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18 pages, 2265 KB  
Article
Retail-Level Microbiomes of Organic and Conventional Fresh Produce: A Multi-Kingdom Analysis of Amoeba-Associated Bacterial Viability
by Lara Soler, Laura Moreno-Mesonero, Jorge García-Hernández, Miguel García-Ferrús, Andrés Zornoza and Yolanda Moreno
Foods 2026, 15(12), 2230; https://doi.org/10.3390/foods15122230 (registering DOI) - 20 Jun 2026
Abstract
The increasing consumption of fresh organic produce has given rise to concerns regarding the microbiological safety of minimally processed foods. Organic cultivation may be associated with increased exposure to environmental microorganisms due to soil-based inputs and reduced chemical interventions, including both beneficial taxa [...] Read more.
The increasing consumption of fresh organic produce has given rise to concerns regarding the microbiological safety of minimally processed foods. Organic cultivation may be associated with increased exposure to environmental microorganisms due to soil-based inputs and reduced chemical interventions, including both beneficial taxa and potential foodborne pathogens. Fresh produce is known to harbour complex microbial ecosystems, which are shaped by farming practices, plant physiology, handling, packaging and storage, particularly in raw-consumed products such as leafy greens and strawberries. In this study, bacterial (16S rRNA) and eukaryotic (18S rRNA) communities were characterized by amplicon sequencing. In parallel, an amoeba-associated bacterial microbiome was analyzed and DVC-FISH was used to assess the viability and metabolic activity of pathogenic bacteria internalized within free-living amoebae (FLA). No significant differences in alpha or beta diversity were observed between organic and conventional products, suggesting microbiome convergence at the retail stage driven by post-harvest handling and processing. Potentially pathogenic genera, including Pseudomonas, Stenotrophomonas, and Acinetobacter (bacterial), as well as Tilletiopsis, Candida, and Naegleria (eukaryotic), were identified in both organic and non-organic microbiomes. The viability of FLA-internalized Pseudomonas spp. was confirmed by DVC-FISH, demonstrating that FLA act as reservoirs, enhancing pathogen persistence in fresh produce. This integrated assessment of organic and conventional fruits and vegetables at the retail stage highlights the importance of post-harvest handling and retail conditions in shaping microbiological safety. The integration of microbiome profiling with targeted viability analyses demonstrates that downstream stages are critical control points for food safety and consumer exposure, beyond the influence of the production system alone. Full article
(This article belongs to the Special Issue Emerging Trends in Food Microbiology and Food Safety)
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32 pages, 969 KB  
Review
Stevia Rebaudiosides Usage as a Sugar Reduction Tool: A Narrative Review of Their Metabolic, Gut Microbiome and Weight Management Effects in Human Clinical Studies
by Corey Scott, Nikoleta Stamataki and John McLaughlin
Nutrients 2026, 18(12), 2002; https://doi.org/10.3390/nu18122002 (registering DOI) - 20 Jun 2026
Abstract
Background/Objectives: Stevia rebaudiosides represent a class of compounds extracted from the Stevia rebaudiana Bertoni plant or produced via yeast fermentation, which provide a sweet taste with little to no calories. These compounds are commercially referred to as stevia and are used in the [...] Read more.
Background/Objectives: Stevia rebaudiosides represent a class of compounds extracted from the Stevia rebaudiana Bertoni plant or produced via yeast fermentation, which provide a sweet taste with little to no calories. These compounds are commercially referred to as stevia and are used in the food industry to reduce sugar in foods and beverages. Stevia is a non-nutritive sweetener (NNS), which is a class of ingredients which represent both artificial and plant-based sweeteners. NNSs are widely used and have been well studied. However, their effects on efficacy for weight management as a sugar reduction tool and overall metabolic effects are inconsistent. Of the approved NNSs for use, stevia is relatively new and one of the least studied. However, recent human clinical research has provided insights into stevia’s metabolic effects, effects on the gut microbiome and effects on weight management when used to replace sugar. The objective of this narrative review of human clinical studies is to provide an overview of the effects of stevia rebaudiosides (largely rebaudioside A) on glucoregulatory and cardiometabolic functions, as well as their effects on gut microbiome and weight management. These studies were typically short term (acute to three months) and heterogeneous by design, and they contained stevia rebaudiosides as lone sweeteners and as part of a binary blend with other NNSs. The majority of metabolic studies on stevia rebaudiosides have evaluated the effects on glucose homeostasis and, to a lesser extent, the effects on cardiometabolic function, the gut microbiome, and weight management. These studies suggest that stevia rebaudiosides have no statistically significant effects on glycemia, insulinemia, blood lipids, appetite hormones, or the gut microbiome. Limited studies suggest that, particularly when compared to sucrose, stevia produces very modest body weight and BMI changes, while studies on subjective appetite and food intake have had inconsistent results. Conclusions: longer-term studies are needed, with more consistent and rigorous design protocols across various populations. However, current human clinical studies suggest that stevia rebaudiosides have a limited impact on metabolic functions, and the observed effects on gut microbiome and changes in body weight, particularly when used to replace sugar, warrant further study. Full article
21 pages, 673 KB  
Review
Bridging Ancestry-Stratified Bias in Pharmacogenomics AI: Toward Metabolomics-Inclusive Multi-Omics Precision Medicine
by Heayyean Lee, Khadijah Sajid and Dayeon Lee
J. Pers. Med. 2026, 16(6), 332; https://doi.org/10.3390/jpm16060332 (registering DOI) - 20 Jun 2026
Abstract
Pharmacogenomics AI offers significant potential for individualized drug therapy; however, its clinical benefits remain unevenly distributed. Models trained predominantly on European-ancestry data consistently underperform in non-European populations, with polygenic risk scores (PRS) showing an estimated 39–73% reduction in predictive accuracy in African-ancestry cohorts [...] Read more.
