Search Results (2,030)

Although nanomedicine has enabled significant advances in drug delivery, the clinical translation of conventional synthetic nanocarriers is limited by immune clearance, non-specific biodistribution, and gastrointestinal instability. This poses major challenges for therapy targeting the intestines. Cell membrane-coated nanotechnology (CMCT) and membrane vesicle-based systems have emerged as biomimetic platforms integrating synthetic nanomaterials with naturally derived biological interfaces. These biohybrid systems inherit biological functions originating from cells, including immune evasion, prolonged circulation, lesion homing, and microenvironment-responsive interactions, through the direct transfer of intact membrane components. This review summarizes recent advances in CMCT and membrane vesicle-based strategies for intestinal drug delivery. It covers fabrication methodologies, programmable manufacturing approaches, and functional regulation enabled by diverse membrane sources and hybrid engineering designs. Applications in inflammatory bowel disease, colorectal cancer, and intestinal infections are highlighted, emphasizing key therapeutic mechanisms, such as targeting inflammation, neutralizing toxins, modulating the immune system, and regulating the microbiome. We also discuss the major challenges of translation, such as preserving membrane and coating integrity, ensuring oral stability, achieving batch reproducibility, and ensuring biosafety. Overall, this review establishes a conceptual and engineering framework to guide the transition of membrane-based nanocarriers from passive biomimicry to adaptive, clinically translatable intestinal delivery systems. Full article

Opioid-induced constipation (OIC) represents a prevalent adverse effect of opioid analgesics, affecting 60–90% of patients and ssignificantly compromising quality of life. This review delineates the multifactorial pathogenesis of OIC. Peripheral μ-opioid receptor (MOR) activation suppresses enteric neuronal excitability, inhibits intestinal motility and secretion, and impairs rectoanal function. Notably, the colon appears to exhibit a distinctive lack of tolerance to opioids. Enteric glial cell activation has been implicated in neuroinflammation, while interstitial cells of Cajal show impaired pacemaker function. Central mechanisms are increasingly recognized to involve the brain–gut axis. Furthermore, opioid-induced barrier disruption, microbiota dysbiosis, and LPS/TLR4-mediated inflammation are proposed to interact and may contribute to a self-reinforcing cycle. Animal models have been instrumental in dissecting these mechanisms. However, they present limitations in reproducibility, clinical phenotype fidelity, and translational validity, particularly regarding microbiome composition and neuroimmune responses. Future research should prioritize the development of standardized, physiologically relevant animal models incorporating multi-omics approaches, and validate mechanism-based therapeutic strategies, including peripherally acting MOR antagonists and microbiota-targeted interventions, for precision management of OIC. Full article

The human virome, comprising eukaryotic viruses, bacteriophages, and viral genetic material, is a dynamic component of the microbiome with growing relevance in infectious diseases. This narrative review is structured to: (i) summarize the general composition of the human virome and methodological challenges, including the fraction of unclassified viral “dark matter”; (ii) describe virome alterations in chronic infections; and (iii) explore site-specific virome dynamics across respiratory, intestinal, and genito-urinary tracts in both chronic and acute infections. In chronic viral infections such as HIV, HBV, HCV, and HPV, a recurrent feature is the expansion of Anelloviridae—particularly torque teno virus—reflecting impaired immune surveillance rather than direct pathogenicity, suggesting their potential as surrogate biomarkers of immune competence. Evidence on virome changes in chronic bacterial and parasitic infections remains limited, highlighting a critical knowledge gap. Acute infections are associated with compartment-specific shifts in eukaryotic viruses and bacteriophage communities, often paralleling changes in bacterial populations and inflammatory responses, with implications for disease severity. Despite advances in metagenomic approaches, a substantial proportion of viral sequences remains unclassified, limiting functional interpretation. Nevertheless, virome profiling provides an ecosystem-level perspective, offering insights beyond single-pathogen detection and supporting emerging applications in diagnostics, immune monitoring, prognosis, and infectious disease surveillance. Full article

