Food BiosciencePub Date : 2025-06-13DOI: 10.1016/j.fbio.2025.107052
Mingwei Ma , Zhenhuan He , Xiaonan Yang , Yinghao He , Leiqian Huang , Chang Liu , Jing Mu , Lei Lei , Gonghe Li , Wende Wu , Min Zheng , Mingxian Shi , Jiafeng Ding
{"title":"A novel phage LTH02 for shiga toxin-producing Escherichia coli: Biological characteristics, whole genomic analysis, and preliminary application in food","authors":"Mingwei Ma , Zhenhuan He , Xiaonan Yang , Yinghao He , Leiqian Huang , Chang Liu , Jing Mu , Lei Lei , Gonghe Li , Wende Wu , Min Zheng , Mingxian Shi , Jiafeng Ding","doi":"10.1016/j.fbio.2025.107052","DOIUrl":"10.1016/j.fbio.2025.107052","url":null,"abstract":"<div><div>Shiga toxin-producing <em>E. coli</em> (STEC) is a kind of crucial foodborne pathogen. At present, numerous studies have shown that phage can effectively eliminate foodborne pathogens as a novel antibacterial agent without affecting the nutrition and flavor of fresh food. This research aimed to investigate the biological characteristics and potential application in food products of a novel phage LTH02 for STEC. Host range determination based on single-layer plates, stability assay based on double-layer plates, lytic activity test, and whole genome analysis were utilized to evaluate the biological characteristics of phage LTH02. The results showed that phage LTH02 had a lysis rate of 85.00 % and displayed stability across pH levels ranging from 5 to 7 and temperatures between 4 °C and 60 °C. Besides, phage LTH02 inhibited STEC proliferation in a period of 30 h at an MOI of 10<sup>2</sup> and lacked antibiotic genes or virulence factors. The sterilization effect on the STEC-contaminated food was evaluated through bacterial counting. Phage LTH02 exhibited an effective elimination in the STEC-contaminated milk, raw beef, and lettuce at temperatures of 4 °C and 24 °C. The effect of phage LTH02 on food quality was evaluated through the measurement of pH, lactose content, TVB-N content, color difference, and sensory score of food. The results showed that phage LTH02 prevented the reduction of food quality caused by STEC. In conclusion, the phage LTH02 may serve as a potential antibacterial agent for controlling STEC in the food industry to enhance food safety and quality.</div></div>","PeriodicalId":12409,"journal":{"name":"Food Bioscience","volume":"71 ","pages":"Article 107052"},"PeriodicalIF":4.8,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144366692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Food BiosciencePub Date : 2025-06-13DOI: 10.1016/j.fbio.2025.107061
Ruhi Walia , Saumya Ray Chaudhuri , Priyankar Dey
{"title":"Reciprocal interaction between gut microbiota and aloe-emodin results in altered microbiome composition and metabolism of aloe-emodin","authors":"Ruhi Walia , Saumya Ray Chaudhuri , Priyankar Dey","doi":"10.1016/j.fbio.2025.107061","DOIUrl":"10.1016/j.fbio.2025.107061","url":null,"abstract":"<div><div><em>Aloe vera</em> is utilized as a functional food due to its health-beneficial effects, including facilitating digestion, enhancing the immune response, and providing antioxidant benefits. This work examines the bidirectional interaction between the gut microbiota and aloe-emodin, a key anthraquinone in <em>A. vera</em>, to understand its microbial metabolism and its impact on the gut microbiota using an anaerobic fecal slurry model. The findings indicated that gut microbiota metabolized aloe-emodin more effectively than individual probiotic species; however, its breakdown was delayed within the whole-leaf matrix. Aloe-emodin enhanced the proliferation of probiotic spp., lowered the Firmicutes-to-Bacteroidetes ratio, and augmented the abundance of <em>Ruminococcus</em> and <em>Oscillospira</em>. Functional investigation revealed a reduction of microbial lipopolysaccharide biosynthesis and energy-harvesting pathways under the influence of aloe-emodin. The whole-leaf matrix exhibited enhanced prebiotic benefits compared to aloe-emodin alone. These findings underscore the dual function of aloe-emodin as a microbiota-modulated phytochemical and a regulator of gut microbial ecology, with the potential for enhancing aloe-based therapeutics for metabolic health.</div></div>","PeriodicalId":12409,"journal":{"name":"Food Bioscience","volume":"70 ","pages":"Article 107061"},"PeriodicalIF":4.8,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144279492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Food BiosciencePub Date : 2025-06-13DOI: 10.1016/j.fbio.2025.107063