Pharmacogenomics AI offers significant potential for individualized drug therapy; however, its clinical benefits remain unevenly distributed. Models trained predominantly on European-ancestry data consistently underperform in non-European populations, with polygenic risk scores (PRS) showing an estimated 39–73% reduction in predictive accuracy in African-ancestry cohorts across complex traits. These disparities have driven increased interest in moving beyond single-layer genomic approaches. Multi-omics frameworks integrating genomic, transcriptomic, proteomic, and metabolomic data have emerged as a promising strategy to improve prediction across heterogeneous clinical populations, as each molecular layer provides distinct and complementary biological information. Among these layers, metabolomics may represent a particularly transferable component across populations. Metabolite profiles capture the downstream functional output of biological systems influenced by genetic, environmental, dietary, and microbiome-related factors, and may therefore be less reliant on ancestry-stratified allele frequency structures that underlie performance disparities in genomic models. This review synthesizes evidence regarding the mechanistic basis of genomic bias in pharmacogenomics AI, the emerging role of multi-omics integration, especially metabolomics, in improving predictive performance, and the current landscape of computational strategies for bias mitigation, including federated learning, transfer learning, domain adaptation, and synthetic data generation. Collectively, current evidence supports metabolomics-inclusive multi-omics frameworks as a biologically plausible, hypothesis-generating strategy to reduce reliance on ancestry-linked genomic features. However, direct evidence that such frameworks reduce ancestry-related bias in clinical AI outputs remains limited, underscoring the need for globally diverse datasets and prospective multi-population validation. Full article
(This article belongs to the Section Omics/Informatics)
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19 pages, 1799 KB  
Article
Bacterial Community Composition and Functional Potential of the Kleptoplastic Sea Slug Elysia papillosa
by Jada L. Brown, Padmanabhan Mahadevan and Michael Middlebrooks
Biomolecules 2026, 16(6), 918; https://doi.org/10.3390/biom16060918 (registering DOI) - 20 Jun 2026
Abstract
Certain sacoglossan sea slugs, often known as “solar-powered sea slugs”, are a group of marine gastropods that have the unique ability to photosynthesize by stealing functional chloroplasts from algae. The sacoglossan Elysia papillosa can maintain functional chloroplasts for up to two weeks after [...] Read more.
Certain sacoglossan sea slugs, often known as “solar-powered sea slugs”, are a group of marine gastropods that have the unique ability to photosynthesize by stealing functional chloroplasts from algae. The sacoglossan Elysia papillosa can maintain functional chloroplasts for up to two weeks after feeding. The microbiome of these slugs may play a crucial role in their metabolism, immunity, development, but more importantly their photosynthesis. Shotgun metagenomic sequencing was conducted on four samples of E. papillosa in order to characterize their microbiome. Sequences were classified and relative abundance was quantified with Centrifuger and functional data was examined using SqueezeMeta. Bacteria were analyzed by taxonomic groups and hypothesized function to the sea slug was determined with literature analysis. All samples were dominated by phyla Actinomycetota, Bacillota, Patescibacteriota, and Pseudomonadota. The presence of the phyla Bacteroidota and Bacillota was notable in all samples, which contain species known to produce enzymes that break down polysaccharides. It is possible that these bacteria could assist in degradation of the polysaccharide xylan found in the cell walls of Penicillus, the algal food source of E. papillosa. One species that was found in all samples was Cutibacterium acnes which has been shown to be an important component of the gut microbiota in other marine invertebrates and may provide the host with vitamin B12 and other beneficial nutrients. Many of these bacteria may be opportunistic rather than commensal. As a result, more research is required to describe the interactions between the slug and its microbiome, but this preliminary report provides a valuable starting point for identifying the microbiome make-up to further understanding of these relationships. Full article
(This article belongs to the Special Issue Metagenomics and Genomics of Marine Organisms)
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20 pages, 6917 KB  
Article
Multi Omics Analysis Reveals That Compound Radix Pulsatillae and Lactic Acid Bacteria Reprogram the Microbiome Metabolome Network in Oat Silage
by Yuanyuan Jing, Haoran Wang, Heng Jiang, Hui Qu, Guolin Yang, Zhennan He, Siyi Wang, Bin Liu and Fengqin Gao
Int. J. Mol. Sci. 2026, 27(12), 5577; https://doi.org/10.3390/ijms27125577 (registering DOI) - 20 Jun 2026
Abstract
Oat (Avena sativa L.) silage fermentation often fails due to insufficient lactic acid bacteria (LAB) and low water-soluble carbohydrate content. We investigated the effects of Compound Radix Pulsatillae (CRP; 40 g/kg FM) alone or combined with a commercial LAB inoculant (containing L. [...] Read more.
