Cholesterol and its metabolites are fundamental to membrane organization and cellular signaling, but their poor ionization efficiency and structural similarity complicate mass-spectrometric (MS) analysis. In this work, we developed pyridyl ethyl diazoacetate (PED) as a stable, efficient derivatization reagent that introduces a permanent positive charge on hydroxyl-containing sterols, thereby enhancing ionization and detection sensitivity. Systematic MS2 characterization established diagnostic fragmentation motifs of PED-tagged sterols, which we encoded into a query-based spectral-mining strategy for reproducible, rule-based annotation of sterol features in complex matrices. Application of the PED workflow to human liver tissues enabled sterol profiling across cirrhotic, hepatocellular carcinoma, and intrahepatic cholangiocarcinoma specimens, suggesting disease-context-dependent differences in sterol profiles. The workflow effectively integrates chemical derivatization and programmable data interrogation, providing a robust analytical framework for sterol profiling in biological samples and a potential basis for broader lipidomic applications.

Rheumatoid Arthritis (RA) greatly affects patient’s life. Systematic reviews of recent epidemic trend and the pathogenesis of RA are inadequate. Although multiple health benefits of lactic acid bacteria (LAB) were reported, comprehensive reviews addressing the mechanisms by which LAB alleviate RA remain limited. This review systematically examines the epidemiology and pathogenesis of RA, emphasizing the potential modulatory role of LAB in maintaining intestinal homeostasis. Drawing on both animal and clinical evidence, the review critically evaluates the molecular mechanisms by which LAB may alleviate RA, thereby offering a theoretical foundation for microbiota-based therapeutic interventions. Meanwhile, it highlighted the challenges and opportunities of LAB for RA. Genetic predisposition, environmental factors, and immune system dysfunction play very important roles in causing RA. LAB provided numerous advantages and had great potential for improving RA as its ability to regulate intestinal barrier, modulate related enzyme activity, inhibit oxidative damage, restore unbalanced gut microbiota, produce bioactive metabolites, and regulate gut-joint immune axis. In addition, this review advice to screen effective LAB by cell models and metabolites, to determined the optimal intake dose of LAB through dose-effect relationship studies, to promote the understanding of LAB by investigating the mechanism, and to improve the design of the clinical study to improve the lives of RA patients. This will contribute to understanding the epidemiological characteristics, pathogenesis, and treatment of RA, and promote the development of targeted therapeutic RA products such as LAB.

Lactic acid bacteria (LAB) are frequently used as health supplements. They enhance digestion, regulate immunity, improve gut microbiota, and prevent and manage diseases. Autophagy has a crucial role in the prevention and treatment of tumors, cardiovascular diseases, and pathogenic infections. Research has indicated that autophagy is a significant pathway by which LAB improve health. In this review, we provide a comprehensive review on cellular and animal studies (a total of 45 studies) and summarize the LAB roles and possible mechanisms for regulating autophagy and enhancing health. Moreover, it identified challenges and opportunities of LAB in regulating autophagy to improve health. LAB provided numerous advantages and had great potential for regulating autophagy to improve health due to its ability to inhibit the proliferation of intracellular pathogens, remove harmful bacteria, alleviate pathogen-induced inflammation, reduce oxidative stress, improve the intestinal barrier, downregulate apoptotic protein, promote cancer cell apoptosis, inhibit cancer cell proliferation, and suppress drug and toxin responses. Moreover, it identified challenges from the aspects of strain selection, dose–response studies, targeted strain delivery, mechanistic analyses, and clinical studies, then predicted the opportunities for future research. This will have an important enlightening and guiding effect on the basic and clinical research of LAB to improve human health and the development of LAB dietary supplements.

