Search Results (1,446)

Diarrhea-predominant irritable bowel syndrome (IBS-D) frequently occurs alongside depression, greatly impairing patients’ life quality, with limited targeted treatments. Low-molecular-weight peptides (LMWPs) from Musca domestica larvae exert gut-protective bioactivities, but their efficacy and molecular mechanisms for comorbid IBS-D and depression remain unelucidated. A chronic–acute combined stress (CACS)-induced rat model of IBS-D complicated with depression was established and treated with LMWPs. The study evaluated intestinal and depressive behavioral phenotypes, and integrated 16S rRNA sequencing, untargeted serum metabolomics and quantitative detection of fecal SCFAs for multi-omics correlation analysis. 1. CACS triggered typical comorbid symptoms, which LMWPs alleviated with effects similar to trimebutine maleate. 2. LMWP treatment was associated with reshaped gut microbiota, restored metabolic pathways, altered levels of 27 disease-associated serum metabolites, and increased fecal SCFA levels. 3. Multi-omics correlation analyses suggested that the therapeutic benefits may involve crosstalk among gut microbiota, SCFAs, and tryptophan metabolites. Larva-derived LMWP relieves IBS-D combined with depression by modulating gut microecology, SCFA generation and serum metabolic balance through the gut–brain axis, which can serve as a novel promising therapeutic candidate. Full article

Background: Celiac disease is a chronic autoimmune enteropathy whose only established treatment is a strict, lifelong gluten-free diet (GFD). Beyond physical symptoms, the disease and its dietary management affect emotional, social, and economic functioning. Objectives: This study aimed to assess health-related quality of life (HRQoL) in adult patients with celiac disease and to identify factors associated with their daily functioning and adherence to the GFD. Methods: A cross-sectional survey was conducted between February and March 2026 among 101 adults with a self-reported diagnosis of celiac disease made by a gastroenterologist, recruited through online support groups. Data were collected using an author-designed sociodemographic questionnaire, the Gastrointestinal Quality of Life Index (GIQLI), and the Celiac Dietary Adherence Test (CDAT). Analyses (Mann–Whitney U and Kruskal–Wallis tests, repeated-measures ANOVA, Spearman correlations with false-discovery-rate correction, and multivariable linear and logistic regression with prespecified sensitivity analyses) were performed in R 4.5.2, with α = 0.05. Results: The most frequently reported difficulties were eating away from home, the high cost of the GFD, and limited product availability; the most common symptoms after inadvertent gluten exposure were abdominal pain, bloating, fatigue, diarrhea, and headache. HRQoL was lowest in the emotional and physical domains. Better dietary adherence was significantly correlated with higher HRQoL across the total score and all domains except the social domain, whose weak internal consistency in this sample (α = 0.57) precludes substantive interpretation (total GIQLI: ρ = −0.50; p < 0.001), and in the multiple regression, adherence remained the strongest independent correlate of HRQoL (β = −0.36; adjusted R² = 0.41). Longer time on the diet was independently associated with better adherence (adjusted OR = 0.55 per duration category; p = 0.017). In a small vocational education subgroup (n = 8), poorer adherence and lower HRQoL were observed relative to participants with higher education, though only the HRQoL difference survived correction for multiple testing (FDR-adjusted p = 0.011 vs. 0.060 for adherence); given the size of this subgroup, this comparison is exploratory and hypothesis-generating. Higher HRQoL was also associated with milder symptoms, better-rated medical care, greater product availability, and higher household income. Conclusions: In this sample, HRQoL scores were lowest in the emotional and physical domains; because the design was cross-sectional and included no comparison group, these data characterize the distribution of HRQoL within the sample and do not establish that celiac disease reduces HRQoL. Dietary adherence was the strongest correlate of patient functioning, alongside symptom burden, self-rated quality of medical care, and product availability. Because the design is cross-sectional, these associations do not establish direction, and whether comprehensive health education and psychological support improve outcomes requires prospective and interventional evaluation. Full article