Oat (Avena sativa L.) silage fermentation often fails due to insufficient lactic acid bacteria (LAB) and low water-soluble carbohydrate content. We investigated the effects of Compound Radix Pulsatillae (CRP; 40 g/kg FM) alone or combined with a commercial LAB inoculant (containing L. plantarum, L. buchneri, and Enterococcus faecium, CRP_LA) on oat silage after 60 days. Compared to control (CK), both CRP and CRP_LA increased dry matter and water-soluble carbohydrate retention while reducing fiber components and ammonia nitrogen (p < 0.05). CRP_LA exhibited superior fermentation quality (lowest pH 4.82, highest lactic acid 47.83 g/kg DM). Using 16S rRNA sequencing and UPLC-MS/MS metabolomics integrated with weighted gene co-expression network analysis (WGCNA), we identified a brown module strongly associated with CRP_LA treatment. Six hub metabolites, belonging to flavonoids, terpenoids, alkaloids, phenolic acids, and nucleotide derivatives, were significantly elevated in CRP_LA silage and showed strong correlations with Lactobacillus abundance and fermentation quality parameters. Correlation-based network analysis revealed that these hub metabolites positively correlated with Lactobacillus abundance, lactic acid, and water-soluble carbohydrate retention, while negatively correlating with spoilage microorganisms (Enterobacter, Acinetobacter, Leuconostoc) and ammonia nitrogen. This multi-omics study provides a metabolite-centric molecular map of the silage microecosystem reshaped by CRP and LAB co-fermentation. The identified hub metabolites—with predicted antimicrobial, antioxidant, and plant-protective functions—represent potential quality markers for functional silage additive development. Mechanistic validation via targeted metabolite supplementation or pathway-specific gene expression analysis is warranted in future studies. Full article
(This article belongs to the Special Issue Microbial Fermentation Optimization and Product Bioactivity)
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23 pages, 1144 KB  
Review
Responsible Use of Large Language Models in Microbial Genomics and Bioinformatics: A Life-Science Framework for Reliability, Reproducibility, and Risk-Aware Interpretation
by Mia Yang Ang, Li Chen, Lanni Song, Leonard Lipovich and Siew Woh Choo
Life 2026, 16(6), 1032; https://doi.org/10.3390/life16061032 (registering DOI) - 20 Jun 2026
Abstract
Large language models (LLMs) are increasingly adopted in life-science research for scientific writing, coding, literature synthesis, workflow troubleshooting, and preliminary data interpretation. In microbial genomics and bioinformatics, their appeal is clear because researchers routinely integrate genome annotations, antimicrobial resistance profiles, virulence determinants, taxonomic [...] Read more.
