Yan Liu, Tian Zhao, Zhangtie Wang, Yansong Zhang, Jianfu Shen, Baiyi Lu
{"title":"The microbiome- and metabolome-modulating activity of dietary cholesterol: insights from the small and large intestines.","authors":"Yan Liu, Tian Zhao, Zhangtie Wang, Yansong Zhang, Jianfu Shen, Baiyi Lu","doi":"10.1039/d4fo03049d","DOIUrl":"10.1039/d4fo03049d","url":null,"abstract":"<p><p>Cholesterol is an important lipid molecule that affects the gut microbiome upon ingestion. We systematically investigated the effects of cholesterol on the microbiota of the large and small intestines using <i>ex vivo</i> and <i>in vivo</i> models, combining flow cytometry, metabolomics, and metagenomics. The results showed that cholesterol directly causes a loss of bacterial membrane polarity and integrity, as well as a reduction in microbial metabolic activity. Cholesterol directly affected the global metabolism of the large and small intestinal microbiota, including amino acid, carbohydrate, and nucleotide metabolism. <i>Ex vivo</i> and <i>in vivo</i> studies shared similar results, showing that cholesterol increased the abundance of the primary bile acid-metabolizing bacteria <i>Clostridium</i> and <i>Dorea</i> in the large intestinal microbiota, confirming the enrichment effect of cholesterol on these bacteria. In the <i>in vivo</i> model, increased conjugated bile acids in the small intestine and decreased abundance of BSH-containing <i>Bifidobacterium</i> were observed due to cholesterol. Only <i>in vivo</i> models have demonstrated that cholesterol increases phosphatidylcholine levels in both the small and large intestines, which may be related to the effects of cholesterol on host metabolism. The pro-inflammatory capacity of the intestinal microbiota was enhanced by cholesterol, as evidenced by the increased levels of IL-1β and TNF-α in THP-1 cells upon stimulation with cholesterol-treated microbiota. This study comprehensively elucidates the effects of cholesterol on the composition and metabolic functions of the microbiota in both the large and small intestines. It offers a novel perspective on the ways in which cholesterol affects host metabolism <i>via</i> the gut microbiome.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389549","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}
Irene Peñaranda, María Dolores Garrido, Purificación García-Segovia, Javier Martínez-Monzó, Marta Igual
{"title":"Effect of protein texturization on amino acids and protein <i>in vitro</i> bioaccessibility of pea and rice protein.","authors":"Irene Peñaranda, María Dolores Garrido, Purificación García-Segovia, Javier Martínez-Monzó, Marta Igual","doi":"10.1039/d4fo04829f","DOIUrl":"https://doi.org/10.1039/d4fo04829f","url":null,"abstract":"<p><p>The growing demand for vegetable proteins, driven by population increase and interest in sustainable protein-rich diets, has generated a focus on the use of legumes and cereals as protein sources for the production of meat analogues due to their complementary nutritional profile and lower environmental impact. However, the analogues should not only imitate the nutritional profile of meat, but their texture is also important for good commercialization. One of the processes used to improve these properties is protein texturization by thermoextrusion, which could modify the availability and digestibility of amino acids. Thus, the objective of this work is to evaluate the <i>in vitro</i> bioaccessibility of proteins and amino acids from pea and rice protein isolates (I) and texturized proteins (T). Proteins from pea (PP), rice (RP) and a 50 : 50 mixture (PRP) were processed by extrusion, evaluating the effects on digestibility and bioaccessibility of essential (EAA) and non-essential (NEAA) amino acids. The results showed higher <i>in vitro</i> digestibility and bioaccessibility of NEAA of texturized proteins compared to isolated proteins, although this effect is not significant for PP. However, texturization significantly reduced the bioaccessibility of some EAA such as lysine. Rice protein showed greater stability during the extrusion process, maintaining a more balanced amino acid profile. Texturization can therefore be a useful tool to improve the functionality of vegetable proteins, but it is necessary to optimize the process to minimize nutritional losses.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381127","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}
Shunyi Zhu, Xing Li, Shixuan Zhang, Ziwen Cai, Jianhao Sun, Qi Ju, Diru Liu
