Search Results (378)

Cleft palate is a congenital anomaly that causes functional and esthetic challenges, and the hard palate is essential for feeding, speech, and separation of the oral and nasal cavities. Yet, current reconstructive techniques do not restore its bony component. Building on previous in vitro work showing that decellularized palatal mucoperiosteum, microperforated with Quantum Molecular Resonance (QMR^®) technology and recellularized with mesenchymal stem cells, preserves the collagen microenvironment, supports engraftment, and shows osteoinductive potential, this study evaluated the early feasibility and regenerative potential of bioengineered mucoperiosteal scaffolds (BEMS) in Landrace pigs model. Bone marrow was collected from recipient pigs to isolate pBM-MSCs. Donor palatal mucoperiosteum was decellularized, microperforated, and recellularized with these cells to generate BEMS. After surgical creation of a cleft palate, four pigs received BEMS, and two controls underwent standard palatoplasty. At one month, scaffold-treated animals showed early mucosal and osseous regeneration, including neo-epithelium, connective tissue, and new bone formation, without clinical or routine histological signs of acute rejection. SPARC (Secreted protein acidic and rich in cysteine) expression supported osteogenic activity. Regenerated palates were stable and fracture-resistant, whereas controls showed incomplete repair and fractures. These findings suggest that BEMS may address limitations of conventional palatal reconstruction and support further investigation for human palatal bone regeneration. Full article

T helper cells (Th) are central to mucosal IgA induction and key targets for modulation by vaccine adjuvants. To improve understanding of cellular mechanisms underlying mucosal vaccine-induced immunity, we analyzed antigen-specific peripheral blood Th responses elicited by the oral enterotoxigenic Escherichia coli (ETEC) vaccine ETVAX, administered with or without the double mutant heat-labile toxin (dmLT) adjuvant. ETVAX, consisting of inactivated E. coli overexpressing colonization factors CFA/I, CS3, CS5, and CS6 with a heat-labile toxin B-subunit toxoid, was given orally in two doses to adult volunteers, either alone or with 10 or 25 µg dmLT. Antigen-specific Th-associated cytokine responses were assessed in stimulated peripheral blood mononuclear cells isolated from 15 to 18 individuals/group using ELISA and electrochemiluminescence assays. ETVAX predominantly induced Th1 (IFN-γ) and Th17 (IL-17A) responses, with minimal Th2-associated cytokines. Responses were markedly reduced after CD4+ T-cell depletion, supporting a Th cell origin. The strongest responses targeted LTB and CS3, with IFN-γ responses detected in 60–80% and IL-17A in 40–60% across all vaccinees. Responses to CFA/I, CS5 and CS6 were generally weaker. Exploratory comparisons suggested broader IFN-γ responses and more consistent IFN-γ and IL-17A responses to lower-dose antigens, particularly CS6, in recipients receiving vaccine plus 10 µg dmLT. These trends paralleled IgA antibody-secreting cell response patterns, with significantly enhanced IgA responses to CS6 in the vaccine plus 10 µg dmLT group. In conclusion, ETVAX induces antigen-specific Th1- and Th17-type responses in peripheral blood, supporting a role for cellular immunity in mucosal responses to oral ETEC vaccines. Full article