Large language models (LLMs) are increasingly adopted in life-science research for scientific writing, coding, literature synthesis, workflow troubleshooting, and preliminary data interpretation. In microbial genomics and bioinformatics, their appeal is clear because researchers routinely integrate genome annotations, antimicrobial resistance profiles, virulence determinants, taxonomic assignments, microbiome outputs, workflow scripts, and primary literature. Yet this domain also highlights major risks, including hallucinated biological claims, inaccurate citations, irreproducible code, unsupported genotype-to-phenotype inference, and inappropriate clinical or public health framing. This narrative review examines responsible LLM use in microbial genomics as a representative life-science setting where interpretation depends on database provenance, validated workflows, expert assessment, and reproducible evidence chains. It considers applications in genome annotation, antimicrobial resistance interpretation, virulence analysis, microbiome and metagenomics workflows, coding support, and scientific writing. The review further presents MicrobeGuardGPT as a conceptual reliability framework for assessing LLM-assisted microbial genomics outputs before scientific, clinical, or public health use. By connecting task domains, evidence verification, expert validation, and reliability classification, the framework supports risk-aware LLM integration in bioinformatics. Responsible implementation will require domain-specific benchmarks, curated database linkage, transparent reporting, reproducible workflows, human oversight, and governance standards tailored to biological interpretation across research, diagnostic, surveillance, outbreak-response, educational, and translational contexts. Full article
(This article belongs to the Section Artificial Intelligence in the Life Sciences)
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23 pages, 1128 KB  
Review
Molecular Mechanisms Underlying the Higher Prevalence of Anemia in Crohn’s Disease Compared with Ulcerative Colitis: A Systematic Review
by Dragos-Florin Tesoi, Laura Mihaela Trandafir, Laura Bozomitu, Otilia Elena Frasinariu, Nina Filip, Cornelia Mircea, Monica Hancianu and Oana-Viola Badulescu
Int. J. Mol. Sci. 2026, 27(12), 5570; https://doi.org/10.3390/ijms27125570 (registering DOI) - 20 Jun 2026
Abstract
Anemia represents one of the most frequent systemic complications of inflammatory bowel disease (IBD), with a consistently higher prevalence reported in patients with Crohn’s disease (CD) compared with ulcerative colitis (UC). While chronic inflammation, impaired iron absorption, and intestinal blood loss are recognized [...] Read more.
Anemia represents one of the most frequent systemic complications of inflammatory bowel disease (IBD), with a consistently higher prevalence reported in patients with Crohn’s disease (CD) compared with ulcerative colitis (UC). While chronic inflammation, impaired iron absorption, and intestinal blood loss are recognized contributors, microbiome-mediated mechanisms influencing host iron availability remain insufficiently explored. Emerging evidence indicates that CD-associated dysbiosis is characterized by an increased abundance of siderophore-producing bacteria, particularly members of the Enterobacteriaceae family. Because siderophores are high-affinity iron-chelating molecules capable of competing with host iron acquisition systems and partially escaping lipocalin-2-mediated sequestration, their expansion may contribute to reduced luminal iron bioavailability. In this systematic review, we analyzed comparative microbiome studies published between 2016 and 2026 that directly evaluated microbial differences between CD and UC. CD microbiota consistently demonstrated enrichment in siderophore-associated taxa relative to UC. Based on these findings, we propose that microbiome-driven iron competition may represent an additional mechanistic contributor to the increased prevalence and persistence of anemia observed in CD. Although direct in vivo quantification of siderophore activity in IBD remains limited, the convergence of ecological, functional, and strain-level microbiome evidence supports a biologically plausible interaction between microbial iron-scavenging strategies and host iron metabolism. Full article
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19 pages, 679 KB  
Article
Maternal and Neonatal Determinants of Respiratory Outcome Following Second-Trimester PPROM: A Multi-Domain Machine Learning Analysis
by Simon Loth, Julia Hauer, Christoph Scholz, Marcus Krüger, Alexander Bieber and Christian Brickmann
Diagnostics 2026, 16(12), 1911; https://doi.org/10.3390/diagnostics16121911 (registering DOI) - 19 Jun 2026
Abstract
Background: Preterm premature rupture of membranes (PPROM) before 32 weeks of gestation with prolonged latency is associated with substantial neonatal morbidity, including Dry Lung Syndrome (DLS), pulmonary hypoplasia (PH), bronchopulmonary dysplasia (BPD), and death. Accurate individualized risk stratification remains elusive, as the [...] Read more.