Thamnaconus septentrionalis is an economically important marine aquaculture species in China. However, the acceptance rate of formulated feeds in commercial farming is only 30–40%, substantially lower than the 80–90% achieved with fresh feeds, which severely constrains the intensive development of this industry. The gut microbiota-mediated regulatory mechanisms underlying the effects of different feed types on growth performance remain unclear, limiting the precise development of efficient formulated feeds. This study established four feed types (commercial pellet feed K, custom-formulated feed P, frozen shrimp X, and fresh fish meat Y) through a 60-day feeding trial. Growth performance data, 16S rRNA sequencing, and untargeted metabolomics were analyzed. Random Forest-Partial Least Squares Regression models were employed to identify key microbial-metabolite features. Results indicated that the Y group exhibited the optimal feed conversion ratio (1.14), with intestinal Firmicutes abundance (45.3%) significantly higher than the K group (28.5%). Short-chain fatty acid levels increased by more than 350-fold, enriching short-chain fatty acid-producing bacteria such as Lactobacillus and Faecalibacterium. The P group, formulated with high fishmeal content (40%), achieved performance levels comparable to the Y group across most indicators. Machine learning models identified key microbial-metabolite features predicting growth performance, providing a multi-omics framework for developing efficient formulated feeds for marine carnivorous fish. Full article

Prophylactic antibiotic use in intensive aquaculture promotes antimicrobial resistance, necessitating the development of microbial-based interventions. This study evaluated the individual, complementary, and synergistic effects of Bacillus subtilis natto (BSN) and Lactobacillus plantarum (LP) on the physiological performance and intestinal microecology of juvenile Japanese flounder (Paralichthys olivaceus). Over a 60-day trial, juveniles (initial weight: 5.81 ± 0.03 g) received a basal diet (CON) or a diet supplemented with 10⁷ CFU/g of BSN, LP, or both (BSN+LP). The BSN+LP consortium elicited complementary improvements in final body weight (21.39 ± 0.75 g vs. 18.66 ± 0.44 g in CON) and feed conversion efficiency (p < 0.05). Transcriptomic analysis revealed synergistic upregulation of digestive proteases (trypsin, chymotrypsin). Notably, an in pro-inflammatory markers (IL-1β, TNF-α) was counterbalanced by substantial upregulation of anti-inflammatory cytokines (IL-10, 5.65-fold; TGF-β1, 4.48-fold), suggesting the induction of mucosal tolerance rather than pathological enteritis. High-throughput 16S rRNA sequencing showed that the control cohort had a potential baseline microbial, characterized by a high relative abundance of Proteobacteria. BSN+LP administration significantly altered this microbial community into a fermentative eubiosis enriched in Firmicutes and Bacteroidota. Correlation network analyses confirmed negative interaction dynamics: increased abundance of Lactobacillus, Bacteroides, and Muribaculaceae was negatively correlated with baseline pathobiont abundance. These findings indicate that co-administration of BSN and LP hypothetically enhances metabolic energy harvest via short-chain fatty acid-producing taxa, strengthens the gut–immune axis, and competitively mitigates opportunistic pathogens. Full article

This study focuses on Lacto-N-neotetraose (LNnT), a core component of human milk oligosaccharides. Although LNnT has been demonstrated to promote early intestinal development and maintain gut homeostasis, its protective mechanism against D-galactose-induced intestinal injury and associated cognitive impairment remains unclear. This investigation systematically examined the protective effects and underlying mechanisms of LNnT against D-gal-induced colonic damage and cognitive impairment in mice. The results demonstrated that LNnT not only significantly improved systemic physiological phenotypes and upregulated the expression of colonic tight junction proteins to repair the intestinal barrier, but also effectively enhanced learning and memory abilities in mice. Concurrently, LNnT reduced serum proinflammatory factor levels, elevated the anti-inflammatory factor IL-10, and alleviated oxidative stress. Furthermore, LNnT remodeled the gut microbiome structure by increasing microbial diversity, enhancing beneficial bacteria abundance, and promoting short-chain fatty acid production. Untargeted metabolomics analysis further revealed that LNnT corrected metabolic disturbances by regulating key sphingolipid molecules (ceramide, sphingosine, S1P) and the expression of related metabolic enzymes (ACER2, SphK2). In summary, this study suggests that LNnT mitigates intestinal injury and improves cognitive function, potentially through modulation of the gut microbiota–sphingolipid metabolism axis, although further causal validation is warranted. These findings provide a mechanistic foundation for future studies exploring its potential as a functional dietary ingredient. Full article

