PubMed

Food Chem X. 2026 Aug 28;39:104377. doi: 10.1016/j.fochx.2026.104377. eCollection 2026 Oct.ABSTRACTThe color of tea beverages is a critical quality determinant, yet photo-induced fading has received little attention compared to browning reactions. This study investigated riboflavin photodegradation in unsweetened green tea beverages under both retail-shelf lighting and simulated solar radiation. Under retail-shelf lighting, approximately 90% of riboflavin degraded within the first 5 days of a 20-day exposure period (p < 0.05), confirming its high susceptibility under realistic retail conditions. Under simulated solar radiation, a comparable 90% degradation occurred within only 8 h. Chlorophyll also degraded by approximately 37.5% after 8 h of sunlight exposure. While riboflavin serves as the primary driver of chromatic deterioration, chlorophyll contributes to a lesser extent in the photo-induced fading process. These findings establish riboflavin as a key target for intervention, with chlorophyll as a secondary contributor, providing a theoretical foundation for developing targeted light-protective strategies to preserve the color quality of green tea beverages.PMID:42713374 | PMC:PMC13551959 | DOI:10.1016/j.fochx.2026.104377

Food Waterborne Parasitol. 2026 Aug 26;44:e00356. doi: 10.1016/j.fawpar.2026.e00356. eCollection 2026 Sep.ABSTRACTParasitic helminths can modulate host inflammatory responses, but whether this regulation involves remodeling of the intestinal neurochemical environment remains unclear. Here, we investigated whether Trichinella spiralis infection alters intestinal neurotransmitter-related metabolism during lipopolysaccharide (LPS)-induced systemic inflammation. In this study, we established an LPS-induced inflammatory model and a T. spiralis-infection with LPS challenge model. At 14 days after infection, mice were challenged with LPS, and inflammatory responses and duodenal neurotransmitter-related metabolites were assessed. T. spiralis infection reduced serum TNF-α and IL-1β levels and alleviated LPS-induced lung pathology. Targeted LC-MS/MS profiling revealed treatment-specific neurochemical signatures in duodenal tissues. Under basal conditions, T. spiralis infection increased histamine levels and reduced norepinephrine, 5-hydroxyindoleacetic acid, and xanthurenic acid. During LPS challenge, prior T. spiralis infection was associated with increased dopamine, epinephrine, levodopa, 5-hydroxytryptophan, histamine, and tyramine compared with LPS challenge alone. These changes suggest that T. spiralis infection remodels tyrosine-, histidine-, and tryptophan-related neurochemical pathways in the intestine. Receiver operating characteristic analysis further identified several metabolites that discriminated LPS-challenged mice from T. spiralis-infected, LPS-challenged mice, although these candidate signatures require validation in larger independent cohorts. Together, our findings indicate that intestinal neurochemical remodeling may represent a previously underappreciated component of helminth-associated anti-inflammatory regulation.PMID:42713351 | PMC:PMC13551873 | DOI:10.1016/j.fawpar.2026.e00356

Struct Dyn. 2026 Sep 8;13(5):050901. doi: 10.1063/4.0001229. eCollection 2026 Sep.ABSTRACTJohn L. Markley was an early pioneer of the application of nuclear magnetic resonance (NMR) spectroscopy to investigate the structure, dynamics, and function of biological macromolecules by NMR. A recurring theme of his career is the development of standards and shared resources that have enabled the biological NMR community to coherently and collectively advance the disciplines of structural biology and metabolomics. Spanning development standards for atom nomenclature, founding shared NMR resources at Purdue and UW-Madison, and founding the Biological Magnetic Resonance Data Bank (BMRB) and shepherding BMRB membership in the Worldwide Protein Data Bank, this appreciation revisits the many and lasting contributions by our friend and colleague John Markley in support of the global structural biology community.PMID:42713328 | PMC:PMC13553183 | DOI:10.1063/4.0001229

