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Keywords = microbiome and metabolomics

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36 pages, 8096 KB  
Article
Enhancing Sheep Rumen Function, and Growth Performance Through Yeast Culture and Oxalic Acid Supplementation in a Hemicellulose-Based Diet
by Natnael D. Aschalew, Jialei Liu, Yuetong Liu, Wuwen Sun, Guopei Yin, Long Cheng, He Wang, Wanzhu Zhao, Longyu Zhang, Ziyuan Wang, Huaizhi Jiang, Tao Wang, Guixin Qin, Yuguo Zhen and Zhe Sun
Microorganisms 2025, 13(12), 2834; https://doi.org/10.3390/microorganisms13122834 - 12 Dec 2025
Viewed by 245
Abstract
Yeast culture (YC) is a microbial product that enhances ruminal fiber breakdown and improves nutrient digestion and utilization. Our previous research showed that oxalic acid (OA) is a crucial metabolite in YC that enhances rumen function. This study aimed to investigate the effects [...] Read more.
Yeast culture (YC) is a microbial product that enhances ruminal fiber breakdown and improves nutrient digestion and utilization. Our previous research showed that oxalic acid (OA) is a crucial metabolite in YC that enhances rumen function. This study aimed to investigate the effects of YC, OA, and their combination (YO) on rumen function, growth, and fattening in sheep. Twenty lambs were divided into 4 groups (ctrl, YC, OA, and YO; n = 5 each) and fed a diet supplemented with 2 levels of YC and 2 doses of OA for 60 days in a 2 × 2 factorial design. Growth and fattening performance, rumen microbiome analysis, serum indices and anti-oxidant levels, and metabolomic profiling were performed. Individual supplementation with YC and OA significantly increased the digestibility of dry matter (DM), organic matter (OM), and crude protein (CP) (p < 0.001); neutral detergent fiber (NDF) (p < 0.05); and acid detergent fiber (ADF) (p < 0.001) and their interaction significantly increased dry matter intake (DMI) (p = 0.05). Serum IgA and IgM levels were higher in the supplemented groups (p < 0.05). Serum calcium levels were higher in the OA and YO groups (p < 0.001). The supplemented groups showed significantly higher growth hormone and superoxide dismutase levels (p < 0.05). The longissimus dorsi muscle had higher levels of iron in the OA and YO groups; zinc in the OA, YO, and YC groups (p < 0.01); and selenium in the YC group (p < 0.05). The OA group had a higher total antioxidant capacity. All supplemented groups showed higher bacterial richness and diversity. Ruminococcus, Succinivibrio, and Fibrobacter were positively correlated with the fermentation and digestibility parameters. The supplementation also altered metabolite levels and types in key physiological pathways. In conclusion, this supplementation improved bacterial composition, nutrient digestibility, weight gain, carcass weight and quality, serum indices, antioxidant levels and metabolomic profiles. This suggests potential for the development of dietary supplements for ruminants. Full article
(This article belongs to the Special Issue Rumen Microorganisms)
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15 pages, 2041 KB  
Article
Gut Microbiome and Metabolome Signatures Associated with Heat Tolerance in Dairy Cows
by Mingxun Li, Peng Chen, Can Liu, Shimeng Wang, Hao Zhang, Jiaxi Li, Niel A. Karrow, Yongjiang Mao and Zhangping Yang
Microorganisms 2025, 13(12), 2829; https://doi.org/10.3390/microorganisms13122829 - 12 Dec 2025
Viewed by 141
Abstract
Heat stress significantly impairs dairy cow health and productivity, highlighting the need to understand the gut microbiome–metabolite interactions that contribute to heat tolerance. Here, we integrated metagenomic sequencing and untargeted metabolomics in twelve holstein cows selected from a previously phenotyped herd of 120 [...] Read more.
