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In vivo genome-wide CRISPR screens identify FOXR1 as a suppressor of CD8+ T cell antitumor immunity.

T cell dysfunction critically limits the efficacy of T cell-based immunotherapies in solid tumors, yet the intrinsic regulators of T cell dysfunction remain incompletely understood. Through an in vivo genome-wide CRISPR screen in tumor-infiltrating CD8+ T cells, we identified Forkhead Box R1 (FOXR1) as a potent transcriptional suppressor of CD8+ T cell effector functions. Genetic ablation of FOXR1 significantly enhanced cytokine production and cytotoxic capacity in both murine and human CD8+ T cells, whereas its overexpression impaired T cell activation and effector molecule expression. Mechanistically, multiomics integration of RNA-seq, CUT&Tag-seq, and ATAC-seq revealed that FOXR1 binds directly to promoter regions of key effector genes, including IL2, GZMB, and PRF1, and represses their expression. Importantly, FOXR1 deletion in human anti-CD19 CAR T cells improved their efficacy against solid tumors, demonstrating that FOXR1 is a checkpoint of T cell effector function and targeting FOXR1 is a promising strategy to enhance CAR T cell efficacy against solid tumors.

Animals

Feeding the disease: The impact of nutritional supplementation on Nosema (Vairimorpha) infection in honey bees (Apis mellifera).

Honey bees (Apis mellifera) experience variable colony losses across regions and years, with infectious diseases representing a key component of colony health challenges. Among the most prevalent pathogens are the microsporidian parasites Nosema apis and Nosema ceranae, whose impacts on host survival and transmission vary widely depending on context. While nutritional supplementation is commonly used to support honey bee health, its effects on Nosema infection outcomes remain unclear. Here, we experimentally tested whether dietary enrichment alters survival and infection intensity following exposure to a mixed Nosema inoculum. Newly emerged worker bees were challenged with Nosema spores and maintained on either a basic sucrose diet or the same diet supplemented with a commercial pollen substitute. Dietary enrichment significantly increased both mortality risk and infection intensity in Nosema-infected bees, while having no detectable effect on survival in uninfected controls. These results indicate that supplementation can, counter intuitively, exacerbate nosemosis by promoting parasite replication rather than enhancing host resistance. Our findings highlight the importance of distinguishing nutritional effects on host tolerance versus resistance, and caution that interventions intended to improve bee nutrition may inadvertently increase pathogen production and transmission potential under certain conditions.

Animals

Structural and physicochemical characterisation of branched dextrans produced by an active α-(1→2) branching sucrase from Apilactobacillus kunkeei PDER37.

Recently, branching sucrases encoded in the genomes of certain Lactic Acid Bacteria (LAB) strains have become novel enzymes to obtain branched α-glucans. In this study an active α-(1 → 2) branching sucrase from Apilactobacillus kunkeei PDER37 was expressed, characterised and distinct branched dextrans was obtained with reactions under different sucrose: dextran ratio. Structural characterisation by 1H and 13C NMR analysis demonstrated the branching of the dextran with (1 → 2)-linked α-d-glucose units with no alteration in the final structure depending on sucrose: dextran ratio (D0) but this ratio was effective for the determination of the molecular weights of the branched dextrans (D1, D2 and D3). FTIR analysis further supported the dextran structures and suggested the higher accumulation of the α-Glc units in the branched dextrans. Thermal characterisation of the branched dextrans obtained by TGA and DSC analysis suggested the increased hygroscopicity of the branching units. Both SEM and AFM analysis demonstrated more porous chain like structures in the branched dextrans. This study provides valuable information on the role of active α-(1 → 2) branching sucrase (BS37) for the production of branched dextrans with potential increased physicochemical status applicable for food and other industries.

Dextrans

Targeting TP53 in triple-negative breast cancer: Molecular pathogenesis, therapeutic implications, and emerging pharmacological strategies.