Front Immunol. 2026 Aug 25;17:1854085. doi: 10.3389/fimmu.2026.1854085. eCollection 2026.ABSTRACTThe maintenance of local immunity requires stable tissue adaptation, implying that persistent environmental cues must continuously reinforce niche-specific immune programs. Microbiota-derived metabolites are increasingly recognized as such cues, acting not merely as metabolic byproducts but as epigenetic inputs that regulate histone modifications, DNA and histone methylation, and non-coding RNA networks. Through these epigenetic mechanisms, microbial metabolites reprogram key immune populations by promoting tolerogenic or immunostimulatory states, tuning effector and memory differentiation, and reshaping subset-specific functions in a tissue-dependent manner. Tissue-level studies have further shown that this microbiota-epigenome crosstalk influences barrier tolerance in the gut and skin, antiviral and inflammatory responses in the lung, metabolic and fibrogenic programs in the liver, and microglial immune tone in the brain. However, studies establishing a complete causal chain from a defined commensal source and metabolite availability to sensing or uptake pathway, chromatin-modifying enzyme or epigenetic mark, target gene locus, responding immune cell type, and validated immune outcome remain to be limited. Future studies should integrate causal microbial genetics, longitudinal metabolomics, cell-type-resolved epigenomics, and human validation to distinguish causal mechanisms from associative findings and enable safe tissue- and patient-specific therapeutic translation. This review therefore outlines the microbiota-metabolite-epigenome axis as a unifying framework for local immunity while emphasizing the mechanistic gaps that must be addressed to develop effective therapeutic strategies.PMID:42713241 | PMC:PMC13551561 | DOI:10.3389/fimmu.2026.1854085

Front Microbiol. 2026 Aug 25;17:1913406. doi: 10.3389/fmicb.2026.1913406. eCollection 2026.ABSTRACTLeukemia care is a clinical experiment in ecosystem stress. Malignant hematopoiesis, intensive chemotherapy, hematopoietic cell transplantation, neutropenia, mucosal injury, broad-spectrum antibiotics and nutritional interruption converge to deplete anaerobic fermentative capacity and favor pathobiont domination. The central gap is not whether dysbiosis occurs, but how loss of fiber-dependent microbial function becomes barrier failure, infection risk, immune dysregulation, treatment toxicity and altered drug exposure. We reviewed adult or non-pediatric full-text literature published from 13 May 2021 to 13 May 2026, after excluding pediatric-focused studies, and integrated foundational evidence on dietary fiber, microbial metabolites and cancer microbiome methodology. The literature supports a therapeutic ecology model in which fermentable substrate, anaerobic redundancy, short-chain fatty acids, indoles, bile-acid derivatives and amino-acid metabolites form a linked fiber-microbiota-barrier axis. When this axis is disrupted by antibiotics, mucositis, sterile or low-residue diets, parenteral nutrition and hospitalization, the ecosystem can enter alternative stable states marked by domination, resistome expansion and reduced metabolite output. Evidence is strongest in acute myeloid leukemia, acute leukemia chemotherapy and hematopoietic cell transplantation, but emerging studies in chronic lymphocytic leukemia, chronic myeloid leukemia, CAR T-cell therapy and pharmacomicrobiomics extend the framework beyond infection prevention. We therefore argue that microbiota-directed nutrition in leukemia should be designed as a timed, safety-bounded ecological intervention rather than as a generic supplement. Future trials should combine dietary quantification, antibiotic metrics, strain-level microbiome profiling, metabolomics, barrier biomarkers, drug-exposure readouts and patient-centered outcomes to test whether restoring the fiber-microbiota-barrier axis improves adult leukemia care.PMID:42713160 | PMC:PMC13552400 | DOI:10.3389/fmicb.2026.1913406

Front Endocrinol (Lausanne). 2026 Sep 4;17:1939488. doi: 10.3389/fendo.2026.1939488. eCollection 2026.ABSTRACTType 2 diabetes mellitus (T2DM) is one of the most pressing global public health challenges. Exercise intervention, as a cost-effective and safe non-pharmacological strategy, exerts its metabolic benefits through coordinated multi-organ and multi-target regulation. Metabolomics technologies provide powerful tools for dissecting the molecular mechanisms underlying exercise intervention in T2DM. This narrative review summarizes current evidence on metabolic dysregulation in T2DM and the metabolic mechanisms underlying exercise intervention, with particular emphasis on insights provided by metabolomics. Furthermore, it elaborates the mechanisms by which exercise intervention systemically reverses T2DM-associated metabolic abnormalities: restoring tricarboxylic acid cycle flux to alleviate glycolytic stress; accelerating branched-chain amino acid oxidative catabolism to rectify aromatic amino acid metabolic disturbances; and promoting fatty acid oxidation while clearing lipotoxic products. In addition, this review highlights the clinical potential of metabolomics for predicting exercise responsiveness, dynamically evaluating intervention outcomes and safety, thereby providing a potential basis for more individualized exercise intervention strategies in T2DM.PMID:42713115 | PMC:PMC13551329 | DOI:10.3389/fendo.2026.1939488