Heat stress significantly impairs dairy cow health and productivity, highlighting the need to understand the gut microbiome–metabolite interactions that contribute to heat tolerance. Here, we integrated metagenomic sequencing and untargeted metabolomics in twelve holstein cows selected from a previously phenotyped herd of 120 individuals, including six heat-tolerant (HT) and six heat-sensitive (HS) cows identified using entropy-weighted TOPSIS scoring. HT cows were enriched in genera such as Faecalimonas and UBA737, which were functionally linked to pathways of energy and lipid metabolism, whereas, HS cows harbored taxa associated with bacterial lipopolysaccharide and glycosphingolipid biosynthesis. A total of 135 metabolites were differentially abundant between groups. Among them, glycerol 2-phosphate and 24(28)-dehydroergosterol showed perfect classification performance (AUC = 1.000), and were mainly involved in membrane lipid remodeling and redox regulation. Integrated analysis revealed coordinated microbial–metabolite networks, exemplified by the Faecalimonas–LysoPS (16:0/0:0) and UBA737–Glycerol 2-phosphate axes, suggesting functional coupling between microbial composition and metabolic adaptation. Together, these findings demonstrate that HT cows harbor gut microbiota and metabolites favoring energy balance, membrane remodeling, and oxidative stress resilience, while HS cows display stress-related metabolic patterns. This study elucidates the microbial–metabolic mechanisms underlying thermal resilience and highlights potential biomarkers and metabolic pathways that could be applied in heat-tolerance breeding and precision management of dairy cattle. Full article
(This article belongs to the Section Veterinary Microbiology)
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18 pages, 4877 KB  
Article
Eurotium cristatum Ameliorates Glucolipid Metabolic Dysfunction of Obese Mice in Association with Regulating Intestinal Gluconeogenesis and Microbiome
by Weirong Yang, Ning Han and Xiangnan Zhang
Foods 2025, 14(24), 4273; https://doi.org/10.3390/foods14244273 - 12 Dec 2025
Viewed by 157
Abstract
Eurotium cristatum (EC), a fungus derived from Fu brick tea, exhibits anti-obesity potential, but its mechanisms regulating intestinal gluconeogenesis (IGN) remain unclear. This study aimed to elucidate whether EC alleviates obesity and glucolipid metabolic disorders by modulating the gut microbiota and activating the [...] Read more.
Eurotium cristatum (EC), a fungus derived from Fu brick tea, exhibits anti-obesity potential, but its mechanisms regulating intestinal gluconeogenesis (IGN) remain unclear. This study aimed to elucidate whether EC alleviates obesity and glucolipid metabolic disorders by modulating the gut microbiota and activating the IGN pathway. The 8-week EC administration at low (104 CFU/mL), medium (106 CFU/mL), and high doses (108 CFU/mL) ameliorated high-fat-diet (HFD)-induced metabolic abnormalities, including aberrant weight gain, dyslipidemia, glucose intolerance and hepatic injury with effects showing a dose-dependent trend. EC treatment significantly activated IGN, as indicated by increased colonic levels of short-chain fatty acids (SCFAs) and succinate (key IGN substrates) and the upregulation of IGN-key enzymes (PEPCK, FBPase, and G6Pase). In addition, EC treatment significantly alleviated the HFD-induced gut dysbiosis by reducing the Firmicutes/Bacteroidetes ratio and enriching beneficial bacteria such as Lachnospiraece_NK4A136_group, Bacteroidota and Alloprevotella. Non-targeted metabolomics analysis revealed that EC significantly altered the linoleic acid metabolism, specifically decreasing the relative levels of bile acid and chenodeoxycholic acid (p < 0.01) while increasing those of linoleic acid and ricinoleic acid (p < 0.05). EC treatment reshaped the gut microbiome, promoted the production of beneficial metabolites (e.g., SCFAs), and consequently activated the IGN pathway, ultimately ameliorating host glucose and lipid metabolic disorders. Our findings provide mechanistic insights into the anti-obesity effects of EC, suggesting its potential for further investigation as a dietary intervention for metabolic diseases. Full article
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21 pages, 4632 KB  
Article
Environmental and Rhizosphere Microbiome Drivers of Metabolic Profiles in Gastrodia elata: An Integrative Analysis of Soil, Metabolomics and Anti-Inflammatory Readouts
by Yan Yang, Longxing Guo, Yongguo Li, Miaomiao Ji, Tingting He, Kaiming Hou, Jian Li, Haonan Zhang, Zhilong Shi and Haizhu Zhang
Foods 2025, 14(24), 4265; https://doi.org/10.3390/foods14244265 - 11 Dec 2025
Viewed by 184
Abstract
Background: Gastrodiae Rhizoma, the dried tuber of Gastrodia elata Bl. (Orchidaceae), is a traditional Chinese medicinal (TCM) and edible plant. Its quality formation is closely associated with rhizosphere microorganisms; however, the specific underlying mechanisms remain unclear. Methods: Tubers and rhizosphere soils were collected [...] Read more.