{"title":"Effects of whey protein-inulin conjugates with varying degrees of glycosylation on hepatic antioxidant capacity, immunomodulation and gut microbiota in mice.","authors":"Shunyi Zhu, Xing Li, Shixuan Zhang, Ziwen Cai, Jianhao Sun, Qi Ju, Diru Liu","doi":"10.1039/d4fo05846a","DOIUrl":"https://doi.org/10.1039/d4fo05846a","url":null,"abstract":"<p><p>In this study, whey protein isolate-inulin (WPI-In) conjugates with varying degrees of glycosylation (DG) were prepared, characterized, and examined for their potential immunomodulatory effects and regulation of gut microbiota in mice. The data indicated that an increase in DG significantly affects the microstructure and functionalities of WPI-In conjugates. The WPI-In conjugates with high DG promoted the growth and development of the thymus while altering gut microbiota composition by increasing the relative abundance of <i>Bacteroidetes</i> and reducing that of <i>Firmicutes</i>. Additionally, the WPI-In conjugates enhanced liver antioxidant capacity and the secretion of immunoglobulin G, and elevated levels of anti-inflammatory cytokines (IL-4 and IL-2), while decreasing pro-inflammatory cytokine (TNF-α) content in serum. Spearman correlation analysis suggested that the enhancement of liver antioxidant capacity and regulation of immune-related indicators may be associated with the gut microbiota altered by WPI-In conjugates. Therefore, WPI-In conjugates demonstrate beneficial properties, indicating potential applications in food systems.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381128","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}
Umberto Lanza, Marilisa Alongi, Barbara Frossi, Carlo Pucillo, Monica Anese, Maria Cristina Nicoli
{"title":"Investigating the hypoglycaemic potential of processed apple and acarbose combination <i>in vitro</i>, <i>ex vivo</i>, and <i>in vivo</i>: the role of quercetin-3-glucoside in steering α-glucosidase inhibition.","authors":"Umberto Lanza, Marilisa Alongi, Barbara Frossi, Carlo Pucillo, Monica Anese, Maria Cristina Nicoli","doi":"10.1039/d4fo06307d","DOIUrl":"https://doi.org/10.1039/d4fo06307d","url":null,"abstract":"<p><p>This study investigated the interaction between apple juice (AJ) and acarbose (A) in modulating glycaemic responses, with the aim of validating <i>in vivo</i> results previously observed <i>in vitro</i>. When administered to rats, AJ alone reduced the glycemic curve, but the combination of AJ with increasing doses of A resulted in higher glycemic responses, suggesting an antagonistic interaction in α-glucosidase inhibition. To explore this mechanism, quercetin-3-glucoside (Q-3-G), a major phenolic compound in AJ, was tested for α-glucosidase inhibition <i>in vitro</i>. Q-3-G and A together showed reduced inhibitory efficacy compared to either compound alone, consistent with <i>in vivo</i> findings. <i>Ex vivo</i> studies in Caco-2 cells further supported this antagonism. Sucrose hydrolysis experiments showed that low concentrations of Q-3-G increased residual sucrose when combined with moderate concentrations of A, but higher concentrations of Q-3-G favoured sucrose hydrolysis regardless of A levels. The results highlight the antagonistic interaction between Q-3-G and A in inhibiting α-glucosidase and emphasise the need to combine <i>in vitro</i>, <i>ex vivo</i> and <i>in vivo</i> studies to evaluate food-drug interactions. This comprehensive approach is essential before advocating the use of functional foods alongside pharmacological therapies.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381236","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":"Identification and efficacy of anti-allergic peptides from phycocyanin hydrolysate.","authors":"Jing Dai, Ishfaq Ahmed, Hailing Yin, Guojing Xu, Zongyu Zhang, Liangtao Lv","doi":"10.1039/d4fo05802j","DOIUrl":"https://doi.org/10.1039/d4fo05802j","url":null,"abstract":"<p><p>Phycocyanin (PC) is a protein that possesses a multitude of bioactive components with nutritional and pharmaceutical properties. This study used continuous chromatographic techniques such as ultrafiltration centrifugation, Superdex™ increase 10/300 GL gel filtration chromatography, liquid chromatography-tandem mass spectrometry (LC/MS/MS), and reverse-phase high-performance liquid chromatography (RP-HPLC). The antiallergic peptides from PC were obtained by alcalase hydrolysis and were then screened and identified. F3-III showed strong anti-allergic activity (77.25%) among the components (F3-I-F3-V) obtained by RP-HPLC. Subsequently, a novel peptide comprising six amino acids, designated FPYTTQ, was identified and demonstrated potent anti-allergic properties by inhibiting the release of β-hexosaminic (β-HEX) acid and histamine during IgE-mediated RBL-2H3 cell threshing. Therefore, it can be concluded that the polypeptide FPYTTQ, derived from PC, can be employed as an effective anti-allergic agent and that PC represents a promising source of novel ingredients for the development of anti-allergic foods and pharmaceuticals.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381140","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}