Traditional solid-state fermented foods rely on stable yet adaptive microbial communities, yet the assembly and inheritance mechanisms remain poorly understood. Jiuyao, a Chinese fermentation starter propagated for 361 generations, achieves century‑long stability through a dual mechanism as object in this study: a static core microbiome (dominated by Pediococcus pentosaceus, Weissella cibaria, Saccharomycopsis fibuligera, and Saccharomyces cerevisiae) and spatially structured functional redundancy. Water content is the primary ecological driver, explaining up to 40.7% of fungal community succession (RDA, P<0.01) and mediating the shift from bacterial‑driven acidification to fungal‑dominated saccharification. Spatial heterogeneity generates a compensation effect: surface communities (enriched in filamentous fungi) hydrolyze macromolecules, while core communities (enriched in yeasts and lactic acid bacteria) drive ethanol production and flavor modification. Core species maintain functional redundancy, buffering inter‑annual metabolite variation. These study offering a mechanistic framework for optimizing solid‑state fermentation and understanding microbial inheritance in traditional fermented foods.​

Soybean is one of the most common sources of plant protein used in plant-based meat alternatives, but the bean flavor in final product limits its wide application. Lipophilic proteins (LPs) constitute approximately 31

Ulcerative colitis (UC) is a long-term inflammatory disorder that has evolved into a worldwide challenge. The development of new therapies against UC is imperative as all current therapies for UC are flawed in some way. Thus, the present study aimed to assess the palliative effects of Lactobacillus rhamnosus MP108 on UC in mice and to explore its potential mechanisms. The results showed that L. rhamnosus MP108 ameliorated the symptoms of UC, including preventing body weight loss, disease activity index (DAI) elevation, and colon shortening, and attenuated colonic pathological damage. L. rhamnosus MP108 dramatically increased the number of goblet cells, MUC2 level, and tight junction protein level in the colon and remarkably inhibited epithelial cell apoptosis, thereby strengthening the intestinal barrier. L. rhamnosus MP108 pronouncedly diminished pro-inflammatory cytokine levels and strikingly augmented anti-inflammatory cytokine levels, in turn suppressing inflammation. Furthermore, L. rhamnosus MP108 conspicuously boosted the proportion of short-chain fatty acids (SCFAs) producers in gut microbiota, contributing to increased levels of acetate and butyrate. Therefore, L. rhamnosus MP108 might alleviate UC via improving the intestinal barrier, inhibiting inflammation, and modulating intestinal microbiota.

This study developed a synbiotic fermented yak milk (F3) by integrating Lacticaseibacillus paracasei YT805 with inulin and evaluated its physicochemical, textural, and functional properties compared to probiotic (F2; L. paracasei YT805 without inulin) and control (F1; commercial starter culture only) fermented milks. Results demonstrated that F3 exhibited significantly higher water-holding capacity (55.17 % vs. 49.14 % in F1) and total solids (33.19 % vs. 26.95 % in F1) on day 0. Microstructural and circular dichroism analyses revealed a denser, homogeneous protein network in F3, characterized by reduced surface hydrophobicity (43.35 % vs. 69.11 % in F1) and increased beta-sheet content (40.12 % vs. 18.35 % in F1). Texture profiles indicated improved elasticity (4.79 N vs. 0.93 N in F1) and chewiness (3.33 N vs. 0.96 N in F1), alongside reduced hardness. After 21 days of storage at 4 degrees C, F3 retained 6.17 x 108 CFU/mL lactic acid bacteria, with L. paracasei YT805 viability maintained at 4.33 x 107 CFU/mL. Inulin content decreased by 27.22 % during storage but remained sufficient to support YT805 activity. Volatile compound diversity increased in F2 and F3, notably with elevated esters, ketones, and terpenes, while sulfur-containing off-flavor compounds decreased. In vitro fermentation of F3 significantly altered gut microbiota composition, enriching Acidaminococcus, Megasphaera, Megamonas, and Parabacteroides-genera linked to short-chain fatty acids (SCFAs) production. Correspondingly, SCFAs levels (acetic, propionic, butyric acids) increased by 25-90 %, highlighting F3's ability to enhance gut health. These findings demonstrate that synbiotic fermented yak milk, combining YT805 and inulin, is a promising functional food for modulating gut microbiota while maintaining desirable sensory and physicochemical qualities.