Bovine coronavirus (BCoV) is a key pathogen causing calf diarrhea and bovine respiratory diseases, bringing sustained economic losses to the cattle industry. As an RNA virus, BCoV possesses high mutation and recombination capacities, leading to prominent genomic genetic diversity. The genome contains hypervariable and conserved regions, with the S (especially S1), HE and Open Reading Frame (ORF4) genes serving as major variation hotspots linked to viral antigenicity, tissue tropism shift and immune evasion. Host immune pressure drives strong positive selection on S protein antigenic variation. This review discusses existing research limitations and proposes future directions including genomic surveillance, reverse genetics verification and broad-spectrum vaccine development to support BCoV prevention and control. Full article

Nontoxigenic Bacteroides fragilis (NTBF) is defined by the absence of the bft gene and corresponding B. fragilis toxin production; however, nontoxigenic status alone does not establish uniform safety or probiotic function. This review critically evaluates strain-level biological characteristics, safety, mechanisms, metabolites, and disease-model evidence. Selected strains and defined strain-derived preparations, including ZY-312, HCK-B3, NCTC 9343-derived polysaccharide A, and ZY-312-derived zwitterionic capsular polysaccharide preparation TP2, have shown immunomodulatory, barrier-associated, and microbial-community-modulating activities, predominantly in vitro and in animal models. Direct causal evidence is limited to specific strain–preparation–host–model combinations, whereas many changes in cytokines, tight-junction-associated proteins, microbial composition, and organic-acid profiles remain functional or associative. Protective effects have been reported in preclinical models of inflammatory bowel disease, necrotizing enterocolitis, antibiotic-associated diarrhea, Clostridioides difficile infection, and enterotoxigenic B. fragilis (ETBF)-associated tumorigenesis. However, findings are highly dependent on the strain, preparation, dose, administration timing, host, and model. Safety remains incompletely resolved because the absence of B. fragilis toxin (BFT) does not exclude opportunistic or systemic infection, antimicrobial-resistance mobility, bacterial translocation, permeability changes, or adverse effects during long-term administration. Metabolic effects may also be beneficial or adverse depending on the strain, host dietary and genetic background, and experimental context. Human evidence is primarily observational, and robust intervention trials are lacking. Accordingly, NTBF should be regarded as a heterogeneous group of strain-specific live-biotherapeutic candidates requiring rigorous strain-specific manufacturing, potency, dose, antimicrobial-susceptibility, and safety evaluation. Full article

Background/Objectives: Micronutrient deficiencies are common in inflammatory bowel disease (IBD) and contribute to anemia, impaired wound healing, neurologic injury, and adverse disease outcomes. Major societies, including ESPEN, ACG, and ECCO, recommend nutritional and micronutrient assessment in patients with IBD, yet few studies describe how comprehensively these recommendations are applied during hospitalization. This study aimed to characterize inpatient testing practices for vitamins B1, B6, B12, and zinc in hospitalized IBD patients, quantify deficiency frequency among those tested, and identify gaps between guideline-recommended and actual micronutrient assessment. Methods: A retrospective chart review was performed on adults with Crohn’s disease (CD) or ulcerative colitis (UC) hospitalized for an IBD flare at a tertiary care center. Demographics, comorbidities, and deficiency-associated clinical features were recorded. Yield was defined as the proportion of tested patients meeting institutional deficiency thresholds. Yield for each non-B12 micronutrient was compared with B12 as an internal benchmark. Results: Among 356 patients (285 CD, 71 UC), inpatient micronutrient testing was markedly imbalanced: B12 was tested in 97.2%, whereas B6, B1, and zinc were tested in only 34.8%, 30.6%, and 18.8%, respectively. Among those tested, deficiencies were common: B6 40.3%, zinc 32.8%, B1 22.9%, and B12 9.0%. Each non-B12 micronutrient yielded deficiency significantly more often per test than B12 (all p < 0.001), a testing-yield mismatch interpreted cautiously given selective testing of non-B12 nutrients. Deficiency frequencies did not differ significantly between CD and UC. Clinical contexts included tachycardia and edema (B1); elevated inflammatory markers and thromboembolism history (B6); anemia and neuropathy (B12); and diarrhea and hypoalbuminemia (zinc). Conclusions: Inpatient micronutrient assessment in IBD is heavily skewed toward B12, with B1, B6, and zinc under-tested despite a substantially higher yield of identified deficiency per test. This testing-yield mismatch represents a measurable implementation gap between guideline-recommended comprehensive assessment and actual inpatient practice; whether systematic panel-based assessment improves clinical outcomes warrants prospective evaluation. Full article

