Search Results (643)

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

Chronic atrophic gastritis (CAG) is a pivotal precancerous condition in gastric carcinogenesis, with progression typically following the classic Correa cascade. Although Helicobacter pylori (H. pylori) infection is widely recognized as the principal etiological factor, the persistence of gastric cancer (GC) risk in a subset of patients after successful eradication suggests that gastric microbiota dysbiosis may also contribute to CAG progression. In recent years, high-throughput sequencing technologies have revealed distinct microbial restructuring in patients with CAG, characterized by decreased microbial diversity, depletion of commensal taxa, and enrichment of opportunistic pathogens. These compositional changes are accompanied by metabolic dysfunction, activation of inflammatory signaling pathways, and disruption of immune homeostasis, which may contribute to a microenvironment permissive for precancerous transformation of the gastric mucosa. Probiotics and related microbiome-based therapeutics, including prebiotics, synbiotics, and postbiotics, have emerged as promising adjunctive strategies for H. pylori eradication and disease management. Their beneficial effects are mediated through multiple mechanisms, including remodeling of the microbial community, inhibition of pathogen colonization, modulation of host immune responses, and restoration of mucosal barrier integrity. However, whether these interventions can reverse established atrophic or metaplastic lesions remains unclear. In addition, how strain specificity, dose dependency, and interindividual heterogeneity influence clinical efficacy has yet to be fully elucidated. In this review, we summarize the compositional and functional features of gastric microbiota dysbiosis in patients with CAG, as well as the mechanisms and clinical applications of microbiome-based interventions. We further highlight current limitations in the field and discuss future directions for precision microecological therapies integrating multi-omics approaches, engineered probiotics, and artificial intelligence. These advances may provide a theoretical framework and practical guidance for the diagnosis and management of CAG and the prevention of GC. Full article

Pernicious anemia (PA) represents a significant diagnostic challenge in neuropsychiatric patients due to its subtle and variable presentation. While PA is traditionally associated with clinical and biochemical manifestations of anemia, many patients, particularly those with neuropsychiatric symptoms, may have normal hematologic parameters, delaying recognition and appropriate treatment. Neurological and psychiatric symptoms, ranging from cognitive impairment and mood disorders to subacute combined degeneration (SCD) of the spinal cord, can precede hematologic abnormalities, leading to misdiagnosis or inappropriate management. The lack of a definitive gold standard test for cobalamin deficiency (CD) further complicates identification. Commonly used biomarkers, such as serum cobalamin, methylmalonic acid (MMA), homocysteine (Hcy), intrinsic factor antibodies (IFAs), and parietal cell antibodies (PCAs), each have limitations in diagnosing PA, especially in the absence of overt anemia. The variability in diagnostic criteria and cutoff values across studies adds to the challenge of achieving early and accurate diagnosis. This article reviews the complexities of diagnosing PA in neuropsychiatric patients, evaluates the limitations of current diagnostic methods, and emphasizes the need for a more comprehensive, standardized approach to early detection and treatment. Combining clinical awareness with improved biomarker interpretation is essential for preventing irreversible neurological damage and improving patient outcomes. Improved diagnostic protocols and further research are essential to optimize detection and minimize the risk of long-term neurological damage. Full article