iScience. 2026 Aug 29;29(9):117371. doi: 10.1016/j.isci.2026.117371. eCollection 2026 Sep 18.ABSTRACTEarly-life exposure to dietary excess of lipids increases lifelong vulnerability to metabolic dysfunction, but the determinants of this susceptibility remain unclear. Here, we combine paired-tissue transcriptomics (whole head and fat body), metabolomics, and gut microbiota profiling in Drosophila melanogaster to define how transient developmental exposure to a high-fat diet (HFD) remodels adult metabolism. Larval HFD exposure was associated with extensive transcriptional remodeling in the adult fat body, including coordinated repression of tricarboxylic acid (TCA) cycle and oxidative phosphorylation genes, accompanied by increased ROS accumulation and reduced mitochondrial bioenergetic function. In contrast, the whole-head transcriptome showed a weaker response to HFD than the fat body. Integrated host-microbiome profiling revealed persistent remodeling of the gut microbial community, with altered bacterial diversity and structure. Targeted adult interventions with the NAD+ precursor nicotinamide riboside, the TCA intermediate α-ketoglutarate, or commensal bacteria (Acetobacter and Lactobacillus spp.) restored mitochondrial redox balance, improved respiratory capacity, and extended lifespan. Together, these findings identify mitochondrial dysfunction and microbial remodeling as enduring features of developmental dietary lipid stress and suggest that this metabolic state remains partially reversible through mitochondrial and microbiota-directed interventions.PMID:42713014 | PMC:PMC13551879 | DOI:10.1016/j.isci.2026.117371

Int J Microbiol. 2026 Sep 7;2026:7551500. doi: 10.1155/ijm/7551500. eCollection 2026.ABSTRACTCongenital central hypoventilation syndrome (CCHS) is a genetic disorder caused by mutations in the PHOX2B gene, characterized by impaired autonomic control of breathing and systemic consequences that may affect gut homeostasis. This study provides the first integrated multi-omics analysis in a CCHS group and matched controls, combining fecal DNA-based gut taxonomic profiling with targeted quantification of fatty acids and aromatic carboxylic acids. While overall microbial diversity and community structure remained largely preserved, significant alterations were observed in specific taxa within the CCHS group. Notably, the control group exhibited an enrichment of short-chain fatty acid (SCFA)-producing genera, which are associated with eubiotic gut ecosystems, whereas the CCHS group showed higher abundance of taxa commonly linked to inflammatory contexts. Consistently, fecal levels of beneficial SCFAs-particularly valeric acid, and to a lesser extent butyric acid-were reduced in CCHS group. These findings point to a dysbiotic gut microbiota in patients with CCHS, likely supporting putative inflammatory processes that would further worsen overall health status if confirmed. Furthermore, this work provides exploratory functional signatures for future studies aimed at understanding systemic consequences, guiding mechanistic investigations, and informing strategies to improve supportive care and long-term health outcomes in this rare patient population.PMID:42712877 | PMC:PMC13550528 | DOI:10.1155/ijm/7551500

Oxf Open Neurosci. 2026 Aug 26;5:kvag011. doi: 10.1093/oons/kvag011. eCollection 2026.ABSTRACTMetabolism and energetics are closely integrated with brain function, and understanding how metabolic dysfunction contributes to neurological disease may help improve therapeutic approaches. Characterization of in situ metabolite levels, spatial distributions, and metabolomes requires special attention to anesthesia use, perimortem conditions, and tissue harvest. Anesthesia, CO2 asphyxiation, vascular perfusion, and decapitation alter metabolism, thereby substantially changing the metabolome, lipidome, and neurotransmitter profile. Analysis of flawed samples produces artifactual data, raising concerns about conclusions regarding the cellular basis of metabolism, metabolite shuttling, pathway activities, labeled metabolite profiling and imaging, and relationships between metabolism, function, and neurological disorders. Appropriate procedures for in vivo metabolic assays and tissue harvest are widely-unrecognized but essential components of metabolic and metabolomic studies.PMID:42712815 | PMC:PMC13550777 | DOI:10.1093/oons/kvag011

