychosocial factor. Modern therapeutics targeting the microbiota and neurogastroenterology pathways show promising results but require further investigation. IBS represents a heterogeneous disorder with complex interrelated mechanisms. Improvements in understanding its multifaceted nature are of paramount importance in developing more effective diagnostic and therapeutic approaches. Continued research is essential to unravel the intricacies of IBS and improve patient outcomes. Full article

The human gut microbiome is intricately linked to systemic and organ-specific immune responses and is highly responsive to dietary modulation. As metagenomic techniques enable in-depth study of an ever-growing number of gut microbial species, it has become increasingly feasible to decipher the specific functions of the gut microbiome and how they may be modulated by diet. Diet exerts both supportive and selective pressures on the gut microbiome by regulating a multitude of factors, including energy density, macronutrient and micronutrient content, and circadian rhythm. The microbiome, in turn, contributes to local and systemic immune responses by providing colonization resistance against pathogens, shaping immune cell activity and differentiation, and facilitating the production of bioactive metabolites. Emerging research has strengthened the connections between the gut microbiome and cardiometabolic disorders (e.g., cardiovascular disease, obesity, type-2 diabetes), autoimmune conditions (e.g., type-1 diabetes, rheumatoid arthritis, celiac disease), respiratory disease, chronic kidney and liver disease, inflammatory bowel disease, and neurological disorders (e.g., Alzheimer’s, Parkinson’s disease, depressive disorders). Here, we outline ways in which dietary factors impact host response in diseases through alterations of gut microbiome functionality and composition. Consideration of diet-mediated microbial effects within the context of the diseases discussed highlights the potential of microbiome-targeted treatment strategies as alternative or adjunct therapies to improve patient outcomes. Full article

Background: Lysosomal storage disorders (LSDs) are rare inherited metabolic diseases characterized by defects in lysosomal enzyme function or membrane transport. These defects lead to substrate accumulation and multisystemic manifestations. This review focuses on gastrointestinal (GI) involvement in LSDs, which is a significant but often overlooked aspect of these disorders. Methods: A comprehensive literature review was conducted to examine the pathophysiology, clinical presentation, diagnosis and management of GI manifestations in several LSDs, including Fabry disease, Gaucher disease, Pompe disease, Niemann–Pick disease type C, mucopolysaccharidoses and Wolman disease. Results: The pathogenesis of GI involvement in LSDs varies and encompasses substrate accumulation in enterocytes, mesenteric lymphadenopathy, mass effects, smooth muscle dysfunction, vasculopathy, neuropathy, inflammation and alterations to the microbiota. Clinical presentations range from non-specific symptoms, such as abdominal pain, diarrhea and malabsorption, to more severe complications, such as protein-losing enteropathy and inflammatory bowel disease. Diagnosis often requires a high level of suspicion, as GI symptoms may precede the diagnosis of the underlying LSD or be misattributed to more common conditions. Management strategies include disease-specific treatments, such as enzyme replacement therapy or substrate reduction therapy, as well as supportive care and targeted interventions for specific GI complications. Conclusions: This review highlights the importance of recognizing and properly managing GI manifestations in LSDs to improve patient outcomes and quality of life. It also emphasizes the need for further research to develop more effective treatments for life-threatening GI complications associated with these rare genetic disorders. Full article

Diarrhea-predominant irritable bowel syndrome (IBS-D) is a functional gastrointestinal disorder characterized by altered motility, abdominal pain, and dysbiosis—particularly reduced biodiversity and a lower abundance of butyrate-producing bacteria. Strategies that modulate the gut microbiota may offer therapeutic benefit. Clostridium butyricum (C. butyricum) CBM588 is a butyrate-producing probiotic with immunomodulatory properties and potential efficacy in treating gastrointestinal disorders. This pragmatic, prospective, open-label, single-arm interventional study assessed the clinical, microbial, and safety-related effects of an 8-week CBM588 supplementation, along with a low-fiber and low-residue diet, in 205 patients with IBS-D who attended Quisisana Nursing Home Hospital, Rome, Italy, between November 2024 and February 2025. The primary outcomes included the global symptom response, the Bristol Stool Scale (BSS), stool frequency, diarrhea episodes, abdominal pain (severity and frequency), bloating, bowel dissatisfaction, quality of life (QoL), safety, and treatment tolerability—measured using the IBS Symptom Severity Scale (IBS-SSS) and a standardized tolerability scale. CBM588, in patients treated with a low-fiber and low-residue diet, significantly improved all clinical endpoints, with a >80% reduction in diarrhea episodes; ~60% reductions in stool frequency and abdominal pain; and >50% improvements in bloating, bowel dissatisfaction, and QoL. Treatment was well tolerated (mean tolerability score 8.95 ± 0.88), with >95% adherence, and no serious adverse events were reported. The secondary outcomes included changes in gut microbiota. In a subset of patients, 16S rRNA gene sequencing showed increased α-diversity and enrichment of butyrate-producing genera (Agathobacter, Butyricicoccus, Coprococcus), which correlated with symptom improvement. Bloating increased in some patients, possibly related to fermentation activity. These findings support the C. butyricum CBM588 probiotic strain as a safe, well-tolerated, and microbiota-targeted intervention for IBS-D. Randomized controlled trials are warranted to confirm efficacy. Full article

Background/Objectives: Gastrointestinal disorders include a broad spectrum of clinical conditions due to various symptoms. Abdominal pain claims attention as it can be associated with multiple diseases, and some of them can lead to chronic abdominal pain, such as chronic gastritis and irritable bowel syndrome. Moreover, dyspepsia is also a prevalent condition, and its symptoms are postprandial fullness, epigastric pain or burn, and early satiety. Conventional therapeutic approaches for gastrointestinal disorders exist, but the Mentha plant has a millenary tradition. Mentha aerial parts and leaves hold therapeutic and pharmacological value, and its components are characterized as non-essential oil with superabundant phenolic compounds, and essential oil classified as volatile secondary metabolites like menthol and menthone. Studies have shown that Mentha species can exert benefits by modulating the inflammatory process and scavenging free radicals, which can benefit gastrointestinal tract disorders. The aim of this review was to systematically investigate the effects of Mentha species on gastrointestinal disorders. Methods: Sixteen clinical trials included patients diagnosed with irritable bowel syndrome, functional dyspepsia, and functional abdominal pain, as well as some healthy volunteers. The COCHRANE tool was utilized to assess the bias of the included studies. Results: Most studies reported significant outcomes for Mentha oil-treated groups, such as better control of abdominal pain and discomfort, even though two trials did not report superior outcomes. Conclusions: Due to the increasing interest in natural compounds, further clinical trials are necessary to confirm the status of Mentha for improvement in gastrointestinal disorders. Full article