Oxidative stress and gut microbiota dysbiosis establish a self-perpetuating loop that disrupts epithelial barrier integrity and fuels chronic inflammatory and metabolic disorders, including inflammatory bowel disease (IBD), metabolic syndrome (MS), and chronic kidney disease (CKD). This systematic review synthesizes mechanistic, preclinical, and clinical evidence linking reactive oxygen species (ROS), microbiota-derived metabolites, and host redox homeostasis, with a focus on probiotic-based interventions. Comprehensive searches of PubMed, Scopus, Web of Science, and Google Scholar (2000–March 2026) identified in vitro, animal, and human studies, as well as systematic reviews and meta-analyses, assessing oxidative biomarkers, microbiome profiles, and barrier function outcomes. Probiotic strains, predominantly Lactiplantibacillus, Bifidobacterium, and emerging next-generation taxa, attenuate oxidative stress by inducing antioxidant enzymes [superoxide dismutase (SOD), glutathione peroxidase (GPx)], activating Nrf2 signaling, and restoring short-chain fatty acid (SCFAs) production, thereby lowering malondialdehyde (MDA) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) while enhancing total antioxidant capacity (TAC). At the mucosal interface, probiotics strengthen tight junction proteins, suppress NF-κB-mediated cytokine release, and mitigate dysbiosis, contributing to clinically meaningful improvements in disease activity, insulin sensitivity, and uremic toxin burden along gut–liver, gut–kidney, and other gut–organ axes. Overall, current evidence supports probiotics and synbiotics as promising adjuncts for nutrition-driven redox modulation, while highlighting the need for strain-resolved, multi-omics, multicenter trials with standardized redox and microbiome endpoints to optimize dosing strategies and long-term safety. Full article

Increasing evidence suggests pancreatic cancer develops within a host–microbe ecosystem in which microbial communities across anatomical niches interact with tumour biology, immune regulation, metabolism, and therapeutic response. This review examines pancreatic cancer through the lens of humans as holobionts, integrating evidence from the oral, gut, biliary, and intratumoural microbiomes. Epidemiological and sequencing studies demonstrate consistent microbial alterations across these niches in pancreatic cancer, including oral dysbiosis associated with periodontal pathogens, gut microbial shifts toward pro-inflammatory taxa, disease-specific biliary microbial signatures, and the presence of distinct intratumoural microbial communities. Mechanistic studies indicate that intestinal barrier disruption, microbial translocation, immune and metabolite signalling can influence tumour immune architecture, macrophage polarisation, T-cell infiltration, oncogenic signalling pathways, and chemotherapeutic metabolism, particularly inactivation by tumour-associated bacteria. Microbiome-driven shifts in immunometabolism can reprogramme immune-cell metabolic pathways, impairing effective T-cell activation, promoting tumour-supportive macrophage phenotypes. Emerging therapeutic strategies aim to modulate the microbiome–tumour axis, including dietary interventions, probiotics and immunonutrition, faecal microbiota transplantation, engineered microbial therapies, and microbiome-informed antibiotic strategies. While pre-clinical findings are compelling and early-phase clinical studies suggest feasibility, most evidence remains associative and heterogeneous across cohorts and methodologies. Understanding pancreatic cancer as a multi-site ecological system may help explain inter-patient variability in disease progression and treatment response. This could usher in a new era for therapeutic manipulation where future progress will depend on longitudinal, multi-omic, and interventional studies to determine whether microbiome-targeted strategies can produce clinically meaningful improvements in pancreatic cancer outcomes. Full article

Allergic asthma is a prevalent chronic inflammatory disease of the airways whose pathogenesis has traditionally been attributed to localized immune dysfunction within the lung. However, accumulating evidence from microbiome research supports a broader system-level perspective in which cross-organ interactions contribute to disease susceptibility and progression. In particular, the gut–lung axis has emerged as a key regulatory pathway linking intestinal microbial ecology, immune development, and respiratory health. This review synthesizes current epidemiological, mechanistic, and experimental evidence supporting the role of gut microbiota dysbiosis in allergic asthma. We examine how early-life environmental and nutritional exposures and gut microbiota establishment during critical developmental windows shape long-term immune tolerance and asthma susceptibility. We then summarize characteristic features of asthma-associated gut dysbiosis and discuss how microbial-derived metabolites, including short-chain fatty acids, tryptophan metabolites, pro-allergic lipid mediators such as 12,13-dihydroxy-9Z-octadecenoic acid, and bacterial-derived histamine, modulate distal airway immune responses through epigenetic, receptor-mediated, and immune trafficking mechanisms. Particular emphasis is placed on the role of diet as a key upstream regulator of gut microbiota composition and metabolic function. Finally, we evaluate experimental and translational studies targeting the gut–lung axis, including dietary modulation, microbiome-targeted interventions such as fecal microbiota transplantation, and emerging postbiotic approaches. Collectively, current evidence indicates that gut microbial composition and metabolic function are critical determinants of respiratory immune homeostasis. Targeting the gut–lung axis through nutrition- and microbiome-based strategies offers a promising avenue for the prevention and precision treatment of allergic asthma. Full article

