Lufang Chen, Yanling Lin, Yi Zhang, Shuting Lai, Shuhuan Zheng, Hui Ni, Feng Chen, Fan He
{"title":"Decoding the relationship between the molecular structure and sweetness intensity of plant-derived chalcones based on 3D-QSAR.","authors":"Lufang Chen, Yanling Lin, Yi Zhang, Shuting Lai, Shuhuan Zheng, Hui Ni, Feng Chen, Fan He","doi":"10.1039/d5fo01775k","DOIUrl":"https://doi.org/10.1039/d5fo01775k","url":null,"abstract":"<p><p>Natural plant-derived chalcones exhibit sweetening properties and bioactive health benefits, making them promising natural sweeteners. However, their unsatisfying sweetness intensity restricts their applications in the food industry. To clarify the structure-sweetness relationship, 25 chalcones were characterized for their sweetness threshold and structural features using sensory evaluation and molecular superposition. The quantitative conformational relationship on the structure-sweetness of chalcones was explored by 3D-QSAR based on comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA). Results showed that introducing a negatively charged group at the C2 site of ring A, a positively charged group at the C4 site, and a small-volume group with a positive charge at the C6 site could effectively increased the sweetness. Additionally, a negatively charged group at the C3' site of ring B and large-volume groups at the C4' and C5' sites were helpful in improving the sweetness. The sweetness intensity of some chalcones was predicted and evaluated, and the results followed with the proposed model, confirming the validation of 3D-QSAR. Molecular docking also verified the model's findings. This study provided theoretical insights into the structure-sweetness relationship of chalcones, offering potential information for understanding the sweetness from natural plants and a foundation for the development of natural sweeteners with improved sweetness and functional benefits.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147328","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":"Beyond the oral niche: <i>Lacticaseibacillus paracasei</i> LPC-37 unlocks oral-gastric-intestinal crosstalk for butyric acid-dependent oral inflammation alleviation.","authors":"Yonglu Li, Xin Gao, Lihan Jiang, Hongdi Song, Chen Yang, Cong Wu, Yapeng Li, Shihai Yan, Ping Li, Qing Gu","doi":"10.1039/d5fo02279g","DOIUrl":"https://doi.org/10.1039/d5fo02279g","url":null,"abstract":"<p><p>Oral inflammatory diseases are prevalent yet poorly understood in the context of systemic microbiota interactions along the oral-gastric-intestinal axis. Current interventions primarily target direct inflammation inhibition <i>in situ</i>, leaving the cross-compartmental microbial mechanisms underlying oral inflammation underexplored. Moreover, the therapeutic potential of probiotics in modulating multi-site microbiota dynamics to alleviate oral inflammation remains limited by insufficient mechanistic insights. Using an acetic acid-induced oral inflammatory mouse model, this study systematically tracked alterations in the digestive microbiota across distinct gastrointestinal compartments during oral inflammation progression, thereby elucidating the microbiota-driven mechanisms of oral inflammation through both holistic and site-specific analyses of the digestive tract. Additionally, the potent anti-inflammatory efficacy of the commercially utilized probiotic <i>Lacticaseibacillus paracasei</i> LPC-37 was evaluated. The anti-inflammatory mechanism of LPC-37 was deciphered through microbiota structural analysis, gastrointestinal survival assessment, co-culture characterization, and short-chain fatty acid profiling. LPC-37, exhibiting robust gastrointestinal resistance, demonstrated enhanced intestinal colonization. This promoted a synergistic interaction with same-family bacteria to elevate <i>Ligilactobacillus</i> abundance, enabling antagonism against the marker microbe <i>Aerococcus</i> while upregulating <i>Clostridium saccharolyticum</i> WM1, a butyrate-producing strain. These microbial shifts drove butyrate biosynthesis, ultimately alleviating oral inflammation. The findings unravel a systemic microbiota interplay along the oral-gastric-intestinal axis and propose a novel probiotic-based strategy for anti-oral-inflammatory therapy.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147256","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}