Background: Gastrodiae Rhizoma, the dried tuber of Gastrodia elata Bl. (Orchidaceae), is a traditional Chinese medicinal (TCM) and edible plant. Its quality formation is closely associated with rhizosphere microorganisms; however, the specific underlying mechanisms remain unclear. Methods: Tubers and rhizosphere soils were collected from seven major production regions of G. elata. Soil physicochemical properties were analyzed, and integrative analyses combining soil microbiome and untargeted metabolome profiling were conducted. The anti-inflammatory activity of G. elata extracts was evaluated using a RAW264.7 macrophage model. Multivariate statistical approaches, including OPLS-DA and correlation network analysis, were used to decipher relationships among environmental factors, microbial communities, metabolic profiles, and bioactivities. Results: A total of 39,250 bacterial ASVs and 10,544 fungal ASVs were identified. The bacterial community, dominated by Proteobacteria and Acidobacteria, was strongly influenced by soil chemical factors, including pH and total nitrogen. The fungal community, primarily composed of Ascomycota and Basidiomycota, exhibited marked sensitivity to altitudinal gradients. Correlation analysis revealed that key secondary metabolites, including flavonoids and phenolic acids, along with their anti-inflammatory activities, were significantly associated with rhizosphere microorganisms such as Edaphobaculum, Hypocrea, and Pseudomonas. Conclusions: Our findings outline the pathways connecting environmental factors, the microbiome, and functional metabolites in G. elata, highlighting the importance of environmental–microbial interactions in determining metabolic outcomes. This work provides new insights into the ecological and molecular mechanisms behind the quality formation of this medicinal plant. Full article
(This article belongs to the Section Food Nutrition)
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20 pages, 1470 KB  
Article
Osmolytes vs. Anabolic Reserves: Contrasting Gonadal Metabolomes in Two Sympatric Mediterranean Sea Urchins
by Estela Carbonell-Garzón, Ricardo Ibanco-Cañete, Pablo Sanchez-Jerez and Frutos C. Marhuenda Egea
Metabolites 2025, 15(12), 787; https://doi.org/10.3390/metabo15120787 - 10 Dec 2025
Viewed by 154
Abstract
Background an Objectives: The Mediterranean sea urchins Paracentrotus lividus and Arbacia lixula co-occur on shallow rocky reefs but display contrasting ecological and physiological traits. We compared their gonadal metabolomes to identify species-specific metabolic strategies. Methods: High-resolution magic angle spinning nuclear magnetic resonance (HR-MAS [...] Read more.
Background an Objectives: The Mediterranean sea urchins Paracentrotus lividus and Arbacia lixula co-occur on shallow rocky reefs but display contrasting ecological and physiological traits. We compared their gonadal metabolomes to identify species-specific metabolic strategies. Methods: High-resolution magic angle spinning nuclear magnetic resonance (HR-MAS NMR) spectroscopy to intact gonadal tissues, combining multivariate chemometric modelling with targeted integration, boxplot-based univariate analysis and pathway analysis. Results:A. lixula showed an osmolyte- and redox-oriented phenotype with elevated betaine, taurine, sarcosine, trimethylamine (TMA), trimethylamine N-oxide (TMAO), carnitine, creatine, malonate, methylmalonate, uridine and xanthine. In contrast, P. lividus exhibited an amino-acid-enriched anabolic profile dominated by lysine, glycine and glutamine, together with higher levels of formaldehyde, methanol and 3-carboxypropyl-trimethylammonium. Pathway analysis indicated that A. lixula metabolites mapped onto glycine/serine–threonine metabolism and the folate-linked one-carbon pool, whereas P. lividus metabolites were enriched in glyoxylate/dicarboxylate, nitrogen and amino-acid pathways. These contrasting osmolyte–C1 versus nitrogen–amino-acid strategies are compatible with species-specific host–microbiota metabolic interactions inferred from published microbiome data. Conclusions: Overall, our results support a framework in which A. lixula adopts a resilience-oriented osmolyte strategy and P. lividus an efficiency-oriented anabolic strategy, highlighting HR-MAS NMR metabolomics as a powerful approach to investigate adaptive biochemical diversity in marine invertebrates. Full article
(This article belongs to the Collection Advances in Metabolomics)
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19 pages, 2350 KB  
Article
Differential Assembly of Rhizosphere Microbiome and Metabolome in Rice with Contrasting Resistance to Blast Disease
by Jian Wang, Deqiang Li, Daihua Lu, Cheng Chen, Qin Zhang, Rongtao Fu and Fu Huang
Microorganisms 2025, 13(12), 2789; https://doi.org/10.3390/microorganisms13122789 - 8 Dec 2025
Viewed by 167
Abstract
Rice blast, caused by Magnaporthe oryzae, is one of the most devastating diseases threatening global rice production. Although host resistance represents a sustainable control strategy, the underlying mechanisms mediated by the rhizosphere microbiome remain poorly understood. In this study, we selected four [...] Read more.