Background/Objectives: Breast cancer is the most commonly diagnosed malignancy among women, with hormone receptor-positive tumors representing the majority of cases. Increasing survival rates have shifted attention toward long-term complications, including the risk of secondary malignancies. Emerging evidence suggests a potential association between breast cancer and gastrointestinal (GI) neoplasia. This study aimed to evaluate the role of colonoscopic and upper gastrointestinal endoscopic monitoring in patients with ER/PR-positive breast cancer and to assess its potential value in the early detection of digestive lesions. Methods: We conducted a prospective observational study including 186 female patients with histologically confirmed ER/PR-positive breast cancer. A total of 95 patients underwent colonoscopy, and 91 patients underwent upper gastrointestinal endoscopy. Clinical, demographic, and risk factor data were collected. A structured questionnaire was used to assess gastrointestinal symptoms. Endoscopic findings, lesion characteristics, and histopathological results were recorded. Bowel preparation quality was assessed using the Boston Bowel Preparation Scale. Results: Colonoscopy identified polyps and other lesions, with the majority located in the rectum and descending colon. A total of 12 biopsies were performed, revealing 1 malignant lesion, 2 borderline lesions, and the remainder benign. Upper gastrointestinal endoscopy showed gastritis as the most frequent finding, followed by gastric ulcers and polyps, while most patients had normal endoscopic results. Overall, 72% of patients presented at least one risk factor for digestive malignancy. Following treatment, most patients reported improvement in gastrointestinal symptoms. Conclusions: Patients with ER/PR-positive breast cancer may present a higher prevalence of gastrointestinal lesions, potentially related to shared risk factors and the systemic effects of endocrine therapy. Targeted, symptom-oriented endoscopic evaluation may facilitate early detection of premalignant and malignant digestive conditions. A multidisciplinary, risk-adapted surveillance approach should be considered to improve patient outcomes. Further large-scale studies are required to establish evidence-based screening strategies in this population. Full article

Argan tree (Argania spinosa L. Skeels), an endemic Moroccan species, is widely recognized for its traditional medicinal and nutritional uses. It has long been employed to promote skin and cardiovascular health, regulate blood glucose levels, and support overall wellbeing. Traditionally, different parts of the argan tree, including argan oil, leaves, and other plant-derived preparations, have been used to manage various health conditions such as diabetes, gastritis, gastric ulcers, rheumatism, joint and muscle pain, skin disorders including acne, eczema, and inflammation, as well as wound healing and dental problems. This narrative critical review compiles and evaluates current knowledge on the ethnobotany, phytochemistry, pharmacology, and toxicology of argan tree to support its evidence-based application. Relevant literature was collected from major English and French scientific databases, focusing on studies addressing the plant and its principal bioactive constituents. Ethnobotanical data indicate the extensive use of argan oil, leaves, and other plant parts in traditional remedies and dietary practices. Phytochemical investigations reveal a rich composition dominated by unsaturated fatty acids, tocopherols, phytosterols, and polyphenolic compounds. Experimental studies highlight a broad spectrum of biological activities, including antioxidant, antidiabetic, antibacterial, and anti-obesity effects, along with emerging applications in nanotechnology. Toxicological findings generally suggest low toxicity and good safety profiles under tested conditions. Overall, A. spinosa exhibits substantial ethnopharmacological relevance and diverse bioactivities, supporting its continued exploration for nutraceutical and therapeutic applications. Full article

Background and Aims: Helicobacter pylori is a major cause of chronic gastritis and peptic ulcer disease. The increasing global spread of antibiotic-resistant strains, particularly against amoxicillin and clarithromycin, poses a significant challenge to eradication therapies. Moreover, treatment-related adverse effects, often linked to antibiotic-induced intestinal dysbiosis, frequently lead to a poor patient compliance; this, in turn, promotes the persistence of resistant bacterial populations. Probiotics may mitigate these effects and improve treatment adherence. This study aimed to assess the genomic safety of new probiotics intended for adjuvant use in H. pylori eradication regimens. Methods: Whole-genome sequencing was performed on three probiotic strains: one of Lactobacillus acidophilus, and two of Bifidobacterium animalis subsp. lactis. Genomes were compared with corresponding wild-type reference strains to identify genetic variations and detect mobile genetic elements. Results: Comparative genomic analysis revealed differences between selected and wild-type strains. Importantly, no plasmids or transposons were identified, suggesting a reduced theoretical risk of horizontal transfer of antimicrobial resistance determinants. Genomic findings were consistent with in vitro phenotypic observations. Conclusions: Whole-genome sequencing provided a robust assessment of the safety profile of these strains. The absence of transferable resistance elements supports their potential use as probiotic candidates to improve tolerability and adherence to H. pylori eradication therapies, contributing to more effective treatment outcomes. Full article