L Bell, G F Dodd, M Jeavons, D R Fisher, A R Whyte, B Shukitt-Hale, C M Williams
{"title":"The impact of a walnut-rich breakfast on cognitive performance and brain activity throughout the day in healthy young adults: a crossover intervention trial.","authors":"L Bell, G F Dodd, M Jeavons, D R Fisher, A R Whyte, B Shukitt-Hale, C M Williams","doi":"10.1039/d4fo04832f","DOIUrl":"https://doi.org/10.1039/d4fo04832f","url":null,"abstract":"<p><p>A healthy diet is essential for optimal brain health and many bioactives from food are linked to cognitive benefits. To examine whether walnuts led to cognitive improvements throughout the day, 32 healthy young adults, aged 18-30, were tested in a double-blind, crossover pilot study, to compare the effects of a breakfast containing 50 g walnuts with a calorie-matched control containing no nuts. Cognition, mood, blood, and EEG measures were recorded at baseline and 2, 4, and 6 hours postprandially. Mood ratings for negative affect appeared worse following walnuts compared to control, possibly due to a general dislike of the intervention. However, walnuts elicited faster reaction times throughout the day on executive function tasks. Memory recall performance at 2 hours was worse for walnuts compared to control, but by 6 hours this finding was reversed with walnuts outperforming the control. EEG PSD analysis revealed differences in frontoparietal activity in the walnut condition compared to the control condition during memory recall and during executive function performance. These results may reflect between-treatment differences in cognitive effort or attentional processes while performing the tasks. Blood analysis revealed lower circulating non-esterified fatty acids and small increases in glucose availability following consumption of walnuts compared to control, suggesting enhanced glucose availability as one possible mechanism of action. Further investigations of other potential mechanisms are needed. Overall, these findings provide evidence for reaction time benefits throughout the day following a walnut-rich breakfast, while memory findings were mixed with benefits only observed later in the day. However, more research is needed into how diets containing walnuts might regulate cognitive improvements in humans postprandially and over the longer term.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381239","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":"γ-Linolenic acid derived from <i>Lactobacillus plantarum</i> MM89 induces ferroptosis in colorectal cancer.","authors":"Yan Chen, Yijie Zhang, Mengmeng Dai, Cheng Qiu, Qinsheng Sun, Tingting Fan, Yuan Guo, Liqing Zhao, Yuyang Jiang","doi":"10.1039/d4fo04790g","DOIUrl":"https://doi.org/10.1039/d4fo04790g","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is one of the most prevalent cancers worldwide; however, current treatment options are inadequate, necessitating the exploration of new therapeutic strategies. The microbiota significantly influences the tumor microenvironment, suggesting that probiotics may serve as promising candidates for cancer treatment. We previously identified a novel probiotic, <i>Lactobacillus plantarum</i> MM89 (<i>L. plantarum</i> MM89), which was found to regulate the immune microenvironment. However, its specific role in CRC remained unclear. In this study, we employed an azoxymethane/dextran sodium sulfate-induced carcinogenesis mouse model to evaluate the therapeutic effects of <i>L. plantarum</i> MM89 <i>in vivo</i>. Transcriptome analysis was conducted to elucidate the mechanisms of action of <i>L. plantarum</i> MM89. Ferroptosis induction in tumor cells was assessed through cell viability assays and C11-BODIPY staining. Liquid chromatography/mass spectrometry was used to identify metabolites derived from <i>L. plantarum</i> MM89. MitoTracker and MitoTracker CMXRos staining and ATP content measurements were performed to assess mitochondrial damage. <i>L. plantarum</i> MM89 significantly inhibited tumor growth <i>in vivo</i> and alleviated intestinal inflammation at non-tumor foci. Transcriptome analysis and immunohistochemistry revealed that <i>L. plantarum</i> MM89 enhanced arachidonic acid metabolism. Small molecules present in the <i>L. plantarum</i> MM89 supernatant induced ferroptosis in cancer cells, as indicated by cell viability and C11-BODIPY assays. Furthermore, γ-linolenic acid (γ-LA) derived from <i>L. plantarum</i> MM89 was shown to induce ferroptosis <i>via</i> mitochondrial damage. In conclusion, γ-LA derived from <i>L. plantarum</i> MM89 triggers ferroptosis in tumor cells by inducing mitochondrial damage, highlighting its potential as a novel therapeutic agent for CRC treatment.