Sarah Blanchet, Mégane Bostoën, Veronique Romé, Isabelle Le Huërou-Luron, Yves Le Loir, Sergine Even, Sophie Blat
{"title":"Human milk metabolites modulate gut barrier and immunity-related genes in an <i>in vitro</i> multicellular model of intestinal epithelium.","authors":"Sarah Blanchet, Mégane Bostoën, Veronique Romé, Isabelle Le Huërou-Luron, Yves Le Loir, Sergine Even, Sophie Blat","doi":"10.1039/d5fo01144b","DOIUrl":"https://doi.org/10.1039/d5fo01144b","url":null,"abstract":"<p><p>Human milk (HM) is a complex food that meets nutritional newborn needs. The role of its bioactive components, particularly metabolites, in neonatal development remains poorly understood. This study focused on evaluating the effects of HM short chain fatty acids (SCFA), polyamines, tryptophan derivatives, gamma-aminobutyric acid (GABA), serotonin and lactate on several neonatal gut functions. The effects of these metabolites, at HM concentration, were analyzed individually or in mixture (MTB mix), on an <i>in vitro</i> multicellular model of intestinal epithelium, including Caco-2 (enterocytes), HT29-MTX (goblet cells), NCI-H716 (enteroendocrine cells) and M cells. Transcriptomic semi-screening revealed the impact of these metabolites, especially combined as a mixture, on various intestinal functions. MTB mix upregulated <i>CLDN3</i> and <i>CLDN4</i> while downregulating <i>CLDN1</i> and this was associated with a higher transepithelial resistance, highlighting its potential role in strengthening the intestinal epithelial barrier (IEB). MTB mix also reduced the expression of genes involved in mucus formation (<i>MUC1</i>, <i>TFF3</i>). Besides, MTB mix decreased immune-related gene expression (<i>CXCL8</i>, <i>MYD88</i>, <i>GPX2</i>), suggesting an immunomodulatory effect. Lastly, MTB mix decreased nutrient transporter and enzyme gene expression (<i>SLC2A1</i>, <i>SLC15A1</i>, <i>LCT</i>), suggesting that the mixture modulates digestive function. SCFA, especially butyrate, drove most of these effects, with a contribution from polyamines also, especially on IEB. Individually, GABA had a significant impact on all the examined functions, although these effects were absent with the MTB mix. Overall, this study highlights the ability of HM metabolites to modulate IEB and some genes related to the immune, digestive and endocrine functions <i>in vitro</i>, with some cumulative or attenuated effects when taken altogether <i>vs.</i> individually, emphasizing the importance of studying them as a mixture.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332091","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":"Comprehensive analysis of yak milk residue peptides for anti-hypoxic functional foods: targeting neuroinflammation and apoptosis in hypoxic mice.","authors":"Feiyan Yang, Zhang Luo, Zhongxing Chu, Zeyu He, Zuomin Hu, Guangfan Qu, Yaping Zhou, Yiping Tang, Shuguo Sun, Feijun Luo","doi":"10.1039/d5fo01223f","DOIUrl":"https://doi.org/10.1039/d5fo01223f","url":null,"abstract":"<p><p>The hypoxia-induced stress response constitutes a physiological disorder that poses a significant, life-threatening risk. This study aims to investigate the anti-hypoxic brain injury effects of peptides derived from yak milk residue and elucidate their underlying mechanisms. Peptidomic analysis identified three bioactive peptides (YPFPGPIPN, PVVPPFLQPEVMGVSK, and T3-LVYPFPGPIPN (T3)) associated with anti-hypoxic activity. <i>In vitro</i> blood-brain barrier (BBB) modeling demonstrated that T3 exhibited significant time- and concentration-dependent permeability. Under hypoxic stress, T3 effectively inhibited neuronal inflammation and apoptosis. Integrated metabolomics and transcriptomics analyses revealed that T3 mitigates hypoxia-induced neuroinflammation by regulating L-glutamine metabolism through the RAS/TNF-α/MAPK signaling pathway. These findings underscore the potential of yak milk residue-derived peptide (T3) as a neuroprotective agent against hypoxic injury. The insights gained from this research are instrumental in utilizing yak milk byproducts and developing functional foods with anti-hypoxia properties, thereby addressing the market needs of specific demographic groups.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332077","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}
