Atopic dermatitis (AD) is characterized by cutaneous dysbiosis marked by Staphylococcus aureus overgrowth, reduced commensal diversity, barrier dysfunction, and chronic inflammation. We investigated acacia gum (AG) as a topical prebiotic to modulate staphylococcal community structure and biofilm ecology in AD. Using both in vitro and in vivo approaches, we examined how AG reshaped microbial interactions and host responses. In coculture systems, AG selectively promoted Staphylococcus epidermidis while suppressing S. aureus. The S. aureus growth inhibition by AG involved direct antibacterial activity and commensal-mediated effects. We found that AG-upregulated glutamyl endopeptidase in S. epidermidis played a role in suppressing S. aureus colonization. AG disrupted both developing and established S. aureus biofilms and reduced intracellular persistence within macrophages, indicating activity across extracellular and host-associated niches. Beyond microbiota modulation, AG attenuated keratinocyte and macrophage activation via downregulation of proinflammatory cytokines and chemokines. In an AD-like mouse model, topical AG reduced S. aureus burden by three orders of magnitude, improved microbial diversity, partially restored barrier integrity, and decreased inflammatory cell infiltration without detectable toxicity. Collectively, AG reprograms staphylococcal dysbiosis and biofilm stability, supporting microbiota-directed prebiotic modulation as a mechanistically defined strategy for AD.

Miscarriage occurs in approximately 15% of all pregnancies, and recent studies have suggested a potential role of the microbiome. A nested case-control study from the Swedish Maternal Microbiome cohort was conducted, including 34 participants who sent at least one vaginal or fecal microbiome sample and questionnaire data before miscarrying (n = 34), and matched controls (n = 105 for regression models, n = 27 for machine learning models). Non-vaccine type HPV (aOR 3.95, 95%CI 1.04-15.06) and vaginal microbiome with community state type (CST) II (aOR 6.52, 95%CI 1.58-26.98) or CST-IVB (aOR 4.18, 95%CI 1.08-16.18) in early pregnancy were associated with an increased risk of miscarriage. Furthermore, we explored six machine learning algorithms using 70% of the cohort for training and 30% for testing, for the prediction of miscarriage using vaginal (AUROC 85%), fecal (AUROC 81%) and questionnaire (AUROC 82%) data separately and combined (AUROC 82%). Our results highlight the urgency of HPV screening and vaccine development for women's reproductive health. Despite limitations, including a small number of miscarriage cases, our results indicate the potential for both vaginal and fecal microbiomes in the prediction of miscarriage.

Preterm birth is the leading cause of neonatal morbidity and mortality, particularly in low- and middle-income countries. The vaginal microbiome influences pregnancy outcomes by effecting immunity, epithelial integrity and inflammation. Lactobacillus-dominance supports immune tolerance, whereas dysbiosis consisting of anaerobes such as Gardnerella and Prevotella promote inflammation and premature cervical remodelling. This review synthesises evidence linking microbiome composition, ancestry-associated disparities and host responses, and discusses emerging microbiome-based interventions for preterm birth.

Alcoholic Heart Disease (AHD) involves gut microbiota dysbiosis, metabolic disturbances, and circadian disruption, yet their interconnections remain unclear. Using a murine AHD model, we integrated echocardiography, metabolomics, cardiac transcriptomics, and 16S rRNA sequencing to investigate alcohol-induced pathology. It evaluated dietary fiber and acetate interventions for their potential to restore gut microbiota balance, lactate homeostasis, and circadian gene expression. Statistical analyses included correlation networks, receiver operating characteristic (ROC) curves, and pathway enrichment. Chronic alcohol consumption led to gut dysbiosis characterized by an overgrowth of Akkermansia muciniphila and a depletion of Lactobacillus intestinalisand and Bacteroides acidifaciens. This condition was associated with hyperlactatemia fraction, myocardial dysfunction, evidenced by a reduced revealed fraction and cardiac fibrosis. Transcriptomic analysis revealed strong dysregulation of circadian-related genes, including BHLHE41, NFIL3, and PER2. Interventions improved microbial diversity, reduced lactate levels, and successfully regulated cardiac related indicators through the lactate-circadian rhythm pathway. ROC analysis validated BHLHE41, NFIL3, and PER2 as high-accuracy biomarkers (AUC > 0.85). Our study reveals a gut‑heart axis in AHD where microbiota‑derived lactate links to circadian disruption, worsening disease. Dietary fiber and acetate are promising therapies that rebalance metabolites and modulate circadian networks, offering novel biomarkers and strategies for alcohol‑related cardiovascular disease.