BACKGROUND:The dried flower (corolla) of Abelmoschus manihot (L.) Medicus, known as Abelmoschi Corolla, contains polysaccharides with therapeutic potential for immunopotentiation; however, the underlying mechanisms remain unclear. PURPOSE:This study aimed to systematically investigate the efficacy and molecular mechanisms through which acidic Abelmoschi Corolla polysaccharides (S-AMFP) reverse cyclophosphamide (CTX)-induced immunosuppression, using integrated analyses of intestinal microbiology, metabolomics, histology, and biochemistry. METHODS:We isolated and purified S-AMFP from Abelmoschi Corolla and subjected it to preliminary structural characterisation. An immunosuppressive mouse model was established through intraperitoneal injection of cyclophosphamide (CTX). The immunorestorative effects of S-AMFP were evaluated using gut microbiomics, non-targeted metabolomics, histopathology, and molecular biology techniques. Immune organ indices, including spleen and thymus weights, were measured in BALB/c mice. Cytokine and immunoglobulin levels (TNF-α, IL-4, IL-6, IgG, IgA, and IgM) were quantified using enzyme-linked immunosorbent assay; T-lymphocyte subsets (CD3⁺/CD4⁺ percentages and CD4⁺/CD8⁺ ratios) were analysed using flow cytometry. Splenic histopathological changes were examined using haematoxylin and eosin staining. Gut microbiota composition was profiled by 16S rDNA sequencing, whereas serum metabolites were analysed through non-targeted metabolomics. Faecal short-chain fatty acids (SCFAs) were quantified using gas chromatography-mass spectrometry. Mitogen-activated protein kinase pathway activity and intestinal barrier integrity were evaluated using reverse transcription quantitative polymerase chain reaction and Western blot. RESULTS:S-AMFP is a pectin-based polysaccharide primarily composed of rhamnose and galacturonic acid. S-AMFP restored body weight, thymic and splenic indices, serum cytokines, immunoglobulin levels, and rectified T lymphocyte dysfunction by rebalancing CD4⁺/CD8⁺ ratios. It improved intestinal barrier function by up-regulating tight junction proteins (Claudin-1 and Occludin), activating the MAPK pathway, and reshaping gut microbiota. S-AMFP increased beneficial bacteria, including Lactobacillus and Lachnospiraceae_NK4A136_group, reduced pathogenic Enterobacteriaceae, elevated SCFA levels, and alleviated CTX-induced metabolic disturbances in amino acid, lipid, and energy pathways. CONCLUSIONS:S-AMFP mitigates CTX-induced immunosuppression by restoring intestinal barrier integrity, modulating gut microbiota composition, and enhancing metabolic homeostasis. These findings advance current understanding of polysaccharide-mediated immunomodulation and highlight S-AMFP's potential as a dietary supplement or adjunctive agent for mitigating drug-induced immunosuppression, particularly through gut ecological and metabolic regulation.

Fermentation represents an effective strategy for promotion of foodstuffs with beneficial effects on human health. Pine pollen has proven efficacy in hepatoprotective. Here, we aimed further onwards to elevate up the hepatoprotective of pine pollen with fermentation. The protective effects of Mucor racemosus-fermented pine pollen on liver damage based on an alcohol-induced HepG2 model was investigated. The compositional changes of pine pollen after fermentation were explored using non-targeted metabolomics, and the compounds contributed to liver-protective activity were also screened with correlation analysis. The findings demonstrate that the fermented pine pollen (FPP) markedly diminished the levels of triglyceride (TG), alanine transaminase (ALT), aspartate transaminase (AST), and malondialdehyde (MDA), while enhancing the activity of antioxidant enzymes, including superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT). These effects were superior to those of unfermented pine pollen (UPP). Furthermore, FPP modulated lipid metabolism by downregulating the expression of the PPAR gamma, SREBP1c, ACC, and CD36 genes, while also increasing the expression of the PPAR alpha and CPT1 genes, thus maintaining lipid metabolic homeostasis. Correlation analysis revealed that 29 metabolites, including 8 lipids, 7 amino acids and derivatives, 6 phenylpropanoids and polyketides, and 8 terpenoids, were positively correlated with the liver-protective activity of fermented pine pollen. This study provides theoretical support for the development of high-value products from fermented pine pollen.