Ying Cheng, Mingjie Zhou, Zishan Hong, Lin Zheng, Mouming Zhao
{"title":"Protective effects of <i>Katsuwonus pelamis</i> hydrolysates against renal injury: Val-Lys as a potent renoprotective peptide.","authors":"Ying Cheng, Mingjie Zhou, Zishan Hong, Lin Zheng, Mouming Zhao","doi":"10.1039/d5fo01092f","DOIUrl":"https://doi.org/10.1039/d5fo01092f","url":null,"abstract":"<p><p>Elevated serum uric acid (UA), a hallmark of diet-induced metabolic dysregulation, induces renal inflammation and oxidative stress, progressively leading to irreversible kidney injury (KI). Although <i>Katsuwonus pelamis</i> hydrolysates (KPHs) exhibit UA-lowering activity, their potential renoprotective effects remain unknown. In this work, KPHs ameliorating UA-induced HK-2 cell injury <i>in vitro</i> were first obtained by controlled enzymatic hydrolysis. Among them, KPHs with a high degree of hydrolysis (DH) showed relatively better activity in enhancing antioxidant enzyme activities and inhibiting the release of cytokines. Utilizing a sophisticated amalgamation of peptidomics, multivariate statistical analysis, and the random forest model, we successfully screened 13 potential renoprotective peptides, among which VK (Val-Lys) had the highest abundance in Pap-H (prepared using Papain with a high DH). <i>In vitro</i> results revealed that VK protected UA-induced HK-2 cells from injury through antioxidant defense. <i>In vivo</i> results demonstrated that VK effectively ameliorated pathological renal injury in KI rats, partially restoring kidney function, as evidenced by significant reductions in serum UA and creatinine levels. Network pharmacology analysis of the underlying mechanisms further indicated that VK might exert renoprotective effects by regulating IL-17 and TNF signaling pathways. Remarkably, our study reveals that VK functions as a potent renoprotective peptide, which may partially account for the superior renoprotective efficacy observed in KPHs.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332092","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}
Aline G A Carvalho, Luana O Oliveira, Hygor M R de Souza, Gabriela R A Soliz, Maria Fernanda C Guimarães, Fabio A Oroski, Vanessa N Castelo-Branco, Tatiana El-Bacha, Alexandre G Torres
{"title":"Biomarkers of fried food intake: a systematic review of <i>in vivo</i> studies.","authors":"Aline G A Carvalho, Luana O Oliveira, Hygor M R de Souza, Gabriela R A Soliz, Maria Fernanda C Guimarães, Fabio A Oroski, Vanessa N Castelo-Branco, Tatiana El-Bacha, Alexandre G Torres","doi":"10.1039/d4fo05008h","DOIUrl":"https://doi.org/10.1039/d4fo05008h","url":null,"abstract":"<p><p>The purpose of this review was to evaluate the evidence of potential biomarkers of fried food intake in human and animal studies, assessing the study design, the biospecimens and the metabolomic approach used. Information about dietary and health biomarkers concerning fried food intake is limited, even though advanced databases exist for human and food metabolomes. The systematic search following the PRISMA protocol selected five articles comprising <i>in vivo</i> intervention studies in humans (<i>n</i> = 4) and in animals (<i>n</i> = 1). Study characteristics were: (a) urine was the most common biospecimen; (b) potato and meat were the most common fried food items; (c) non-targeted MS-metabolomics and lipidomics were the main approaches used. Current and previous research commonly address potential biomarkers of fried food intake by dietary surveys, which are subject to inaccuracies. Controlled intervention trials combined with advanced metabolomics technologies to investigate biomarkers in humans or animals are scarce, highlighting the need of efforts for a better comprehension of the mechanisms involved and the health effects of fried food consumption. Biomarkers of deep-fried and pan-fried food intake included short-chain fatty acids and amino acids. Acrolein and acrylamide derivatives in urine were common biomarkers of fried food intake. In conclusion, the number of published papers in this research subject shows that it remains largely uninvestigated. This is a timely subject due to the high appeal to the consumption of fried foods and the possible harmful health effects related to the products formed during frying. Future studies describing robust biomarkers of fried food intake will contribute to the understanding of health outcomes related to the consumption of fried food.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323892","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}
