Search Results (7,227)

Chronic non-communicable conditions—type 1 and type 2 diabetes mellitus (T1DM, T2DM), metabolic obesity syndrome (MOS), polycystic ovary syndrome (PCOS), colorectal and extra-intestinal cancers, and systemic autoimmune disease—share a prolonged asymptomatic phase during which conventional screening is invasive, insensitive, or resource-intensive. This review synthesizes the 2021–2026 literature on fecal microbiome-based artificial intelligence (AI) diagnostics across these conditions, extracting reported discrimination, validation strategy, microbial and short-chain fatty acid (SCFA) biomarkers, and cross-cohort reproducibility. Across the primary classifier studies tabulated here, reported areas under the curve (AUCs) span 0.76–0.99 under internal validation but 0.69–0.91 under external or cross-population validation; in the four studies reporting both, the median AUC falls from 0.875 to 0.810. Verified external-validation values include 0.82 for colorectal cancer, 0.79 for T2DM and 0.792 for discrimination of systemic lupus erythematosus from rheumatoid arthritis and controls. Clinical readiness turns on this internal-to-external gap more than on the headline AUC. We propose a multimodal deep learning architecture coupled with explainable AI; no component has been implemented or evaluated on data, and it is presented as a design proposal. Fecal-microbiome-based multimodal AI is technically feasible but clinically unvalidated, pending prospective, harmonized cross-cohort trials. Full article

Background: Hyperlipidemia is a major risk factor for cardiometabolic disorders, including non-alcoholic fatty liver disease (NAFLD), and is closely associated with oxidative stress. Opuntia ficus-indica (OFI) cladodes are recognized as a rich source of bioactive phytochemicals; however, the molecular mechanisms underlying their metabolic benefits remain incompletely understood. Objectives: This study aimed to comprehensively evaluate the hypolipidemic and hepatoprotective potential of a polyphenol-rich O. ficus-indica cladode extract (OCE) using an integrated approach combining in vivo evaluation, untargeted metabolomics (UHPLC-Orbitrap-MS/MS), molecular docking, and ADMET prediction. Methods: Hyperlipidemic mice fed a high-fat diet (HFD) were treated with OCE, while molecular docking was performed on ten major annotated phytochemicals against twelve key proteins involved in lipid metabolism and cholesterol homeostasis, including HMGCR, FAS, PPARα, PCSK9, and NPC1L1, using simvastatin as the reference compound. Results: OCE treatment significantly improved plasma and hepatic lipid profiles, improved glucose homeostasis, and markedly reduced hepatic malondialdehyde (MDA) levels, indicating attenuation of oxidative stress. Histopathological analysis further supported a pronounced hepatoprotective effect, with a substantial reduction in hepatic steatosis. Untargeted metabolomics enabled the annotation of 102 metabolites, putatively identifying piscidic acid as the predominant phenolic constituent together with a diverse profile of flavonoids and phenolic acids. Molecular docking supported the potential contribution of these phytochemicals to the regulation of lipid metabolism through favorable interactions with multiple therapeutic targets, while ADMET prediction suggested an overall favorable pharmacokinetic and toxicity profile despite the lower intestinal permeability predicted for glycosylated derivatives. Conclusions: Overall, these findings support O. ficus-indica cladodes as a promising source of dietary bioactive compounds with potential applications in the nutritional management and prevention of hyperlipidemia and related cardiometabolic disorders. Full article