Background: Preterm premature rupture of membranes (PPROM) before 32 weeks of gestation with prolonged latency is associated with substantial neonatal morbidity, including Dry Lung Syndrome (DLS), pulmonary hypoplasia (PH), bronchopulmonary dysplasia (BPD), and death. Accurate individualized risk stratification remains elusive, as the interacting contributions of amniotic fluid dynamics, inflammatory status, and microbiological burden are inadequately captured by traditional statistical approaches. Methods: We performed a retrospective, exploratory–predictive analysis of 66 pregnancies complicated by second-trimester PPROM with latency exceeding 14 days. Elastic Net and Random Forest models were trained across six clinically defined predictor domains using a multi-stage block modelling strategy. To address the clinically relevant distinction between antenatal and postnatal information, results are reported separately for Model A—comprising exclusively antenatal predictors available during expectant management (gestational age at PPROM, latency, amniotic fluid trajectory, inflammatory status, vaginal microbiome at admission)—and Model B, which additionally incorporates postnatal variables and characterizes the full mechanistic perinatal risk trajectory. Binary and ordinal outcomes included DLS, PH, BPD, intraventricular hemorrhage (IVH), and neonatal death. Pairwise interaction models were additionally computed to identify cross-domain risk constellations. Results: Distinct predictor architectures emerged per outcome. Pulmonary hypoplasia was most strongly associated with temporal features of oligohydramnios—particularly the persistence and timing of SDP < 1 cm—rather than isolated measurements. For DLS, the antenatal model (Model A) achieved AUC 0.776, driven by gestational maturity and inflammatory status; surfactant administration—a postnatal variable reflecting therapeutic response rather than an antenatal risk factor—dominated only the mechanistic Model B. Neonatal death was driven by a combined profile of respiratory support burden, amniotic fluid persistence, and co-morbidity. IVH showed consistently high ordinal predictability (accuracy 0.863), with amniotic fluid dynamics and microbiological burden as leading contributors. BPD remained the least linearly separable endpoint across all configurations. Conclusions: Multi-domain machine learning reveals outcome-specific, cross-domain risk architectures following second-trimester PPROM that are invisible to conventional statistical models. Longitudinal amniotic fluid trajectory is the dominant antenatal determinant of structural pulmonary morbidity, while microbiological burden independently shapes neurological risk. These findings support prospective validation of integrated ML-based risk stratification tools for individualized antenatal counselling in this high-risk population. Full article
(This article belongs to the Special Issue Advancements in Maternal–Fetal Medicine: 3rd Edition)
20 pages, 1632 KB  
Review
The Gut Microbiome in Heart Failure: Pathways to Inflammation and Therapeutic Targets
by Uday Sankar Akash Vankayala, Ali Sohail, Bivin George, Madhu Singh, Omar Khayat, Malek Kreidieh, Alia Hasham and Luis Quiel
Metabolites 2026, 16(6), 431; https://doi.org/10.3390/metabo16060431 (registering DOI) - 19 Jun 2026
Abstract
Heart failure (HF) continues to be a major global health burden, with persistent morbidity and mortality despite guideline-directed and device-based therapies. Evidence suggests the gut–heart axis is a critical and underrecognized contributor to HF progression. Alterations in cardiac output and systemic venous congestion [...] Read more.
Heart failure (HF) continues to be a major global health burden, with persistent morbidity and mortality despite guideline-directed and device-based therapies. Evidence suggests the gut–heart axis is a critical and underrecognized contributor to HF progression. Alterations in cardiac output and systemic venous congestion in HF lead to intestinal hypoperfusion, mucosal edema, and loss of barrier integrity, increasing intestinal permeability, gut dysbiosis, and translocation of microbial products. This systemic translocation is associated with chronic low-grade inflammation that activates innate immune pathways that correlate with endothelial dysfunction, oxidative stress, fibroblast activation, and adverse cardiac remodeling. Gut-derived metabolites derived by microbial metabolism modulate cardiovascular health by altering the metabolic profiles. Dysbiosis results in loss of protective short-chain fatty acid (SCFA)-producing bacteria and enriches pro-inflammatory taxa such as trimethylamine N-oxide (TMAO)-producing bacteria. Elevated TMAO is associated with increased mortality and hospitalization in HF, whereas SCFAs enhance barrier integrity and immune tolerance. Secondary bile acids and uremic toxins such as indoxyl sulfate and p-cresyl sulfate further link dysbiosis to fibrosis and vascular stiffness. Circulating markers such as TMAO, lipopolysaccharide-binding protein (LBP), and soluble CD14 carry prognostic value beyond traditional cardiac biomarkers. This review highlights current experimental, translational, and clinical evidence describing gut dysbiosis and its molecular links to HF progression. Targeting the gut–heart axis represents a novel therapeutic approach in HF. Dietary modulation, probiotics/prebiotics, fecal microbiota transplantation, and inhibitors of microbial metabolic pathways show promise. Future research should emphasize microbiota-based interventions in HF management. Full article
(This article belongs to the Special Issue Metabolite Profiles in Inflammatory Diseases)
29 pages, 2009 KB  
Review
Molecular, Microbial, and Ecological Drivers of Duckweed Phytoremediation in Aquatic Environments
by Doni Thingujam, Antonino Malacrinò, Karolina M. Pajerowska-Mukhtar and M. Shahid Mukhtar
Biology 2026, 15(12), 963; https://doi.org/10.3390/biology15120963 (registering DOI) - 19 Jun 2026
Abstract
Aquatic ecosystems are under severe stress from a diverse combination of contaminants, including heavy metals, pesticides, pharmaceuticals, and microplastics, driven by rapid industrialization, intensive agriculture, and urbanization. Globally, 80% of wastewater remains untreated, and conventional systems often fail to address emerging contaminants. Consequently, [...] Read more.