Jeng-Rong Lin, Wen-Chieh Liao, Yin-Hung Chu, Yu-Cheng Chou, Chiung-Hui Liu
{"title":"Phenethyl isothiocyanate modulates macrophage migration inhibitory factor and suppresses malignant phenotypes of glioblastoma cells.","authors":"Jeng-Rong Lin, Wen-Chieh Liao, Yin-Hung Chu, Yu-Cheng Chou, Chiung-Hui Liu","doi":"10.1039/d5fo00415b","DOIUrl":"https://doi.org/10.1039/d5fo00415b","url":null,"abstract":"<p><p>Phenethyl Isothiocyanate (PEITC) is a well-studied compound within the isothiocyanate family. Accumulating evidence indicates that PEITC induces apoptosis and inhibits the growth of various cancer cells <i>in vitro</i>, including aggressive glioblastoma cells. However, its tumor suppression effects and mechanisms <i>in vivo</i> remain largely unexplored. In this study, we utilized cell culture experiments and an orthotopic transplant brain tumor model in mice to evaluate the impact of PEITC on tumor growth, physiological changes, and immune cell populations. Our results showed that PEITC significantly reduced the viability of glioma cells while having moderate effects on astrocytes. <i>In vitro</i>, PEITC effectively inhibited cell viability, migration, and invasion in GL-261 cells. <i>In vivo</i>, PEITC treatment led to prolonged survival rates and reduced tumor volumes in mice without significant toxicity. Notably, PEITC increased the populations of natural killer (NK) cells and natural killer T (NKT) cells in peripheral blood, indicating an immunomodulatory effect. Migration Inhibitory Factor (MIF) was identified as a potential direct target of PEITC. Our findings revealed that PEITC significantly reduced MIF expression in GL-261 cells, both in culture and in orthotopic tumor tissue, and decreased MIF-induced cellular signaling. These results suggest that PEITC has potential to be a therapeutic agent for glioblastoma by inhibiting tumor growth and modulating the immune response through MIF suppression.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315597","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":"D-Tagatose attenuates DSS-induced ulcerative colitis by inhibiting inflammation, reducing intestinal barrier damage and modulating the intestinal flora composition.","authors":"Le Wang, Houzhen Lu, Haitao Gui, Zifu Ni, Zhongke Sun, Zihua Wang, Zhihua Wang, Xuanyan Liu, Qipeng Yuan","doi":"10.1039/d4fo06475e","DOIUrl":"https://doi.org/10.1039/d4fo06475e","url":null,"abstract":"<p><p>Ulcerative colitis (UC) is a prevalent inflammatory bowel disease (IBD) posing a significant health threat. This study explored the protective effects of D-tagatose against DSS-induced colitis in mice and its underlying mechanisms using H&E staining, AB-PAS staining, immunofluorescence, immunohistochemistry, ELISA, qPCR, western blotting, and other assays. D-Tagatose improved colitis by increasing body weight and colon length, with decreased DAI (disease activity index) and histopathological scores. The results showed that D-tagatose inhibited the secretion of myeloperoxidase (MPO), inflammatory enzymes (iNOS and COX-2) and pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) as well as increased the content of anti-inflammatory cytokines (IL-10) <i>in vitro</i>. In addition, D-tagatose enhanced the expression of tight junction proteins (ZO-1 and Occludin) and mucin (MUC-2). Furthermore, D-tagatose was able to modulate the gut microbiota dysbiosis caused by DSS-induced UC and increased the content of short-chain fatty acids (SCFAs). This study indicated that D-tagatose attenuated DSS-induced UC by modulating inflammatory cytokines, restoring intestinal barrier function, maintaining gut microbiota homeostasis, and enhancing SCFA production. These findings provide D-tagatose as a safe and effective novel functional food strategy for the prevention and treatment of UC.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315595","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}