Rice blast, caused by Magnaporthe oryzae, is one of the most devastating diseases threatening global rice production. Although host resistance represents a sustainable control strategy, the underlying mechanisms mediated by the rhizosphere microbiome remain poorly understood. In this study, we selected four rice varieties with varying resistance to blast and demonstrated, through an integrated approach of 16S rRNA/ITS amplicon sequencing, untargeted metabolomics, and soil physicochemical analysis, that the rice genotype reprograms the genotype-root exudate-rhizosphere microbiome system. Results showed that the resistant variety P104 significantly decreased the soil pH while increasing the contents of total nitrogen, ammonium nitrogen, and nitrate nitrogen. On the other hand, the susceptible variety P302 exhibited higher pH and available phosphorus content. Furthermore, the rhizosphere of P104 was enriched with specific beneficial microbes such as Desulfobacterota, Ascomycota, and Pseudeurotium, and activated defense-related metabolic pathways including cysteine and methionine metabolism and phenylpropanoid biosynthesis. In contrast, susceptible varieties showed reduced bacterial diversity and fostered a microecological environment more conducive to pathogen proliferation. Our findings indicate that blast-resistant rice genotypes are associated with a protective rhizosphere microbiome, potentially mediated by alterations in root metabolism, thereby suppressing pathogen establishment. These insights elucidate the underground mechanisms of blast resistance and highlight the potential of microbiome-assisted breeding for sustainable crop protection. Full article
(This article belongs to the Section Plant Microbe Interactions)
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20 pages, 2770 KB  
Article
Spatial Multi-Omics Analysis of the Qianqiu Goat Gut Microbiome and Metabolome
by Panpan Guo, Wenjuan Qin, Wencheng Song and Hongquan Chen
Int. J. Mol. Sci. 2025, 26(24), 11815; https://doi.org/10.3390/ijms262411815 - 7 Dec 2025
Viewed by 184
Abstract
This study profiled the rumen (RM), small intestine (SI), and large intestine (LI) of 24 samples collected from eight 6-month-old Qianqiu goats (body weight 28.40 ± 1.80 kg), with the samples equally divided into three groups. A combination of methods was used, including [...] Read more.
This study profiled the rumen (RM), small intestine (SI), and large intestine (LI) of 24 samples collected from eight 6-month-old Qianqiu goats (body weight 28.40 ± 1.80 kg), with the samples equally divided into three groups. A combination of methods was used, including 16S rRNA sequencing, untargeted liquid chromatography–mass spectrometry (LC-MS) metabolomics, Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and weighted gene co-expression network analysis-based module detection (WGCNA) with network integration. An uncommon composition of organisms dominated the SI: the hydrogenotrophic methanogens Methanobrevibacter (SI 24.51%; RM 1.92%; LI 2.19%) and Methanosphaera (SI 0.43%; RM 0.02%; LI 0.02%), together with the acetogen Acetitomaculum (SI 1.58%; RM 0.34%; LI 0.11%), were markedly more abundant compared to the RM or LI. Correlation and pathway analyses indicated that Methanobrevibacter was positively correlated with a steroid-type lipid metabolite (r = 0.52, p < 0.05) and with bile-acid-related metabolites. Acetitomaculum was positively correlated with several metabolites: 4-Hydroxyphenyl 4-hydroxybenzoate (r = 0.79, p < 0.05), 2-Aminoethyl dihydrogen phosphate (r = 0.76, p < 0.05), 1-Myristoyl-2-stearoyl-sn-glycero-3-phosphocholine (r = 0.76, p < 0.05), and 1,2-Dioleoyl-sn-Glycero-3-Phosphocholine (r = 0.74, p < 0.05). Together, these data define a small-intestinal microbial–metabolite module in Qianqiu goats characterized by elevated abundances of specific methanogens and acetogens in the SI. Specific positive correlations were identified between these taxa and metabolites associated with lipids and bile acids. Full article
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16 pages, 3723 KB  
Article
Lactobacillus delbrueckii subsp. lactis CKDB001 Ameliorates Scopolamine-Induced Cognitive Impairment Through Metabolic Modulation
by Hyerim Kim, Hyun Kim, Yeonmi Lee, Changho Park, Beomki Cho, Suyoung Son, Hyeyoung Kim, Gihyeon Kim, Jaeseong Park and Hansoo Park
Int. J. Mol. Sci. 2025, 26(24), 11804; https://doi.org/10.3390/ijms262411804 - 6 Dec 2025
Viewed by 194
Abstract
Microbiome-derived metabolites have emerged as key mediators of the gut–brain axis, influencing cognitive function and neuroprotection. This study investigated whether Lactobacillus delbrueckii subsp. lactis CKDB001 alleviates scopolamine-induced memory impairment through metabolic modulation, and how its effects compare with those of donepezil. ICR mice [...] Read more.