Triple-negative breast cancer (TNBC) remains a highly aggressive and therapeutically challenging subtype, defined by the absence of oestrogen, progesterone, and HER2 expression. Tumour Protein 53 (TP53) mutations represent the most frequent genetic alteration, occurring in over 80% of cases and driving tumour initiation, progression, and therapeutic resistance. Mutant p53 proteins not only lose canonical tumour-suppressive functions but also often acquire gain-of-function (GOF) oncogenic properties that promote metastasis, genomic instability, and resistance to mechanisms like ferroptosis. This review examines the biological role of TP53 in TNBC pathogenesis and evaluates emerging pharmacological strategies aimed at targeting these vulnerabilities. Key approaches include the pharmacological reactivation of mutant p53 using small molecules such as APR-246, COTI-2, and the mutation-specific reactivator rezatapopt (PC14586), which has shown significant clinical tumour reduction in Y220C-mutant patients. Other strategies involve targeted protein degradation, the exploitation of synthetic lethal interactions (e.g., Chk1 or Aurora kinase B inhibition), and the use of natural products like cryptolepine or piperine derivatives. Recent clinical evidence further highlights the potential of combining epigenetic agents like decitabine with chemotherapy in TP53-mutant populations. Integrating TP53 mutation status into biomarker-driven treatment paradigms is a pivotal step toward achieving precision oncology and improving clinical outcomes for patients with TNBC.

Precision oncology

L-glutamine supplementation improves porcine sperm quality and early embryo development during in vitro fertilization.

L-glutamine (Gln), as a key additive in porcine sperm capacitation medium and in vitro fertilization (IVF) systems, has been shown to significantly improve sperm motility and survival rates. However, its precise roles during porcine IVF and subsequent early embryonic development remain elusive. This study utilized an IVF model in pigs to investigate the effects of glutamine on sperm quality and embryonic development. We found that Gln supplementation during sperm treatment significantly improved sperm quality, as evidenced by reduced reactive oxygen species (ROS) production and early apoptosis, while enhancing calcium ion levels and endoplasmic reticulum activity. Supplementing glutamine during embryo culture reduced polyspermy rates, promoted zygotic genome activation (ZGA) and accumulation of 5-ethynyluridine (EU) and histone modifications (H3K4me3 and H3K27ac) at the two-cell and four-cell stages, increased blastocyst formation rates and total cell numbers, while simultaneously reducing DNA damage and early apoptosis during the blastocyst stage. In summary, these findings demonstrate that Gln enhances porcine IVF outcomes by improving sperm quality, reducing polyspermy, and facilitating early embryonic development, thereby providing a basis for optimizing culture systems.

Animals

Effects of apple phenolics on the human metabolome: modulation of key metabolic pathways.

Apples are widely recognized for their potential health benefits, partly attributed to their phenolic compounds. However, their impact on human metabolism remains incompletely understood. This study investigated metabolic effects of apple-derived phenolic compounds using untargeted metabolomics approach across multiple biofluids. In a crossover intervention study, 30 healthy men consumed a phenolic-rich apple juice or a placebo for two weeks. Blood, urine and saliva samples were collected before and after each intervention and analyzed by direct infusion ultra-high resolution mass spectrometry. Consumption of apple phenolic compounds resulted in significant alterations of the human metabolome, including increased levels of phenolic-derived degradation products and microbial-associated metabolites across all biofluids. Pathway enrichment analysis revealed pronounced effects on phenylalanine and tyrosine metabolism, as well as linoleic and arachidonic acid metabolism, Overall, these findings demonstrate that apple phenolic compounds induce measurable, microbiota-associated and systemic metabolic changes, providing new insights into their metabolic fate and biological relevance.

Humans

Mitochondrial translocation of DNMT3L suppresses oxidative phosphorylation and restrains megakaryopoiesis.

DNMT3L, a catalytically inactive member of the DNA methyltransferase family, is identified here as a negative regulator of megakaryopoiesis. In K562 cells undergoing PMA-induced megakaryocytic differentiation, DNMT3L protein levels declined progressively, and shRNA-mediated depletion enhanced differentiation, whereas overexpression attenuated it. Consistent with these findings, Dnmt3l-knockout mice exhibited elevated peripheral blood platelet counts and expanded bone marrow megakaryocytes. Mechanistically, megakaryocytic differentiation triggered rapid mitochondrial translocation of DNMT3L within 6 h; mitochondrial DNMT3L suppressed oxidative phosphorylation (OXPHOS) capacity and ATP production and downregulated mitochondrial-encoded genes spanning Complex I, III, IV, and ATP synthase, without altering mitochondrial DNA copy number. This metabolic suppression was mediated through compartment-specific remodeling of DNMT3L-containing protein complexes: upon differentiation, DNMT3L selectively dissociated from DNMT1 and DNMT3B in mitochondria, relieving the repressive constraint on OXPHOS, whereas in the nucleus DNMT3L remained associated with DNMT3A, which concomitantly accumulated during differentiation. These findings reveal a previously unrecognized mechanism by which a catalytically inactive epigenetic co-regulator spatially redistributes to coordinate mitochondrial metabolic output with nuclear epigenetic control, thereby facilitating terminal megakaryocytic maturation.