M Pilar Vaquero, María Dolores Álvarez, Belén Zapatera, Arancha Saiz, Susana Cofrades
{"title":"Postprandial metabolism of a reduced-fat meat product with added silicon from diatomaceous earth. A pilot randomized controlled four-way assay in humans.","authors":"M Pilar Vaquero, María Dolores Álvarez, Belén Zapatera, Arancha Saiz, Susana Cofrades","doi":"10.1039/d5fo00973a","DOIUrl":"https://doi.org/10.1039/d5fo00973a","url":null,"abstract":"<p><p>The use of silicon (Si) in functional foods is innovative. Because meat products are versatile, nutritious and highly accepted by the population, in this study a reduced-fat meat product (pâté) with added Si from diatomaceous earth was assayed. The design was a four-way postprandial randomized crossover-controlled trial. Eighteen adults (<i>n</i> = 18, mean age 58 ± 8 years, 68% women) consumed a standard meal with the following pâtés: control (C), with normal fat content; reduced-fat (RF), in which pork backfat was fully replaced by emulsions; the C with added diatomaceous earth powder as a source of Si (C-Si); and the RF pâté with the same Si source (RF-Si). Volunteers were characterized in terms of fasting lipemia, body weight, body composition, blood pressure, smoking habits, and medication. Blood samples were collected at 0, 1, 2, and 4 h after ingesting the standard meal containing each of the pâtés. Results show that, regardless of the type of patê, postprandial serum Si and triglycerides increased (<i>p</i> = 0.015 and <i>p</i> < 0.001), and insulin increased during the first hour and decreased thereafter (<i>p</i> < 0.001) while glucose was unchanged. In conclusion, Si from diatomaceous earth is unabsorbed and has no effect on normal postprandial metabolism in adult men and women, suggesting that this inorganic source of Si should not be used as a bioactive ingredient in functional foods.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147245","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}
Abel Wend-Soo Zongo, Kaili Gao, Silvere D Zaongo, Daniel Zogona, Duoxia Xu, Ningxiang Yu, Xianghe Meng
{"title":"Polyphenol-rich extract from <i>Torreya grandis</i> peel attenuates lipopolysaccharide-induced inflammation in RAW264.7 macrophages <i>via</i> inhibition of the TLR4/NF-κB pathway.","authors":"Abel Wend-Soo Zongo, Kaili Gao, Silvere D Zaongo, Daniel Zogona, Duoxia Xu, Ningxiang Yu, Xianghe Meng","doi":"10.1039/d5fo02981c","DOIUrl":"https://doi.org/10.1039/d5fo02981c","url":null,"abstract":"<p><p><i>Torreya grandis</i> (TG) peel is an overlooked byproduct, often discarded as waste during the processing of TG nuts, despite its potential as a good source of health-promoting bioactive compounds. To explore the potential of TG peel as a value-added resource, this study examined the phenolic composition and anti-inflammatory activity of its polyphenol extract (TGAP) using a lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage model. The results show that flavonoids were the dominant phenolic class in TGAP, with major compounds including hesperidin <i>O</i>-glucuronic acid, naringenin 7-<i>O</i>-neohesperidoside, chrysoeriol 7-<i>O</i>-hexoside, daidzein, orobol, and epigallocatechin. TGAP treatment (50-200 μg mL<sup>-1</sup>) significantly reduced intracellular reactive oxygen species (ROS) levels by 8-68% and mitigated LPS-induced inflammation by decreasing nitric oxide production and downregulating pro-inflammatory mediators, including iNOS, COX-2, interleukin-1β (IL-1β), IL-2, IL-6, and TNF-α, at both the mRNA and protein levels. It was found that TGAP decreased Toll-like receptor 4 (TLR4) expression and inhibited NF-κB signaling by preventing IκBα phosphorylation and nuclear translocation of the NF-κB p65 subunit, suggesting that TGAP exerts its anti-inflammatory effects through the inhibition of the TLR4/NF-κB pathway. Molecular docking also revealed that key TGAP polyphenols, including epigallocatechin, chrysoeriol, daidzein, genistein, hesperidin, and naringenin, exhibited strong binding affinities (-7.0 to -8.3 kcal mol<sup>-1</sup>) with TLR4 and NF-κBp65 proteins, primarily through hydrogen bonding, π-stacking interactions, and van der Waals forces. These results suggest that these compounds play a central role in the anti-inflammatory activity of TGAP. Overall, TGAP is a promising natural anti-inflammatory agent, with potential therapeutic applications in inflammatory disorders.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147259","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}