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381243","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":"Higher dietary intake of live microbes is inversely associated with accelerated biological aging.","authors":"Da Gan, Xiaoyan Wang, Xuebiao Wu, Shuang Han","doi":"10.1039/d4fo04230a","DOIUrl":"https://doi.org/10.1039/d4fo04230a","url":null,"abstract":"<p><p><i>Objective</i>: It remains unclear whether dietary live microbe intake is associated with biological aging. Therefore, the present study aimed to investigate the associations between dietary live microbe intake and biological aging. <i>Methods</i>: Our study included 7719 participants aged 20 years and older from the 2007-2010 cycles of the National Health and Nutrition Examination Survey (NHANES). Participants were categorized into groups using two distinct methods. The first method grouped participants based on the live microbial level of the consumed foods, dividing them into three dietary live microbe intake groups: low, medium, and high. The second method classified participants according to the quantity of live microbe-containing foods they consumed (referred to as MedHi), with three groups: G1 (no MedHi intake), G2 (MedHi intake below the median), and G3 (MedHi intake above the median). Biological age was evaluated using the Klemera-Doubal method biological age (KDM-BA) and phenotypic age (PA). KDM-BA acceleration and PA acceleration was determined if participants' KDM-BA or PA exceeded their chronological age, respectively. Multivariable logistic regression models were conducted to explore the associations of dietary live microbe intake groups and dietary MedHi intake groups with the acceleration of KDM-BA and PA. <i>Results</i>: Compared with participants in the low dietary live microbe intake group, those in the high dietary live microbe intake group had a 20% (95% CI: 2% to 35%) reduced risk of KDM-BA acceleration and a 25% (95% CI: 4% to 42%) reduced risk of PA acceleration. Similarly, participants in the G3 group with higher dietary MedHi intake had a 24% (95% CI: 10% to 35%) lower risk of KDM-BA acceleration and a 29% (95% CI: 17% to 39%) lower risk of PA acceleration compared with those in the G1 group. The stratified analyses showed that the associations of dietary MedHi intake with accelerated KDM-BA and PA were not influenced by age, gender, race, smoking, alcohol consumption, physical activity, race, and history of hypertension, diabetes, and cardiovascular disease. <i>Conclusion</i>: Higher dietary intake of live microbes was inversely associated with accelerated biological aging. A diet rich in live microbes may help slow down the aging process.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381139","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}
Rui Long, Shimei Lu, Xiuhui Chen, Weijun Ye, Tengfei Wang, Xingyun Wang, Fengdan Xu, Ning Li
{"title":"Human milk peptide MAMP-1 alleviates necrotizing enterocolitis <i>via</i> inhibition of the TLR4-mediated PI3K-AKT-NF-κB signaling pathway.","authors":"Rui Long, Shimei Lu, Xiuhui Chen, Weijun Ye, Tengfei Wang, Xingyun Wang, Fengdan Xu, Ning Li","doi":"10.1039/d4fo05556j","DOIUrl":"https://doi.org/10.1039/d4fo05556j","url":null,"abstract":"<p><p><i>Background</i>: Necrotizing enterocolitis (NEC) is a disease with prevalent and serious intestinal inflammation that poses a significant threat to the lives of newborns. Human milk has been shown to prevent and treat the occurrence of NEC; however, the underlying mechanisms remain unclear. MAMP-1 is a significantly overexpressed endogenous peptide derived from β-casein extracted from the human milk of premature mothers, which is resistant to gastrointestinal conditions and exhibits favorable physicochemical properties. This study aims to investigate the mechanism by which the human milk-derived peptide MAMP-1 mitigates NEC in mice, offering new insights for clinical treatment. <i>Methods</i>: The C57BL/6 mice were categorized into three distinct groups randomly on the 