Treat-to-target management in inflammatory bowel disease (IBD) combines symptoms, fecal and serum biomarkers, endoscopy, histology, and cross-sectional imaging, but these measures frequently diverge. Discordance may reflect analytical variation, timing, disease location, phenotype, comorbidity, or partially non-overlapping biological processes. We performed a critical narrative review using a structured PubMed/MEDLINE search, supplemented by citation chaining and publisher searches. Guidelines, systematic reviews, diagnostic studies, cohorts, randomized trials, and selected mechanistic studies were prioritized. Fecal calprotectin (FC) and lactoferrin primarily reflect intestinal neutrophilic inflammation, whereas C-reactive protein (CRP) and related serum indices reflect a nonlocalizing systemic response. The fecal immunochemical test (FIT) detects gastrointestinal bleeding, and leucine-rich alpha-2 glycoprotein (LRG) remains promising but insufficiently standardized. We distinguish five biological biomarker domains—namely, fecal–neutrophil; serum–systemic; epithelial/barrier; restitution/resolution; and fibrosis/extracellular matrix (ECM) remodeling—from symptoms and clinical indices, pharmacologic measurements, and phenotype-directed reference assessments. Circulating barrier, repair, and matrix-turnover markers remain investigational. Reactive therapeutic drug monitoring (TDM) for anti-tumor necrosis factor (anti-TNF) agents has the most mature evidence. Vedolizumab and ustekinumab show exposure–response associations, but actionable thresholds are unvalidated, and clinical TDM is not established for newer biologics or oral small molecules. After objective confirmation of disease activity, the framework may support phenotype-directed therapeutic decisions but is not a validated algorithm. Clinically important disagreement should prompt assessment of sampling, assay, timing, infection, medication-related confounding, and pretest probability before phenotype-directed endoscopy, histology, imaging, or reactive TDM is selected. A single discordant result should neither trigger treatment escalation nor exclude active or structural disease. Full article

Inflammatory bowel disease (IBD) and colorectal cancer (CRC) are heterogeneous intestinal disorders that pose significant threats to human health and share common pathological features, including intestinal mucosal barrier disruption and gut microbiota dysbiosis, in which fucosylation acts as a critical regulatory mediator. Fucosylation is a highly conserved post-translational glycosylation modification involving the enzymatic transfer of fucose residues to glycoproteins and glycolipids. This tightly regulated process plays essential roles in maintaining intestinal homeostasis, mediating host–microbiota interactions and regulating immune responses. This review adopts a physiology-to-pathology framework, delineating fucosylation’s operational principles in healthy intestines and its dysregulation in IBD and CRC. It summarizes the spatial distribution of fucosylation, its regulatory mechanisms, and its roles in disease pathogenesis, and also discusses its potential as a diagnostic biomarker and therapeutic target. Finally, this review highlights future research directions to bridge mechanistic insights with clinical translation, emphasizing the promise of fucosylation in the precision diagnosis and treatment of intestinal disorders. Full article

The tea tree (Melaleuca alternifolia) essential oil (TTEO) exhibited in vitro antioxidant activities with an inhibition concentration (IC50) of 29.02 ± 0.57 µg/mL. This is due to its content of bioactive compounds; practically α-pinene (1.52%), eucalyptol (9.05%), 2-bornanone (57.94%), 1-dotriacontanol (1.82%), 1-decanol, 2-hexyl- (1.99%), and 1-heptatriacotanol (4.90%). Therefore, this research aimed to determine changes in growth, antioxidant capacity, immune functions, and disease resistance in Nile tilapia (Oreochromis niloticus) when fed on a low-fishmeal (FM) diet enriched with TTEO. Nile tilapia juveniles (14.6–15.9 g) were fed on a low-FM diet containing 0.0 (the control), 0.1, 0.15, 0.2, and 0.25 g TTEO/kg feed up to apparent satiety three times a day for 70 days. Following the feeding trial, fish were intraperitoneally injected with Aeromonas hydrophila, and fish mortality was recorded for an additional 10 days. It is noted that feeding the fish on 0.2 g TTEO/kg feed increased the feed intake as well as the growth indices. Marked declines in FCR values were seen in fish fed on 0.15–0.25 g TTEO/kg feed. However, fish fed on a diet with 0.2 g TTEO/kg feed exhibited highest enhancements in intestinal villi width/length and absorption area compared with other TTEO levels. No statistical (p > 0.05) differences were observed in glucose and cortisol levels among TTEO-fed groups, indicating no stress effects on fish. Conversely, ALT and AST activities in Nile tilapia declined significantly (p < 0.05), especially at 0.20 and 0.25 g TTEO/kg feed, with no difference (p > 0.05) between the two treatments. It is noted that high TTEO levels (0.2–0.25 g/kg feed) increased hepatic superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities as well as the mRNA expression of hepatic SOD, CAT, and GPx genes. Compared with other TTEO groups, feeding the fish with 0.2 g TTEO/kg feed showed higher alkaline phosphatase, lysozyme, complement C3, and ACH50 levels, along with marked increases in IL-8 and IL-10 genes expression and declines in the expression TNF-α, IL-1ß, HSP70, Caspase-3, and Caspase-9 genes. After A. hydrophila infection, fish fed on the control diet exhibited the highest mortality (76.7%), whereas fish fed on 0.2 and 0.25 g TTEO/kg feed were more resistant to bacterial infection, with mortality rates of 23.3% and 26.7%, respectively, with no difference (p > 0.05) between them. The results confirmed that dietary TTEO enhanced growth, antioxidant capacity, immunological biomarkers, and disease resistance in Nile tilapia when added to low-FM diets, with an optimum dose of 0.2 g TTEO/kg feed. Full article