Yifan Lei, Shuyan Sun, Liping Chen, Yongzhong Wang
{"title":"2'-Fucosyllactose evokes colonization of <i>Alloprevotella</i> and alleviates renal injury in hyperuricemia mice.","authors":"Yifan Lei, Shuyan Sun, Liping Chen, Yongzhong Wang","doi":"10.1039/d5fo00580a","DOIUrl":"https://doi.org/10.1039/d5fo00580a","url":null,"abstract":"<p><p>Hyperuricemia (HUA) is a metabolic disease characterized by the overproduction of uric acid (UA) in the blood, with an increasing prevalence of associated renal injury. Intestinal microbiota and its associated metabolites are important mediators in the gut-kidney axis that can induce renal impairment. This study investigated the effect of 2'-fucosyllactose (2'FL) on HUA and its underlying mechanisms. In a hyperuricemic <i>Caenorhabditis elegans</i> model, 2'FL reduced the xanthine-induced UA levels and oxidative stress. In a HUA mice model induced with potassium oxonate and UA, 2'FL intervention (200 mg per kg body weight per d) improved UA metabolism and decreased the serum UA concentration, xanthine oxidase activity, blood urea nitrogen, and creatinine levels. 2'FL also alleviated renal injury, inflammatory response and oxidative stress, as evidenced by the reduced lipopolysaccharide, interleukin-6, and malondialdehyde levels and myeloperoxidase activity and increased interleukin-10 level and total antioxidant capacity. 2'FL enhanced renal UA excretion by upregulating ATP-binding cassette subfamily G member 2 (ABCG2) expression and downregulating urate transporter 1 (URAT1) expression. It inhibited renal ferroptosis by restoring the nuclear factor erythroid 2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPX4) pathway and alleviated renal injury. In the gut, 2'FL protected the intestinal barrier, increased fecal short-chain fatty acids, and modulated intestinal microbiota composition. In particular, it reversed the HUA-induced changes in the <i>Firmicutes</i>/<i>Bacteroidetes</i> ratio and affected the abundance of certain genera correlated with UA metabolism. These findings suggest that 2'FL is a potential natural agent for HUA treatment with multiple beneficial effects on metabolism, renal function, and gut microbiota.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323891","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}
Pengkui Xia, Bin Li, Yudie Yu, Wanxu Yu, Mahmoud Youssef, Tao Hou, Jing Li
{"title":"Dietary strategies for appetite regulation: satiety and obesity management.","authors":"Pengkui Xia, Bin Li, Yudie Yu, Wanxu Yu, Mahmoud Youssef, Tao Hou, Jing Li","doi":"10.1039/d5fo01349f","DOIUrl":"https://doi.org/10.1039/d5fo01349f","url":null,"abstract":"<p><p>Increased prevalence of diseases associated with obesity has driven research into appetite suppression to reduce high-calorie intake. Dietary modulation of appetite is recognized as one of the most significant and effective ways to reduce the risk of obesity-related diseases. This review evaluates the roles of dietary nutrients and their metabolites in satiety and proposes dietary strategies for appetite regulation. Brain circuits of hunger, hormones and organs that directly control the appetite, and the role of gut microbiota in indirect appetite modulation are discussed in detail. We explored the impact of dietary nutrients and their metabolites on appetite, based on the basic mechanics of hunger. Additionally, based on the impact of different dietary factors on satiety, we outlined three strategies for appetite regulation: systems for controlled nutrient delivery to decelerate digestion, alteration of dietary physicochemical characteristics, and establishment of dietary rhythms. This review presents a theoretical framework for examining the influence of dietary nutrition on appetite regulation.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309318","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}
Qi Cheng, Kun Na, Chunsheng Xu, He Peng, Xiaojian Lin, Jiajun Chen, Yan Li, Die Wu, Menghao Du, Xingya Wang