Front Bioinform. 2026 Aug 25;6:1893206. doi: 10.3389/fbinf.2026.1893206. eCollection 2026.ABSTRACTAntimicrobial resistance (AMR) has been identified as one of the 21st century's severest global public health crises. AMR led to an estimated 4.95 million deaths in 2019 and will claim 10 million lives a year by 2050 in the absence of targeted interventions. During the same period, the number of novel antibiotics discovered has decreased drastically as many researchers are rediscovering known antibiotics, non-model microorganisms are poorly understood or difficult to culture and antibiotic research and development investment has declined drastically. However, high-throughput whole genome sequencing and the subsequent application of bioinformatics in bacterial and fungal genomes have shown that a numerous of cryptic or silent biosynthetic gene clusters (BGCs) remain latent at ambient laboratory conditions since their genes are transcriptionally inactive. Cryptic BGCs represent a vast source of unique secondary metabolites, many of which may yield novel antibacterial, antifungal, anti-cancer and other potentially valuable natural products. This review discusses the biological relevance of cryptic BGCs, the major limiting factors that restricts their activation and novel strategies that have been employed to activate them and exploit their potential to produce novel natural products. The review focuses on biological approaches including CRISPR-Cas mediation for the activation of cryptic BGCs, promoter engineering, pathway refactoring, and heterologous expression; biochemical strategies such as Osman, OsMAC, Precursor Feeding, Chemical Elicitation, Epigenetic Regulation and Co-cultivation and technology-based strategies such as Genome mining, Microfluidic Cultivation systems, High-Throughput Screening, Metabolomics, Molecular Networking and Artificial Intelligence and Machine Learning based prediction of BGCs and their metabolites. The use of multi-omics technologies combined with synthetic biology to achieve better discovery, characterization and large-scale production of novel natural products is also discussed herein. Finally, we will talk about the ecological significance and evolutionary advantage of cryptic BGCs' role in interactions between microorganisms, such as competition, communication, symbiosis and environmental adaptability, so as to provide a useful background for accelerating next-generation antibiotics.PMID:42712777 | PMC:PMC13550855 | DOI:10.3389/fbinf.2026.1893206

Front Immunol. 2026 Aug 25;17:1902981. doi: 10.3389/fimmu.2026.1902981. eCollection 2026.ABSTRACTBACKGROUND: Coronaviruses (CoVs), including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Middle East respiratory syndrome (MERS-CoV), cause respiratory infections with distinct clinical outcomes and case fatality rates. However, the molecular basis of these differences remains unclear. In this study, we sought to define virus-specific host metabolic programs by directly comparing multiomics profiles of the lungs of lethally infected mouse models.METHODS: We performed integrated multiomics analyses, including untargeted metabolomics, transcriptomics, and targeted lipidomics, of lung tissues from human angiotensin-converting enzyme 2 (hiACE2)-human dipeptidyl peptidase 4 (hDPP4) double-knock-in (DKI) mice infected in SARS-CoV-2 or MERS-CoV. Data Integration Analysis and Biomarker discovery using Latent cOmponents (DIABLO) was applied across all three omics layers to identify key distinguishing molecular patterns. Additionally, in vitro lipid droplet kinetics were examined in infected Vero E6 cells to validate temporal differences in lipid remodeling.RESULTS: We identified two distinct strategies for lipid utilization. SARS-CoV-2 infection showed strong activation of energy and amino acid metabolism at an early stage of infection (3 days post infection, DPI), whereas MERS-CoV infection was characterized by sustained alterations in lipid and nucleotide metabolism. Integrative DIABLO analysis of all three omics layers revealed that the key distinguishing features clustered into virus-specific molecular signatures: a triacylglycerol-lipid droplet-interferon axis for SARS-CoV-2 and a phospholipid-sphingolipid-membrane hub for MERS-CoV. In vitro lipid droplet kinetics in infected Vero E6 cells confirmed this temporal difference, with SARS-CoV-2 peaking earlier than MERS-CoV.CONCLUSION: These findings show that β-CoVs exploit host lipid metabolism through virus-specific and time-dependent remodeling programs, providing a framework for understanding differential pathogenesis and developing host-directed antiviral strategies.PMID:42712680 | PMC:PMC13550176 | DOI:10.3389/fimmu.2026.1902981