Binbin Ouyang , Zhaolin Huang , Chengfei Wang , Yurong Sun , Junmei Ding , Wei Xu , Wanmeng Mu
{"title":"Identification of a novel DON dehydrogenase and computational insights into the decisive role of cofactor affinity in DON detoxification","authors":"Binbin Ouyang , Zhaolin Huang , Chengfei Wang , Yurong Sun , Junmei Ding , Wei Xu , Wanmeng Mu","doi":"10.1016/j.fbio.2025.107063","DOIUrl":"10.1016/j.fbio.2025.107063","url":null,"abstract":"<div><div>Deoxynivalenol (DON) is a pervasive mycotoxin contaminating cereal crops, thereby posing significant risks to both human and animal health. A novel DON dehydrogenase, <em>Kv</em>DDH, was identified as an efficient catalyst for degrading DON. The enzyme exhibited optimal activity at 35 °C and pH 6.0, in the presence of preferred cofactor phenazine methosulfate (PMS). Computational approaches integrated AI-driven structural modeling, molecular docking, density functional theory (DFT) calculations, and molecular dynamics (MD) simulation to reveal the affinity between enzyme and cofactors. DFT-based molecular surface electrostatic potential analysis revealed that the nucleophilic sites of PMS, 2,6-dichlorophenolindophenol (DCPIP), and pyrroloquinoline quinone (PQQ) are strategically positioned to accept protons, thereby facilitating protonation. Notably, MD simulations demonstrated that the proton-accepting group of PMS maintains the shortest average distance (5.88 Å) to the catalytic residue Asp306 in <em>Kv</em>DDH, accompanied by the lowest binding free energy (ΔG<sub>bind</sub> = −28.67 kcal/mol) among the cofactors tested. Furthermore, degradation product analysis confirmed the conversion of DON to 3-keto-DON, supporting a catalytic mechanism that involves cyclic regeneration of PMS and DCPIP. Asp306 appears to mediate proton transfer from the C3-hydroxyl group of DON to the cofactors, thereby promoting electron transfer and cofactor regeneration during dehydrogenation. These findings underscore the utility of computational strategies for accurately predicting cofactor-DON dehydrogenase interactions.</div></div>","PeriodicalId":12409,"journal":{"name":"Food Bioscience","volume":"71 ","pages":"Article 107063"},"PeriodicalIF":4.8,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144296915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comparative quality assessment of plant-based kefir as a vegan alternative to traditional kefir","authors":"Hacer Meral-Aktaș , Burcu Bazu-Çırpıcı , Haktan Aktaș , Hafsa Kadi̇roğlu , Bülent Çeti̇n","doi":"10.1016/j.fbio.2025.107062","DOIUrl":"10.1016/j.fbio.2025.107062","url":null,"abstract":"<div><div>Plant-based milk is emerging as a promising alternative for vegan and vegetarian diets and for people who are allergic to animal products. In this study, kefir was produced using hazelnut, walnut, and cashew milk, and fermented with a combination of <em>Bifidobacterium longum</em> (human origin) and selected autochthonous microbial strains with probiotic potential found in traditional kefir. Significant variation was identified in the physicochemical, microbiological and sensory analyses of kefir produced with plant-based milk and cow milk kefir as a control. In particular, phenolic compound and total phenolic contents were found to be greater in plant-based kefir than in cow milk kefir. Notably, walnut kefir exhibited the highest total phenolic content at 843 mg GAE/L, compared to 83 mg GAE/L in cow milk kefir, highlighting a significant increase in antioxidant potential. On the other hand, the sensory properties of cow milk kefir were rated higher than those of kefir made with plant-based milk. These findings suggest that plant-based kefir can serve as a vegan beverage alternative, although further development is needed to improve flavour acceptability.