{"title":"Untargeted metabolomics reveals the inhibition effect of a high-fat diet on colorectal cancer tumorigenesis in obesity-resistant mice <i>via</i> regulating bile acid, glutathione, and glycerophospholipid metabolisms.","authors":"Qi Cheng, Kun Na, Chunsheng Xu, He Peng, Xiaojian Lin, Jiajun Chen, Yan Li, Die Wu, Menghao Du, Xingya Wang","doi":"10.1039/d4fo06132b","DOIUrl":"https://doi.org/10.1039/d4fo06132b","url":null,"abstract":"<p><p>The interplay between high fat intake and cancer is complex and multifaceted. Contradictory results exist between obesity, high-fat diet (HFD), and colorectal cancer (CRC), necessitating further research. In this study, we investigated the effect of HFD on tumorigenesis in obesity-resistant and obesity-susceptible mouse models. Our results revealed that HFD significantly inhibited CRC HCT116 and HT-29 xenograft tumor growth in obesity-resistant BALB/c nude mice in comparison with a low-fat diet (LFD). HFD feeding did not induce increases in body weight, serum pro-inflammatory cytokines, and lipid accumulation in the liver and white adipose tissue (WAT) in nude mice. However, HFD promoted tumor growth in melanoma B16-F10-bearing C57BL/6J mice, accompanied by obesity and increased pro-inflammatory cytokine levels. Untargeted metabolomics showed that HFD induced significantly changed metabolites in serum, tumor, and liver samples of the HCT116 xenograft model. In all samples, many glycerophospholipids (<i>e.g.</i> LysoPE (0:0/20:1) and LysoPC (16:1)) and bile acids (<i>e.g.</i> glycocholic acid and chenodeoxycholic acid) were significantly reduced by HFD. Enrichment and pathway analyses suggested that bile acid biosynthesis and metabolisms of lipids, amino acids, and organic acids were significantly regulated by HFD. Additionally, the glutathione metabolism was significantly downregulated, while the TCA cycle was upregulated by HFD in tumor samples. Moreover, univariate and multivariate analyses on the differential metabolites in tumors suggested that uracil, chenodeoxycholic acid, glutathione, LysoPE (0:0/20:1), and SM (d18:1/18:0) were the main metabolite biomarkers for discrimination between LFD- and HFD-fed xenograft tumors. These findings suggest that HFD elicits an anti-tumorigenic effect against CRC in obesity-resistant BALB/c nude mice <i>via</i> regulating bile acid, glutathione, and glycerophospholipid metabolisms.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315598","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":"Effect comparison of inulin with different molecular weights ameliorating intracerebral neuroinflammation induced by advanced glycation end products (AGEs) in diabetic mice.","authors":"Yanqi Li, Aizhen Zong, Cuiju Xu, Lina Liu, Yashi Zhang, Baorui Li, Fangling Du, Tongcheng Xu","doi":"10.1039/d5fo00867k","DOIUrl":"https://doi.org/10.1039/d5fo00867k","url":null,"abstract":"<p><p>Inulin is widely recognized for reducing glucose levels in diabetes mellitus, but its role in concurrent diabetic encephalopathy has rarely been reported. In this study, type 2 diabetic KK-Ay mice were administered inulin with different molecular weights for 10 weeks. Intriguingly, a significant decrease in the level of inflammatory factors IL-1β and Aβ protein deposition occurred in brain tissue based on immunofluorescence analysis when the mice were treated with inulin with different molecular weights, especially in the H (5-10 kDa) group, indicating that inulin was beneficial for ameliorating intracerebral neuroinflammation. RNA-seq analysis indicated that this effect might be related to the inactivation of the RAGE-mediated inflammatory pathway. Based on ELISA and western blot analysis, inulin in the H group significantly decreased AGEs content and downregulated the expression of RAGE as well as downstream NFκB and its phosphorylation, validating the above speculation. This was attributed to the fact that inulin has excellent scavenging ability of AGEs intermediate dicarbonyl compounds to block the glycation reaction, according to the <i>in vitro</i> BSA-FRU model analysis. Gut microbes such as <i>Desulfovibrionaceae</i> also contributed to the degradation of AGEs <i>in vivo</i>. In conclusion, this study highlighted a new application perspective of inulin in the treatment of diabetic complications.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309319","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}