Front Pharmacol. 2026 Aug 25;17:1899068. doi: 10.3389/fphar.2026.1899068. eCollection 2026.ABSTRACTBACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a major global health issue strongly associated with obesity. Available treatments have significant limitations. The traditional Chinese medicine Huatan Qushi Huoxue (HTQSHX) granules represent a potential alternative therapeutic option. This study evaluates their effects and safety in patients with obesity-associated NAFLD.METHODS: This multicenter, randomized, double-blind, placebo-controlled, parallel-group trial recruited 248 patients with obesity-associated NAFLD from three clinical sites. Participants were randomized 1:1 to receive HTQSHX granules or placebo granules for 12 weeks. The primary outcome was the absolute change in hepatic fat fraction from baseline to week 12, as measured by MRI-proton density fat fraction (MRI-PDFF), which is recommended as a primary endpoint in early-phase NAFLD clinical trials for its precision and objectivity. Secondary outcomes included the proportion of patients achieving ≥30% relative reduction in MRI-PDFF-assessed hepatic fat fraction, serum liver enzyme indicators, glucose and lipid metabolism parameters, non-alcoholic steatohepatitis-related serum biomarkers, anthropometric measures, and serum metabolomics analysis.RESULTS: Among 228 participants included in the modified intention-to-treat (mITT) analysis, the median hepatic fat fraction decreased from 16.15% at baseline to 12.12% in the HTQSHX group (median change: 3.27%), and from 15.64% to 14.95% in the placebo group (median change: 0.96%). The between-group difference in absolute change was statistically significant (-2.32%; 95% CI, -4.50 to -0.23; P = 0.029). The proportion of patients achieving a ≥30% relative reduction in hepatic fat fraction was significantly higher in the HTQSHX group than in the placebo group (41.23% vs. 20.18%; P < 0.001). The HTQSHX group also showed significantly greater improvements in serum alanine aminotransferase (P = 0.048), aspartate aminotransferase (P = 0.033), free fatty acids (P = 0.026), cytokeratin-18 fragment M30 (P < 0.001), soluble triggering receptor expressed on myeloid cells 2 (P < 0.001) and anthropometric parameters (body mass index, waist-to-hip ratio, body fat percentage). Metabolomics analysis of 30 HTQSHX-treated participants revealed that the formula restored multiple phospholipid levels and reduced markers of oxidative stress and mitochondrial dysfunction, with enrichment in fatty acid and sphingolipid metabolism pathways.CONCLUSION: HTQSHX granules may represent a potentially beneficial therapeutic option for obesity-associated NAFLD, with observed effects including significant reduction in hepatic fat fraction and modulation of lipid metabolism and oxidative stress, alongside an acceptable safety profile. These findings warrant further investigation in longer-term studies.CLINICAL TRIAL REGISTRATION: https://www.chictr.org.cn/, identifier ChiCTR2200060901.PMID:42712610 | PMC:PMC13550174 | DOI:10.3389/fphar.2026.1899068

Front Endocrinol (Lausanne). 2026 Aug 25;17:1909718. doi: 10.3389/fendo.2026.1909718. eCollection 2026.ABSTRACTBACKGROUND: Impaired semen quality may involve concurrent abnormalities in sperm concentration, total sperm number, motility, morphology, and DNA integrity. The corresponding alterations in the seminal plasma metabolome remain incompletely characterized.OBJECTIVES: To characterize seminal plasma metabolic alterations in men with multiple concurrent semen abnormalities and identify candidate signals associated with semen quality parameters.MATERIALS AND METHODS: Untargeted LC-MS/MS metabolomics was performed in a discovery cohort comprising 10 men with impaired semen quality and 9 normozoospermic controls. Candidate metabolites were screened using nominal p value and fold-change thresholds, followed by pathway and correlation analyses, post hoc ROC analysis, and qualitative comparisons with public datasets. External-calibration-derived estimates assigned to cytidine and 2-hydroxy-3-methylbutyric acid (2-HMBA) were subsequently evaluated by HPLC-UV in an independent cohort of 18 men with impaired semen quality and 18 controls.RESULTS: Eighty-nine putatively annotated metabolites met the nominal screening criteria, but no individual metabolite remained significant after Benjamini-Hochberg false discovery rate correction. Discovery-level pathway analyses highlighted nucleotide- and nucleoside-related processes as hypothesis-generating signals. Qualitative comparison with heterogeneous publicly available reproductive metabolomics datasets provided limited directional context but was not considered formal external validation. In the independent HPLC-UV cohort, external-calibration-derived estimates assigned to 2-HMBA were nominally lower in the group with impaired semen quality (p = 0.030), but the difference did not remain significant after correction across the two candidate comparisons (q = 0.060). Cytidine showed no between-group difference (p = 0.812; q = 0.812).DISCUSSION AND CONCLUSION: The discovery-level nucleotide-related pathway signal and the independent observation concerning 2-HMBA represent distinct lines of evidence; the latter does not validate the former. Given the small sample sizes in both the discovery and independent HPLC-UV evaluation cohorts, the absence of FDR-significant metabolites, heterogeneity across the public datasets, and limitations of the HPLC-UV assay, these findings remain exploratory and hypothesis-generating. They do not constitute quantitative validation, establish a specific mechanism, or support clinical biomarker use. Larger multicenter cohorts and targeted quantitative metabolomic analyses using validated methods are needed.PMID:42712394 | PMC:PMC13549830 | DOI:10.3389/fendo.2026.1909718