Hepatocellular carcinoma (HCC) remains a major global health challenge and one of the leading causes of cancer-related mortality, with advanced disease continuing to be associated with limited therapeutic options and substantial heterogeneity in response to systemic treatment. Recent evidence has established the gut microbiota, through the gut–liver axis, as a critical determinant of immunotherapy efficacy, while also influencing antitumor immunity and liver carcinogenesis. Microbial dysbiosis may promote chronic inflammation, intestinal barrier disruption, bacterial translocation, and immune dysfunction, thereby contributing to hepatocarcinogenesis. Moreover, gut microbial composition and microbial-derived metabolites, including bile acids, short-chain fatty acids (SCFAs), and inosine, have been associated with modulation of antitumor immune responses and differential outcomes to immune checkpoint inhibitors (ICIs). Emerging clinical evidence in HCC has identified distinct gut microbial signatures associated with response to nivolumab, pembrolizumab, and atezolizumab-based regimens, including enrichment of Akkermansia muciniphila and SCFA-producing taxa such as Ruminococcaceae, Roseburia, and Prevotella in responders. However, these findings remain inconsistent across studies, with no reproducible microbial signature identified because of small cohort sizes, heterogeneous patient populations, geographic variation, cirrhosis-related confounding factors, and methodological differences in microbiome analysis. This review summarizes the current understanding of microbiome–immune interactions in HCC, examines mechanistic pathways linking the microbiota to immunotherapy response, critically evaluates available clinical evidence, and discusses current limitations and future therapeutic strategies, including fecal microbiota transplantation, probiotics, dietary modulation, and engineered bacterial platforms. Collectively, microbiome-based approaches may contribute to the development of personalized immunotherapeutic strategies in HCC, although larger standardized prospective studies are required before microbiome-derived biomarkers can be implemented in routine clinical practice. Full article

Peptide therapeutics occupy a unique position between small organic compounds and large protein biomolecules, combining high specificity, strong pharmacological efficacy, and favourable safety profiles. Consequently, they have emerged as important therapeutic agents for a wide range of diseases, including metabolic and oncological disorders. However, oral administration of peptide drugs remains a major challenge due to extensive enzymatic degradation, low intestinal permeability, mucus entrapment, and presystemic metabolism within the gastrointestinal tract. This review provides a comprehensive overview of contemporary strategies for improving oral peptide delivery, with special emphasis on emerging pharmaceutical formulation technologies, bioinspired delivery systems and ingestible device-assisted approaches. A qualitative literature search was conducted using major scientific databases and included relevant publications available up to May 2026. The analysis identified the main barriers responsible for low oral bioavailability of peptide drugs, as well as promising approaches to overcoming these obstacles, including peptide modification, enzyme inhibition, permeation enhancement, mucolytic strategies, and advanced carrier systems. Special attention is given to multifunctional carrier systems, ingestible medical devices and bile acid-inspired technologies as emerging directions in oral peptide delivery. The convergence of pharmaceutical sciences, bioinspired formulation strategies and biomedical engineering is expected to accelerate the clinical translation of oral peptide formulations and enable their therapeutic potential to be fully exploited. Full article