Smaragdi Antonopoulou, Maria Detopoulou, Filio Petsini, Maria Choleva, Agathi Ntzouvani, Elizabeth Fragopoulou, Meropi Kontogianni, Michalis Georgoulis, Arkadios Dimitroglou, Dimitrios Barkas, Leonidas Papacharisis, Anthi Panara, Nikolaos S Thomaidis
{"title":"Consumption of a Mediterranean lean fish enriched with platelet-activating factor inhibitors extracted from olive pomace favorably modulates hemostasis and thrombosis in healthy adults with overweight.","authors":"Smaragdi Antonopoulou, Maria Detopoulou, Filio Petsini, Maria Choleva, Agathi Ntzouvani, Elizabeth Fragopoulou, Meropi Kontogianni, Michalis Georgoulis, Arkadios Dimitroglou, Dimitrios Barkas, Leonidas Papacharisis, Anthi Panara, Nikolaos S Thomaidis","doi":"10.1039/d5fo02487k","DOIUrl":"https://doi.org/10.1039/d5fo02487k","url":null,"abstract":"<p><p>Blood coagulation prevents excessive bleeding but also contributes to thrombosis. Studies suggest that consuming more than two fish meals weekly reduces platelet aggregation induced by various agonists. Among them, Platelet-Activating Factor (PAF), a potent inflammatory lipid, plays a key role in atherogenesis. Previous studies demonstrated that a polar lipid extract from olive pomace (OOPLE), containing PAF inhibitors, reduced atherogenesis in animals. This double-blind, randomized, crossover trial investigated the effects of consuming gilthead sea bream fed with OOPLE-enriched feed (EF) <i>versus</i> conventional feed (CF) on platelet aggregation and hemostatic markers in adults with overweight. Participants (35-70 years, BMI 25-35 kg m<sup>-2</sup>) consumed two servings of EF or CF per week for one month, separated by a one-month washout. EF intake significantly reduced platelet aggregation in response to PAF (44%) and ADP (67%) compared with CF (<i>p</i> = 0.002), and slightly decreased activated partial thromboplastin time by 0.82 seconds (<i>p</i> = 0.025). No significant differences were found in glucose and lipid metabolism, other hemostatic biomarkers, or red blood cell membrane fatty acid profiles between the two interventions. These findings suggest that incorporating olive pomace-derived polar lipids into aquaculture feed may enhance the cardioprotective effects of fish by reducing platelet activation-supporting a novel strategy to improve the health benefits of farmed fish.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147325","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}
Lijuan Zhu, Li Kong, You Huang, Zhaoping Ou, Chunlin Huang, Wenjiang Yang, Jiayu He, Mingqi Yang, Shuiping Liu, Jine Yi
{"title":"Betulinic acid protects against LPS-induced intestinal inflammatory damage <i>via</i> inhibiting Nrf2/TXNIP/NLRP3 signaling pathways in mice.","authors":"Lijuan Zhu, Li Kong, You Huang, Zhaoping Ou, Chunlin Huang, Wenjiang Yang, Jiayu He, Mingqi Yang, Shuiping Liu, Jine Yi","doi":"10.1039/d5fo00925a","DOIUrl":"https://doi.org/10.1039/d5fo00925a","url":null,"abstract":"<p><p>Betulinic acid (BA) is a pentacyclic triterpenoid and found in various fruits and vegetables, known for its anti-inflammatory and antioxidant properties as well as intestinal protective roles. This study aimed to investigate the effects and mechanisms of BA on lipopolysaccharide (LPS)-induced intestinal inflammation in mice. Our results indicated that BA pretreatment alleviated LPS-induced body weight loss, morphological damage and intestinal cell apoptosis in the duodenum, jejunum, ileum and colon. BA pretreatment effectively regulated the disturbance of inflammatory cytokines in the duodenum, jejunum, ileum and colon induced by LPS. Meanwhile, BA pretreatment significantly inhibited the protein expression of TXNIP, NLRP3, ASC, caspase-1, GSDMD, IL-1β and IL-18 in the jejunum, suggesting that BA mitigated LPS-induced intestinal inflammation by inhibiting the TXNIP/NLRP3 signaling pathways. Furthermore, BA pretreatment decreased MDA content, while increasing the activities of the CAT and SOD in the jejunum. Subsequently, BA pretreatment down-regulated the protein expression of Nrf2 and HO-1 in the jejunum, indicating that BA alleviated LPS-induced intestinal oxidative impairment by inhibiting the Nrf2 signaling pathway. In conclusion, BA pretreatment exhibited protective effects on LPS-induced intestinal inflammatory damage by inhibiting Nrf2/TXNIP/NLRP3 signaling pathways in mice. This study established a theoretical foundation for the application of BA as a functional food factor in the alleviation of inflammatory bowel diseases.