Search Results (16,775)

The clinical relevance of food-specific IgG antibodies in pediatric gastrointestinal disorders remains controversial. Although current international guidelines discourage their use as standalone diagnostic tools, their significance within a broader immune–gut inflammatory framework has not been sufficiently explored. This study aimed to investigate associations between food-specific IgG reactivity, inflammatory and permeability biomarkers, microbiological findings, and abdominal ultrasound abnormalities in children with chronic gastrointestinal symptoms. Methods: (1) Children presenting chronic gastrointestinal symptoms associated with food-specific IgG polysensitization, elevated inflammatory and permeability biomarkers, and abdominal ultrasound abnormalities (number (n) = 196); (2) a symptomatic gastrointestinal group without the complete multimodal profile (n = 146); and (3) a control group with normal abdominal ultrasound findings and biomarkers within reference ranges (n = 210). All participants underwent food-specific IgG testing using a 216-antigen ELISA panel, abdominal ultrasound examination, and assessment of intestinal inflammatory and permeability biomarkers. Food-specific IgG antibodies were not interpreted as diagnostic markers of food allergy or food intolerance. Comparative analyses, correlation analyses, multivariable logistic regression, and receiver operating characteristic (ROC) analyses were performed. Results: Food-specific IgG polysensitization was significantly more frequent among children presenting the multimodal inflammatory profile compared with symptomatic and control groups (all p < 0.001). Reactivity predominantly involved gluten-containing cereals, dairy proteins, and mixed gluten–dairy patterns. Elevated fecal calprotectin, zonulin, and fecal histamine concentrations were more frequently observed in this subgroup, together with a higher prevalence of ultrasound abnormalities, including bowel wall thickening and mesenteric lymphadenopathy. Correlation analyses demonstrated significant associations between cumulative IgG burden and bowel wall thickness (r = 0.48, p < 0.001), while fecal calprotectin showed the strongest association with ultrasound abnormalities (r = 0.62, p < 0.0001). Multivariable logistic regression identified elevated calprotectin, increased zonulin, IgG polysensitization, and mixed gluten–dairy reactivity as independent predictors of pathological ultrasound findings. The integrated multimodal model demonstrated higher classification performance than isolated biomarkers. Conclusions: Children presenting chronic gastrointestinal symptoms, food-specific IgG polysensitization, inflammatory biomarker abnormalities, and ultrasound changes represented a multimodal clinical subgroup within the study population. These findings support evaluating food-specific IgG reactivity within a broader immune–gut assessment framework rather than as a standalone diagnostic biomarker. The observed associations should be considered exploratory and hypothesis-generating, requiring prospective validation and mechanistic investigation. Full article

Background/Objectives: White–Sutton syndrome (WHSUS; OMIM 616364) is a rare neurodevelopmental disorder caused by pathogenic variants in the POGZ gene and characterized by developmental delay, intellectual disability, speech impairment, autism spectrum features, and dysmorphic traits. Although most reported cases are sporadic, inherited forms are exceptionally rare. We describe a familial case of WHSUS involving an affected mother and two children carrying a heterozygous POGZ nonsense variant, highlighting marked intra-familial phenotypic variability and expanding the clinical spectrum of the disorder. Methods: Clinical evaluation included multidisciplinary assessments. Genetic testing was performed using clinical exome sequencing (CES) with a virtual neurodevelopmental disorder (NDD) gene panel, followed by Sanger confirmation and segregation analysis in family members. The POGZ transcript reference NM_015100.3 was used for variant nomenclature and verified with the Mutalyzer tool. CNV detection from NGS data was performed using the Alissa CNV caller (Agilent) and visualized via IGV; the Xp11.22 microduplication was confirmed by chromosomal microarray (aCGH) and parental segregation analyses. Results: CES identified the heterozygous pathogenic POGZ variant c.1522C>T (p.Arg508*) in the female proband (III₆), an infant presenting with global developmental delay, hypotonia, speech impairment, gait abnormalities, and characteristic dysmorphic features. Segregation analysis demonstrated maternal inheritance and confirmed the presence of the variant in her affected brother (III₄), who also carries a de novo 1.79 kb microduplication at Xp11.22, while the maternal grandparents tested negative, indicating a de novo origin in the mother. The mother exhibited an attenuated phenotype, including mild neuropsychiatric and gastrointestinal manifestations. The variant is predicted to undergo nonsense-mediated decay (NMD), consistent with a moderate clinical presentation; however, experimental validation was not performed. Conclusions: This report documents a rare familial occurrence of WHSUS with highly variable expressivity. Our findings broaden the phenotypic and molecular characterization of POGZ-related disorders and emphasize the importance of comprehensive segregation studies and early genomic diagnosis. While experimental data link POGZ deficiency to DNA repair defects, no longitudinal clinical studies have demonstrated increased cancer risk in WHSUS; therefore, formal malignancy screening guidelines cannot be established at present, and this issue deserves future study in larger cohorts or registries. Full article