Colorectal cancer (CRC) represents the third most common cancer worldwide. Consequently, there is an urgent need to identify novel preventive and therapeutic strategies for CRC. This study aimed to screen for beneficial bacteria that have a preventive effect on CRC and to elucidate the potential mechanisms. Initially, we compared gut bacteria and bacterial metabolites of healthy volunteers and CRC patients, which demonstrated that intestinal conjugated linoleic acid (CLA), butyric acid, and Bifidobacterium in CRC patients were significantly lower than those in healthy volunteers, and these indicators were significantly negatively correlated with CRC. Next, spontaneous CRC mouse model were conducted to explore the effect of supplemental CLA-producing Bifidobacterium on CRC. Supplementation of mice with CLA-producing Bifidobacterium breve CCFM683 and B. pseudocatenulatum MY40C significantly prevented CRC. Moreover, molecular approaches demonstrated that CLA and the CLA-producing gene, bbi, were the key metabolites and genes for CCFM683 to prevent CRC. Inhibitor intervention results showed that PPAR-γ was the key receptor for preventing CRC. CCFM683 inhibited the NF-κB signaling pathway, up-regulated MUC2, Claudin-1, and ZO-1, and promoted tumor cell apoptosis via the CLA-PPAR-γ axis. Additionally, fecal microbiota transplantation (FMT) and metagenomic analysis showed that CCFM683 up-regulated Odoribacter splanchnicus through CLA production, which then prevented CRC by producing butyric acid, up-regulating TJ proteins, regulating cytokines, and regulating gut microbiota. These results will contribute to the clinical trials of Bifidobacterium and the theoretical research and development of CRC dietary products.

Nattokinase (NK), a serine protease with high thrombolytic activity, has significant potential for application in foods intended for special health benefits. However, the NK production in wild-type Bacillus subtilis natto is relatively low. In this study, a high-yielding NK and genetically stable mutant strain (B. subtilis JNC002.001, 300.0 ± 4.7 FU/mL) was obtained through atmospheric and room temperature plasma (ARTP) mutagenesis. It increased NK activity by 1.84 times compared to the initial strain SD2, demonstrating significant prospects for NK production and food fermentation applications. Additionally, the B. subtilis JNC002.001 exhibited notable alterations in growth characteristics, glucose consumption, and sporulation. This study further elucidated the mechanism of enhanced NK production at the molecular level. Genome resequencing revealed that the mutant genes in JNC002.001 included 10 single nucleotide polymorphisms (SNPs) and one insertion, among which the kinA and gltA genes were associated with sporulation and NK synthesis, respectively. In terms of the transcriptional level, the NK-coding gene aprN was up-regulated 9.4 times relative to the wild-type strain. Most of the genes related to central carbon metabolism and the Sec secretion pathway were up-regulated. In addition, the expression of regulatory factors associated with the transcription of the aprN gene and the sporulation process provided evidence for high NK expression and sporulation deficiency in JNC002.001. These results could provide insights into the mechanism of NK production and facilitate the construction of engineered strains with high NK yield.