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147297","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":"Anthocyanin-enriched purple potato flour modulates gut microbiota and short-chain fatty acids to prevent hypertension: insights from preclinical models and mendelian randomization analysis.","authors":"Yixin Ye, Yingyi Deng, Ruolan Yi, Yexin Qin, Tong Zhang, Jinlian Huang, Lini Nong, Guangqiu Qin, Hai Li, Xu Zheng, Lihong Zhou","doi":"10.1039/d5fo03028e","DOIUrl":"https://doi.org/10.1039/d5fo03028e","url":null,"abstract":"<p><p>Hypertension remains a global health challenge with limited effective non-pharmacological interventions. This study investigated the antihypertensive effects of a potato-based functional diet using purple potato (PP) flour enriched with anthocyanins and potassium in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. Over a 9-week dietary intervention, SHR and WKY rats were fed PP or yellow potato (YP) flour supplemented diets for preventive intervention. Blood pressure, serum biomarkers (angiotensin II, endothelin-1, nitric oxide), gut microbiota composition (16S rRNA sequencing), and cecal metabolites (untargeted metabolomics) were analyzed. Molecular docking assessed interactions between purple potato anthocyanins and hypertension-related proteins (endothelin-1, angiotensin II), while Mendelian randomization (MR) analysis evaluated genetic causality between potato intake and hypertension. Compared to YP, PP reduced both systolic blood pressure (SBP) by more than 18.23% in WKY rats but did not significantly affect SBP in SHR rats. PP also lowered serum angiotensin II by 33.08% in SHR rats and increased microbial diversity with elevated <i>Bacteroidota</i> abundance and reduced <i>Firmicutes</i>/<i>Bacteroidetes</i> ratio. Metabolomics analysis identified enriched pathways in bile acid metabolism and fatty acid biosynthesis, correlating with increased short-chain fatty acid (SCFA)-producing bacteria (<i>e.g.</i>, <i>Ruminococcus</i>, <i>Oscillibacter</i>). The metabolomics and gut microbiota correlation analysis indicated important interactions between metabolites and gut microbiota. Potato anthocyanins demonstrated strong binding affinity to endothelin-1/angiotensin II, suggesting direct bioactive potential. MR analysis revealed no causal link between potato intake and hypertension, highlighting the safety of nutrition intervention with potato for hypertension. The findings from this study underscore purple potato as a promising dietary strategy to modulate gut microbiota, enhance SCFA production, and prevent hypertension, emphasizing the role of whole-food interventions in cardiovascular health. Clinical translation, supported by estimated human-equivalent doses (75-150 g dry potato rice noodles per day), warrants further investigation.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145135968","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":"Modulation of hyperglycemia, insulin resistance responses and gut microbiota composition in type 2 diabetic mice by capsicum residue soluble dietary fiber.","authors":"Yaxing Feng, Wenxiu Wang, Xiangyun Liu, Fengjuan Wang, Yuwei Dong, Qianyun Ma, Jianfeng Sun","doi":"10.1039/d5fo01390a","DOIUrl":"https://doi.org/10.1039/d5fo01390a","url":null,"abstract":"<p><p>Type 2 diabetes mellitus (T2DM) poses substantial health risks, emphasizing the need to identify natural ingredients from biological sources that can alleviate its symptoms. Capsicums produce a large amount of capsicum residue (CR) by-products during processing, which are underutilized. CR is rich in soluble dietary fiber (SDF) and has shown potential as an adjunctive hypoglycemic dietary supplement. This study investigated the structure of capsicum residue soluble dietary fiber (CR-SDF), its hypoglycemic effects in T2DM mice fed a high-fat diet combined with streptozotocin, and its hypoglycemic mechanism through glucose and lipid metabolism indexes, blood biochemistry indexes, short-chain fatty acids (SCFAs), gut microbiota, and the expression levels of genes related to the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. The results indicated that CR-SDF mainly contains galacturonic