Severe anaemia remains a major public health challenge, disproportionately affecting children and women of reproductive age in sub-Saharan Africa. In high-burden settings, the aetiology of severe anaemia is multifactorial, encompassing nutritional deficiencies, infections, and host genetic factors. Beyond its direct clinical consequences, severe anaemia is also associated with increased susceptibility to invasive bacterial infections, particularly those caused by enteric pathogens such as non-typhoidal Salmonella and Escherichia coli. In this review, we present an integrated framework linking severe anaemia and invasive bacterial infection through three interconnected biological pathways, collectively termed the gut–iron–immune axis: gut microbial dysbiosis and impaired intestinal barrier integrity; disrupted iron homeostasis; and impaired immune function. We examine context-specific modifiers in endemic settings, including iron deficiency, malnutrition, malaria, sickle cell disease, and environmental enteric dysfunction. We also discuss how management of severe anaemia, including blood transfusion and iron supplementation, reshapes the gut microbiome, with direct implications for microbial translocation, invasive bacterial infection, and clinical outcomes. Finally, we identify key knowledge gaps and research priorities to guide safer and more effective prevention and management of severe anaemia in high-burden settings. Full article

Organoid and organ-on-chip technologies are rapidly evolving platforms for viral research that integrate stem cell biology, tissue engineering, and microfluidics to recapitulate key structural, mechanical, biochemical, and cellular features of human and animal physiology. By incorporating multicellular organoids into perfused microfluidic systems, these models can provide complex, dynamic, and physiologically relevant micro-environments for investigating virus–host interactions that are difficult to capture in conventional two-dimensional cultures and static organoids. Controlled flow, shear stress, extracellular matrix organization, tissue–tissue interfaces, and multicellular signaling enable mechanistic investigation of viral infectivity, dissemination, tissue injury and immune activation. Integration of real-time imaging and biosensors further permits longitudinal monitoring of viral replication, host responses, and tissue integrity, expanding the potential of these platforms for antiviral drug discovery. Recent organoid-on-chip studies using brain, skin, vaginal, respiratory, and intestinal models have demonstrated how tissue architecture, mechanical forces, glycocalyx dynamics, and immune–stromal interactions influence viral tropism and pathogenesis. In this review, we provide a mechanistic and translational overview of organoid and organ-on-chip technologies for studying viral infections, with particular emphasis on models of herpes simplex virus (HSV)-mediated disease. We further examine advances in immune integration, multi-organ systems, biosensing, and computational approaches that are expanding the complexity and predictive potential of these models. Importantly, patient-derived organoids and organ-on-chip platforms can capture interindividual differences in viral susceptibility, host responses, and therapeutic efficacy, providing pharmaceutical research with more precise, patient-relevant data to support drug prioritization and precision antiviral medicine. Finally, we discuss key barriers to broader adoption, including organoid maturation, biological and technical variability, reproducibility, scalability, biosafety, cost, standardization, and regulatory validation. Collectively, these advances position organoid and organ-on-chip technologies as powerful human-relevant models that bridge reductionist in vitro systems and human disease, while continued optimization, standardization, and validation will be essential to realize their full potential for mechanistically informed antiviral discovery, therapeutic development, and precision medicine. Full article

Background: Metabolic syndrome is closely linked to chronic systemic inflammation and intestinal dysbiosis. Anti-inflammatory nutrition is an approach based on the interaction between dietary intake, chronic low-grade inflammation, and the pathophysiological mechanisms of metabolic syndrome and cardiometabolic diseases. This narrative review evaluates the impact of plant-based dietary models, including vegan and modified Mediterranean variants, on key metabolic and inflammatory parameters. Methods: Literature data published in PubMed, Science Direct, Scopus, and Google Scholar between 2017 and 2026 were used to evaluate the relation between diet, inflammation, and cardiometabolic diseases. We focused on multiple biomarkers, including inflammatory, metabolic, and oxidative-stress indicators measured by standardized laboratory methods to estimate the overall relationship between diet and chronic inflammation. Results: Dietary indices such as eADI-17 allow quantification of the inflammatory potential of anti-inflammatory nutrition and correlate with biomarkers such as hsCRP, IL-6, and soluble TNF receptors. Conclusions: Integrated nutritional strategies that combine plant-based models, temporal control of meals, and microbiota-directed interventions provide efficient support by improving endothelial dysfunction, the thrombotic profile, and chronic inflammation. Full article