Aquatic ecosystems are under severe stress from a diverse combination of contaminants, including heavy metals, pesticides, pharmaceuticals, and microplastics, driven by rapid industrialization, intensive agriculture, and urbanization. Globally, 80% of wastewater remains untreated, and conventional systems often fail to address emerging contaminants. Consequently, toxic heavy metals like lead and mercury can persist in water sources for decades. In response, phytoremediation has emerged as a scalable, eco-friendly, nature-based alternative. Among phytoremediation agents, duckweeds are increasingly recognized for their rapid growth, simple morphology, and continuous water-column contact. This review outlines the landscape of duckweed-based remediation, detailing molecular detoxification pathways and the synergistic role of associated microbiomes in enhancing environmental cleanup. Evidence indicates that contaminant removal is often supported by plant-microbe interactions. Despite extensive laboratory validation, field-scale implementation remains constrained by environmental complexity, pollutant mixtures, and variable climatic conditions. Furthermore, while duckweed systems hold promise within circular bioeconomy frameworks, converting wastewater into nutrient-rich biomass, contaminant accumulation in plant tissues raises concerns about biomass utilization and contaminant carryover. Addressing these challenges requires an integrative approach that links molecular detoxification, ecological interactions, and engineered system design to realize the full potential of duckweeds for sustainable aquatic pollution management. Full article
(This article belongs to the Section Microbiology)
21 pages, 900 KB  
Review
The Gut-Bone Axis and Skeletal Health: Regulatory Mechanisms and Therapeutic Applications of Plant-Derived Bioactive Compounds
by Tianzhu Zhang, Yufei Li, Jiahui Pei, Qingxia Zhang, Fengyun Lin and Shuzhen Li
Biomolecules 2026, 16(6), 912; https://doi.org/10.3390/biom16060912 (registering DOI) - 19 Jun 2026
Abstract
The gut microbiota and its metabolites, as components of the gut–bone axis, play a pivotal role in regulating skeletal homeostasis through the bidirectional communication network. In this systematic review, evidence was collected from mainstream databases following standardized inclusion/exclusion criteria for screening, to comprehensively [...] Read more.
The gut microbiota and its metabolites, as components of the gut–bone axis, play a pivotal role in regulating skeletal homeostasis through the bidirectional communication network. In this systematic review, evidence was collected from mainstream databases following standardized inclusion/exclusion criteria for screening, to comprehensively retrieve and screen eligible studies from multiple mainstream databases according to standardized inclusion and exclusion criteria, and systematically summarize current research progress on plant-derived bioactive compounds targeting the gut–bone axis for skeletal health regulation. This review systematically explores the underlying mechanisms of the gut–bone axis and critically evaluates the regulatory effects and therapeutic potential of plant-derived bioactive compounds. Particular attention is given to targeted interventions involving prebiotics, probiotics, synbiotics, and plant-rich diets or functional foods. Among these interventions, synbiotics represent the most successful strategy and show the most prominent therapeutic possibilities in bone-related disorders. Different from single prebiotics (only nourish endogenous intestinal microbes), individual probiotics (easy to be degraded in gastrointestinal tract with poor colonization) and ordinary plant-rich diets (unfixed effective dosage and weak targeting property), synbiotics combine prebiotic carriers and viable probiotic strains to produce complementary advantages, which is the core reason for its outstanding therapeutic prospect against bone diseases. Synbiotics exert synergistic effects on gut microecology, mineral absorption, and immune regulation, leading to more robust and consistent improvements in bone health than single prebiotics, probiotics, or general plant-rich diets. They have been verified in preclinical and clinical studies to ameliorate osteoporosis and related skeletal diseases via the gut–bone axis. These strategies offer novel insights into the prevention and treatment of bone metabolic disorders, such as osteoporosis, by targeting the gut–bone axis with phytochemicals. Key outcomes of this review include that synbiotics, soy isoflavones, naringin, curcumin, and resveratrol effectively improve bone mineral density, restore gut microbiota balance, and inhibit pathological bone resorption via the gut–bone axis. Collectively, the above bioactive substances realize bone protection mainly by reshaping gut flora, elevating mineral uptake and suppressing excessive osteoclast activity. Representative cases include soy isoflavones mitigating estrogen-deficient bone loss in OVX models, naringin improving the trabecular microarchitecture, and probiotic BL-11 promoting longitudinal bone growth in children. Future directions will focus on clarifying dose–response relationships, developing standardized synbiotic formulations, constructing microbiome-guided precision diets, and conducting large-sample randomized controlled trials to translate plant-derived compounds into clinical therapies. Full article
(This article belongs to the Section Natural and Bio-derived Molecules)
30 pages, 1772 KB  
Review
Horizontal Gene Transfer in Listeria monocytogenes: Evolution of Antimicrobial Resistance and Virulence in a One Health Context
by Georgeta Stefan, Maria Rodica Gurau, Nicoleta Ciocîrlie, Laurențiu Tudor, Stelian Bărăităreanu, Diana-Lidia Tache-Codreanu, Corina Sporea, Alexandru Gligor, Ionica Iancu and Viorel Herman
Biology 2026, 15(12), 961; https://doi.org/10.3390/biology15120961 (registering DOI) - 19 Jun 2026
Abstract
Listeria monocytogenes is a ubiquitous Gram-positive bacterium responsible for listeriosis, a foodborne zoonotic disease affecting humans and animals. Although infection in immunocompetent individuals is often asymptomatic or limited to mild self-limiting gastroenteritis, Listeria monocytogenes may cause severe invasive disease in vulnerable groups, including [...] Read more.