Microbiome-derived metabolites have emerged as key mediators of the gut–brain axis, influencing cognitive function and neuroprotection. This study investigated whether Lactobacillus delbrueckii subsp. lactis CKDB001 alleviates scopolamine-induced memory impairment through metabolic modulation, and how its effects compare with those of donepezil. ICR mice were administered CKDB001 or donepezil for 4–5 weeks and evaluated through behavioral, microbiome, metabolomic, and molecular analyses. CKDB001 significantly improved spatial working memory in a dose-dependent manner, with the high-dose group showing improvements comparable to those of the donepezil-treated group, while passive avoidance showed a non-significant but positive trend. Both CKDB001 and donepezil modulated gut microbial composition, leading to a partial divergence from the scopolamine-disrupted community structure, with CKDB001 inducing dose-dependent intestinal colonization. Metabolomic profiling revealed that both treatments increased tryptophan-derived indole metabolites and altered lipid and short-chain fatty acid metabolite profiles, although these effects were more pronounced in CKDB001-treated mice. At the molecular level, both CKDB001 and donepezil reduced hippocampal tau phosphorylation, downregulated glycogen synthase kinase-3 (GSK-3) signaling, enhanced intestinal tight-junction proteins, and partially normalized acetylcholinesterase activity, with CKDB001 restoring AChE levels more closely toward the normal control. Together, these findings suggest that CKDB001 mitigates cognitive deficits through coordinated modulation of microbial, metabolic, and neuronal pathways, offering a microbiome-based therapeutic approach that may provide benefits comparable to donepezil with potentially fewer limitations. Full article
(This article belongs to the Section Molecular Microbiology)
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23 pages, 4578 KB  
Article
Modulation of Gut Microbes and Hepatic Metabolites by PCP Ameliorates NASH and Fatigue-like Performance in Mice
by Yanyan Hong, Jianmei Yang, Yuanfei Wang, Dongliang Chen, Aiping Wu, Minhui Li, Wanyi Ou, Guiru Lin, Chenli Lin and Yinji Liang
Nutrients 2025, 17(23), 3797; https://doi.org/10.3390/nu17233797 - 3 Dec 2025
Viewed by 383
Abstract
Background/Objectives: Non-alcoholic steatohepatitis (NASH) is a progressive liver condition closely associated with gut microbial dysbiosis and hepatic metabolic abnormalities. Poria cocos polysaccharide (PCP), a bioactive component derived from the medicinal fungus Poria cocos, possesses hepatoprotective properties, yet the therapeutic mechanisms of [...] Read more.
Background/Objectives: Non-alcoholic steatohepatitis (NASH) is a progressive liver condition closely associated with gut microbial dysbiosis and hepatic metabolic abnormalities. Poria cocos polysaccharide (PCP), a bioactive component derived from the medicinal fungus Poria cocos, possesses hepatoprotective properties, yet the therapeutic mechanisms of PCP in NASH, particularly those involving microbial and metabolic regulation, remain incompletely elucidated. This study aimed to investigate the effects of PCP on improving NASH and explore its mechanisms related to prebiotic activity. Methods: Mice were induced to develop NASH using a Western diet, followed by PCP intervention for 12 weeks. Hepatic function, including liver enzymes and lipids, glucose metabolism, and liver histopathological changes, was assessed. Fatigue and neurobehavioral alterations were evaluated via rotarod, open field, and tail suspension tests. Hepatic pro-inflammatory cytokines were measured using RT-qPCR. Gut microbiota were analyzed through 16S RNA gene sequencing, and metabolites of liver tissue were analyzed through untargeted metabolomics. Results: PCP decreased blood glucose and hepatic lipid levels in NASH mice, alleviating liver inflammation, ballooning degeneration, and fibrosis. It also improved fatigue-like performance on rotarod test and reduced the hepatic expression of IL-6, IL-1β, TNF-α, and IL-18. Microbiota analysis revealed that PCP restored gut microbial diversity, promoted the growth of beneficial taxa such as Alistipes and Butyricoccaceae_UCG-009, and inhibited harmful bacteria, including Romboutsia ilealis. Liver metabolomics showed that PCP normalized key metabolites like taurocholate and regulated taurine and hypotaurine metabolism, which were correlated with reduced inflammation, fatigue-like performance, and fibrosis. Conclusions: PCP, as a promising edible agent, alleviates hepatic damage, metabolic disorders, and fatigue-like performance on rotarod test in NASH mice, probably by reshaping gut microbiota and modulating hepatic taurine and hypotaurine metabolism. Full article
(This article belongs to the Section Nutrition and Metabolism)
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27 pages, 1443 KB  
Review
Beyond Digestion: The Gut Microbiota as an Immune–Metabolic Interface in Disease Modulation
by Imran Mohammad, Md. Rizwan Ansari, Mohammed Sarosh Khan, Md. Nadeem Bari, Mohammad Azhar Kamal and Muhammad Musthafa Poyil
Gastrointest. Disord. 2025, 7(4), 77; https://doi.org/10.3390/gidisord7040077 - 3 Dec 2025
Viewed by 1018
Abstract
The gut microbiota has emerged as a critical immune–metabolic interface, orchestrating a complex network of interactions that extend well beyond digestion. This highly diverse community of bacteria, viruses, archaea, and eukaryotic microbes modulates host immunometabolism, metabolic reprogramming, and systemic inflammatory responses, thereby shaping [...] Read more.