Animals

Impaired adaptation to smoke-derived phenolic compounds in Listeria monocytogenes CC204 from smoked salmon and trout.

Listeria monocytogenes is a major foodborne pathogen in ready-to-eat smoked fish products. This study evaluated whether clonal complex affiliation contributes to variability in growth responses to stresses representative of smoked salmon and trout processing. Ten strains were studied, including strains from CC121, CC26 and CC204, the three major clonal complexes reported in the French smoked salmon and trout sectors, together with the EGDe reference strain. Strains were exposed to salt, cold, smoke-derived phenolic compounds and combined stress conditions. Growth responses were compared with whole-genome-based phylogeny, and the impaired phenotype observed under phenolic exposure was further investigated using viable counts, live/dead microscopy and comparative genomics. Growth profiles were partly structured by clonal complex, with strains from the same clonal complex showing similar behaviour across stress conditions. Salt and cold reduced growth globally, while smoke-derived phenolic compounds were the most discriminating conditions. CC204 strains showed markedly lower growth rates under phenolic exposure than CC121, CC26 and EGDe. This phenotype was not associated with loss of cultivability or significant loss of membrane integrity. Comparative genomics did not identify a clear gene-content determinant explaining the CC204 phenotype. These results suggest that CC204 has an impaired adaptive response to smoke-derived compounds, likely involving regulatory or physiological mechanisms.

Listeria monocytogenes

Watershed-scale risk assessment of cadmium contamination in Chinese cropland soils: Dual pathways of irrigation input and flood-driven transport.

Irrigation and flood events serve as critical pathways for the transport of cadmium (Cd) from industrial sources into cropland soils at the watershed scale, constituting a major driver of widespread Cd contamination in China's cropland soil. This study evaluated the risk of Cd contamination in cropland soils across China's nine major river basins at the watershed scale, focusing on the contributions of irrigation and flood events, and conducted a sensitivity analysis of key risk factors. The assessment was conducted within a framework that considered factors including hazard, exposure, and vulnerability. The results revealed that numerous watersheds in southeastern China are exposed to dual pressures of Cd contamination risks in cropland soils, driven by both irrigation practices and flood events. Watersheds categorized as High-High, High-Moderate, or Moderate-High risk, reflecting combined Cd contamination risks from irrigation and flood, are vital to China's grain production, contributing 67.1 % of the national cropland area and 66.4 % of the grain yield. The study suggests localized strategies for managing cropland soils Cd contamination risks from irrigation and flood at the watershed scale in China, alongside strengthened cross-regional collaboration in southeastern China.

Cadmium

Functional characterization of the MdFLZ2 gene in drought and salt stress tolerance in apple.

Drought and salt stress are significant environmental limitations that severely constrain plant growth and productivity, therefore, enhancing stress tolerance is a key goal in crop improvement. The plant-specific FCS-like zinc finger (FLZ) proteins have been identified as important regulators of stress adaptation. In this study, we conducted a genome-wide characterization of the FLZ gene family in apple and functionally characterized MdFLZ2. qRT-PCR analysis revealed that MdFLZ2 was differentially expressed across various tissues and transcriptionally induced by both drought and salt stress. Subcellular localization assays demonstrated that the MdFLZ2 protein is localized to both the nucleus and the cytoplasm. The overexpression of MdFLZ2 in apple calli, Arabidopsis and tomato conferred increased resistance to drought and salt stress. In addition, yeast two-hybrid (Y2H) assays confirmed that MdFLZ2 interacted with MdSnRK1.1, and similar interactions were also detected between other MdFLZ family members and MdSnRK1.1. Collectively, our findings suggest MdFLZ2 as a positive regulator of drought and salt tolerance and highlight its potential to serve as a genetic resource for abiotic stress improvement.

Malus

Free polyphenols and multi-omics traits underlying antioxidant variation across Paeonia lactiflora leaf cultivars.