Listeria monocytogenes is a ubiquitous Gram-positive bacterium responsible for listeriosis, a foodborne zoonotic disease affecting humans and animals. Although infection in immunocompetent individuals is often asymptomatic or limited to mild self-limiting gastroenteritis, Listeria monocytogenes may cause severe invasive disease in vulnerable groups, including pregnant women, neonates, elderly individuals, and immunocompromised patients. Although the incidence of listeriosis is relatively low compared with many other foodborne pathogens, the high hospitalization and mortality rates associated with clinical cases make this bacterium a major concern for food safety and public health. The evolutionary success of L. monocytogenes reflects the interaction between a conserved core genome and a dynamic accessory genome shaped by horizontal gene transfer (HGT), ecological selection, and expansion of specific clones. Transient intestinal carriage in humans and animals, potentially influenced by gut microbiome composition, creates ecological interfaces where plasmids, transposons, prophages, and integrative conjugative elements contribute to the exchange of antimicrobial resistance determinants, virulence factors, and stress tolerance systems. Virulence diversification is further influenced by the differential distribution of pathogenicity islands such as LIPI-1, LIPI-3, and LIPI-4 across specific clonal lineages. These evolutionary processes occur across interconnected farm, food-production, environmental, and clinical ecosystems consistent with the One Health framework. Advances in whole-genome sequencing have clarified lineage-specific gene flow, expansion of specific clones, and the dynamics of the resistome and mobilome in L. monocytogenes populations. This narrative review aims to synthesize current knowledge on the mobile genetic elements and ecological interfaces that shape horizontal gene transfer in L. monocytogenes. Its novelty lies in integrating antimicrobial resistance, virulence-associated genomic islands, stress adaptation, and gut microbiome-mediated selection within a One Health and metapopulation framework. The main message of this review is that HGT should be interpreted as a context-dependent contributor to L. monocytogenes adaptation, acting together with clonal background, ecological selection, and mobile genetic elements. Full article
(This article belongs to the Section Microbiology)
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21 pages, 647 KB  
Review
Clinical Significance of Intestinal Fungal Overgrowth: Integrating the Gut Mycobiome into Modern Gastroenterology
by Jisoon Im, Kyucheol Lee, Sang-Hoon Lee, Soohwan Jung, Kyu-Nam Kim and Jiyoung Lee
Microorganisms 2026, 14(6), 1365; https://doi.org/10.3390/microorganisms14061365 - 19 Jun 2026
Abstract
Intestinal fungal overgrowth (IFO) is an increasingly recognized yet underexplored component of gut dysbiosis with potential implications for gastrointestinal and systemic disease. While bacterial microbiota have historically garnered research attention, recent advances in sequencing technologies have highlighted the importance of the gut mycobiome [...] Read more.
Intestinal fungal overgrowth (IFO) is an increasingly recognized yet underexplored component of gut dysbiosis with potential implications for gastrointestinal and systemic disease. While bacterial microbiota have historically garnered research attention, recent advances in sequencing technologies have highlighted the importance of the gut mycobiome in maintaining intestinal homeostasis. Disruption of fungal–bacterial balance, particularly involving Candida albicans, C. tropicalis, and C. glabrata, may contribute to symptom generation through immune activation, epithelial barrier dysfunction, biofilm formation, and the production of toxic metabolites such as acetaldehyde and candidalysin. Emerging clinical evidence suggests that IFO is associated with persistent gastrointestinal symptoms, including bloating, abdominal discomfort, and altered bowel habits, particularly in patients who do not respond to conventional therapies targeting bacterial overgrowth. Furthermore, fungal dysbiosis involving Malassezia restricta and Saccharomyces cerevisiae has been associated with inflammatory bowel disease, metabolic disorders, and systemic immune dysregulation; however, the nature and directionality of these relationships remain incompletely understood. Despite increasing recognition, the diagnosis of IFO remains challenging due to a lack of standardized criteria and validated non-invasive tools. Therapeutic strategies, including antifungal agents such as fluconazole and nystatin, as well as microbiome-targeted interventions, show promise but require further validation. This review provides a comprehensive synthesis of current evidence regarding the epidemiology, pathophysiology, clinical manifestations, diagnostic challenges, and therapeutic implications of IFO, with particular emphasis on species-specific mechanisms. Recognition of the intestinal mycobiome as a potentially important component of gut health may provide new perspectives for understanding gastrointestinal disorders and inform future precision medicine approaches. Full article
(This article belongs to the Special Issue Gut Microbiota and Diseases)
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12 pages, 1506 KB  
Article
Molecular Detection of Coxiella-like Endosymbionts in Ticks in Hebei, China
by Ze-Yun Xu, Guo-Qing Chen, Jing Xue, Yu-Xin Chi, Rui Jian and Wen-Ping Guo
Pathogens 2026, 15(6), 647; https://doi.org/10.3390/pathogens15060647 (registering DOI) - 18 Jun 2026
Abstract
Ticks are widely distributed in China and can carry and transmit a variety of pathogens that potential to cause serious impacts on public health and the economy. Little is known about the broader spectrum of Coxiella-like endosymbiont (CLE) in ticks under natural [...] Read more.