7th day after birth, with 40 mice in each group. The NEC model was established using \"artificial feeding + hypoxia + cold\", and the MAMP-1 group received daily MAMP-1 gavage during NEC modeling. Ileum tissues and feces were collected. Pathological damage in the intestines was evaluated by H&E staining. ZO-1 expression was analyzed through immunofluorescence staining and western blot. Apoptosis in the intestine was assessed using western blot and TUNEL staining. The effects of signaling pathways were confirmed through western blot and RNA sequencing. The expression of inflammatory factors was assessed using RT-PCR. 16S high-throughput sequencing was used to determine the diversity and abundance of the gut microbiota. <i>Results</i>: MAMP-1 reduced the mortality rate of NEC mice, alleviated ileum injury, increased the ZO-1 expression of the intestinal barrier, reduced the apoptotic protein expression, lowered the TUNEL positive area, increased anti-apoptotic protein expression, and reduced the levels of TLR4, P-PI3K, P-AKT, and NF-κB, leading to a reduction in the release of inflammatory cytokines. Furthermore, MAMP-1 decreased the abundance of harmful bacteria and increased the abundance of beneficial bacteria at both the phylum and genus levels. <i>Conclusion</i>: MAMP-1 might inhibit the TLR4-PI3K-AKT-NF-κB signaling pathways, further reducing inflammation factor release, and might decrease intestinal cell apoptosis. Results indicated that MAMP-1 might alleviate intestinal damage in NEC mice. Meanwhile, MAMP-1 might positively modulate the composition of the microbiota of NEC mice and further achieve the preventive and therapeutic effect of MAMP-1 on NEC.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363350","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}
Bart G. J. Moerings, Coen Govers, Jeroen van Bergenhenegouwen, Jurriaan J. Mes, Miriam van Dijk, Renger F. Witkamp, Klaske van Norren and Suzanne Abbring
{"title":"Induction of endotoxin tolerance in murine monocyte and macrophage cell populations – optimal LPS dose and compartment-specific reversal by β-glucan†","authors":"Bart G. J. Moerings, Coen Govers, Jeroen van Bergenhenegouwen, Jurriaan J. Mes, Miriam van Dijk, Renger F. Witkamp, Klaske van Norren and Suzanne Abbring","doi":"10.1039/D4FO05223D","DOIUrl":"10.1039/D4FO05223D","url":null,"abstract":"<p >Beta-glucans, naturally present in foods like wheat, mushrooms, and yeast, have shown potential in reversing immunosuppression. However, the existing evidence solely relies on <em>ex vivo</em> studies assessing direct effects of β-glucans on macrophages. To investigate whether such effects also occur after their oral administration, this study first systematically examined the immunosuppressive effects of LPS in mice. Subsequently, we assessed the ability of yeast-derived whole β-glucan particles (yWGP), administered through the diet, to counteract LPS-induced immunological tolerance. Immunosuppression following intraperitoneal administration of 20, 200, or 2000 μg kg<small><sup>−1</sup></small> LPS was demonstrated by reduced TNF-α and IL-6 release upon <em>ex vivo</em> LPS stimulation of immune cells harvested from the peritoneal fluid, spleen, and bone marrow. Immunosuppression in blood was detected only after 200 and 2000 μg kg<small><sup>−1</sup></small> LPS. LPS tolerance extended to heterologous stimuli (PAM3Cys, heat-killed <em>Pseudomonas aeruginosa</em>), indicating cross-tolerance. Due to animal discomfort at 2000 μg kg<small><sup>−1</sup></small> LPS, as evidenced by a significantly enhanced clinical severity score, a dose of 200 μg kg<small><sup>−1</sup></small> LPS was selected for the follow-up trial. In this experiment, mice fed a yWGP-supplemented diet for two weeks prior to LPS administration showed effective reversal of LPS tolerance, reflected by restored TNF-α levels in peritoneal cells but not in other monocyte- and macrophage-containing cell populations. Together, these studies demonstrate that peritoneal administration of 200 μg kg<small><sup>−1</sup></small> LPS induced <em>ex vivo</em> LPS tolerance in all immunological organs studied, without significantly compromising animal welfare. The selective efficacy of dietary β-glucans to counteract immunosuppression, which is often observed in vulnerable and immunocompromised patient populations, warrants further clinical evaluation.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" 4","pages":" 1576-1587"},"PeriodicalIF":5.1,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11803501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}