</div></div>","PeriodicalId":12409,"journal":{"name":"Food Bioscience","volume":"70 ","pages":"Article 107062"},"PeriodicalIF":4.8,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144289088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"6,7-Dimethoxy-3H-Quinazolin-4-One as a dual-function inhibitor of polyphenol oxidase and bacteria: biological evaluation, mode of action, and anti-browning studies","authors":"Xiu-Zhen Li , Jin-Rui Qiao , Yi-Rui Wu, Dong-Yan Zhou, Yu-Dan Shi, Shu-Meng Zhu, Qiu-Han Bai, Xiao-Lei Xia, Wei-Ming Chai","doi":"10.1016/j.fbio.2025.107056","DOIUrl":"10.1016/j.fbio.2025.107056","url":null,"abstract":"<div><div>This research investigated the inhibitory effect and mechanism of 6,7-dimethoxy-3H-quinazolin-4-one (DMQ) on polyphenol oxidase (PPO) and bacteria (<em>Escherichia coli</em> and <em>Staphylococcus aureus</em>), as well as its anti-browning properties on fresh-cut apples. The findings demonstrated that DMQ potently inhibited PPO activity with an <em>IC</em><sub><em>50</em></sub> of 98 ± 3 μmol L<sup>−1</sup>. Subsequently, the inhibitory mechanism of DMQ against PPO was elucidated through enzyme kinetics, fluorescence analysis, as well as computer molecular simulation. The results revealed that the interaction between DMQ and PPO led to structural elongation and relaxation of the enzyme, and influenced the microenvironment of amino acid residues at the binding region. These changes modified secondary structure and molecular conformation of PPO, ultimately resulting in the reduction of catalytic activity. Antibacterial experiments demonstrated that DMQ exhibited remarkable antibacterial properties by enhancing cell membrane permeability in <em>E</em>. <em>coli</em> and <em>S</em>. <em>aureus</em>, contributing to cellular contents leakage and bacterial cell death. Furthermore, DMQ delayed the enzymatic browning of fresh-cut apples by controlling phenolic metabolism. In particular, it was confirmed by cytotoxicity and stability tests that DMQ was safe at experimental concentrations and had good thermal stability and photostability. These discoveries offered a theoretical framework for the potential application of DMQ in food preservation.</div></div>","PeriodicalId":12409,"journal":{"name":"Food Bioscience","volume":"71 ","pages":"Article 107056"},"PeriodicalIF":4.8,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144296911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Fungi diversity and volatile in spontaneously fermented Cabernet Sauvignon wines: Insights into four sub-regions Penglai's Terroir","authors":"Xue Zhang , Xixi Zhao , Yue Gao , Xiaomin Zhong , Yanying Liang , Xuedong Shao , Yi Qin , Yanlin Liu","doi":"10.1016/j.fbio.2025.107049","DOIUrl":"10.1016/j.fbio.2025.107049","url":null,"abstract":"<div><div>Numerous studies have demonstrated a link between wine characterization and the regional microbial community in a large geographical region, but few have addressed the composition of microbial communities within smaller geographical regions and their impact on wine aroma. This study aimed to investigate differences in fungal communities during the fermentation of winemaking grapes in sub-regions within 30 km, as well as the terroir characteristics of regional wines. High-throughput sequencing identified <em>Colletotrichum</em> and <em>Alternaria</em> as the predominant fungi in the grape mash, with substantial microbial composition differences among sub-regions. During fermentation, <em>Saccharomyces</em> and <em>Hanseniaspora</em> emerged as key contributors, influencing alcoholic fermentation and preserving vineyard-specific characteristics. VPA results highlighted that fermentation substrates, organic acids, and fermentation products jointly propel the microbial community dynamics in Cabernet Sauvignon fermentation, achieving an explanation degree of 93.70–98.00 %. A total of 64 volatile compounds were identified across the wines, with ethyl acetate, 1-propanol, 2-methyl-1-propanol, 3-methyl-1-butanol acetate, 2-hydroxy-propanoic acid ethyl ester, 2-methyl-propanoic acid, phenylethyl alcohol showing significant inter-regional differences. Based on OAV values and distribution frequencies, 11 volatile compounds were determined as characteristic aroma compounds of the Penglai region, aligning with the outcomes of sensory evaluation. The relationship between fungal flora diversity and wine chemistry indicated that the predominant species during fermentation had a significant impact on the volatile composition of wine. This research enhanced our comprehension of the distinctive terroir flavors in Penglai regional wines, facilitating the further production of high-quality wines with local characteristics.</div></div>","PeriodicalId":12409,"journal":{"name":"Food Bioscience","volume":"71 ","pages":"Article 107049"},"PeriodicalIF":4.8,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144322704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Food BiosciencePub Date : 2025-06-13DOI: 10.1016/j.fbio.2025.107070
Ling Kang , Hailing Zhang , Yuting Fan , Jiang Yi