Background/Objectives: Triple-negative breast cancer (TNBC) remains a highly aggressive malignancy with limited therapeutic options due to the absence of well-defined molecular targets. Diet-induced obesity (DIO) promotes TNBC progression by reshaping systemic metabolism and inflammatory responses; however, the key circulating metabolites involved and their mechanisms remain largely unclear. This study aimed to identify key metabolites associated with TNBC progression and further investigate their biological functions and molecular mechanisms. Methods: Targeted metabolomics profiling was performed on serum samples from MMTV-PyMT spontaneous breast cancer mice to identify differential metabolites associated with DIO. Functional assays were conducted to evaluate the effects of hippuric acid on TNBC cell proliferation, migration, and invasion. RNA sequencing was conducted to explore downstream regulatory pathways, followed by validation of candidate targets using gain- and loss-of-function approaches as well as rescue experiments. Results: Hippuric acid was identified as a significantly altered metabolite in DIO conditions. Functional studies demonstrated that hippuric acid markedly inhibited the proliferation, migration, and invasion of TNBC cells, with minimal effects on non-TNBC cells. Transcriptomic analysis identified EGFL8 as a potential downstream target, which was further confirmed by qPCR and functional assays. Overexpression of EGFL8 suppressed malignant phenotypes, whereas its knockdown promoted tumor progression. Rescue experiments showed that EGFL8 partially mitigated the inhibitory effects of hippuric acid on TNBC, suggesting that it functions as an important mediator in this process. Mechanistically, hippuric acid exerted its anti-tumor effects at least in part through modulation of the EGFL8-Notch signaling axis. Conclusions: Hippuric acid suppresses TNBC progression via the EGFL8-Notch signaling pathway. These findings highlight a previously unrecognized role of a gut microbiota-derived metabolite in TNBC and suggest its potential as a therapeutic candidate, providing new prospective targets and a theoretical basis for metabolic intervention for TNBC. Full article

Background: Benzimidazole (BZ) resistance in the gastrointestinal nematode Haemonchus contortus is a major constraint to sheep production worldwide. However, data on the prevalence and molecular mechanisms of resistance in Yili Prefecture, Xinjiang—a key livestock region in Northwestern China—remain limited. This study aimed to determine the frequency of BZ resistance-associated single nucleotide polymorphisms (SNPs) in H. contortus populations from Zhaosu and Tekesi counties. Methods: Adult male worms (n = 150) were collected from naturally infected sheep at local abattoirs. Species identity was confirmed morphologically by sequencing the internal transcribed spacer 2 (ITS-2) region. A 385 bp fragment of the isotype-1 β-tubulin gene was amplified and sequenced to detect SNPs at codons 167 (F167Y), 198 (E198A), and 200 (F200Y). Results: The F167Y mutation was absent in all individuals. In contrast, the E198A mutation occurred at exceptionally high frequencies, with resistant allele frequencies (RAF) of 64.7% in Zhaosu and 52.7% in Tekesi. The F200Y mutation showed clear geographical variation: it remained low in Zhaosu (RAF = 9.3%) but was substantially higher in Tekesi (RAF = 33.3%). Haplotype analysis revealed that resistance in Zhaosu was driven primarily by the E198A mutation, whereas the Tekesi population exhibited complex patterns of co-selection of both E198A and F200Y, with a high proportion of double-heterozygous individuals (29.3%). Conclusions: This study provides comprehensive molecular evidence of severe BZ resistance in H. contortus populations from Zhaosu and Tekesi counties, Yili Prefecture. The marked predominance of the E198A mutation, together with the emergence of multi-locus resistance in Tekesi, indicates a rapid escalation of resistance beyond historical levels. These findings suggest that benzimidazoles are likely ineffective in this region and highlight the urgent need to revise local parasite control strategies. Full article