J Sep Sci. 2026 Sep;49(9):e70527. doi: 10.1002/jssc.70527.ABSTRACTDanshen-Chuanxiong is a traditional herb pair used for cardiovascular and cerebrovascular disorders, but its chemical basis and potential effects in Alzheimer's disease (AD)-related endothelial injury remain incompletely defined. Here, an integrated analytical workflow combining reversed-phase liquid chromatography (RPLC) and hydrophilic interaction liquid chromatography (HILIC) with quadrupole time-of-flight mass spectrometry (Q-TOF-MS), cellular assays, metabolomics, and network pharmacology was applied in an amyloid-β1-42 (Aβ1-42) oligomer-induced human brain microvascular endothelial cell (hBMEC) injury model. The complementary RPLC/HILIC and positive/negative electrospray-ionization strategy expanded coverage across a broad polarity range. UHPLC-Q/TOF-MS detected 90 compounds, mainly phenolic acids, phthalides, tanshinones, diterpenoids, and other aromatic or terpenoid constituents. The reductions in cell viability and zonula occludens-1 expression following Aβ1-42 exposure confirmed the successful establishment of the cellular injury model, whereas pretreatment with Danshen, Chuanxiong, or their combination increased cell viability and alleviated Aβ1-42-induced cellular injury. Untargeted metabolomics annotated 38 differential metabolites, of which 30 showed a recovery-associated shift toward the control state after Danshen-Chuanxiong treatment; the associated pathways included amino-acid, purine, glutathione, and glycerophospholipid metabolism. Integrative analysis prioritized seven candidate targets of Danshen-Chuanxiong, namely ACHE, VEGFA, NOS2, NOS3, AKR1B1, MDM2, and XDH. These findings provide a separation-MS-based chemical characterization and mechanistic framework for further validation of Danshen-Chuanxiong in AD-related endothelial injury models.PMID:42712219 | DOI:10.1002/jssc.70527

Gut Microbes. 2026 Dec 31;18(1):2728828. doi: 10.1080/19490976.2026.2728828. Epub 2026 Sep 8.ABSTRACTThis report summarizes the deliberations of a working group convened by the International Scientific Association for Probiotics and Prebiotics (ISAPP) at their 2025 annual meeting to identify the key targets that mediate the host response to biotics. Probiotics, prebiotics, synbiotics, and postbiotics have been explored in numerous contexts, but results of clinical trials are mixed. In most studies performed to date, a therapeutic product and its dose and administration strategy were selected based on factors other than rigorous mechanistic evidence. Given recent advances in our understanding of interactions between biotics, the host, and the gut microbiome, we sought to determine whether a more rational, informed approach might now guide the more precise selection of a biotic for a specific indication. The panel addressed biotic modulation of the immune system, host metabolism, the enteric nervous system, human commensal microbes, and the gut-brain axis and developed five recommendations to increase the likelihood that biotic interventions will lead to meaningful clinical impacts. Interventions should: (1) strive to modulate or refine, rather than "boost," host metabolism and the immune system to achieve specific outcomes; (2) consider the human metabolome, in addition to the microbiome, as a readout and therapeutic target; (3) determine context-dependent responses to biotics in terms of spatial location within the gut, host genetics, environmental influences, and diet; (4) explore a wide range of microbial fermentation substrates that yield biologically active products in addition to prebiotic fibers; and (5) leverage new approach methods including ex vivo human tissue-based approaches, novel in vitro methods, and advanced computational tools including artificial intelligence to complement human studies. The roadmap proposed by this panel aims to accelerate the translation of biotic research into discoveries that will more readily impact clinical practice.PMID:42712126 | DOI:10.1080/19490976.2026.2728828