Leaves of Paeonia lactiflora are underutilized by-products with potential as natural antioxidant sources. In this study, 18 cultivars were evaluated for phytochemical composition and in vitro antioxidant capacity. Total phenolic content correlated strongly with DPPH and ABTS activities, and the comprehensive antioxidant index identified 'Coral Charm' and 'Hangshao' as representative high- and low-antioxidant cultivars, respectively. Untargeted metabolomics detected 2677 metabolites and identified 908 differential metabolites between the two cultivars. Targeted phenolic profiling quantified 27 compounds, among which 11 differed significantly between the two cultivars. Catechin and epicatechin were enriched in 'Coral Charm', with contents of 6.62 and 0.397 ng/mg, respectively, compared with 0.012 and 0.002 ng/mg in 'Hangshao'. (+)-Dihydroquercetin was also more abundant in 'Coral Charm', while caffeic acid showed an upward trend. Proteomic analysis identified 423 differentially expressed proteins, mainly associated with secondary metabolite biosynthesis, redox homeostasis, and central carbon metabolism. Integrated analysis identified pyruvate metabolism as the only pathway significantly enriched in both metabolomic and proteomic datasets. Molecular docking predicted favorable binding between representative phenolics and selected proteins. These findings link cultivar-dependent antioxidant variation in peony leaves with free-phenolic accumulation and pathway-level metabolic differences, supporting the selection and utilization of antioxidant-rich peony leaf resources.

Antioxidants

Bergamottin, a bioactive component of bergamot: dual inhibition of Japanese encephalitis virus internalization and genome replication.

Japanese encephalitis virus (JEV) is associated with high mortality and severe neurological sequelae, and existing prevention and control strategies remain insufficient. Therefore, the development of novel antiviral agents is of critical public health importance. This study systematically evaluated the antiviral activity and underlying mechanism of bergamottin, a natural product. Bergamottin exhibited significant dose-dependent inhibitory effects against JEV in multiple cell lines, including BHK-21, HuH-7, and Vero cells, demonstrating potent antiviral efficacy. Mechanistic investigations revealed that bergamottin primarily targeted the internalization and replication stages of the JEV life cycle, thereby effectively suppressing viral proliferation. Additionally, adaptive mutation screening indicated that the D389G mutation in envelope protein E confers drug resistance by potentially changing E protein conformation or reducing endocytic efficiency. In vivo experiment, bergamottin significantly reduced viral loads in mouse brain tissue and effectively improved the survival rate of infected mice. Our findings indicated that bergamottin exerted antiviral activity by dual targeting of key steps in the viral life cycle, making it a highly promising candidate for anti-JEV therapy. Further exploration of the antiviral properties of bergamottin is expected to facilitate its clinical development as a treatment for JEV infection.

Animals

Post-exercise rehydration: a randomized cross-over trial comparing a 100% fruit juice, a glucose-based sports drink, and water.

BACKGROUND: Previous studies indicate that sports drinks may improve rehydration, compared to water, an effect likely achieved by manufacturing sports drinks to contain carbohydrates and sodium. However, there is a growing preference for natural products and a "food first" approach to sports nutrition. Fruit juices naturally contain similar concentrations of carbohydrates to sports drinks, but fruit juices may produce a more stable blood glucose profile. Fruit juices also naturally contain electrolytes, particularly potassium, but their potential as effective rehydration alternatives to sports drinks, which have higher sodium concentrations, is not well understood. This study compared the rehydration efficacy and glucose responses following consumption of a 100% fruit juice (Raw Hydrate&#xae;; FRU), a glucose-based sports drink (SPO), and water (WAT) after exercise-induced hypohydration. Importantly, rehydration beverages were matched for water volume, rather than total volume, to ensure that any potential differences in water balance were not due to unequal water volumes between trials, a limitation affecting previous rehydration research. METHODS: After familiarization, 17 adults (age: 28&#x2009;&#xb1;&#x2009;8&#x2009; years; BMI: 23.8&#x2009;&#xb1;&#x2009;2.9&#x2009;kg/m2) completed three trials in a randomized cross-over design. The participants cycled in the heat (~35&#xb0;C) to induce ~2% body mass loss (BML), then rehydrated over a 1&#x2009;h period in a laboratory (~21&#xb0;C) with a water volume equivalent to 150% of BML from either FRU, SPO, or WAT. This was followed by an additional 4&#x2009;h of seated rest (5&#x2009;h rehydration period), when blood glucose was measured (0, 0.25, 0.5, 0.75, 1, 1.5, and 2&#x2009;h after beverage consumption), and all urine produced was collected. RESULTS: During the 5&#x2009;h rehydration period, there was no effect of trial on total urine volume (FRU: 1266&#x2009;&#xb1;&#x2009;403&#x2009;mL, SPO: 1338&#x2009;&#xb1;&#x2009;361&#x2009;mL, WAT: 1394&#x2009;&#xb1;&#x2009;360&#x2009;mL; P&#x2009;=&#x2009;0.156) or water retention (FRU: 42&#x2009;&#xb1;&#x2009;12%, SPO: 37&#x2009;&#xb1;&#x2009;10%, WAT: 35&#x2009;&#xb1;&#x2009;11%; P&#x2009;=&#x2009;0.059). The blood glucose area under the curve differed by trial (P&#x2009;<&#x2009;0.001), with all beverages significantly different from each other (FRU: 10.12&#x2009;&#xb1;&#x2009;0.72 mmol/L/2h, SPO: 12.48&#x2009;&#xb1;&#x2009;1.34 mmol/L/2h, WAT: 7.90&#x2009;&#xb1;&#x2009;0.47 mmol/L/2h; P&#x2009;<&#x2009;0.003). CONCLUSION: Rehydration efficacy was similar between all beverages, but each elicited a distinct glycemic response. For sports drink consumers seeking a natural alternative or implementing a "food first" nutritional strategy, switching to a 100% fruit juice will not compromise rehydration effectiveness, but may elicit a lower blood glucose response. Although, it should be noted that an additional three participants were withdrawn from the study because of gastrointestinal issues after consuming the 100% fruit juice. This was likely a product of the present study's design, where a large volume of 100% fruit juice (average ~2,300 mL) was consumed in a short period of time (1&#x2009;h). Whilst this is a commonly used study design to robustly assess the rehydration efficacy of different beverages, future studies should distribute fluid intake over a longer duration, in order to improve ecological validity and reduce the risk of gastrointestinal issues.