Background: Ulcerative colitis (UC) is a multifactorial disease characterized by aberrant mucosal immune activation in response to intestinal dysbiosis. Contemporary management strategies aim to target inflammation and microbiome alterations while reducing relapse risk. A multidimensional assessment integrating clinical, inflammatory, immune, and microbial endpoints may better capture therapeutic effects beyond symptom control. Aims: To evaluate whether supplementation with Lactobacillus rhamnosus GG co-formulated with vitamin D3 (Dicoflor IBD Immuno) as an adjunct to optimized mesalamine (5-ASA) is associated with coordinated changes across clinical and biological domains in mild-to-moderate UC, using a multidimensional assessment framework. Methods: This single-center, randomized, double-blind, placebo-controlled pilot trial was conducted at Fondazione Ca’ Granda IRCCS Policlinico di Milano between May 2022 and May 2024. Thirty-six patients with mild-to-moderate UC receiving optimized 5-ASA were randomized to LGG+VitD3 (ALD3) or placebo (AP) for 4 weeks. Clinical activity, health-related quality of life (HRQoL), fecal calprotectin, peripheral immune cell subsets, and gut microbiota composition were assessed at baseline and week 4. Results: Both 5-ASA-LGG+VitD3 (ALD3)- and 5-ASA-placebo (AP)-treated patients showed significant improvement in clinical activity and HRQoL, without between-group differences. A higher proportion of clinical responders was observed in the ALD3 group, although this was not statistically significant. LGG+VitD3-supplemented patients showed reduced fecal calprotectin levels and increased frequencies of IL-22-producing CD4⁺ T cells. Microbiome analysis revealed enrichment of short-chain fatty acid-producing taxa, including Coprococcus and Fusicatenibacter, in ALD3-treated patients. Conclusions: In patients with mild UC receiving optimized 5-ASA, LGG+VitD3 supplementation does not improve short-term clinical outcomes beyond placebo but is associated with favorable modulation of inflammatory, immune, and microbial parameters, supporting the relevance of multidimensional biological endpoints in adjunctive UC management. Full article

Campylobacter (C.) jejuni and C. coli are common zoonotic bacteria in pigs, which typically act as asymptomatic carriers. However, the effects of Campylobacter colonisation on the porcine intestinal microbiota and metabolome remain poorly understood. This study investigated microbiome and metabolome alterations associated with co-colonisation by C. jejuni and C. coli in the different intestinal segments of pigs. Thirty-two weaned piglets were assigned to a control group and a group inoculated with C. coli ST5777/CT828 and C. jejuni ST122/CT206. Four weeks post inoculation, jejunal and caecal contents were analysed for Campylobacter counts, metabolite profiles and microbial composition. All animals remained clinically healthy. Both Campylobacter species colonised the jejunum and caecum, with higher C. coli counts in the caecum. Campylobacter-colonised pigs showed significantly altered metabolite profiles, including reduced cysteine and urea and increased glycine in the jejunum, as well as elevated 3-hydroxybutyrate levels in the caecum. In contrast, short-chain fatty acid concentrations in the caecum were unaffected by infection. Microbiota analysis revealed a significant reduction in caecal alpha diversity, whereas jejunal diversity remained unchanged. Infected pigs exhibited increased relative abundances of Lactobacillaceae and Bifidobacteriaceae and a decreased abundance of Pseudomonadota, including Enterobacteriaceae. In conclusion, Campylobacter co-colonisation induces distinct microbiome and metabolome alterations in pigs despite the absence of clinical disease. These findings highlight complex host-microbiota–pathogen interactions that may be relevant for future Campylobacter control strategies in pig production. Full article

The prevalence of Crohn’s disease has increased over the last few decades, even in developing countries, whereas that of intestinal tuberculosis has decreased, which places both diseases at an epidemiological crossroads. Crohn’s disease and intestinal tuberculosis share many clinical, endoscopic, imaging, and pathological features, which sometimes make differential diagnosis very difficult; an accurate diagnosis is, however, very important since an erroneous treatment can worsen the evolution or delay proper therapy. The association between past TB infection and Crohn’s disease can make the diagnosis especially hard. This review summarizes current data on specific features that allow differentiation between Crohn’s disease and intestinal tuberculosis, paying particular attention to the microbiome, clinical signs, endoscopy, cross-sectional imaging, bacteriological, and immunological findings detailed. The importance of computerized models and scores for the differentiation is also detailed, because common features may make the differentiation based on a single criterion difficult. Full article