The gut microbiota has emerged as a critical immune–metabolic interface, orchestrating a complex network of interactions that extend well beyond digestion. This highly diverse community of bacteria, viruses, archaea, and eukaryotic microbes modulates host immunometabolism, metabolic reprogramming, and systemic inflammatory responses, thereby shaping human health and disease trajectories. Dysbiosis, or disruption of microbial homeostasis, has been implicated in inflammatory bowel disease, cardiometabolic disorders, neurodegeneration, dermatological conditions, and tumorigenesis. Through the biosynthesis of short-chain fatty acids (SCFAs), bile acid derivatives, tryptophan metabolites, and microbial-derived indoles, the gut microbiota regulates epigenetic programming, barrier integrity, and host–microbe cross-talk, thereby influencing disease onset and progression. In oncology, specific microbial taxa and oncomicrobiotics (cancer-modulating microbes) are increasingly recognized as key determinants of immune checkpoint inhibitor (ICI) responsiveness, chemotherapeutic efficacy, and resistance mechanisms. Microbiota-targeted strategies such as fecal microbiota transplantation (FMT), precision probiotics, prebiotics, synbiotics, and engineered microbial consortia are being explored to recalibrate microbial networks and enhance therapeutic outcomes. At the systems level, the integration of multi-omics platforms (metagenomics, transcriptomics, proteomics, and metabolomics) combined with network analysis and machine learning-based predictive modeling is advancing personalized medicine by linking microbial signatures to clinical phenotypes. Despite remarkable progress, challenges remain, including the standardization of microbiome therapeutics, longitudinal monitoring of host–microbe interactions, and the establishment of robust ethical and regulatory frameworks for clinical translation. Future directions should prioritize understanding the causal mechanisms of microbial metabolites in immunometabolic regulation, exploring microbial niche engineering, and developing precision microbiome editing technologies (CRISPR, synthetic biology). Full article
(This article belongs to the Special Issue Feature Papers in Gastrointestinal Disorders in 2025–2026)
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13 pages, 724 KB  
Review
The Gut–Muscle–Immune Axis in Motion: Mechanistic Synergies of SCFA Metabolism, Exercise, and Microbial Cross-Feeding
by Fritz Réka, Bere Zsófia, Bóday Ádám and Fritz Péter
Nutrients 2025, 17(23), 3786; https://doi.org/10.3390/nu17233786 - 2 Dec 2025
Viewed by 393
Abstract
Background: The gut microbiota plays a fundamental role in metabolic and immune homeostasis through the production of short-chain fatty acids (SCFAs). These metabolites influence mitochondrial biogenesis, muscle energetics, epithelial barrier stability, and inflammatory regulation via G-protein-coupled receptors, AMPK–PGC-1α signaling, and epigenetic remodeling. Objective: [...] Read more.
Background: The gut microbiota plays a fundamental role in metabolic and immune homeostasis through the production of short-chain fatty acids (SCFAs). These metabolites influence mitochondrial biogenesis, muscle energetics, epithelial barrier stability, and inflammatory regulation via G-protein-coupled receptors, AMPK–PGC-1α signaling, and epigenetic remodeling. Objective: This review synthesizes current evidence on the gut–muscle–immune axis, emphasizing how dietary fermentable substrates, microbial cross-feeding interactions, and structured exercise modulate SCFA production and shape host physiological adaptation. Methods: We integrated findings from human and animal studies, multi-omic analyses, metabolomic and microbiome research, and exercise physiology to outline mechanistic links between microbial metabolism and systemic resilience. Results: Key mechanistic pathways connecting dietary fiber fermentation to mitochondrial function, redox regulation, immune homeostasis, and metabolic plasticity are summarized. We further present the Targeted Gut Protocol 2.0, a conceptual 12-week framework combining fiber-diversity targets, lactate-guided exercise periodization, biomarker monitoring, and adaptive feedback mechanisms to enhance endogenous SCFA availability. Conclusions: SCFA-driven metabolic plasticity provides an integrative model through which lifestyle behaviors can modulate host physiology. Future research should prioritize standardized sampling approaches, causal inference methods, multi-omic integration, and AI-supported personalization to refine mechanistic understanding and strengthen translational potential. Full article
(This article belongs to the Special Issue Effects of Exercise and Diet on Health)
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18 pages, 2044 KB  
Article
Genitourinary Microbiome and Volatilome: A Pilot Study in Patients with Prostatic Adenocarcinoma Submitted to Radical Prostatectomy
by Layla Musleh, Sara Passerini, Francesca Brunetti, Linda Maurizi, Giulio Bevilacqua, Lorenzo Santodirocco, Beatrice Sciarra, Martina Moriconi, Caterina Fraschetti, Antonello Filippi, Maria Pia Conte, Valeria Pietropaolo, Marisa Di Pietro, Simone Filardo, Alessandro Sciarra and Catia Longhi
Cancers 2025, 17(23), 3841; https://doi.org/10.3390/cancers17233841 - 29 Nov 2025
Viewed by 282
Abstract
Background/Objectives: The genitourinary microbiome and metabolome may contribute to prostate cancer (PC) biology, but evidence remains limited. This pilot study characterizes the urinary microbiota and volatilome in men with PC and investigates microbial and viral DNA in prostate tissue, comparing findings with [...] Read more.