Humans

Chemical and sensory profiling of fermented, washed, and artificially flavored coffee beans: Insights into flavour quality, authenticity, and food safety implications.

This study establishes an integrated framework combining chemical profiling, sensory analysis, and molecular mechanism evaluation to compare flavour quality and authenticity among fermented, washed, and artificially flavored coffees. GC&#xa0;&#xd7;&#xa0;GC-TOF-MS and UHPLC-HRMS showed that fermented samples had markedly higher ester and aromatic alcohol levels (total esters 74.5&#xa0;&#xb1;&#xa0;7.8&#xa0;mg&#xa0;kg-1; phenylethanol 27.5&#xa0;&#xb1;&#xa0;3.2&#xa0;mg&#xa0;kg-1, p&#xa0;<&#xa0;0.01), enhancing fruity-floral notes. Washed coffees contained the highest organic acid concentrations (45.2&#xa0;&#xb1;&#xa0;3.8&#xa0;mg&#xa0;kg-1, p&#xa0;<&#xa0;0.01), supporting brightness and umami. Artificially flavored coffees exhibited elevated exogenous aromatics (vanillin 21.5&#xa0;&#xb1;&#xa0;3.1&#xa0;mg&#xa0;kg-1) but significantly fewer Maillard products (p&#xa0;<&#xa0;0.05) and reduced flavour retention (55% after 14 days). Molecular docking revealed higher theoretical binding affinities for naturally generated compounds, suggesting a potential molecular basis for their greater sensory persistence. The framework supports constructing coffee quality fingerprints and verifying flavour authenticity.

Flavoring Agents

Formation of environmental persistent free radicals in soil of ammunition demolition site: Roles of 2,4,6-trinitrotoluene and heavy metals.

Environmental Persistent Free Radicals (EPFRs) are a particular type of contaminant present in soil. This study investigated the formation process, environmental behavior, and main influencing variables of EPFRs in soils contaminated with heavy metals and 2,4,6-trinitrotoluene (TNT) from an ammunition demolition site. The results showed that the concentration of total organic carbon (TOC) in the soil was negatively correlated with EPFRs (r = -0.29). In contrast, the content of TNT and copper was significantly positively correlated with EPFRs (r = 0.90 and 0.78, respectively), indicating that TNT acts as a precursor macromolecule in the formation of EPFRs in this type of contaminated soil. Transition metal Cu may be an essential carrier in EPFR production. In order to explore the possible formation mechanism of EPFRs, a simulation experiment was carried out under different temperature and light conditions. The results showed that the photolysis process of TNT was impacted by external energy sources such as heat and light. TNT was firstly adsorbed onto the surface of a transition metal (Cu), and then EPFRs were formed through further electron transfer. This is the first study to detect significant levels of EPFRs in the soil at ammunition demolition sites.