The gastrointestinal microbiota plays a key role in the health and productivity of llama crias, yet its dynamics under disease conditions remain poorly understood. This study aimed to characterize and compare the fecal microbiota of healthy and diseased llama crias. Fecal samples collected from nine llama crias (six with diarrhea and three clinically healthy controls) were analyzed using 16S rRNA gene sequencing targeting the V4 region, followed by bioinformatic processing and statistical analyses, including diversity metrics and generalized linear mixed models. Results showed that microbial communities were dominated by Bacillota and Bacteroidota in both groups; however, diseased animals exhibited increased abundance of Pseudomonadota, particularly Gammaproteobacteria and Enterobacteriaceae. Beta diversity analysis revealed significant differences in community structure between groups, with diseased samples showing higher dispersion. Additionally, a greater number of unique ASVs was observed in diseased individuals, indicating increased microbial heterogeneity. Differential abundance analysis identified distinct microbial signatures associated with health status, with opportunistic taxa enriched in diseased animals and fiber-degrading taxa more prevalent in healthy individuals. Overall, the findings demonstrate an association between diarrhea and differences in the fecal microbiota of llama crias. Because this was a cross-sectional observational study, causal relationships cannot be inferred. These results provide a foundation for future investigations into host–microbiota interactions and gastrointestinal health in South American camelids. Full article

Diarrhea and impaired intestinal development are major constraints in newly hatched domestic pigeons raised for meat production, leading to reduced growth performance and increased reliance on antimicrobial interventions. Cecropin AD (CAD) is a broad-spectrum antimicrobial peptide with potential activity against bacterial pathogens and may represent an alternative strategy for improving intestinal health in poultry. In this study, we evaluated the safety and biological effects of a recombinant Newcastle disease virus (NDV) expressing CAD (rTS-CAD₃) in one-day-old domestic pigeons. Pigeons were inoculated with rTS-CAD₃, parental TS09-C, or PBS and monitored for growth performance, diarrhea incidence, viral RNA persistence, inflammatory responses, intestinal bacterial abundance, gut microbiota composition, intestinal morphology, and epithelial barrier function. rTS-CAD₃ caused no mortality, detected only transient viral RNA, and did not induce excessive inflammatory responses. Compared with TS09-C and PBS controls, rTS-CAD₃ significantly increased body weight gain and average daily gain while reducing diarrhea incidence. Importantly, rTS-CAD₃ decreased intestinal Escherichia coli abundance, reshaped the gut microbiota by reducing Proteobacteria and Escherichia–Shigella while increasing Firmicutes and Lactobacillus, improved villus height and the villus-to-crypt ratio, and enhanced occludin expression. These findings demonstrate that NDV-vectored CAD delivery can reduce intestinal bacterial burden, increase occludin expression, and alleviate diarrhea in domestic pigeons. The rTS-CAD₃ represents a promising antimicrobial peptide-based strategy for reducing spontaneous diarrhea and dependence on conventional antibiotics in poultry production. Full article