Ticks are widely distributed in China and can carry and transmit a variety of pathogens that potential to cause serious impacts on public health and the economy. Little is known about the broader spectrum of Coxiella-like endosymbiont (CLE) in ticks under natural conditions in China. The aim of this study was to detect, analyze, and characterize phylogenetically CLE found in ticks in Hebei Province, China. A total of 947 ticks collected from Hebei Province were identified as Haemaphysalis longicornis based on morphological characteristics and cytochrome c oxidase gene PCR analysis of extracted DNA. Subsequently, DNA was analyzed via PCR for the IS1111 gene (frequently associated with Coxiella burnetii), and the amplified DNA was then sequenced and analyzed phylogenetically using a set of primers targeting the 16S rRNA, groEL, and rpoB genes. A total of 8.24% (78/947) of ticks from the Chengde, Baoding, and Cangzhou regions were positive in the IS1111 PCR. Phylogenetic analysis using the 16S rRNA, groEL, and rpoB genes revealed the presence of CLE in Ha. longicornis ticks from these regions and the formation of two distinct clades, suggesting horizontal gene transfer events. Our results strengthen the growing evidence that CLE, not Coxiella burnetii, is ubiquitously associated with ticks across diverse geographic locations—a distinction critical for accurately interpreting tick microbiome surveys and avoiding false assumptions of zoonotic risk. Full article
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20 pages, 4642 KB  
Article
Abdominal Symptoms During the Febrile Phase Indicate Profound Innate Immune Responses in Dengue
by Huy Thanh Do, Thansita Bhunyakarnjanarat, Kanthaporn Dityen, Yadah Kaewopas, Niramol Thammachareonrach, Supaporn Paiboonkasarp, Thiranut Jaroonwitchawan, Siwaporn Boonyasuppayakorn, Wiwat Chancharoenthana and Asada Leelahavanichkul
Biology 2026, 15(12), 960; https://doi.org/10.3390/biology15120960 (registering DOI) - 18 Jun 2026
Abstract
Gastrointestinal symptoms (GI) (abdominal pain, vomiting, and diarrhea) during the febrile phase of dengue (less than 5 days from fever onset) might indicate prominent innate immune responses. Serum and feces samples from cases with GI symptoms versus those without GI symptoms (n [...] Read more.
Gastrointestinal symptoms (GI) (abdominal pain, vomiting, and diarrhea) during the febrile phase of dengue (less than 5 days from fever onset) might indicate prominent innate immune responses. Serum and feces samples from cases with GI symptoms versus those without GI symptoms (n = 20 per group) were analyzed. From these, only the neutrophil extracellular traps (NETs), serum fibroblast growth factor (FGF) 21, and fecal microbiome analyses, but not the routine parameters, endotoxemia, or serum cytokines, were higher in the GI cases than in the non-GI cases. From the in vitro experiments, both lipopolysaccharide (LPS) and the dengue virus (DENV) upregulated the FGF receptor 1 (FGFR1) and cytokines in hepatocytes (HepG2) and THP-1-differentiated macrophages. Meanwhile, LPS and DENV induced NETs in isolated neutrophils from healthy volunteers. Only the starvation protocol, but not LPS or DENV, enhanced supernatant FGF-21 from hepatocytes. Incubation of recombinant FGF-21 in LPS + DENV-activated cells (hepatocytes, macrophages, and neutrophils) attenuated inflammation, as determined by supernatant cytokines and NETs. Hence, abdominal symptoms in dengue during the febrile phase indicate prominent innate immune responses, as detected by NETs and FGF-21 (an acute-phase protein), implying significant hepatic stress with a possible counteracting anti-inflammation. Full article
(This article belongs to the Section Microbiology)
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