Trinitrotoluene

MARK1 suppresses infectious bursal disease virus replication via phosphorylating VP3.

Infectious bursal disease virus (IBDV) of the Birnaviridae family is a non-envelope, double-stranded RNA virus that encodes a VP3 protein with multiple functions, which controls viral genome replication, IFN-&#x3b2; production, and virus traffic in infected cells. Posttranslational modifications (PTMs), such as ubiquitination, of VP3 have been demonstrated for affecting its function and stability. To clarify the mechanism by which VP3 is regulated in IBDV infected cells, we focused on the phosphorylation of VP3. Mass spectrometry analysis identified that microtubule-affinity regulating kinases 1 (MARK1) was a kinase interacting protein of VP3. Inhibitory function of MARK1 in affecting viral replication was validated. We describe the phosphorylation event at the serine 130 (S130) and serine 163 (S163) residues of VP3 mediated by MARK1 via mass spectrometry analysis. Alanine replacement of the phosphorylation sites in VP3 significantly enhanced its RNA-binding activity. Additionally, the mutation of two serine residues led to remarkably improved in its polymerase-enhancing function. We then incorporated the two mutations to rescue recombinant IBDV. Viral growth curve analysis revealed that replication of mutant IBDV was significantly enhanced relative to wild type (WT) virus. In conclusion, we found that VP3 functions are specifically regulated by MARK1 mediated phosphorylation at S130 and S163 and that this regulation suppresses IBDV replication ultimately.

Infectious bursal disease virus

Unconfined compressive strength prediction for the ordinary Portland cement-steel slag-silica fume ternary system based on response surface methodology.

This research was undertaken to address environmental concerns associated with industrial solid waste and to reduce cement consumption in geotechnical engineering. It specifically investigates the feasibility of using steel slag (SS) and silica fume (SF) as partial substitutes for ordinary Portland cement (OPC) in soil stabilization. The effects of SS, SF, OPC, and initial moisture content on the unconfined compressive strength (UCS) of stabilized soil were investigated through single-factor experiments and response surface methodology (RSM). The results show that SS and SF can synergistically enhance the strength of stabilized soil, although their interaction effect was not statistically significant within the investigated ranges. Compared with soil stabilized solely with OPC, the addition of 18 % SS and 10 % SF reduced OPC consumption by 3 % without compromising strength. Microstructural and compositional analyses further revealed that SS mainly supplied calcium- and silica-bearing components, while SF provided highly reactive silica and micro-filling effects, jointly promoting hydration reactions and improving the compactness of the stabilized soil matrix. As a result, more hydration products were formed in the OPC/SS/SF-stabilized soil than in the OPC-stabilized soil, which contributed to pore filling and strength enhancement. This study provides useful guidance for the sustainable utilization of industrial solid waste and the low-carbon development of soil stabilization materials.

Construction Materials

Gut microbiota and metabolic alterations in participants with flatulence identify Faecalibacterium prausnitzii as a key microbial target for clinical intervention.

Flatulence is closely associated with gut dysbiosis, yet the characteristic microbial signatures, metabolic alterations, and actionable intervention targets remain unclear. This limited mechanistic understanding has hindered the development of precise microbiota-based strategies for managing flatulence. Here, we found that participants with flatulence exhibited marked shifts in gut microbial functions and fecal metabolic profiles compared with healthy controls, characterized by enhanced abnormal fermentation, enrichment of oxidative stress-related functions, elevated low-grade inflammatory signatures, and reduced anti-inflammatory and mucosal-protective metabolic features. Faecalibacterium prausnitzii was significantly negatively associated with the high-gas-producing phenotype. In vitro replenishment experiments further validated the role of F. prausnitzii in reducing gas production, promoting butyrate generation, and remodeling butyrate-associated microbial communities. Based on microbial interaction analysis, we identified Bifidobacterium longum CCFM1319 as a candidate strain for targeting F. prausnitzii. In a double-blind, randomized, placebo-controlled clinical trial, supplementation with B. longum CCFM1319 significantly increased intestinal F. prausnitzii abundance and improved flatulence-related symptoms. Collectively, these findings reveal the microbiota and metabolic dysbiosis underlying flatulence, highlight the key regulatory role of F. prausnitzii, and lays the foundation for targeted microbiota-based intervention strategies for flatulence.

Humans