{"title":"Formation, characterization and delivery of quercetin-loaded α-lactalbumin fibril-based hydrogels through metal ions","authors":"Ling Kang , Hailing Zhang , Yuting Fan , Jiang Yi","doi":"10.1016/j.fbio.2025.107070","DOIUrl":"10.1016/j.fbio.2025.107070","url":null,"abstract":"<div><div>The purpose was to apply metal ions to induce the formation of α-lactalbumin fibril-based hydrogel to create a versatile nano-carrier for effective quercetin encapsulation and delivery. Quercetin could be successfully embedded into the hydrogel primarily through hydrogen bonding and hydrophobic interaction, as demonstrated by FTIR and XRD. Quercetin encapsulation effectiveness in α-lactalbumin fibril-based hydrogel via metal ions was up to 91.82 %, 7.41-fold higher than that with α-lactalbumin directly. Rheological results revealed elasticity was the dominant behavior of these hydrogels and quercetin addition could lead to a slight decrease of both G′ and G″, presumably due to the formation of soluble macroparticle aggregates and insoluble aggregates caused by polyphenol like quercetin. Quercetin bioaccessibility was increased to 32.62 % by 2.82-fold with this hydrogel. Additionally, the hydrogel demonstrated strong UV stability, antioxidant activity, and water retention. This research could provide practical and theoretical support to widen the development of new α-lactalbumin-derived food products.</div></div>","PeriodicalId":12409,"journal":{"name":"Food Bioscience","volume":"70 ","pages":"Article 107070"},"PeriodicalIF":4.8,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144289087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Food BiosciencePub Date : 2025-06-13DOI: 10.1016/j.fbio.2025.107050
Ying Ju , Liling Huang , Hailing Luo , Yongcai Huang , Xianya Huang , Ge Chen , Jie Gui , Shengli Lin , Xuzhou Liu , Liu Yang
{"title":"Passion fruit peel pectin improves glucose and lipid metabolism in high-fat diet-induced obesity through gut microbiota and insulin sensitivity regulation","authors":"Ying Ju , Liling Huang , Hailing Luo , Yongcai Huang , Xianya Huang , Ge Chen , Jie Gui , Shengli Lin , Xuzhou Liu , Liu Yang","doi":"10.1016/j.fbio.2025.107050","DOIUrl":"10.1016/j.fbio.2025.107050","url":null,"abstract":"<div><div>This study investigated the effects of passion fruit peel pectin (PFP) on glucose and lipid metabolism in mice fed a high-fat diet (HFD). Fifty mice were divided into five groups: (1) normal diet (ND), (2) HFD, (3) HFD with orlistat (20 mg/kg/day, positive control, PC-HFD), (4) HFD with 300 mg/kg/day PFP (PFP1), and (5) HFD with 600 mg/kg/day PFP (PFP2) for 8 weeks. Compared to HFD, both PFP1 and PFP2 groups exhibited significant reductions in body weight (−3.9 % and −4.4 %), serum glucose (−17.6 % and −20.4 %), and hepatic lipid accumulation (−68.6 % and −65.2 % in oil red O-stained area). 16S rRNA analysis showed that PFP increased SCFA-producing gut bacteria. Tax4Fun2 analysis predicted enrichment of microbial functional potential related to the host insulin resistance pathway in PFP-treated mice. Fecal metabolomics and SCFA analyses revealed increased levels of pyruvic acid, triglycerides, and acetic acid in feces. Liver transcriptomics showed enrichment of 7 genes in the insulin resistance pathway. Integrated analyses of 16S rRNA and multi-omics data suggested associations between PFP intervention and modulation of pathways related to insulin resistance and hepatic lipid metabolism. qRT-PCR analysis demonstrated that PFP increased the mRNA expression of <em>PI3K</em>, <em>AKT, INSR, IRS1</em>, and <em>GLUT4</em>, while decreasing <em>G6P</em> expression. These findings suggest that PFP might improve certain aspects of metabolic dysregulation in HFD-fed mice, potentially through modulation of insulin sensitivity and hepatic lipid handling.</div></div>","PeriodicalId":12409,"journal":{"name":"Food Bioscience","volume":"70 ","pages":"Article 107050"},"PeriodicalIF":4.8,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144279567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Food BiosciencePub Date : 2025-06-12DOI: 10.1016/j.fbio.2025.107057
Yongping Xin , Dingyi Guo , Yuhang Nan , Pu Yang , Mingqiang Qiao