The accurate evaluation of gastrointestinal (GI) diseases such as celiac disease (CeD) relies on the assessment of villous architecture, yet progress in imaging-based diagnostics, particularly video capsule endoscopy (VCE), is constrained by the absence of anatomically realistic and reproducible physical models of the intestinal mucosa. Existing benchtop phantoms typically reproduce gross luminal curvature but fail to capture the sub-millimeter villous microstructure, the optical scattering behavior, and the luminal folding of native mucosa that together shape its endoscopic appearance. We developed a modular fabrication framework for an anatomically realistic small intestinal phantom with controlled villous microstructure. High-resolution drop-on-demand photopolymer material jetting was used to print discrete patches of villous-like micropillar arrays with tunable height, diameter, and spacing parameterized from histological data spanning Marsh 0 to 3c classifications. The printed patches were then dyed for mucosal-color realism, bonded onto a polyester–spandex substrate, rolled into a continuous tube, and shaped with adjustable retainer rings to introduce luminal folds. Optical microscopy confirmed dimensional fidelity within ±10% of design values with patch-to-patch variation below 7%, and VCE imaging of healthy and atrophic configurations achieved structural similarity (SSIM) values of 0.625 and 0.761 against clinical mucosal imagery. This reproducible platform supports VCE device validation, imaging dataset generation, and clinician training in gastrointestinal imaging. Full article

Sphingolipids, a class of lipids, are widely present in the cell membranes of all eukaryotic and some prokaryotic organisms. These lipids play crucial roles in the formation of the lipid bilayer and are categorised into several groups, including sphingomyelins, ceramides, sphingosine-1-phosphate, and glycosphingolipids. In addition to their structural significance, sphingolipids also show bioactivity, regulating various signalling pathways involved in cell growth, differentiation, ageing, and apoptosis, and are closely associated with several chronic diseases, including obesity and type 2 diabetes mellitus. Notably, dysregulated sphingolipid metabolism contributes to obesity-related metabolic dysfunction through altered lipid accumulation, insulin signalling, organelle stress, and inflammation. This review summarises the various mechanisms and recent research advances related to sphingolipids and their association with obesity. It further examines how the metabolic effects of ceramides vary according to their acyl-chain length, enzyme of origin, tissue distribution, and metabolic context, as well as how adipose depot, sex, age, and metabolic phenotype influence the sphingolipid response to obesity. It further considers plant-derived sphingolipids as a compositionally distinct exogenous input to host sphingolipid pools, comparing their structural and enzymatic features with those of mammalian sphingolipids. Pharmacological, dietary, and lifestyle approaches that modify sphingolipid metabolism are also considered. Accordingly, the review summarises our current knowledge regarding the dietary occurrence, intestinal handling, and metabolic effects of sphingolipids and identifies the evidence gaps that currently limit conclusions regarding their relevance to obesity. Full article

Background/Objectives: The aim of the present study was to investigate the mechanisms in Parkinson’s disease (PD), a progressive neurodegenerative disorder characterized by loss of dopaminergic neurons, aggregation of α-synuclein, mitochondrial dysfunction, oxidative stress, neuroinflammation, gut dysbiosis, and blood–brain barrier (BBB) impairment. Although there are several approved therapies that have been developed, their aqueous solubility, oral bioavailability, first-pass metabolism, and inability to penetrate the BBB make them less effective over time. This review is intended to critically analyze the potential of self-nanoemulsifying drug delivery systems (SNEDDSs) as a pathogenesis-related approach to enhance the delivery and therapeutic activity of repurposed drugs and conventional drugs for PD. Methods: A comprehensive literature search was conducted to address the pathogenic mechanisms of PD, the deficiencies of current pharmacotherapy, recent developments in SNEDDS formulation strategies and their application in improving oral bioavailability, lymphatic transport, BBB penetration and targeted brain delivery. A special focus was dedicated to drug repurposing, functionalized SNEDDSs, PEGylation, and gut–brain axis modulation. Results: SNEDDSs significantly enhance the water solubility, stability, intestinal absorption and systemic exposure of poorly water-soluble therapeutic agents and, to a certain extent, lymphatic uptake to avoid first-pass metabolism. These systems include improved brain delivery, decreased pharmacokinetic variability, and prolonged drug levels within the therapeutic range. Moreover, SNEDDSs can be used to deliver multiple molecules that are found to be neuroprotective, antioxidant, anti-inflammatory and probiotic, all at once, which can act on multiple pathogenic mechanisms associated with PD. Functionalized and PEGylated SNEDDSs add further to formulation stability, extend systemic circulation and increase efficiency of brain targeting. Conclusions: SNEDDSs are a promising translational nanomedicine platform for enhancing the effectiveness of conventional and repurposed therapeutics in PD, which address key pharmacokinetic and biological challenges. The next generation of oral therapies with targeted surface engineering, precision drug repurposing and clinical validation will be expected to bring about a faster advancement of drugs that can alter the course of disease rather than giving only symptomatic relief. Full article