Shilajit is a complex natural phytomineral substance whose composition and biological activity may vary depending on geographical origin. This study compared three commercially available Shilajit samples from Russia (S1), Nepal (S2), and Iran (S3) in terms of phenolic acid profile, antimicrobial activity, and their effects on selected intestinal microorganisms and β-glucuronidase activity after simulated gastrointestinal digestion. The samples differed markedly in their phenolic composition, with S3 showing the highest total content of the quantified phenolic acids. All samples exhibited antimicrobial activity, although their intensity depended on the microorganism tested. The in vitro digestion model revealed clear sample-dependent effects: S2 showed the lowest net β-glucuronidase activity and the most beneficial modulation of Lactobacillus and Bifidobacterium, whereas S1 exerted the strongest suppressive effect on Escherichia coli. In contrast, S3, despite the richest phenolic profile, showed the highest β-glucuronidase activity. These findings indicate that the biological activity of Shilajit depends not only on the quantified phenolic acids but also on the broader, region-specific chemical matrix of the material. Full article

Poor aqueous solubility and consequently low bioavailability of various NSAIDs (non-steroidal anti-inflammatory drugs) usually result in high and multiple dosing with potentially serious side effects. Therefore, systems for the effective transport of NSAIDs through the GIT (gastrointestinal tract), ensuring enhanced bioavailability, remain in high demand. In the present work, we studied chitosan (CS) hydrogel lyophilizates as carrier systems for a model NSAID, namely ibuprofen (IBU). The CS-IBU lyophilizates were prepared from homogeneous or heterogeneous CS-IBU hydrogels to assess their influence on the resulting lyophilizate microstructure and IBU dissolution profiles. To gain a complex view of the CS-IBU behavior and its practical consequences, dissolution profiles of free IBU (reference) and CS-associated IBU (CS-IBU) were examined and compared to each other at variable pH (1.2 and 6.5) in two separate dissolution systems and in one discontinuous dissolution system mimicking GIT conditions. The results of dissolution experiments were supported by kinetic model data. This study demonstrated that the dissolution of IBU from the CS-IBU lyophilizates is affected by two main pH-dependent competitive effects; i.e., dissolved CS acts as an IBU solubilizer and the undissolved CS matrix serves as an IBU trap, which could be used in the rational design of innovative stimuli (pH)-responsive oral dosage forms of IBU. Full article

Background/Objectives: Adult patients supported with extracorporeal membrane oxygenation (ECMO) frequently require invasive diagnostic, therapeutic, surgical, or bedside procedures during ongoing extracorporeal support. These procedures are clinically challenging because ECMO-related anticoagulation, platelet dysfunction, acquired coagulopathy, and circuit-related coagulation activation may increase both bleeding and thrombotic risks. This systematic review evaluated the safety of invasive procedures performed during adult ECMO support, excluding tracheostomy/tracheotomy because this procedure has recently been addressed in a dedicated systematic review. Methods: A systematic search of PubMed/MEDLINE and Scopus was performed. The final bibliographic data collection was completed in April 2026. Studies were eligible if they included adult ECMO or extracorporeal life support patients undergoing invasive procedures during ongoing ECMO support, or with ECMO used as procedural support, and reported at least one procedure-specific safety outcome. Primary outcomes were procedure-related complications, bleeding, major bleeding, and transfusion requirements. Secondary outcomes included thrombotic and circuit-related complications, oxygenator exchange, reintervention, reoperation, procedural failure, ECMO duration, intensive care unit and hospital length of stay, and mortality. Results: The final qualitative synthesis included 46 studies, comprising 26 studies from PubMed/MEDLINE and 20 additional unique studies from Scopus. Included procedures were grouped into six domains: airway, bronchoscopic, and tracheobronchial procedures; thoracic surgery and lung resections; abdominal surgery, gastrointestinal endoscopy, and decompressive laparotomy; lung transplantation and perioperative extracorporeal life support; cardiovascular, vascular, pulmonary embolism-related, and mechanical circulatory support-related procedures; and mixed non-cardiac surgery. Airway and bronchoscopic procedures generally showed high procedural success in selected cohorts, although registry-level tracheal procedure data reported hemorrhagic complications in 26.0% and surgical-site bleeding in 13.0%. Emergency thoracic and abdominal procedures carried the highest bleeding, transfusion, reintervention, and mortality burden. Lung transplantation studies showed that ECMO can be integrated into perioperative pathways, but hemothorax, transfusion, thromboembolism, and anticoagulation strategy remained central safety issues. Conclusions: Invasive procedures during adult ECMO are feasible in selected patients and experienced centers, but procedural safety varies markedly by procedure type, urgency, baseline disease severity, and anticoagulation strategy. A procedure-centered, multidisciplinary approach with individualized anticoagulation management and careful planning is essential. Full article