Porcine epidemic diarrhea virus (PEDV) G2c variants have recently emerged, posing significant challenges to swine health management. As a major coronavirus affecting the swine industry, PEDV exhibits extensive genetic variability, which has greatly complicated disease control. Current vaccines provide suboptimal protection under field conditions. Therefore, the isolation of recently circulating strains and the establishment of a robust reverse genetics system are critical for advancing the study of emerging variants and facilitating rational vaccine development. In this study, a PEDV field strain designated PEDV-BJ-2023 was isolated from diarrheic piglets in Guizhou, China. Phylogenetic analysis based on the complete genome and spike gene classified PEDV-BJ-2023 within the emerging G2c lineage. To facilitate functional studies, a full-length infectious cDNA clone was constructed using transformation-associated recombination cloning in yeast. Furthermore, an enhanced green fluorescent protein reporter virus was generated via CRISPR/Cas9-assisted homologous recombination by inserting an EGFP-2A cassette upstream of the nucleocapsid gene. The recombinant viruses displayed virion morphology and plaque characteristics similar to those of the parental wild-type PEDV-BJ-2023 strain, although the parental virus exhibited faster replication during the early stage of infection in vitro. In 5-day-old piglets, all three viruses caused severe diarrhea, weight loss, and intestinal lesions; however, recombinant viruses exhibited slightly reduced viral shedding and pathogenicity, with rPEDV-EGFP being the most attenuated. Notably, rPEDV-EGFP maintained stable EGFP expression over eight serial passages. This study establishes a reverse genetics platform for an emerging G2c PEDV strain and provides a stable fluorescent reporter virus, offering valuable tools for visualizing viral infection and investigating virus–host interactions. Full article

Background: The movement of endemic diseases from tropical and disadvantaged areas is gradually spreading to developed countries as well. Amoebiasis, in particular, represents a significant threat to public health, amplified by globalization and increasing contact between humans and animals or vectors. In this way, atypical diseases may emerge in our country, also through an unusual mode of transmission—likely sexual, as “sexually transmitted enteric (STE) diseases”. Objective: We report and discuss the clinic approach to a rare case of dual human infestations by ecto- and endo-parasites with multiple liver abscesses presentation in a young truck driver residing in Northern Italy. Methods: The patient underwent a comprehensive screening with laboratory and microbiological tests, and CT images. Results: In July, the patient was admitted to our hepatology unit following the ultrasound identification of two hypoechoic lesions in the right lobe of the liver. In his medical history, in April, after a seemingly harmless infestation of body lice, effectively treated, he suffered from a prolonged and debilitating episode of acute diarrhea, lasting a month. This status was also accompanied by intestinal cramps, weight loss, and recurring fever episodes. Afterwards also appeared a Quincke’s-like angioedema involving the lips and mouth mucosa, with evening time exacerbation. Conclusions: The differential diagnosis of this complex and unusual clinical picture, together with the temporal evolution of the patient’s signs and symptoms, led us to hypothesize the presence of concomitant infections. These were most likely borreliosis and a STE disease, the latter ultimately diagnosed as amebiasis with hepatic invasion, allowing appropriate treatment and a favorable clinical outcome. Full article

The gut microbiota and its metabolic functions are critical for intestinal homeostasis, but their integrated responses to diarrhea remain poorly understood in non-model mammals, such as the complex-toothed flying squirrel (Trogopterus xanthipes). Here, we collected fecal samples from six captive animals with diarrhea and six healthy controls; the diarrheal animals had been provided with moldy corn, but mycotoxin levels were not measured. Fecal microbiota was profiled by full-length 16S rRNA sequencing and untargeted metabolomics with integrative analyses. Diarrheal animals showed significantly decreased fecal microbial alpha-diversity and distinct community separation. LEfSe analysis identified Lawsonia intracellularis and Streptococcus macedonicus as the most enriched taxa in the diarrhea group. Untargeted metabolomics revealed 2216 differential metabolites (1931 downregulated), primarily enriched in steroid hormone biosynthesis, arachidonic acid metabolism, and bile secretion pathways. Procrustes and Mantel tests confirmed significant microbiome–metabolome concordance (M² = 0.422, p < 0.001). Spearman correlation networks showed that L. intracellularis was positively correlated with multiple differential metabolites, while S. macedonicus exhibited predominantly negative correlations. These findings suggest that diarrhea in T. xanthipes may be associated with moldy corn exposure and is accompanied by gut dysbiosis and metabolic disturbances. L. intracellularis and S. macedonicus may be associated with disease progression through pathways linked to lipid and bile acid metabolism and inflammation. This study provides novel microbial–metabolic insights into diarrhea in a medicinal mammal, supporting disease prevention and healthy breeding. Full article