Background/Objectives: It remains unclear whether sleep deprivation induces constipation. This study aimed to evaluate the intervention effects of Bifidobacterium longum 151-1 and BN-BB01 on constipation induced by sleep deprivation in mice, and to explore the underlying mechanism from the perspective of the gut-brain axis, so as to provide a theoretical basis for probiotic intervention in sleep-related gastrointestinal dysfunction. Methods: A mouse model of sleep deprivation was established via the multiple platform water environment method. Through the detection and analysis of relevant indicators, the effects of sleep deprivation on intestinal function in mice were systematically investigated, and the changes in various indicators of mice after Bifidobacterium longum intervention were observed. Results: Sleep deprivation significantly impaired intestinal motility and intestinal mucosal barrier function in mice, reducing fecal water content by approximately 21.4%, prolonging the time to first black stool defecation by about 57 min, and decreasing goblet cell count by nearly 50%. In terms of gastrointestinal hormones and neurotransmitters, sleep deprivation significantly downregulated the levels of excitatory gastrointestinal hormones (MTL, GAS) and excitatory neurotransmitter SP by 22.3%, 14.8%, and 16.2%, respectively. Additionally, sleep deprivation promoted the secretion of the inhibitory neurotransmitter VIP and stress hormone CORT, with their levels increased by 53.1% and 23.8%, respectively. The levels of neurotransmitters including 5HT and GABA were reduced by 15.6% and 23.2%, which ultimately led to a decrease in short-chain fatty acid (SCFA) levels. Intervention with Bifidobacterium longum significantly reversed the above abnormalities. It elevated SCFA levels and upregulated the expression of SCFA receptors GPR41 and GPR109A, promoted the expression of BDNF and GDNF, inhibited HDAC activity, increased the abundance of the beneficial bacterium Akkermansia, and reduced the abundance of the harmful intestinal bacterium Alistipes. Conclusions: Bifidobacterium longum can alleviate sleep deprivation-induced constipation in mice by regulating gut-brain axis function, optimizing intestinal flora structure, modulating the secretion of gastrointestinal hormones and neurotransmitters, and repairing the intestinal mucosal barrier. This study provides a solid theoretical basis for the clinical application of probiotics in the intervention of sleep-related gastrointestinal disorders. Full article

Nasal polyposis is a multifactorial disorder arising from complex interactions among cellular, molecular, and inflammatory mechanisms. The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and other ion channels are essential for epithelial ion transport, mucosal hydration, and barrier integrity in the nasal airway. Prostaglandin E₂ (PGE₂) acts not only as an inflammatory mediator but also as a regulator of ion exchange through CFTR-dependent and CFTR-independent pathways. Ionocytes, specialized epithelial cells that regulate ion balance and fluid secretion in the respiratory tract, are closely associated with CFTR function. Both eosinophilic and non-eosinophilic inflammation may alter ionocyte abundance and function, thereby reducing normal CFTR activity. Chronic rhinosinusitis with nasal polyps (CRSwNP) is also characterized by diminished PGE₂ production. The I³PGE₂ hypothesis proposes that CRSwNP results from the combined effects of ion channel dysfunction, persistent inflammation, altered ionocyte number and function, and impaired PGE₂ synthesis. Together, these abnormalities disrupt nasal physiology and promote polyp formation. We hypothesize that corticosteroids and biologic therapies may improve CRSwNP by reducing inflammation, restoring ion channel activity, improving ionocyte function, and recovering PGE₂ production. These effects enhance hydration and mucociliary clearance, limit mucus accumulation, restore epithelial homeostasis and mucosal host defense, and ultimately contribute to the reduction or resolution of nasal polyps. Full article

Tryptophan (Trp) metabolism lies at the intersection of nutrition, gut microbiota, mucosal immunology, and systemic inflammation—processes that play key roles in many gastrointestinal and extraintestinal diseases. Trp is an essential amino acid obtained through dietary intake. Beyond its role in protein synthesis, it is metabolized through three principal pathways: the kynurenine pathway, the serotonin/melatonin pathway, and microbial metabolism in the gut leading to indole and related derivatives. The kynurenine pathway represents the primary route of Trp degradation and is strongly linked to inflammatory signaling. The serotonin pathway is particularly important for gastrointestinal physiology, influencing motility, secretion, and visceral sensitivity. In parallel, microbial Trp metabolism produces metabolites that regulate epithelial barrier integrity, modulate mucosal immune responses, and contribute to communication along the gut–organ axes. Across different disease states, several recurring patterns emerge. Inflammatory conditions frequently shift Trp metabolism toward the kynurenine pathway through increased IDO1 or TDO activity, resulting in changes in kynurenine metabolites and in the kynurenine-to-tryptophan (Kyn/Trp) ratio. At the same time, reduced microbial production of indole derivatives may impair aryl hydrocarbon receptor signaling and weaken barrier-protective and immunoregulatory mechanisms. Alterations in the serotonin pathway are also associated with disturbances in gastrointestinal motility and gut–brain communication. Together, these observations highlight Trp metabolism as an important framework for understanding interactions between diet, microbiota, and host responses in health and disease. However, it is important to clarify that much of the currently available evidence remains associative or is derived primarily from preclinical models. This narrative review, based on literature retrieved from major biomedical databases (e.g., PubMed/MEDLINE, Scopus, and Web of Science), aims to provide an updated synthesis of current knowledge on Trp metabolism in disease pathophysiology. Furthermore, while we highlight potential translational applications—such as proposed biomarker development and targeted therapeutic strategies—these perspectives have been moderated to acknowledge the limited level of clinical validation established to date. Full article

Eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP) is characterized by type 2 inflammation, including M2 macrophage infiltration. Baicalein is a flavonoid with anti-inflammatory properties. This study aimed to investigate the therapeutic effect of baicalein in a papain-induced eosinophilic rhinosinusitis model and to determine whether it acts through arachidonate 15-lipoxygenase (ALOX15)-dependent M2 macrophage function. Clinical nasal samples from controls, non-eosinophilic CRSwNP (neCRSwNP), and eCRSwNP were analyzed for ALOX15 expression and localization. THP-1 cells were differentiated and polarized toward M2 macrophages, and the effects of baicalein on ALOX15 expression, lipid peroxidation, cytokine secretion, and transcriptomic profile were examined. The ALOX15 inhibitor PD146176 was used for target validation. A murine eosinophilic rhinosinusitis model was established by intranasal papain instillation, followed by baicalein treatment. Mucosal inflammation, IgE levels, proteoglycan 2 (PRG2)/ALOX15 expression, and immune cell infiltration were evaluated. ALOX15 was upregulated in eCRSwNP tissues and localized to CD68⁺CD206⁺ M2 macrophages. In vitro, M2 polarization increased ALOX15 expression and lipid peroxidation. Baicalein suppressed ALOX15 expression, lipid peroxidation, and the secretion of CCL22, CCL2, CXCL12, FGF-2, and IL-15. PD146176 produced similar effects, and baicalein showed no additional effect after ALOX15 blockade. RNA sequencing revealed transcriptional remodeling in M2 macrophages after baicalein treatment. In vivo, papain increased ethmoid sinus mucosal thickening, serum IgE, PRG2/ALOX15 positive cells, and infiltration of CD45⁺ immune cells, CD170⁺ eosinophils, F4/80⁺ macrophages, and B220⁺ B cells. Baicalein significantly alleviated all these pathological changes. In conclusion, baicalein attenuates papain-induced eCRSwNP-like inflammation by inhibiting lipid peroxidation and ALOX15-associated M2 macrophage secretory function. The ALOX15/M2 macrophage axis may represent a potential therapeutic target for eCRSwNP. Full article

Antiretroviral therapy (ART) is essential for controlling human immunodeficiency virus (HIV) infection, requiring strict daily adherence for lifelong viral suppression. However, this continuous oral dosing results in persistent exposure of the gastrointestinal tract (GIT), raising the need to investigate the effects of TC-ART (Tri-combinationL: Abacavir, Dolutegravir, Lamivudine–ART) on epithelial integrity, barrier recovery mechanisms, and surface barrier architecture. TC-ART exposure (125 µM to 4000 µM) showed marked alterations in transepithelial resistance, permeability, and wound-healing abilities even at sub-cytotoxic doses. The dose exposure range at the mid-dose level showed the highest transcriptional activity, characterized by a downregulation of junctional genes [claudins (CLDNs), desmogleins (DSGs), and junctional plakoglobin (JUP)] and signaling mediators [the signal transducer and activator of transcription 3 (STAT3), mitogen-activated protein kinase 1 and 3 (MAPK1/3), and catenin beta 1 (CTNNB1)], along with reduced IL-9 expression that is linked to mucin loss. These transcriptional changes were consistent with structural findings, including partial transepithelial electrical resistance (TEER) recovery followed by a decline, delayed wound closure, and waning of the apical mucin layer in a dose-dependent manner. However, several cytokines, like IL-2 and IL-6, showed increased secretion despite lower transcriptional levels, suggesting alternative regulatory control during early stress responses. Together, these results support that TC-ART exposure alters epithelial responses in a way that may transition from early adaptation to signs of impaired recovery, leading to a gradual decline in mucosal barrier function. Such concentration- and time-dependent epithelial stress may contribute to gastrointestinal disturbances observed in treated HIV populations, emphasizing the need for incorporating intestinal epithelial health endpoints in drug safety evaluations. Full article