The biofilm formation of Lactobacilli is regulated by the LuxS/AI-2 quorum sensing (QS) system, but the mechanism of QS regulating the formation of Lactobacilli biofilm is not clear. This study aimed to investigate the mechanism of producing biofilm in L. plantarum R and its effect on the quality of fermented pickles based on LuxS/AI-2 QS system. Compared with L. plantarum R, the AI-2 activity of L. plantarum RΔluxS was significantly reduced, but the biofilm, extracellular protein, and eDNA were significantly increased. Moreover, expression of oppA, livJ, livH and comD genes was up-regulated and luxS, peg.3090 and peg.3093 was down-regulated. Results showed that peg.3093 was most significantly down-regulated in L. plantarum RΔluxS, and extremely significant negatively correlated with biofilm. The biofilm, eDNA, and extracellular protein of L. plantarum RΔpeg.3093 was higher than those of L. plantarum R. Moreover, metabolomics showed that deletion of luxS gene could decrease AI-2 level, promote anthocyanin and flavonol biosynthesis, lead to improving the antioxidant properties and quality of pickles. Thus, luxS gene knockout may increase biofilm by down-regulating the expression of peg.3093 to increase extracellular protein and eDNA. This study provides a theoretical basis for the enhancement of Lactobacillus biofilm and its application.

The methoxylated modification of flavonoids has been reported to enhance stability and permeability; however, its effect on the improvement of activity is not clear. In this study, Citrus depressa flavonoid O-methyltransferase 5 and Sorghum vulgare 7-O-methyltransferase were recombinantly expressed and successfully converted quercetin (QUE) into eight methoxylated products, which were isolated and identified with a purity exceeding 95%. All products except rhamnetin (RHA) showed improved stability, while only 5,7,3',4'-EMQ, 7,3',4'-TMQ, and 3,7,3',4'-EMQ had higher uptake ratios. Compared to QUE, 5,7,3',4'-EMQ and RHA significantly reduced the intracellular triglyceride level, while 3,5,7,3',4'-PMQ, 3,3',4'-TMQ and 3,7,3',4'-EMQ increased it. 5,7,3',4'-EMQ and RHA also significantly downregulated both the mRNA and protein levels of peroxisome proliferator-activated receptor γ, while 3,5,7,3',4'-PMQ and 3,7,3',4'-EMQ upregulated PPARγ at the transcriptional level to about ten times higher than that of QUE. The structure-activity relationship analysis highlighted the importance of C3-OH retention and dual methoxylation of the A-ring. In summary, this study efficiently produced eight structurally well-defined QUE methoxylation products via biotransformation, established an in vitro initial structure-activity relationship for regulating adipogenesis, and provided a potential structure for PPARγ regulation, a central target of lipid metabolism.

Colorectal cancer (CRC) is characterised by microbial dysbiosis. Trimethylamine (TMA) and trimethylamine-N-oxide (TMAO) are gut microbiota-derived metabolites produced from dietary precursors that are implicated in CRC progression. However, the underlying mechanisms by which TMA or TMAO affect CRC progression remain largely unexplored. Therefore, in this study, we aimed to investigate the effects of TMA and TMAO on CRC progression. The methods used included real-time PCR, western blotting, cell viability and migration assays, apoptosis analysis, single-cell RNA sequencing, and tumor xenograft models. We demonstrated that exposure to both TMA and TMAO promoted CRC cell proliferation. Notably, treatment with 1 μM TMA and 100 μM TMAO had the greatest effect on enhancing CRC cell invasion and migration, while also reducing apoptosis. Mechanistically, TMA and TMAO modulated the expression of sterol regulatory element-binding factor 1 (SREBF1) and activated the phosphoinositide 3-kinase (PI3K)/ protein kinase B (AKT) signalling pathway, thereby contributing to CRC progression. In mouse subcutaneous tumour experiments, a high-TMAO diet accelerated CRC progression, leading to significantly larger tumour volumes than those in the control group. Collectively, these findings suggest a potential correlation between elevated serum TMAO levels and CRC progression. Notably, we provide the first evidence that TMA and TMAO promote CRC cell proliferation via activation of the PI3K/AKT signalling pathway, with SREBF1 serving as a key mediator of TMA- and TMAO-induced CRC proliferation. Reducing TMA and TMAO intake through dietary intervention and the use of SREBF1 inhibitors may delay CRC progression, offering considerable clinical potential for therapeutic applications.