Background: Next-generation sequencing (NGS)-detected ERBB2 amplification occurs in a subset of urothelial carcinomas, but its role as a treatment-selection marker for trastuzumab deruxtecan (T-DXd) remains uncertain. Methods: We retrospectively reviewed four patients with metastatic urothelial carcinoma treated with T-DXd in routine practice from 2024. Treatment selection was based on NGS-detected ERBB2 amplification because HER2 immunohistochemistry and in situ hybridization were unavailable. Results: Four men aged 65–76 years received T-DXd: one in the second line and three in the fourth or fifth line. The best radiological responses, abstracted from contemporaneous radiology reports and oncology medical records, were complete response in one patient, partial response in one, and stable disease in two. Three patients had previously received enfortumab vedotin. Documented adverse events included fatigue, anemia, diarrhea, rash, and leukopenia. No interstitial lung disease or pneumonitis was documented in the available records. Conclusions: These observations are descriptive and hypothesis-generating. They do not establish the efficacy or safety of T-DXd or validate ERBB2 amplification as a predictive biomarker, but they support prospective evaluation of genomic ERBB2 amplification when standard HER2 testing is unavailable. Full article

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the intestine. Although current therapies can provide symptomatic relief, they are often associated with high costs and adverse effects. Coptis chinensis Franch., a traditional Chinese medicine long used for inflammatory intestinal conditions such as bacterial dysentery, is a promising alternative. However, the specific alkaloid components that inhibit cell death and alleviate colitis remain unclear. Major isoquinoline alkaloids from Coptis chinensis Franch. were screened in a TNF-α/cycloheximide (CHX)-induced epithelial cell death model using CCK-8 and Annexin V staining. Caspase-3 and GSDME cleavage, HMGB1 release, phosphorylation of ERK and JNK, and inflammatory gene expression were assessed by Western blotting and qPCR. In vivo, a Citrobacter rodentium-induced colitis model was established and mice were treated with a specific alkaloid. Disease severity, histopathological injury, bacterial burden, barrier-related structural markers, and colonic GSDME cleavage were then evaluated. Berberine (BBR) exhibited the strongest cytoprotective activity in the screening system, reducing epithelial cell death, reversing pyroptosis-associated morphology, and inhibiting GSDME cleavage. BBR also reduced HMGB1 release, attenuated the phosphorylation of ERK and JNK, and downregulated pro-inflammatory gene expression. In the C. rodentium-induced infectious colitis model, BBR alleviated body weight loss, diarrhea, colon shortening, and histopathological injury without significantly reducing bacterial burden under the present experimental conditions. In parallel, BBR enhanced Tjp1 and Muc2 expression, and diminished colonic GSDME cleavage in vivo. Collectively, these findings suggest that BBR is a promising candidate for colitis involving bacterial infection-associated epithelial pyroptosis, potentially via GSDME modulation. Full article