Antibiotic-associated diarrhea (AAD) is primarily driven by disruption of the gut microbiota accompanied by intestinal mucosal injury. Although multiherb formulations are widely used in East Asian medicine, their collective ecological effects and integrated microbiome–host mechanisms have not been systematically synthesized. This systematic review included 17 preclinical studies that investigated multiherbal formulations in AAD models. Given the substantial heterogeneity in the formulation composition, experimental design, and analytical platforms, a descriptive synthesis was performed. The included formulations were categorized into four clusters based on their shared herbal composition: Qiwei Baizhu San (QWBZP), Lizhong Tang (LZT), Gegen Qinlian Tang (GQT), and other supportive multiherbal formulations. The cluster-based synthesis revealed distinct convergent therapeutic strategies. The QWBZP and LZT clusters primarily supported the restoration of host metabolic and digestive functions, whereas the GQT cluster exhibited potent pathogen control effects with the suppression of opportunistic taxa. Across all clusters, a convergent microbiome–host response emerged, characterized by enrichment of commensal bacteria (e.g., Lactobacillus), upregulation of tight junction proteins (e.g., ZO-1, occludin), and attenuation of pro-inflammatory mediators (e.g., TNF-α, myeloperoxidase). Multiherb formulations in AAD models not only act as microbial modulators but also function as host-directed modulators that stabilize the intestinal homeostatic niche. Botanical interventions may facilitate endogenous microbiome recovery by reinforcing mucosal integrity and reducing environmental resistance. This ecological framework provides a rationale for future translational studies evaluating integrated herbal–probiotic strategies and precise microbiome management for patients with AAD, while further clinical validation is warranted. Full article

Probiotics are commonly applied to maintain the balance of gut microbiota and regulate the intestinal metabolic function of companion animals. In the present study, complex probiotics (Bacillus coagulans SNZ-1969, Bacillus subtilis, and Bacillus licheniformis) were added into the basal diet of domestic cats to investigate their influence on the intestinal microbiome and metabolic characteristics. Results revealed that the alpha diversity of the gut microbiota in the probiotic group was enhanced when compared to the control group. The beta diversity of the gut microbiota was also altered by the oral consumption of the complex probiotics. Compared to the control group, the relative abundance of beneficial microbes (such as Clostridium, Bacteroides, Phocaeicola, and Ruminococcus) in the probiotic group was enhanced, while the relative abundance of opportunistic pathogens (such as Escherichia, Gallibacter, Corynebacterium) was decreased. Additionally, the intestinal metabolic characteristics of domestic cats were also changed. The metabolomic analysis identified 408 differential metabolites between the two groups, and the KEGG function pathway analysis proved that the dominant pathway related to the differential metabolites were the amino acid metabolism, lipid metabolism, carbohydrate metabolism, energy metabolism, endocrine system, digestive system, immune system, and other metabolic pathways. Spearman’s correlation analysis revealed that the beneficial microbes had positive correlations with the differential metabolites. In conclusion, the current study demonstrated that oral administration of complex probiotics could regulate overall health and well-being in domestic cats through modulating the gut microbiome and metabolic characteristics. Full article

Necrotizing enterocolitis (NEC) and sepsis/late-onset sepsis (LOS) are significant contributors to preterm infant morbidity and mortality, with prematurity and low birth weight representing major risk factors for these interconnected conditions. Although the pathogenesis of NEC and LOS is not fully understood, there is a clear association with an immature intestinal mucosal barrier, which may enable bacterial invasion and translocation, resulting in an inflammatory cascade. Increasing recognition of the gut microbiome as a marker for health and disease has driven interest in probiotics, particularly Bifidobacterium spp. and Lactobacillus spp., as potential adjunctive agents for the prevention and management of NEC and LOS in preterm infants, which is the area of focus of this review. The focus of this paper was to analyze clinical studies using different probiotic strains, and compare single-strain versus multi-strain probiotic formulations. Several studies support that probiotic supplementation in preterm infants has the potential to decrease NEC incidence and, to a lesser extent, sepsis/LOS. Nonetheless, inconsistent results due to strain differences and clinical heterogeneity limit the widespread adoption of this mode of therapy, as do safety concerns in this vulnerable population. Further high-quality standardized studies are necessary to establish consistent guidelines for probiotic use in preterm infants. Full article