Background: Helicobacter pylori is a globally prevalent gastric pathogen associated with chronic gastritis, peptic ulcer disease, and gastric adenocarcinoma. Its persistence within the gastric niche is strongly linked to biofilm formation, contributing to immune evasion and antibiotic therapy resistance. Methodology: In the present study, we investigated the antibiofilm potential of capsaicin, a natural phytochemical derived from Capsicum species, against H. pylori using experimental and computational approaches. Results: Capsaicin treatment significantly reduced biofilm biomass (up to 75.66 ± 4.00%), metabolic activity (up to 61.23 ± 6.88%), and cell surface hydrophobicity in a dose-dependent manner. Microscopic analyses revealed disrupted biofilm architecture and diminished extracellular polymeric substance at higher concentrations. Molecular docking analysis revealed that capsaicin interacts with target H. pylori proteins (GTP cyclohydrolase II, α-carbonic anhydrase, and urease) through stable hydrogen bonds and hydrophobic contacts. Molecular dynamics simulations further supported the stability of these complexes and demonstrated reduced structural fluctuations upon ligand binding. Free energy landscape analysis suggested ligand-induced conformational alterations in α-carbonic anhydrase, indicating possible structural effects associated with capsaicin interaction. Conclusions: Overall, the findings provide insight into the antibiofilm activity of capsaicin against H. pylori and highlight its potential as a natural adjunct strategy for combating biofilm-associated persistence and antimicrobial resistance. Full article

Background: Plasticizers, including phthalate esters and phthalate-free alternatives, are widely detected environmental chemicals. Although increasing evidence suggests that plasticizers may disrupt gastrointestinal homeostasis, their potential molecular links with inflammatory gastrointestinal disorders (IGDs) remain unclear. Methods: This study aimed to systematically identify potential molecular targets and pathways linking representative plasticizers with IGDs. An integrative network toxicology framework was applied to investigate four plasticizers, including dimethyl phthalate (DMP), diethyl phthalate (DEP), dioctyl phthalate/di(2-ethylhexyl) phthalate (DOP/DEHP), and acetyl tributyl citrate (ATBC), in relation to Crohn’s disease (CD), ulcerative colitis (UC), esophagitis, and gastritis. Plasticizer- and disease-related targets were collected from public databases, followed by overlapping target screening, protein–protein interaction network analysis, functional enrichment analysis, GEO-based transcriptomic validation, molecular docking, molecular dynamics simulation, and single-cell RNA-seq analysis. Results: Disease-specific candidate targets were identified, including CXCL8 and FN1 for CD, IL1B for UC, MAPK3, FASN, FN1, PPARG, CXCL8, FOS, and HIF1A for esophagitis, and MMP9, TNF, TLR4, IL6, CCR2, IFNG, and PTGS2 for gastritis. Cross-disease analysis further identified plasticizer-associated signature targets, including MMP7 for DMP, HMOX1 and NOS2 for DEP, and LTF and CCL11 for ATBC. Enrichment analysis indicated that these targets were mainly involved in inflammatory, chemokine, MAPK-related, and xenobiotic response pathways. Molecular docking and dynamics simulations suggested stable interactions between selected plasticizers and candidate targets, while single-cell analysis revealed their cell-type-specific expression patterns in epithelial, immune, and stromal compartments. Conclusions: This study provides an exploratory network toxicology framework for identifying potential molecular associations between plasticizer exposure and IGDs. The findings highlight disease-specific and plasticizer-associated candidate targets that may guide future experimental validation and environmental risk assessment. Full article