Background/Objectives: The genitourinary microbiome and metabolome may contribute to prostate cancer (PC) biology, but evidence remains limited. This pilot study characterizes the urinary microbiota and volatilome in men with PC and investigates microbial and viral DNA in prostate tissue, comparing findings with benign prostatic hyperplasia (BPH). Methods: We prospectively enrolled 21 non-metastatic PC patients undergoing radical prostatectomy and 17 BPH controls. Lesional and non-lesional prostate tissues and urine were collected from PC patients, as well as urine samples from BPH participants. DNA samples were tested for sexually transmitted pathogens by multiplex real-time PCR. Urine and prostate tissue were analyzed for human polyomaviruses (JCPyV, BKPyV, MCPyV) by qPCR, bacterial profiles via 16S rRNA gene sequencing, and urinary volatile organic metabolites (VOMs) using HS-SPME/GC-MS. Microbial and metabolic profiles were compared, and taxa–metabolites were assessed. Results: JCPyV and BKPyV were detected in urine and tissue from PC patients; MCPyV was detected only in tissue, at low frequency. In BPH, viral prevalence was lower and MCPyV was absent. JCPyV/BKPyV co-infection was common in cancer. No sexually transmitted pathogen emerged. PC patients showed greater urinary microbial diversity and five enriched genera, along with specific metabolic pathways. 36 urinary VOMs were identified, with 14 differing significantly, with positive correlations between PC-associated genera and metabolites. In contrast, prostate tissue was low-biomass, dominated by Pseudomonas, and showed no significant differences between lesional and non-lesional areas. Conclusions: This preliminary, hypothesis-generating study indicates that urinary, rather than tissue, microbial and volatilome signatures show clearer differences between PC and BPH. These findings suggest possible microbiota–metabolite interactions in PC but require validation in larger cohorts. Full article
(This article belongs to the Section Cancer Therapy)
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34 pages, 8371 KB  
Article
Rumen Fluid Metabolomics and Microbiome Profiling of Dairy Cows Fed Combinations of Prebiotics, Essential Oil Blend, and Onion Peel Using the RUSITEC System
by Joel O. Alabi, Ahmed E. Kholif, Kelechi A. Ike, Deborah O. Okedoyin, Oludotun O. Adelusi, Michael Wuaku, Chika C. Anotaenwere, James M. Enikuomehin, Olatunde A. Oderinwale, John O. Adebayo, Andrea R. Gentry-Apple and Uchenna Y. Anele
Metabolites 2025, 15(12), 762; https://doi.org/10.3390/metabo15120762 - 25 Nov 2025
Viewed by 347
Abstract
Background and Objectives: Dairy products provide vital energy, high-quality protein, and micronutrients for over six billion people worldwide, with dairy cows contributing nearly 81% of global milk production. Sustainable strategies to enhance productivity are therefore critical. Feed additives such as essential oil blends [...] Read more.