Background/Objectives: Tordylium trachycarpum Boiss. (Apiaceae) is traditionally used in Kurdish ethnomedicine for the management of gastrointestinal disorders; however, its pharmacological efficacy and safety profile remain insufficiently investigated. This study evaluated, for the first time, the gastroprotective activity and associated antioxidant, inflammatory, and apoptotic responses of the methanolic extract of T. trachycarpum using an ethanol-induced gastric ulcer model in Sprague–Dawley rats. Methods: Preliminary phytochemical screening revealed the presence of phenolics, flavonoids, terpenoids, tannins, coumarins, and glycosides. Acute oral toxicity testing demonstrated no signs of toxicity at doses up to 5 g/kg. Gastric ulceration was induced by absolute ethanol, and animals were pretreated with the extract (250 and 500 mg/kg) or omeprazole (20 mg/kg). Results: The extract significantly decreased the gastric lesion area from 258.50 ± 6.38 mm² in the ulcer control group to 143.70 ± 0.76 mm² and 115.50 ± 0.76 mm², corresponding to ulcer inhibition rates of 44.41% and 55.31%. Additionally, the extract increased mucus production, maintained mucosal structure, and raised stomach pH. Biochemical analysis showed a significant increase in antioxidant enzymes [superoxide dismutase (SOD) and catalase (CAT)] and a reduction in malondialdehyde (MDA) levels, indicating attenuation of oxidative stress. In addition, the extract modulated pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-10). Blood-based ELISA analysis demonstrated increased expression of heat shock protein 70 (HSP70) and reduced Bax levels, suggesting anti-apoptotic activity. Conclusions: These findings indicate that T. trachycarpum exerts significant gastroprotective activity through antioxidant, anti-inflammatory, and anti-apoptotic mechanisms, supporting its traditional use and highlighting its potential as a natural therapeutic candidate for the management of gastric ulcers. Full article

Background/Objectives: Patients with unresectable pancreatic ductal adenocarcinoma (UR-PDAC) are vulnerable to rapid nutritional deterioration. The clinical relevance of short-term nutritional change during the diagnostic-to-treatment interval (DTI) remains unclear. In this study, we evaluated whether a dynamic change in the Geriatric Nutritional Risk Index (ΔGNRI) during the DTI is associated with treatment tolerability, treatment continuity, and survival. Methods: This single-center retrospective study included 120 patients with histologically confirmed UR-PDAC who initiated first-line palliative chemotherapy between January 2016 and April 2024. ΔGNRI was defined as the GNRI immediately before chemotherapy minus the GNRI at the initial visit. ΔGNRI was primarily analyzed as a continuous variable, and an exploratory cut-off value of −6.8 was determined by receiver operating characteristic analysis. One-to-one propensity score matching was performed as a sensitivity analysis. Clinically significant adverse events (AEs) were defined as grade ≥3 AEs or AEs requiring treatment modification, hospitalization, or treatment discontinuation. Results: Patients in the GNRI-decreased group had more frequent clinically significant non-hematologic AEs, including gastrointestinal AEs, higher hospitalization rates due to AEs, and more frequent early treatment discontinuation. ΔGNRI remained independently associated with early treatment discontinuation and failure to transition to second-line therapy in multivariable analyses. Patients in the GNRI-decreased group also had significantly shorter times to treatment failure and overall survival. These findings were consistent in propensity score-matched analyses. Conclusions: Dynamic nutritional decline during the DTI was associated with impaired treatment resilience and poor survival outcomes in UR-PDAC. ΔGNRI may help identify patients with emerging nutritional vulnerability before chemotherapy. Full article