Chronic atrophic gastritis (CAG) is the principal precursor lesion for gastric adenocarcinoma and represents a key target for endoscopic surveillance and early intervention. Although the global age-standardised incidence of gastric cancer has declined over recent decades, the absolute number of cases continues to rise because of population ageing and increasing incidence in younger individuals. The prognosis remains poor in advanced disease, whereas early gastric cancer (EGC) detected at a mucosal stage is associated with excellent long-term survival and may be curable with endoscopic resection. Consequently, high-quality endoscopic detection of premalignant gastric lesions is essential to reduce gastric cancer mortality. This review summarises current concepts in the endoscopic diagnosis of CAG, gastric intestinal metaplasia (GIM), and EGC, from conventional white-light endoscopy through to advanced imaging and artificial intelligence (AI)-assisted systems. Fundamental principles of high-quality oesophagogastroduodenoscopy are discussed, including adequate inspection time, systematic mucosal assessment, mucosal cleansing, and standardised photo-documentation. Characteristic endoscopic appearances of normal gastric mucosa, atrophy, and intestinal metaplasia are reviewed, alongside established staging systems including the Kimura–Takemoto and EGGIM classifications. The role of image-enhanced endoscopy is examined in detail, including narrow-band imaging, linked colour imaging, texture and colour enhancement imaging, and magnification optical enhancement. These modalities improve visualisation of pit patterns, microvascular architecture, and hallmark features of intestinal metaplasia such as the light blue crest sign, substantially increasing diagnostic sensitivity and specificity compared with conventional white light imaging alone. Advanced imaging combined with magnification also enhances the detection and characterisation of EGC. Emerging evidence regarding AI-assisted endoscopy demonstrates promising diagnostic accuracy for CAG, GIM, and early neoplasia, with improved lesion detection and reduced miss rates in several studies. However, limitations relating to external validation, generalisability, and integration into routine practice remain. Continued advances in optical imaging, structured training, and AI-supported diagnostics are likely to play an increasingly important role in improving early gastric cancer detection and surveillance outcomes worldwide. Full article

Background/Objectives: Autoimmune gastritis (AIG), celiac disease (CD), and gastric surgery (GS) often cause iron deficiency anemia (IDA) due to iron malabsorption. In this clinical context, IDA treatment is often challenging. The first-line IDA treatment is oral iron supplementation followed by intravenous (IV) iron administration when ineffective or not tolerated. Ferric carboxymaltose (FCM) showed efficacy in various clinical settings. Prospective data evaluating the efficacy of IV FCM in IDA patients secondary to iron malabsorption are scant. The aim of the current study was to assess the tolerability, efficacy, and QoL impact of IV FCM for the treatment of IDA patients with iron malabsorption. Methods: Study design: single-center, prospective observational study: n = 37 adults with AIG, CD, or GS with IDA receiving IV FCM were consecutively included. Endpoints were (i) safety tolerability, (ii) efficacy on IDA recovery (Hb normalization), and (iii) QoL impact. At baseline (T0) and 12 weeks after treatment (T12), a QoL-SF12 questionnaire was assessed. Complete blood count (CBC) and iron status (ferritin, iron, transferrin, transferrin saturation (TS)) were assessed at T0, 4 weeks (T4), and T12 after treatment. Results: Of the 37 IDA patients, 19 (51.4%) had AIG, 9 (24.3%) CD, and 9 (24.3%) GS; Based on Ganzoni’s formula, 24 (64.9%) patients received a single IV FCM infusion (mean ± SEM dosage of 975 ± 12 mg); 13 (35.1%) required two IV infusion sessions with a mean ± SEM cumulative dose of 1400 ± 77 mg. One patient (2.7%) experienced mild adverse events without need for treatment interruption or hospitalization. At T0, anemia was moderate in 7 (18.9%) patients and severe in 1 (2.7%). IDA recovery was achieved in 26 (70.3%) patients at T4 and in 29 (78.4%) at T12. At T4, mean ± SEM Hb increased from 10.8 ± 0.2 g/dL to 12.7 ± 0.1 g/dL, ferritin from 28.5 ± 11.2 ng/mL to 188.2 ± 25.7 ng/mL, and TS from 6.7 ± 0.5% to 23.7 ± 1.9% (p < 0.0001). At T12, mean ± SEM Hb further increased to 13.1 ± 0.2 g/dL (p < 0.05 vs. T4), ferritin slightly decreased to 125 ± 26.7 ng/mL, and TS to 22.7 ± 2.8%. At T12, nonsignificant increases in QoL scores relative to baseline were observed. Conclusions: IV FCM is a safe and effective treatment leading to IDA recovery in nearly 80% of patients at T12. Thus, when oral iron treatment is not feasible or has failed, IV FCM treatment might be considered a first-line therapeutic option for IDA consequent to iron malabsorption. Full article