Background and Objectives: Dairy products provide vital energy, high-quality protein, and micronutrients for over six billion people worldwide, with dairy cows contributing nearly 81% of global milk production. Sustainable strategies to enhance productivity are therefore critical. Feed additives such as essential oil blends (EOB), onion peel (OPE), and prebiotics including mannan oligosaccharides (MOS) and galacto-oligosaccharides (GOS) have been proposed to improve rumen fermentation, modulate microbial ecology, and mitigate greenhouse gas emissions. This study evaluated the combined effects of EOB, OPE, MOS, and GOS on rumen metabolism using the rumen simulation technique (RUSITEC). Materials and Methods: Rumen inoculum from three cannulated Holstein Friesian cows was incubated across 16 vessels (four treatments × four replicates) for nine days. Treatments included a control (CON; TMR only), GEO (TMR + GOS + EOB + OPE), MEO (TMR + MOS + EOB + OPE), and OLEO (TMR + a 1:1 mixture of GOS and MOS + EOB + OPE). Additives were included at 3 µL/g TMR for EOB and 30 mg/g TMR (3% w/w) for OPE, GOS, MOS, or OLG. Rumen effluents were collected for untargeted metabolomic profiling by liquid chromatography–mass spectrometry, identifying 661 metabolites. Results: Partial least squares-discriminant analysis revealed clear separation between CON and additive groups, confirming distinct metabolic shifts. GEO primarily enhanced tryptophan, tyrosine, and purine metabolism; MEO stimulated phosphonate and pyrimidine pathways and bile acid biosynthesis; OLEO promoted phosphonate, nicotinamide, and taurine metabolism. Microbial analysis showed enrichment of taxa such as Lachnospira, Succinivibrionaceae, Macellibacteroides, Lysinibacillus, and Christensenellaceae, indicating complementary effects on fermentation and microbial stability. Conclusions: These results demonstrate that dietary supplementation with GEO, MEO, or OLEO modulates rumen metabolism and microbial ecology without impairing fermentation, supporting improved nutrient utilization, antioxidant defenses, and metabolic resilience in dairy cows, with potential benefits for productivity and sustainability. Full article
(This article belongs to the Special Issue Dysbiosis and Metabolic Disorders of the Microbiota)
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23 pages, 5959 KB  
Article
Involvement of the Gut–Lung Axis in LMW-PAHs-Induced Pulmonary Inflammation
by Jiali Qin, Shiyao Jiang, Zhengyi Zhang, Jianding Wang, Yuanjie Li, Yunting Li, Haojun Zhang, Chengyun Li, Haitao Ma and Junling Wang
Toxics 2025, 13(12), 1017; https://doi.org/10.3390/toxics13121017 - 25 Nov 2025
Viewed by 479
Abstract
Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants recognized for their toxicological significance. Increasing evidence suggests that chronic exposure to low-molecular-weight PAHs (LMW-PAHs) contributes to heightened disease vulnerability and immune dysregulation, particularly among rural female populations. Recent studies have further linked a significant [...] Read more.
Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants recognized for their toxicological significance. Increasing evidence suggests that chronic exposure to low-molecular-weight PAHs (LMW-PAHs) contributes to heightened disease vulnerability and immune dysregulation, particularly among rural female populations. Recent studies have further linked a significant association between PAH exposure and gut microbiome (GM) modifications. Considering the common embryonic origin of the intestinal and respiratory systems, cross-organ communication under conditions of PAH exposure warrants deeper exploration. Although current gut–lung axis research largely emphasizes microbial metabolites such as short-chain fatty acids and bile acids, the contribution of arachidonic acid (AA) metabolites in LMW-PAH-induced pulmonary inflammation via this axis remains poorly defined. To address this knowledge gap, we developed an animal model employing integrated 16S rRNA sequencing and metabolomics approaches to systematically examine phenanthrene (Phe) and fluorene (Flu) induced GM compositional shifts and associated metabolic reprogramming. Through comprehensive profiling, we identified candidate microorganisms and metabolites potentially involved in dysbiosis-mediated pulmonary inflammation, thereby elucidating the mechanistic basis of Phe and Flu-associated health risks. Full article
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28 pages, 361 KB  
Review
Pecans and Human Health: Distinctive Benefits of an American Nut
by Amandeep K. Sandhu, Indika Edirisinghe and Britt Burton-Freeman
Nutrients 2025, 17(23), 3686; https://doi.org/10.3390/nu17233686 - 25 Nov 2025
Viewed by 1356
Abstract
Pecans are a tree nut native to America with a rich content of unsaturated fatty acids, minerals, fiber, and a diverse array of bioactive components, including polyphenols, tocopherols, and phytosterols. This review summarizes variations in the phenolic composition of pecans from various parts [...] Read more.
Pecans are a tree nut native to America with a rich content of unsaturated fatty acids, minerals, fiber, and a diverse array of bioactive components, including polyphenols, tocopherols, and phytosterols. This review summarizes variations in the phenolic composition of pecans from various parts of the world based on cultivar, maturity stage, postharvest storage, and processing. Additionally, the review delves into the bio-accessibility and bioavailability of bioactive components from pecans and their potential influence on diet quality, body weight, satiety, cardiometabolic, brain and gut health. Data from human clinical trials suggest that replacing foods/snacks with pecans improves overall diet quality and lipid profiles. However, inconsistent effects are observed on vascular function, glycemia, and inflammation. Body weight changes after pecan intake are reported as neutral, with promising results on satiety peptides and appetite regulation. Cognition and gut health are emerging areas of research with very limited data from both human and preclinical models, warranting further investigation. Overall, the current literature supports the cardiometabolic benefits of pecans within healthy dietary patterns. Future research should focus on well-controlled studies targeting at-risk populations to understand mechanistic endpoints such as metabolomics, microbiome, and vascular function assessments to substantiate the role of pecans in dietary guidance. Full article
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