Host-associated microbiomes are increasingly recognized as key determinants of plant health, disease development, and ecosystem functioning. Plant pathogens, especially fungal pathogens, have been reported to secrete antimicrobial effectors to modulate the host microbiota and promote colonization. Plant-parasitic nematodes (PPNs) could also modulate host microbial communities, but the processes involved remain to be clarified. Here, we identify a secreted antifungal effector, BxylTLP6, from Bursaphelenchus xylophilus, the causal agent of pine wilt disease. BxylTLP6 degrades fungal cell walls and inhibits multiple plant-associated fungi, while the released oligoglucans serve as food-derived cues that guide nematode foraging toward fungal resources. In planta, silencing Bxyltlp6 significantly delayed disease progression. ITS-based mycobiome profiling revealed that BxylTLP6 modulates the pine endophytic fungal community by promoting Ascomycota, suppressing Basidiomycota, inhibiting wood-decaying fungi, and enriching pathogenic or parasitic taxa. These shifts are associated with enhanced nematode survival and pathogenicity. Our findings support the view that a TLP effector can modulate behavior and influence the host fungal microbiome, shedding light on how PPN may manipulate microbial environments to enhance their fitness.

Chronic liver disease (CLD) causes 2 million annual deaths (4% of all global deaths). While gut bacteria are widely studied, intestinal fungi remain largely overlooked despite their critical roles in maintaining microecological homeostasis. This review summarizes fungal characteristics in alcohol-related liver disease, metabolic dysfunction-associated steatotic liver disease, primary sclerosing cholangitis, and cirrhosis, analyzing roles of fungi and their metabolites. Targeting the gut fungal community may offer therapeutic strategies for CLD.

Dietary faba bean enhances fish muscle quality but concurrently reduces growth performance. The gut microbiota critically modulates muscle growth and quality. However, the specific microbial taxa, metabolites, and regulatory mechanisms responsible remain to be elucidated. This study established a differential gut microbiota model in faba-bean-fed Yellow River carp (Cyprinus carpio), used whole-intestinal microbiota transplantation (WIMT) to directly test its effect on muscle quality, and supplemented the key bacterium and its metabolite to confirm their contribution. After a 6-week faba bean diet, growth performance declined, whereas muscle texture improved (P < 0.05). This improvement was concomitant with a higher abundance of the genera Aeromonas and Cetobacterium in the gut. Following 8 weeks of daily WIMT from faba-bean-fed donors, Yellow River carp maintained normal growth performance (P > 0.05) and simultaneously showed improved muscle texture, characterized by more small-diameter fibers, lower fat content, and higher collagen levels (P < 0.05), recapitulating the donor's key muscle phenotype. Meanwhile, WIMT reshaped the gut microbiome composition and its metabolic profile, and the marker species Cetobacterium somerae and its metabolite acetic acid showed associations with improvements in muscle quality. Further in vivo validation indicated that C. somerae reduced fat deposition and improved muscle texture, an effect possibly linked to activation of the AMPK-PGC-1α-FoxO pathway, and its metabolite acetic acid mirrored these changes. This study reveals the direct impact of gut microbiota on muscle quality through WIMT in Yellow River carp, provides novel evidence of the fish gut-muscle axis, and offers a scientific basis for improving muscle quality.