acid, glucose, and galactose. CR-SDF was loose and porous with a rough surface. It exhibited characteristic polysaccharide absorption peaks and a cellulose I crystalline structure. After four weeks of CR-SDF intervention, T2DM mice showed improvements in glucose and lipid levels, insulin resistance, and liver and pancreas health. Analysis of fecal SCFAs revealed increased concentrations in diabetic mice after CR-SDF intervention, while fecal microbiota analysis showed enrichment of beneficial bacteria (<i>Bacteroides</i> and <i>Akkermansia</i>) and inhibition of harmful bacteria (norank_f__<i>Lachnospiraceae</i>, unclassified_f__<i>Lachnospiraceae</i>, and <i>Aerococcus</i>). In addition, RT-PCR results indicated that CR-SDF upregulated the relative mRNA expression levels of insulin receptor substrate-1, PI3K, Akt, and glucose transporter 2. These findings suggest that CR-SDF could be an effective intervention for T2DM by improving gut microbiota dysbiosis and promoting intestinal fermentation to produce more SCFAs, which drive insulin secretion to improve the efficiency of blood glucose utilization. Moreover, CR-SDF promotes insulin signaling and improves insulin resistance by activating the PI3K/AKT signaling pathway, thereby lowering blood glucose.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145135966","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}
Ashley M McAmis, Michael G Sweet, Sydney Chadwick-Corbin, Juanita G Ratliff, Molla Fentie Mengist, Nahla V Bassil, Pon Velayutham Anandh Babu, Massimo Iorizzo, Andrew P Neilson
{"title":"Inhibition of pro-atherogenic trimethylamine production from choline by human gut bacteria is not determined by varying chlorogenic acid content in highbush blueberries.","authors":"Ashley M McAmis, Michael G Sweet, Sydney Chadwick-Corbin, Juanita G Ratliff, Molla Fentie Mengist, Nahla V Bassil, Pon Velayutham Anandh Babu, Massimo Iorizzo, Andrew P Neilson","doi":"10.1039/d5fo02676h","DOIUrl":"https://doi.org/10.1039/d5fo02676h","url":null,"abstract":"<p><p>Elevated blood levels of trimethylamine <i>N</i>-oxide (TMAO) are linked to increased risk of atherosclerosis. TMAO is produced when gut bacteria metabolize quaternary amines such as choline to trimethylamine (TMA), which is then converted to TMAO in the liver. Chlorogenic acid (CGA), a phenolic abundant in blueberries, inhibits TMA production. Blueberries may therefore be a TMA (and TMAO)-lowering food. CGA content in blueberries varies significantly. It remains unclear whether variations in CGA levels influence the TMA-lowering activity of different cultivars. We investigated the impact of blueberry CGA content on inhibition of choline-d<sub>9</sub> conversion to TMA-d<sub>9</sub> in our upper gastrointestinal and <i>in vitro</i> human fecal model. Preliminary experiments indicated near-total inhibition of TMA-d<sub>9</sub> production when whole blueberries were tested. Blueberry pulp and sugars recapitulated this complete inhibition, whereas blueberry skins and fiber showed more moderate inhibition. We proceeded with skins (to avoid interferences from sugar-rich pulp, which would not be present in the colon <i>in vivo</i>) from 20 highbush blueberry genotypes, chosen for extremes in CGA content. CGA in whole berries was 2.6-146 mg per 100 g fresh weight, while CGA in skins was 13.6-975 mg per 100 g fresh weight. No differences were observed in TMA-d<sub>9</sub> production among the 4 highest and 4 lowest CGA genotypes in kinetic curves or area under the curve (AUC) values when skin digesta were fermented with choline-d<sub>9</sub>. However, significant differences were observed between all genotypes compared to blank digesta, with ∼19.4.% reduction in TMA-d<sub>9</sub> AUCs, indicating that skins provide similar TMA-lowering benefits across genotypes. The levels of free CGA in fermenta of skin digesta were 0.05-0.3 μM, >1000-fold lower than the minimum effective dose we observed for pure CGA <i>in vitro</i>, suggesting that blueberry CGA content is not a crucial factor for lowering TMA. Fiber also does not account for most of the inhibitory activity of blueberry skins. Further studies are needed to confirm these <i>in vitro</i> results and understand how blueberries inhibit TMA and potentially TMAO production <i>in vivo</i>.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145123797","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}