Environmental heat stress disrupts cellular homeostasis through coordinated molecular responses involving protein quality control, oxidative stress regulation, inflammatory signaling, and water homeostasis. Although saliva plays an essential role in maintaining oral homeostasis, the molecular pathways underlying salivary adaptation to heat stress remain insufficiently characterized. We hypothesized that integrating the human salivary proteome with systems biology approaches would identify a reproducible heat-stress-responsive molecular signature. Human salivary proteomic datasets retrieved from the Human Salivary Proteome Wiki were integrated into a non-redundant dataset comprising 15,594 protein accessions corresponding to 2540 distinct proteins. Following deduplication, functional annotation, and biological curation, proteins associated with heat stress response, oxidative stress regulation, inflammatory signaling, water homeostasis, salivary secretion, and mucosal protection were assembled into a Salivary Climate Stress Panel (SCSP). Protein–protein interaction and functional enrichment analyses were performed, and the biological relevance of the identified proteins was independently evaluated using a human heat stress transcriptomic meta-analysis comprising 322 comparisons and the GEO dataset GDS3004. Functional filtering identified 2050 heat-stress-associated salivary proteins, from which a curated SCSP of 35 proteins was established. Network analysis identified HSP90AB1, HSP90AA1, and IL1B as the principal hub proteins linking heat stress, oxidative stress, inflammatory signaling, and water homeostasis pathways, while transcriptomic validation confirmed consistent activation of representative SCSP genes under heat stress conditions. These findings provide a reproducible systems-level framework for investigating heat-stress-responsive molecular pathways in the human salivary proteome and support future studies on salivary biomarkers of environmental heat exposure. Full article

Background/Objectives: Mastication may influence oral mucosal immunity; however, its association with postprandial salivary secretory immunoglobulin A (s-IgA) dynamics remains unclear. This pilot study examined the association between mean chewing count per bite during rice ball consumption and the postprandial salivary s-IgA response in healthy men. Methods: Thirty-seven healthy adult men were enrolled. Mean chewing count per bite was analyzed continuously and secondarily in exploratory groups defined by the median (<30, n = 18; ≥30 chews/bite, n = 19). Unstimulated whole saliva was collected before, 0–5, 10–15, and 25–30 min after eating. Salivary s-IgA concentration, saliva weight, and s-IgA secretion rate were evaluated as absolute values and baseline ratios. Baseline-adjusted, repeated-measures, and sensitivity analyses were performed. Results: Mean chewing count per bite correlated positively with normalized salivary s-IgA concentration at 10–15 min (ρ = 0.347, p = 0.036) and 25–30 min (ρ = 0.352, p = 0.033), but these associations were attenuated after false discovery rate correction (q = 0.053 for both). Baseline salivary s-IgA was inversely associated with normalized responses. In exploratory group comparisons, normalized salivary s-IgA concentration was higher in the ≥30 chews/bite group at 10–15 and 25–30 min, whereas absolute s-IgA concentration, saliva weight, and s-IgA secretion rate did not differ between groups. Baseline-adjusted associations were not statistically significant. Conclusions: Higher mean chewing count per bite may be associated with greater relative postprandial salivary s-IgA responses in healthy adult men, but these findings are exploratory and should be interpreted cautiously. Full article