Background/Objectives: Celiac disease (CeD) is a complex autoimmune enteropathy triggered by gluten intake in genetically predisposed individuals. While the bacterial microbiome has been extensively studied in CeD, the role of the gut virome and mycobiome is less well defined. Emerging evidence suggests that viruses and fungi may influence mucosal immunity, intestinal permeability and gluten tolerance, acting as potential environmental cofactors in the onset of this disease. Methods: A narrative review of the literature was conducted to summarize current knowledge of the composition, development and function of the gut virome and mycobiome and to explore their potential involvement in CeD pathogenesis. Results: The gut virome shows high interindividual variability and dynamic maturation early in life. Multiple studies have associated early enterovirus or parechovirus infections with an increased risk of celiac autoimmunity, supporting a virus–gluten “double hit” model. Viral dysbiosis in CeD has been reported to include an enrichment of human polyomavirus 2 (JC polyomavirus) and of specific enterobacterial phages. The mycobiome, although less abundant, also displays disease-associated alterations: cross-sectional mycobiome studies have reported higher relative abundance of Saccharomyces, Candida, and Tricholomataceae and lower relative abundance of Pichia and Pneumocystis taxa in children with CeD. Conclusions: Current evidence, although preliminary, supports associations between selected viral exposures and CeD-related immune alterations, whereas current phageome and mycobiome findings mainly describe cross-sectional compositional differences. These data do not establish temporal direction or causality, and further longitudinal and mechanistic investigations are required before preventive or therapeutic implications can be considered. Full article

Background/Objectives: Aluminium is a widespread environmental element and food contaminant to which the general population is continuously exposed, primarily through diet and drinking water. Although gastrointestinal absorption is generally low, bioavailability varies according to chemical form, food matrix, and interactions with dietary components. Prolonged exposure can nevertheless result in gradual tissue accumulation. This review summarises current evidence on dietary aluminium exposure, factors influencing its bioavailability, toxicokinetics, biological effects, gut microbiota interactions, and population-level health risk. Methods: A comprehensive narrative literature review was conducted using publications retrieved from PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar. Original research articles, review papers, and reports issued by international organisations were critically evaluated with particular emphasis on dietary sources, drinking water, food additives, food contact materials, gastrointestinal absorption, toxicokinetics, biological mechanisms, gut microbiota, and health risk assessment. Results: Food represents the principal source of aluminium exposure in the general population, while drinking water usually contributes a smaller but continuous fraction of total oral intake. Dietary exposure varies substantially between populations and is influenced by food composition, processing practices, the use of aluminium-containing additives, and migration from food contact materials. Aluminium bioavailability is modified by chemical speciation and dietary constituents, including citrate, phosphates, silicates, phytates, polyphenols, and essential minerals. Despite limited absorption, prolonged exposure can lead to gradual aluminium accumulation, particularly in bone tissue and the central nervous system. Proposed biological mechanisms include oxidative stress, mitochondrial dysfunction, disruption of mineral homeostasis, and inflammatory signalling. Emerging evidence also indicates that aluminium may alter the gut microbiota, impair intestinal barrier integrity, and influence the gut–brain axis. Population exposure assessments show considerable regional variation, with some groups approaching or exceeding established tolerable weekly intake values. Conclusions: Dietary aluminium exposure represents a relevant issue in nutritional toxicology and food safety. Although current evidence does not establish that typical dietary exposure directly causes chronic disease, long-term exposure, differences in bioavailability, and the possibility of elevated intake in selected population groups justify continued monitoring and further prospective human studies. Future research should integrate dietary intake, aluminium speciation, nutritional status, biomarkers of internal exposure, and long-term health outcomes to improve risk assessment and support effective exposure-reduction strategies. Full article