Appendiceal mucinous neoplasms (AMNs) are a rare but clinically significant category of gastrointestinal tumors, ranging from low-grade appendiceal mucinous neoplasm (LAMN), the main precursor of pseudomyxoma peritonei (PMP), to high-grade appendiceal mucinous neoplasm (HAMN), poorly differentiated and signet-ring-cell adenocarcinomas, and goblet cell adenocarcinoma. Although current WHO and PSOGI classifications provide well established diagnostic criteria, controversies persist regarding the biological behavior and prognostic significance of the most aggressive subtypes and the relationship between HAMN and mucinous adenocarcinoma. While appendectomy is sufficient for localized LAMN, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is the treatment of choice for peritoneal dissemination This review integrates the histopathological and molecular classification of AMN and PMP with the evolution of intraperitoneal chemotherapy. Key findings indicate that KRAS and GNAS mutations are central drivers of mucin overproduction and peritoneal spread, that tumor grade and mucin cellularity remain the strongest prognostic determinants, and that the evidence supporting HIPEC and PIPAC derives largely from observational rather than randomized data. As a novel insight, we highlight the emerging role of patient-derived organoids as translational models for functional drug testing. Progress will depend on integrating molecular characterization, critical appraisal of intraperitoneal therapies, and organoid-based testing to advance individualized treatment for peritoneal surface malignancies. Full article

This preliminary study characterises type I collagen in the digestive system of the greater weever (Trachinus draco L.) by integrating histochemical and biochemical techniques. To the best of our knowledge, this study represents the first baseline mapping of type I collagen within the gastrointestinal tract of this species. Mallory staining and indirect immunofluorescence confirmed collagen presence across the oesophagus, stomach, and intestine. The histochemical quantification of the fluorescent area (100 measurements per organ across 15 fish specimens) showed no significant differences (p = 0.1315), indicating a uniform spatial distribution. However, biochemical analysis via hydroxyproline assay and a two-way ANOVA revealed significant differences in collagen content among organs (p = 0.0308). The stomach yielded the highest concentration (4.199 µg/mg), significantly exceeding that of the intestine (1.713 µg/mg; Šídák’s post hoc, p = 0.0300). This discrepancy suggests that the higher gastric content is due to greater fibre density rather than distribution area. SDS-PAGE and Western blot confirmed protein molecular weights of 100–130 kDa, corresponding to α1 and α2 chains typical of type I collagen. The combination of these histochemical and biochemical methods effectively detects and characterises collagen in fish gastrointestinal by-products. By introducing T. draco as a novel subject in this context, these findings provide essential baseline anatomical and histological data and offer a clear scientific justification for the biotechnological valorisation of unutilised commercial fishing by-products, fully aligning with sustainable marine circular economy principles. Full article

Background/Objectives: Numerous studies have investigated the responses of the gastrointestinal tract to tastants, particularly in specialized enteroendocrine and other chemosensory cells. However, many of these investigations used various taste stimuli often at high concentrations or relied on immortalized cell lines or heterogeneous cell populations, which can limit their physiological relevance and reproducibility. To establish a stable, physiologically representative model system for consistently investigating gut epithelial responses to tastants, our study developed 3D murine intestinal organoids (MIOs). Methods: Murine intestinal organoids were generated from isolated intestinal crypts and cultured under defined conditions to maintain epithelial differentiation. Organoids were stimulated with selected nutrients and tastants, and downstream signaling responses were assessed using hormone secretion assays. Results: The 3D MIO culture system was successfully established, providing a robust in vitro platform for studying extraoral bitter sensing and release of the enteroendocrine hormone cholecystokinin. Moreover, 5 mM denatonium benzoate and 30 mM L-glutamic acid specifically induced cholecystokinin secretion in MIOs, whereas other bitter or non-bitter stimuli did not. Conclusions: Murine intestinal organoids provide a stable model for studying nutrient- and tastant-evoked signaling in the gut. This approach enables precise investigation of underlying mechanisms and may advance our understanding of gut chemosensation and metabolic regulation. Full article

The aim of the present study was to investigate the bioactive composition of pomegranate peel and to produce a phenolic-rich extract for encapsulation using vibrating nozzle technology. Conventional heat- and advanced microwave-assisted extraction of phenolic compounds were investigated, and the extract with the highest phenolic content was used to perform encapsulation with alginate-based delivery solutions containing fava bean proteins, mucin, carboxymethyl cellulose, nutriose, and collagen hydrolysates. The formulated beads were characterized for their physico-chemical (morphology, size distribution parameters, and FT-IR spectra) and bioactive (encapsulation efficiency and simulated gastrointestinal digestion) properties. The highest yields of punicalin, punicalagin, and ellagic acid (9.40, 44.51, and 3.95 mg g⁻¹ DM, respectively) were achieved by heat-assisted extraction at 80 °C. The addition of fava bean proteins and carboxymethyl cellulose to the alginate-based delivery solutions resulted in the highest encapsulation efficiency of total phenols (83.99 and 83.78%, respectively). However, the beads formulated with fava bean proteins were irregularly shaped, while those with carboxymethyl cellulose were predominantly spherical. All beads showed limited phenolic release under simulated gastric conditions, followed by enhanced release in the intestinal phase. Overall, the obtained results indicate that encapsulation efficiency was governed by the combined effects of rheological parameters, bead morphology, and molecular interactions, highlighting the importance of a multi-parameter design approach in the development of effective delivery systems. Full article