BackgroundChemoresistance is a critical factor contributing to poor prognosis in clinical patients with cancer undergoing postoperative adjuvant chemotherapy. The role of gut microbiota in mediating resistance to tumour chemotherapy remains to be investigated.MethodsPatients with CRC were categorised into clinical benefit responders (CBR) and no clinical benefit responders (NCB) based on chemotherapy efficacy. Differential bacterial analysis using 16S rRNA sequencing revealed Desulfovibrio as a distinct microbe between the two groups. Employing a syngeneic transplantation model, we assessed the effect of Desulfovibrio on chemotherapy by measuring tumour burden, weight, and Ki-67 expression. We further explored the mechanisms underlying the compromised chemotherapeutic efficacy of Desulfovibrio using metabolomics, western blotting, colony formation, and cell apoptosis assays.FindingsIn comparison, Desulfovibrio was more abundant in the NCB group. In vivo experiments revealed that Desulfovibrio colonisation in the gut weakened the efficacy of FOLFOX. Treatment with Desulfovibrio desulfuricans elevates serum S-adenosylmethionine (SAM) levels. Interestingly, SAM reduced the sensitivity of CRC cells to FOLFOX, thereby promoting the growth of CRC tumours. These experiments suggest that SAM promotes the growth and metastasis of CRC by driving the expression of methyltransferase-like 3 (METTL3).InterpretationA high abundance of Desulfovibrio in the intestines indicates poor therapeutic outcomes for postoperative neoadjuvant FOLFOX chemotherapy in CRC. Desulfovibrio drives the manifestation of METTL3 in CRC, promoting resistance to FOLFOX chemotherapy by increasing the concentration of SAM.FundingThis study is supported by Wuxi City Social Development Science and Technology Demonstration Project (N20201005).

Background: Bioactive components (BCs) have been used in food, pharmaceutical and cosmetic fields. Due to chemical instability, low solubility and low bioavailability, it is necessary to design the edible carriers for their encapsulation, protection and delivery. Proteins assemble to form various supramolecular structures as potential carriers of BCs. With the development of food science, it puts forward higher requirements for structural design and functional customization of edible carriers. In order to provide multiple health benefits, synergistic bioactivity and improved stability, these provide motivation to simultaneously encapsulate multiple BCs in a carrier. Scope and approach: This review introduces the necessary for simultaneous encapsulation of multiple BCs in a carrier and the co-encapsulation of BCs with similar solubility and highlights the separated co-encapsulation of multiple BCs with different solubility using protein assemblies, including their partition, protection and delivery.Key findings and conclusions: Protein-based assemblies can be used for the co-encapsulation of multiple BCs. The encapsulation of multiple BCs with similar solubility resembles that of a single one at high content to some extent. The co-encapsulation of BCs with different solubility could be achieved using the assemblies with different domains, such as emulsion gels, oil-in-water emulsions, water-in-oil-water emulsions. Furthermore, BCs could also be separately co-encapsulated using molecular complexes and nano/micro-particles with homogeneous, core-shell and hollow structures. It would be advantageous to co-encapsulate, protect and delivery BCs by designing protein-based carriers with novel structure, clarifying mass transfer of BCs in a carrier, and considering the interaction of proteins with BCs or their decomposition products.