Survivors of primary gastric lymphoma (PGL) face a significantly elevated and persistent risk of developing second primary malignancies (SPMs), with gastric adenocarcinoma representing the most frequent SPM and standardized incidence ratios reaching up to 16-fold above the general population. This excess risk persists for decades after initial treatment and is associated with increased cause-specific mortality compared to matched primary cancers. Among patients with PGL, approximately 5% develop gastric cancer (with two-thirds being metachronous), and nearly 15% harbor precancerous lesions including atrophic gastritis, intestinal metaplasia, and dysplasia. Beyond gastric malignancies, survivors also experience elevated rates of extra-gastric SPMs, particularly digestive system tumors (43%), respiratory cancers (21%), and urinary tract malignancies (13%). Key risk factors include treatment with immunochemotherapy or radiotherapy, advanced age, male sex, advanced stage at diagnosis, ulcerative-type lymphoma morphology, and persistent Helicobacter pylori (HP) infection. Patients receiving combined chemoradiotherapy demonstrate the highest SPM risk, particularly for gastric and pancreatic cancers. These findings underscore the critical importance of lifelong, risk-adapted surveillance strategies integrating both hematology and gastroenterology follow-up. Annual endoscopic surveillance is recommended for high-risk patients, with intervals adjusted according to lymphoma histology, HP status, and the presence of precancerous gastric lesions. Mandatory HP eradication with confirmation of response is essential for reducing gastric cancer risk. Future research priorities include prospective, standardized studies to better quantify SPM risk, validation of molecular and microbiological biomarkers for individualized risk stratification, and development of predictive models to enable personalized surveillance protocols and improve long-term outcomes in this vulnerable population. Full article

Helicobacter pylori (H. pylori) infection is closely associated with the development of chronic gastritis, peptic ulcers, and gastric cancer, highlighting the importance of rapid and accurate detection for disease prevention and clinical management. In this study, a one-pot LAMP-CRISPR/Cas12b assay targeting the CagA gene was developed for H. pylori detection. First, the LAMP system was optimized by systematically screening key reaction components. Subsequently, a one-step LAMP-CRISPR/Cas12b detection platform was established through optimization of the ratio between the LAMP premix and CRISPR buffer, reaction temperature, Cas12b concentration, and ssDNA reporter concentration. Under optimal conditions, the assay achieved a detection limit of 3.14 × 10¹ copies/µL, representing a tenfold improvement in sensitivity compared with conventional LAMP and PCR assays (3.14 × 10² copies/µL). In addition, the entire detection process could be completed within 1 h. Validation using 17 culture-positive and 17 culture-negative samples demonstrated complete concordance with culture-based results, with no false-positive or false-negative detections observed. These findings indicate that the proposed platform possesses high sensitivity, excellent specificity, rapid turnaround, and operational simplicity, demonstrating strong potential for point-of-care testing and applications in resource-limited settings. Full article

At present, the gold standard for gastric cancer (GC) confirmation relies mostly on histopathology, an invasive procedure. Noninvasive detection methods using serum for large-scale screening may be useful for the early diagnosis of GC. Helicobacter pylori (HP) infection and chronic atrophic gastritis are major GC risk factors. We recently developed a noninvasive test called the DSC test-based on the patient’s age, sex, their serum PGI and PGII, anti-HP immunoglobulin (IgG), and gastrin G17 levels-predicting GC risk as low (score 0, S0) or high (score 2, S2). The comparative investigation at the serum protein level of the two different patient groups detected by our DCS test (S0 and S2) may undoubtedly help to identify gastric disease-dependent proteins, resulting from bacterial infection or gastric mucosa inflammation, as well as get better insight into the molecular scenario associated with pre-cancerous conditions. We used an untargeted liquid chromatography–tandem mass spectrometry (LC-MS/MS)-based proteomic profiling approach, followed by univariate statistical analysis to compare the different DSC groups across two patient cohorts (exploratory and validation). Significantly differentially abundant proteins differing more than 1.5-fold between S0 and S2 groups were selected and validated, and their putative role(s) in gastritis and GC were discussed. In both the exploratory and the validation cohorts, four proteins (beta-2-microglobulin, EGF-containing fibulin-like extracellular matrix protein 1, complement factor D, and cystatin-C) were more abundant, while two (sex hormone-binding globulin and pregnancy zone protein) were less abundant in the sera of S2 individuals (|fold change| ≥ 0.6, p < 0.05, t-test). The higher presence of beta-2-microglobulin (B2M) and the lower content of pregnancy zone protein (PZP) in S2 sera were validated by immunoblotting. Replacing age and sex in our DSC model with two specific candidate biomarkers can lead to a refined, albeit modest, improvement in classification accuracy. This study identified a proteomic signature that was differentially associated with the sera of patients with a different risk to develop advanced atrophy/GC according to the DSC test. Moving from a demographic model to a proteomic-driven model can better reflect the personalized biology of pathological processes associated with DSC. Full article