Fucoidan (FUC) exhibits immunomodulatory activity; however, its effects on intestinal mucosal immunity through dendritic cell (DC)-mediated regulation remain unclear. In this study, fucoidan was extracted from Saccharina japonica by hot-water extraction and characterized by chemical composition analysis, gel permeation chromatography (GPC), and Fourier-transform infrared spectroscopy (FT-IR). Bone marrow-derived DCs were used to evaluate the effects of FUC on DC maturation and immune function. An LPS-induced acute enteritis mouse model was used to assess intestinal injury, barrier function, and DC-mediated T/B cell immune responses. Structural analysis confirmed that purified FUC has the sulfated polysaccharide characteristics. FUC promoted DC maturation and enhanced antigen-presenting capacity. In LPS-induced enteritis, FUC reduced IL-1β, IL-6, and TNF-α levels and improved intestinal barrier integrity by restoring the mRNA expression of tight-junction-related genes. Mechanistically, FUC regulated the excessive activation of the TLR4/MyD88/NF-κB pathway, increased TGF-β and IFN-γ expression, modulated Th1/Th17/Treg immune balance, and promoted B cell homing and sIgA secretion. FUC regulates DC-mediated immune responses, repairs intestinal mucosal barrier function, and restores the intestinal immune microenvironment, thereby alleviating LPS-induced intestinal inflammation and maintaining intestinal homeostasis. Full article

Ethanol (EtOH)-induced gastric ulcer (GU) is a common model used to investigate mechanisms of mucosal injury and repair. Omeprazole (OMP) is a conventional anti-ulcer drug that effectively suppresses gastric acid secretion, but its efficacy may be enhanced by combining it with bioactive phytochemicals derived from a Glycyrrhiza glabra L. (licorice; LIQ) extract that possess potent antioxidant and anti-inflammatory properties. The aim of the present study was to evaluate the gastroprotective effects of OMP, LIQ extract, and their combined treatment against EtOH-induced GU in rats, focusing on modulation of TLR4/NF-κB/NLRP3 signaling and PI3K/AKT/mTOR gene expression. The ethanolic extract of LIQ was chemically characterized by LC-ESI-QTOF-MS/MS, and molecular docking was performed to evaluate the potential binding interactions of its major constituents with H⁺/K⁺-ATPase and COX-2. Thirty male Wistar rats were randomly allocated into control, ulcer (ULC), OMP-treated, LIQ-treated, and combined treatment groups. GU was induced by absolute EtOH. Subsequently, gastric pH, stomach coefficient, oxidative stress, inflammatory mediators, and PI3K, AKT, and mTOR gene expression were assessed. Histopathological and immunohistochemical analyses of mucosal architecture and the expression of TNF-α, caspase-3, and PCNA were performed. Coadministration of OMP and LIQ demonstrated the greatest gastroprotective activity, marked by a significant increase in gastric pH, restoration of antioxidant status, and substantial reduction in ROS, TLR4, NF-κB, and NLRP3 levels. The combined therapy significantly upregulated the expression of PI3K, AKT, and mTOR genes in comparison to ULC. Histopathological and immunohistochemical findings further demonstrated preservation of gastric mucosal integrity, reduced inflammatory cell infiltration, and decreased TNF-α, caspase-3, and PCNA immunoreactivity, indicating attenuation of mucosal injury. In conclusion, LIQ extract enhanced the gastroprotective effect of OMP against EtOH-induced GU, supporting its potential as an adjunct to OMP. Further studies are warranted to confirm the underlying molecular mechanisms. Full article