Adv Sci (Weinh). 2026 Sep 8:e77489. doi: 10.1002/advs.77489. Online ahead of print.ABSTRACTTumor and host interaction contributes to cancer cachexia, a systemic wasting syndrome characterized by tissue loss (adipose and skeletal muscle), anorexia, fatigue, and metabolic reprogramming. Nevertheless, the spatio-temporal molecular dynamics of multiple tissues during cancer cachexia development remain elusive. Here, we present a comprehensive overview of the biological alterations and metabolic reprogramming of cancer cachexia across two species, 25 organs, and 3230 samples, by integrating transcriptomic, proteomic, and metabolomic profiles spanning different cachectic stages and sexual dimorphism. Using this cancer cachexia atlas (CCAtlas), we identified dysregulated tissues of cancer cachexia, including skeletal muscle, liver, and blood. We revealed coordinated metabolic reprogramming across tissues, including dysregulated amino acid metabolism and one-carbon metabolism. Temporal profiling illustrated dynamic molecular signatures during cancer cachexia progression. The exacerbated inflammatory status in males potentially contributed to a more severe whole-body wasting phenotype. The liver-muscle crosstalk potentiated skeletal muscle atrophy through creatine deficiency via hepatic Gamt downregulation in the LLC model. Creatine supplementation and hepatic Gamt overexpression in the LLC model attenuated skeletal muscle wasting. Together, CCAtlas provides fundamental and systemic insights into multi-omic molecular dynamics and metabolic rewiring of cancer cachexia from the perspective of tumor and/or inter-organ crosstalk across species.PMID:42711909 | DOI:10.1002/advs.77489

Lett Appl Microbiol. 2026 Sep 9:ovag068. doi: 10.1093/lambio/ovag068. Online ahead of print.ABSTRACTHyperuricaemia is a common chronic metabolic disorder characterised by urate crystal deposition and systemic inflammation. Lactic acid bacteria have been demonstrated to exert probiotic effects against hyperuricaemia. This study investigated the probiotic effects and potential mechanisms of Lactiplantibacillus plantarum P10 in a murine hyperuricaemic model. The results showed that L. plantarum P10 significantly reduced serum uric acid levels, inhibited xanthine oxidase activity, and decreased the activity of hepatic function markers, including aspartate aminotransferase and alanine aminotransferase, as well as the levels of renal function markers, including creatinine and blood urea nitrogen. Notably, these functional improvements were accompanied by alleviated histopathological inflammatory lesions in the liver and kidney, together with reduced levels of the pro-inflammatory cytokines interleukin-1β and tumour necrosis factor-α. Further investigation revealed that L. plantarum P10 modulated renal expression of the urate transporters ABCG2 and GLUT9, promoting uric acid excretion. Moreover, multi-omics analyses indicated that L. plantarum P10 enriched the relative abundance of Lactobacillus johnsonii and Limosilactobacillus reuteri, ameliorated gut dysbiosis, and altered the histidine pathway. In conclusion, L. plantarum P10 alleviates urate overload-induced renal injury and inflammation by modulating gut microbiota and histidine metabolism, offering potent urate-lowering, anti-inflammatory, and renoprotective benefits for hyperuricaemia intervention.PMID:42711808 | DOI:10.1093/lambio/ovag068

J Anim Sci Biotechnol. 2026 Sep 9;17(1):177. doi: 10.1186/s40104-026-01490-z.ABSTRACTBACKGROUND: Microplastics are emerging environmental contaminants with male reproductive toxicity; however, their effects on ruminants and underlying mechanisms remain poorly understood.RESULTS: In this study, male Hu lambs were exposed to dietary polystyrene microplastics (PS-MPs) at 0, 75, and 150 mg/kg diet for 120 d, followed by a 180-d recovery period. PS-MPs exposure caused persistent testicular injury, characterized by disrupted seminiferous architecture and enhanced germ cell apoptosis. Single-cell transcriptomic analysis revealed impaired spermatogonial differentiation, accompanied by suppression of Nrf2-associated antioxidant responses. Metabolomic profiling further identified dysregulation of glutathione metabolism in both testis and plasma. Importantly, PS-MPs were not detected in testicular tissue, suggesting that detectable direct particle accumulation was unlikely to be the primary driver of toxicity. Instead, rumen analyses showed that PS-MPs altered microbial composition, notably reducing butyrate-producing bacteria, accompanied by sustained decreases in ruminal butyrate and circulating β-hydroxybutyrate (BHB). To investigate the potential involvement of rumen-derived butyrate in PS-MPs-induced testicular toxicity, sodium butyrate was supplemented to PS-MPs-exposed lambs. Dynamic analyses showed that ruminal butyrate recovered first, followed by circulating BHB, then systemic inflammation and oxidative status, and finally testicular damage was alleviated with restoration of Nrf2 signaling.CONCLUSIONS: These findings suggest that PS-MPs exposure disrupts spermatogenesis in sheep through rumen-derived butyrate alterations rather than detectable direct tissue accumulation. This study provides insight into microplastic-induced testicular toxicity and supports the rumen microbiota-metabolite axis as a potential mechanistic link underlying distal organ toxicity in ruminants.PMID:42711729 | DOI:10.1186/s40104-026-01490-z