{"title":"An efficient platform for markerless large-scale genomic deletions in Lactococcus lactis","authors":"Yongping Xin , Dingyi Guo , Yuhang Nan , Pu Yang , Mingqiang Qiao","doi":"10.1016/j.fbio.2025.107057","DOIUrl":"10.1016/j.fbio.2025.107057","url":null,"abstract":"<div><div>The strain fitness and stress resistance of the starters, which are important to industrial applications, can be enhanced by large-scale genomic deletions. However, the low efficiency of large-scale genomic deletions has limited the efforts to improve the <em>Lactococcus lactis</em> fermentation performance through this method. In this study, we developed an efficient and time-saving platform for markerless large-scale genomic deletions in <em>L. lactis</em> by integrating temperature-sensitive plasmids, the SacB/pG15A counterselection system, and the Cre/<em>loxP</em> site-specific recombination system. First, the p15A origin, upstream and downstream homologies flanking the <em>galK</em> gene from MG1363 were integrated into the temperature-sensitive pG<sup>+</sup>Host9 plasmid, enabling the resulting plasmid pG15A-UD to replicate in <em>Escherichia coli</em>. The <em>SacB</em> gene from <em>Bacillus subtilis</em>, which encodes levansucrase, was then expressed from the plasmid pG15A-UD to establish the SacB/pG15A counterselection system. Furthermore, the SacB/pG15A counterselection system was demonstrated to be functional in <em>L. lactis</em> MG1363 and N8, achieving 40 %–60 % efficiency for markerless gene deletion and insertion. Finally, by combining the temperature-sensitive plasmid, SacB/pG15A and Cre/<em>loxP</em> system, we successfully deleted the 14,646 bp nisin biosynthetic gene cluster and a ∼58.5 kb nonessential genomic region in <em>L. lactis</em> N8. Our results provide an effective, rapid platform for large-scale genomic deletion in <em>L. lactis</em> to enhance the strain fitness and stress resistance and investigate their mechanisms.</div></div>","PeriodicalId":12409,"journal":{"name":"Food Bioscience","volume":"70 ","pages":"Article 107057"},"PeriodicalIF":4.8,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144279568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Food BiosciencePub Date : 2025-06-12DOI: 10.1016/j.fbio.2025.107060
Xi Deng , Md Zuki Abu Bakar , Zhongming Yang
{"title":"Calcium carbonate nanoparticles loaded with thymoquinone derived from medicine food homology plants combined with 5-fluorouracil for colon cancer Treatment: Proteomic and metabolomic insights","authors":"Xi Deng , Md Zuki Abu Bakar , Zhongming Yang","doi":"10.1016/j.fbio.2025.107060","DOIUrl":"10.1016/j.fbio.2025.107060","url":null,"abstract":"<div><div>Colon cancer is a malignant tumor posing a significant threat to global human health, and its effective treatment remains a major challenge. In this study, we explored the potential of combining calcium carbonate nanoparticles loaded with thymoquinone, a bioactive compound derived from the medicine food homology plant <em>Nigella sativa</em>, with the chemotherapeutic agent 5-fluorouracil (5-FU). The therapeutic efficacy of this combination was evaluated using CT26 tumor-bearing Balb/c mice, and its underlying molecular mechanisms were investigated through analytical techniques, including proteomics and metabolomics. Our results demonstrated that thymoquinone-loaded calcium carbonate nanoparticles (TQ-CaCO<sub>3</sub>np) significantly enhanced the anti-tumor efficacy of 5-FU while mitigating its associated toxicity. Proteomics and metabolomics analyses collectively revealed that the therapeutic benefits of the TQ-CaCO<sub>3</sub>np and 5-FU co-treatment were primarily mediated through the regulation of 2-oxocarboxylic acid metabolism pathway, biosynthesis of amino acids pathway, and HIF-1 signaling pathway. Six proteins (ACO2, GAPDH, PSPH, PDHA1, PDHB, and RPS6) and nine metabolites (alanine, glutamate, proline, glutamine, threonine, adenosine 5′-triphosphate, lactate, leucine, and isoleucine) were identified as critical targets within these pathways. Bioinformatics analyses, including bulk RNA-seq, single-cell RNA-seq, and immunohistochemical staining, confirmed the clinical relevance of these targets. These findings highlight the potential of combining traditional chemotherapies with bioactive compounds derived from medicine food homology plants and employed with nanobiotechnology, offering new insights into therapeutic strategies for colon cancer and providing the identified targets as potential biomarkers for therapeutic intervention.</div></div>","PeriodicalId":12409,"journal":{"name":"Food Bioscience","volume":"70 ","pages":"Article 107060"},"PeriodicalIF":4.8,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144289085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}