Bacterial extracellular vesicles (BEVs) are nano-sized lipid bilayer particles secreted by bacteria, capable of carrying various proteins, lipids, nucleic acids, and pathogen-associated molecular patterns (PAMPs). The biosynthetic pathway of BEVs determines their load components, physicochemical properties, and different biological activities. Increasing evidence indicates that BEVs play an important role in mediating host immune responses and the dynamic regulation of bacterial biofilms. Additionally, BEVs may serve as a molecular bridge between the two. BEVs derived from pathogens can trigger pro-inflammatory cascades, assist bacteria in immune evasion, and further accelerate the maturation of biofilms, forming a vicious cycle of persistent infection and inflammatory damage. In contrast, BEVs derived from probiotics can maintain host immune homeostasis and exert direct anti-biofilm and synergistic antibacterial effects, thereby breaking the pathological cycle. However, significant methodological research bottlenecks have greatly hindered the comparability and clinical translation of BEVs research. This article systematically summarizes the classification of BEVs and their biosynthetic mechanisms, compares the differential effects of BEVs from pathogenic bacteria and probiotic bacteria on immunity, clarifies the dual regulatory role of BEVs throughout the life cycle of biofilms, and highlights the bridging function of BEVs in the immune–biofilm interaction. Additionally, this article also discusses the current development of BEVs in clinical translation applications, such as vaccine development, antibiotic delivery, and mucosal inflammation intervention, and outlines the key industrial and clinical challenges faced in the future development of BEVs-based therapeutic approaches. Full article

Background/Objectives: Heavy metals are environmental hazards that are recognized as neurotoxic agents that may impair olfactory pathways in susceptible individuals. This study aimed to determine the concentrations of cadmium (Cd), arsenic (As), lead (Pb), chromium (Cr), manganese (Mn), nickel (Ni), copper (Cu), zinc (Zn), iron (Fe), and mercury (Hg) in the nasal mucosa and secretions of patients diagnosed with nasal septal deviation, nasal polyposis, or chronic rhinosinusitis, and to investigate their associations with olfactory function, nasal airflow, and pathohistological changes in the nasal mucosa. Methods: This prospective study included 97 adult patients who underwent nasal surgery. We used the Smell Diskettes Olfaction Test to assess olfactory function and rhinomanometry to evaluate nasal airflow resistance. Nasal mucosal tissue samples were collected intraoperatively. Heavy metal concentrations were analyzed using inductively coupled plasma mass spectrometry and atomic absorption spectrometry. Results: Preoperative olfactometry scores in patients with olfactory dysfunction differed to those in patients without olfactory dysfunction (3.4 ± 1.3 vs. 4.1 ± 1.2). Inferential analysis of heavy metals and olfactometry revealed that Cr, Fe, and Pb concentrations were negatively associated with olfactory performance before exposure (Cr: β = −0.12, p = 0.018; Fe: β = −0.08, p = 0.009; Pb: β = −0.10, p = 0.048). Rhinomanometry parameters showed positive associations with olfactory function, independently of age, sex, and groups of patients with or without olfactory dysfunction (R1: β = 0.45, p < 0.001; R2: β = 0.30, p = 0.003). Stepwise regression identified Fe, Pb, and Cr as the strongest predictors of olfactory dysfunction. The adverse effects of Fe and Pb exposure were significantly amplified with age. MANOVA revealed significant differences in heavy metal concentrations across pathohistological categories (Wilks’ Lambda = 0.038, p < 0.001). Carcinoma tissue exhibited significantly higher Cr concentrations, whereas precancerous lesions exhibited increased Cd concentrations. Conclusions: Cr, Fe, and Pb accumulation in nasal mucosa secretion is significantly associated with impaired olfactory function and pathohistological changes. Prolonged exposure to environmental heavy metals may affect olfactory function in the elderly population. Full article