Abstract Copper-induced transmission of antimicrobial resistance has been well documented in livestock farming environments, but the in vivo mechanisms driving fecal resistome development remain unclear. Here, 120 mg/kg CuSO 4 and copper-peptide were supplemented to piglets, and the fecal resistome development was first analyzed by metagenomic sequencing. In this study, dietary CuSO 4 drove abundant and diverse ARGs and MRGs. Following CuSO 4 deprivation, ARGs and copper resistance exhibited a persistent promotion, whereas most MRGs rapidly declined. The resistance development was characterized by abundant MGEs. This phenomenon expanded the multiple-antibiotic resistance reservoir in fecal community, which was preferentially harbored by pathogens. Furthermore, dietary CuSO 4 disturbed colonic homeostasis, characterized by impaired epithelial integrity and reduced butyrate-producing bacteria abundance, which coincided with an oxidative stress environment and increased prevalence of multiple-resistant pathogens, such as Escherichia coli and Enterococcus spp . In vitro validation further supported these associations, showing that butyrate supplementation and hypoxic conditions alleviated Cu 2+ -induced ROS generation and reduced the frequency of ARGs conjugative transfer. Overall, this study suggests that dietary inorganic copper may contribute to microbial disturbances linked to oxidative stress and potentially facilitate antimicrobial resistance transmission among pathogens, highlighting organic copper as a sustainable alternative for mitigating resistance risks in farmed animals.

Disruption of the gut mucus barrier is critical in the development of infectious or chronic inflammatory diseases. The suckling-to-weaning transition is pivotal to the barrier maturation and is associated with a high incidence of gastrointestinal infections. Using a novel microfluidic device, we investigated the penetration and organizational properties of motile Escherichia coli bacteria at the interface of purified intestinal mucus from piglets before and after weaning. In weaned piglets, bacteria penetrated more than 100 μm into the mucus. Meanwhile, significant bacterial aggregation was observed in the mucus of suckling piglets, hindering penetration. Although we observed, on average, higher immunoglobulin A (IgA) concentrations in suckling piglet mucus, the high variability across samples suggested that concentration alone is insufficient to account for the aggregation behavior. Supernatant from purified suckling piglet mucus restored bacterial aggregation and limited penetration in weaned piglet mucus, similar to the effect observed with human breast milk IgA. Our results emphasize the importance of mucosal IgA specificity in relation to the mother's immunological history, primarily transmitted through breast milk and lost during weaning. This microfluidic ex-vivo approach provides an original platform to interrogate bacterial behavior in complex mucosal environments, opening new avenues for predictive and translational research.

Viruses are integral yet underexplored components of coral holobionts, with their roles in shaping microbial diversity, modulating symbioses, and contributing to Darwin's paradox remaining largely unresolved. Here, we present the Global Coral Holobiont Virome Database (GCHVD), encompassing 76,755 viral contigs and 36,860 unique viral operational taxonomic units (vOTUs) identified from 36 coral species across 18 regions worldwide. The virome is dominated by Uroviricota, Nucleocytoviricota, Preplasmiviricota, and Artverviricota, with lytic lifestyles prevailing. Host identity emerged as the primary determinant of viral community structure, exerting a stronger influence than geographic factors. Extensive virus-microbe interaction networks revealed that viruses enhance biogeochemical cycling by augmenting host metabolic processes. Functional profiling uncovered a diverse repertoire of auxiliary metabolic genes (AMGs) associated with P, Fe, S, N, and CH₄ metabolism. Moreover, controlled microcosm experiments demonstrated that viral addition reshapes microbial community composition, enhances diversity, and drives elemental cycling within the holobiont. Together, these findings establish viruses as previously overlooked regulators of coral symbioses, orchestrating microbial dynamics, fueling nutrient fluxes, and sustaining reef productivity. Our work provides new insights into resolving Darwin's paradox from a viral ecological perspective.