This study investigated the gastroprotective effects of Salvia plebeia extract (SPE) against acute gastric mucosal injury induced by 150 mM HCl/60% ethanol in rats and explored its antioxidant and anti-inflammatory mechanisms. SPE exhibited strong in vitro antioxidant activity, with DPPH and ABTS radical scavenging rates of 86.2 ± 2.4% and 89.1 ± 1.9%, respectively, along with a high total polyphenol content (96.4 ± 3.1 mg gallic acid equivalents/g extract). In lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, SPE attenuated LPS-induced inflammatory signaling, as evidenced by reduced TLR4 and JNK expression and restoration of IκBα levels. In vivo, oral administration of SPE (100 or 300 mg/kg) 1 h prior to HCl/ethanol challenge significantly reduced gastric lesion area and improved histopathological damage compared with the HCl/ethanol-treated control group. SPE also increased gastric pH, reduced gastric juice volume, decreased serum levels of TNF-α and IL-6, and downregulated gastric mucosal mRNA expression of Nos2 and Ptgs2. Immunohistochemical analysis further showed that SPE attenuated NF-κB p65 immunoreactivity in gastric tissues. Collectively, these findings suggest that SPE exerts gastroprotective effects through antioxidant activity and suppression of inflammatory responses associated with the MAPK/NF-κB pathway in acute HCl/ethanol-induced gastric injury. Full article

Lymphoplasmacytic gastritis (LPG) is one of the most prevalent chronic diseases affecting cheetahs (Acinonyx jubatus) under human care, yet its underlying cause remains unresolved. Gastric inflammation occurs in the majority of adult captive cheetahs but is uncommon in free-ranging populations, suggesting that management-related factors contribute to disease pathogenesis. This review proposes that LPG represents a bile acid-driven gastroenteropathy arising from disruption of the natural feeding ecology of the cheetah. In free-ranging systems, cheetahs consume large episodic meals separated by prolonged fasting intervals and ingest whole-prey containing substantial connective tissue and collagen. In captivity, feeding patterns are typically characterized by smaller, more frequent meals and diets dominated by lean skeletal muscle with reduced structural complexity. I hypothesize that this mismatch alters gastric emptying kinetics, disrupts coordinated pancreatic and biliary secretion, and destabilizes fat digestion. Inefficient lipolysis may impair micelle formation and promote bile acid mislocalization within the gastrointestinal tract, increasing mucosal exposure to hydrophobic bile acids capable of inducing chemical epithelial injury. Within this framework, lymphoplasmacytic gastritis is interpreted as a secondary inflammatory reaction to chronic bile acid-mediated mucosal stress rather than a primary immune-mediated disorder. The model also provides a mechanistic explanation for the frequent coexistence of gastritis with fat and protein maldigestion in captive cheetahs. Differential responses to antimicrobial therapy, glucocorticoids, sulfasalazine, pancreatic enzyme supplementation, and bile acid-modifying agents are broadly consistent with this proposed mechanism. Recognition of LPG as a physiologically driven gastroenteropathy has important implications for management, emphasizing restoration of feast–fast feeding patterns, inclusion of collagen-rich carcass components, and targeted modulation of bile acid composition and signaling. Full article