Virulence. 2026 Dec;17(1):2721757. doi: 10.1080/21505594.2026.2721757. Epub 2026 Sep 8.ABSTRACTThe mosquito gut microbiota plays a pivotal role in regulating arbovirus transmission, yet the specific antiviral metabolites produced by native symbiotic bacteria and their underlying mechanisms remain poorly understood. In this study, we isolated a natural gut symbiotic bacterium, Serratia marcescens strain WZ1, from field-caught Aedes albopictus in Wenzhou, China, and demonstrated its potent ability to inhibit dengue virus (DENV) infection. Through integrated metabolomic analysis, we identified the red pigment prodigiosin (PG) as a functional antiviral metabolite secreted by this strain. PG treatment suppressed DENV infection in mosquito cells in a dose- and time-dependent manner and significantly reduced DENV2 RNA levels in adult Ae. albopictus midguts. Mechanistic investigations revealed that PG preferentially localizes to the endoplasmic reticulum (ER), where it induces ER stress and upregulates the chaperone protein GRP78. This process subsequently activates a complete autophagic flux, as evidenced by enhanced conversion of Atg8-I to Atg8-II, increased autophagosome formation, and elevated lysosomal activity. Crucially, we further demonstrated that PG facilitates the convergence of autophagosomes and lysosomes, culminating in the colocalization of DENV with lysosomal compartments and subsequent viral clearance. Both genetic knockdown of the autophagy gene Atg8 and pharmacological inhibition of ER stress substantially attenuated PG-mediated viral suppression, confirming the functional link between PG-induced ER stress, autophagy activation, and viral clearance. Our findings elucidate a novel mechanism by which a native mosquito gut symbiont metabolite restricts arboviral infection through activation of the host ER stress-autophagy pathway, providing a mechanistic basis and candidate leads for future transmission-blocking studies.PMID:42711671 | DOI:10.1080/21505594.2026.2721757

Int Microbiol. 2026 Sep 9. doi: 10.1007/s10123-026-00891-4. Online ahead of print.ABSTRACTBACKGROUND: Shen-Ling-Bai-Zhu-San (SLBZS) recorded in the Song Dynasty text "Tai Ping Hui Min He Ji Ju Fang," is traditionally used to "strengthen the spleen, eliminate dampness and stop diarrhea." making it a commonly used prescription for treating antibiotic-associated diarrhea (AAD). This study examined microbial and metabolite changes accompanying SLBZS treatment for AAD and analyzed their potential biological correlates.METHODS: Juvenile rats were randomly assigned to control, model, and SLBZS groups. An antibiotic cocktail was administered orally to induce AAD, followed by SLBZS decoction treatment. Body weight and fecal characteristics were monitored. Gut microbiota and fecal metabolites were analyzed using 16 S rDNA sequencing and widely targeted metabolomics, respectively, with correlation analysis performed on the data.RESULTS: SLBZS significantly reduced diarrhea incidence and fecal consistency scores in AAD rats. Antibiotic gavage induced gut microbiota dysbiosis and metabolic disturbances. The abundances of Muribaculaceae, Tannerellaceae, Parabacteroides, and Parabacteroides distasonis were favorably modulated by SLBZS. Twenty-nine common differential fecal metabolites exhibited favorable regulation, with 11 metabolites enriched in the ABC transporter pathway. Correlation analysis revealed that seven metabolites significantly correlated with Parabacteroides distasonis, five of which culstered in the ABC transporter pathway.CONCLUSIONS: SLBZS treatment for AAD was associated with altered Parabacteroides distasonis abundance and ABC transporter pathway changes. These factors likely represent key biological targets of SLBZS therapy.PMID:42711619 | DOI:10.1007/s10123-026-00891-4