Irinotecan is a first-line medication for metastatic colorectal cancer. It is known that irinotecan-induced delayed diarrhea is closely related to metabolic processes in the human body. In particular, the synergies of multiple metabolic enzymes/transporters mediate the transport/regeneration of intestinal SN38. This efficient metabolite derived from irinotecan not only exerts robust cytotoxic effects, but also extends contact duration with the intestinal wall during enterohepatic circulation. These factors further affect the intestinal microenvironment, including intestinal flora disorder, intestinal immune dysregulation, and intestinal barrier impairment, which ultimately causes the occurrence of delayed diarrhea. At present, dose adjustment of irinotecan and combining drugs are common measures for clinical use. However, these regimens have shown limited therapeutic efficacy and face the risk of chemotherapy failure. Numerous studies have shown that herbal medicines and derived phytochemicals may also be promising complementary treatments. The characteristics of multi-target regulation of herbs are very suitable for the intervention strategy of complex diseases with multiple pathogenic links. This review focuses on the development of irinotecan-induced delayed diarrhea. We generalized the complex pathogenesis in detail and summarized relevant potential drugs and clinical agents. Special attention was paid to the feasibility of traditional Chinese medicine treatment. This will help expand medication regimens for irinotecan-related diarrhea and provide a reference for the development of precision drugs. Full article

Neonatal calf diarrhea (NCD) is one of the most important problems of calf breeding across the world. It causes deaths in calves in the first 10 days of their life, and it is mainly caused by Escherichia coli(E. coli), Bovine Rotavirus (BRV) and Bovine Coronavirus (BCoV). The lack of vaccines with consistently high protective efficacy against the main causes of NCD makes disease control highly challenging. The current study aims to design a multi-epitope mRNA-based vaccine targeting the major pathogens responsible for NCD using immunoinformatic tools and molecular modeling approaches. BRV capsid protein VP6, BCoV Spike glycoprotein and E. coli F5 fimbrial protein were used as antigenic proteins to predict potential epitopes. Fifteen selected epitopes were linked with suitable linkers and conjugated with a built-in adjuvant, resulting in the design of a stable, antigenic and non-allergenic vaccine candidate against NCD pathogens. Furthermore, molecular docking analysis shows strong binding affinity between the vaccine candidate and the bovine toll-like receptors TLR2 and TLR4 at low energy and high stability. Based on these findings, the proposed multi-epitope vaccine represents a promising approach for the prevention and control of neonatal calf diarrhea and provides a solid scientific foundation for future experimental studies to validate its efficacy and safety in vivo. Full article

Bovine viral diarrhea virus (BVDV) is a major cause of economic losses in the global cattle industry. This study investigated the clinical involvement and genetic diversity of BVDV in clinically affected cattle from the Thrace region in Türkiye, a critical border area with the European Union. A total of 533 nasal and rectal swabs were collected from 26 farms exhibiting clinical respiratory disease or diarrhea and analyzed using real-time RT-PCR. Positive samples were further characterized by sequencing and phylogenetic analysis to determine viral genotypes and subgenotypes. BVDV RNA was detected in 9 out of 26 farms (34.6%), with an overall positivity rate of 17.8% (95/533). Statistical analysis revealed significant associations between PCR positivity and both sampling year (p < 0.05) and animal age (p < 0.05). Genetic analysis of partial 5′-UTR sequences identified nine Pestivirus bovis subgenotype 1a strains, one Pestivirus bovis subgenotype 1f, and one Pestivirus brazilense. The Pestivirus bovis 1a strains clustered distinctly from previously reported Turkish BVDV-1 isolates, showing 97.32–99.11% nucleotide similarity with strains from Türkiye, Germany, China, Japan, the USA, Iran, and Argentina. Among the 533 samples tested, one Pestivirus brazilense isolate was identified, indicating its rare occurrence in the studied population despite targeted screening. This study represents the first report of Pestivirus brazilense in the Thrace region of Türkiye, expanding its known geographic range. The epidemiological data and genetic diversity analysis of BVDV strains characterized in this study offer critical insights for refining BVDV control programs, informing regional risk assessment, and supporting vaccine development. Full article