Background/Objectives: Hydrochloric acid (HCl)/ethanol-induced gastric mucosal injury is closely associated with oxidative stress and inflammatory responses. Probiotics are promising therapeutic agents for gastrointestinal disorders. Therefore, this study evaluated the preventive effects of Cheonggukjang-derived Bacillus strains on HCl/ethanol-induced gastric mucosal injury in a rat model (n = 5 per group), with emphasis on inflammatory mechanisms. Methods: Eight-week-old male Sprague–Dawley rats were orally administered Bacillus amyloliquefaciens C393 1.0 × 10⁹ CFU (B393), Bacillus subtilis C439 1.0 × 10⁹ CFU (B439), or B. subtilis C512 1.0 × 10⁹ CFU (C512). Gastric injury was induced by oral administration of HCl/ethanol (150 mM HCl in 60% ethanol). Results: HCl/ethanol exposure significantly increased symptom scores, gastric mucosal lesion area, and histopathological damage. Pretreatment with B393 and B439 significantly attenuated these alterations. Moreover, HCl/ethanol administration increased gastric secretion volume and decreased gastric pH, both of which were significantly normalized by B393 and B439. Serum levels of pro-inflammatory cytokines, including tumor necrosis factor-α and interleukin-6, were significantly elevated following HCl/ethanol exposure but were markedly reduced by B393 and B439. Immunohistochemical analysis demonstrated that nuclear factor-kappa B activation in gastric tissues was significantly suppressed in these groups. Conclusions: These findings indicate that Cheonggukjang-derived Bacillus strains exert strain-specific gastroprotective effects possibly by suppressing NF-κB-mediated inflammatory signaling. Full article

Background: Chronic atrophic gastritis (CAG) is a prevalent precancerous gastric disorder characterized by persistent inflammation, glandular atrophy, and progressive mucosal damage, for which effective multi-target therapeutic strategies remain insufficient. The Lian-Huo-Hua-Zhuo formula (LHHZ), a traditional Chinese herbal prescription, has demonstrated potential anti-inflammatory and gastrointestinal protective effects in clinical practice; however, its active constituents and mechanisms of action against CAG remain undefined. This study aimed to clarify the absorbed bioactive components of LHHZ and explore its therapeutic mechanism for CAG. Methods: Ultra-high-performance liquid chromatography coupled with quadrupole Orbitrap high-resolution mass spectrometry was employed to identify the absorbed components of LHHZ in the gastric and intestinal tissues of mice. The therapeutic effects of LHHZ on CAG were assessed through histopathological staining, ultrastructural observation, and evaluation of serum and gastric functional indicators. Network pharmacology, molecular docking, and molecular dynamics simulations were integrated to predict the core targets and key signaling pathways, while the regulatory effects on the interleukin-17 (IL-17) signaling pathway were further validated by immunofluorescence staining, real-time quantitative polymerase chain reaction, and Western blotting. Additionally, 16S ribosomal RNA gene sequencing and targeted metabolomics were applied to investigate the effects of LHHZ on gut microbiota composition and short-chain fatty acid (SCFA) metabolism. Results: The results revealed that 55 and 48 absorbed components were identified in the gastric and intestinal tissues, respectively, predominantly derived from Coptis chinensis Franch. and Pogostemon cablin (Blanco) Benth. LHHZ significantly alleviated gastric mucosal lesions, reduced intestinal metaplasia, restored the ultrastructure of gastric mucosal cells, improved gastric functional indicators including pepsinogen I (PG I), pepsinogen II (PG II), and gastrin-17 (GAS-17), and decreased the levels of pro-inflammatory cytokines. Network pharmacology combined with in vitro and in vivo experiments demonstrated that the core bioactive components of LHHZ can target and regulate interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α), attenuate activation of the IL-17 signaling pathway, and suppress the secretion of downstream pro-inflammatory factors. Furthermore, LHHZ enhanced the alpha diversity of gut microbiota, reduced the Firmicutes to Bacteroidetes (F/B) ratio, restored the abundance of SCFA-producing bacteria such as Bacteroidales and Oscillospirales, and normalized the aberrant levels of eight SCFAs. Significant correlations were also observed between gut microbiota composition and SCFA metabolism. Conclusions: These findings suggest that LHHZ alleviates CAG by inhibiting inflammation via the IL-17 signaling pathway and by modulating the gut microbiota–SCFA axis, thereby providing preclinical evidence supporting its further investigation and development for multi-target therapeutic strategies against CAG. Full article