The migrating myoelectric complex (MMC) is the electrical basis of fasting small intestinal motility. Although oxytocin (OT) regulates gastrointestinal functions through oxytocin receptors (OTRs), its effect on jejunal MMC activity during fasting remains unclear. This study investigated the effects of OT on jejunal MMC activity in fasted rats and evaluated the involvement of OTRs, glucagon-like peptide-1 receptors (GLP-1Rs), and nitric oxide (NO) pathways. Bipolar electrodes were implanted at three jejunal sites in adult male Sprague Dawley rats for MMC recordings. After recovery and 18 h fasting, OT was administered intraperitoneally (4–32 µg/kg) following one hour of basal recording. To assess mechanisms, rats were pretreated with the OTR antagonist atosiban (2 mg/kg), the GLP-1R antagonist exendin (9–39) (200 µg/kg), or the nitric oxide synthase inhibitor NG-nitro-L-arginine (L-NNA; 5 mg/kg) before OT (16 µg/kg). Oxytocin dose-dependently reduced spike frequency and MMC cycle number (p < 0.05–0.001 vs. vehicle). Atosiban completely reversed these effects (p < 0.001 vs. OT), while exendin (9–39) partially attenuated them (p < 0.01–0.001 vs. OT). L-NNA showed no significant effect. These findings indicate that OT inhibits jejunal MMC activity via OTR-dependent mechanisms with partial involvement of GLP-1R signaling but not NO pathways. Full article

The gut microbiota and its metabolites, as components of the gut–bone axis, play a pivotal role in regulating skeletal homeostasis through the bidirectional communication network. In this systematic review, evidence was collected from mainstream databases following standardized inclusion/exclusion criteria for screening, to comprehensively retrieve and screen eligible studies from multiple mainstream databases according to standardized inclusion and exclusion criteria, and systematically summarize current research progress on plant-derived bioactive compounds targeting the gut–bone axis for skeletal health regulation. This review systematically explores the underlying mechanisms of the gut–bone axis and critically evaluates the regulatory effects and therapeutic potential of plant-derived bioactive compounds. Particular attention is given to targeted interventions involving prebiotics, probiotics, synbiotics, and plant-rich diets or functional foods. Among these interventions, synbiotics represent the most successful strategy and show the most prominent therapeutic possibilities in bone-related disorders. Different from single prebiotics (only nourish endogenous intestinal microbes), individual probiotics (easy to be degraded in gastrointestinal tract with poor colonization) and ordinary plant-rich diets (unfixed effective dosage and weak targeting property), synbiotics combine prebiotic carriers and viable probiotic strains to produce complementary advantages, which is the core reason for its outstanding therapeutic prospect against bone diseases. Synbiotics exert synergistic effects on gut microecology, mineral absorption, and immune regulation, leading to more robust and consistent improvements in bone health than single prebiotics, probiotics, or general plant-rich diets. They have been verified in preclinical and clinical studies to ameliorate osteoporosis and related skeletal diseases via the gut–bone axis. These strategies offer novel insights into the prevention and treatment of bone metabolic disorders, such as osteoporosis, by targeting the gut–bone axis with phytochemicals. Key outcomes of this review include that synbiotics, soy isoflavones, naringin, curcumin, and resveratrol effectively improve bone mineral density, restore gut microbiota balance, and inhibit pathological bone resorption via the gut–bone axis. Collectively, the above bioactive substances realize bone protection mainly by reshaping gut flora, elevating mineral uptake and suppressing excessive osteoclast activity. Representative cases include soy isoflavones mitigating estrogen-deficient bone loss in OVX models, naringin improving the trabecular microarchitecture, and probiotic BL-11 promoting longitudinal bone growth in children. Future directions will focus on clarifying dose–response relationships, developing standardized synbiotic formulations, constructing microbiome-guided precision diets, and conducting large-sample randomized controlled trials to translate plant-derived compounds into clinical therapies. Full article