Vanadium oxide has become a promising electrode material for supercapacitors because of its high capacitance and multiple redox states. However, low intrinsic conductivity, narrow interlayer spacing and poor structural stability limit its practical application. The study reports the construction of Co-doped V2O3 using asparagic acid-functionalized graphene quantum dots (GQD) and biomass carbon (BC). V5+ and Co2+ were combined with GQD to form the Co/V-GQD complex. Then, it was adsorbed on cotton, dried and annealed. The resulting Co-V2O3-GQD@BC shows the three-dimensional carbon framework. The formed V2O3 nanocrystals with rich edges and corners are dispersed on the carbon sheets. V5+ was partly reduced to form low-valent V2+ species. V2+ and Co2+ self-doping narrows the bandgap and creates new electron transfer pathways. Graphene modification accelerates the electron transfer from V2O3 to graphene and improves structural stability. The integration of double doping with graphene modification realizes a significant improvement in electrical conductivity and a safe voltage window (1.8 V). The specific capacitance of V2O3 in Co-V2O3-GQD@BC reaches 2182.89 F g(-1), which is more than that of the other vanadium oxide electrodes. The symmetrical supercapacitor with Co-V2O3-GQD@BC electrodes provides a high capacitance (664.89 F g(-1) at current density of 1 A g(-1)), rate capacity (366.67 F g(-1) at 50 A g(-1)), cycling stability (97.65% capacitance retention after 10 000 cycles) and energy density (74.8 W h kg(-1) at a power density of 425 W kg(-1)).

This study investigated the efficacy of using plasma-activated water (PAW) as a novel and additive-free pretreatment in reducing the formation of free and bound heterocyclic aromatic amines (HAAs) and advanced glycation end products (AGEs) in roasted fish patties. PAW activated for different durations (50 s, 100 s, and 150 s), significantly decreased the levels of HAAs and AGEs. The highest inhibition rates were observed at 35.44% and 19.82% for free and bound HAAs, respectively, and 42.76% and 23.23% for free and bound AGEs, respectively. PAW pretreatment reduced the formation of HAAs and AGEs and mitigated their increase during storage. Analysis using electron paramagnetic resonance and UPLC-MS/MS showed a decrease in free radicals and reactive carbonyls (phenylglyoxal, glyoxal, and methylglyoxal), which can serve as intermediates for HAAs and AGEs. Correlation analysis indicated a significant positive correlation between HAAs/AGEs and phenylacetaldehyde, glyoxal, methylglyoxal, and the total spin number (P < 0.05). This suggests that PAW suppresses the production of reactive carbonyls by quenching free radicals, thereby inhibiting the formation of HAAs and AGEs. In conclusion, with its additive-free approach, PAW pretreatment holds promise for reducing HAAs and AGEs and improving the safety of roasted fish products.

Colorectal cancer (CRC) is the third-largest cancer worldwide. Lactobacillus can regulate the intestinal barrier and gut microbiota. However, the mechanisms of Lactobacillus that alleviate CRC remained unknown. This study aimed to explore the regulatory effect of Lactobacillus plantarum on CRC and its potential mechanism. CCFM8661 treatment significantly ameliorated CRC compared with phosphate-buffered solution (PBS) treatment in ApcMin/+ mice. In addition, conjugated linoleic acid (CLA) was proved to be the key metabolite for CCFM8661 in ameliorating CRC by molecular biology techniques. Peroxisome proliferator-activated receptor γ (PPAR-γ) was proved to be the key receptor in ameliorating CRC by inhibitor intervention experiments. Moreover, supplementation with CCFM8661 ameliorated CRC by producing CLA to inhibit NF-κB pathway and pro-inflammatory cytokines, up-regulate ZO-1, Claudin-1, and MUC2, and promote tumor cell apoptosis in a PPAR-γ-dependent manner. Metagenomic analysis showed that CCFM8661 treatment significantly increased Odoribacter splanchnicus, which could ameliorate CRC by repairing the intestinal barrier. Clinical results showed that intestinal CLA, butyric acid, PPAR-γ, and Lactobacillus were significantly decreased in CRC patients, and these indicators were significantly negatively correlated with CRC. CCFM8661 alleviated CRC by ameliorating the intestinal barrier through the CLA-PPAR-γ axis. These results will promote the development of dietary probiotic supplements for CRC.