{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T21:14:48Z","timestamp":1784322888043,"version":"3.55.0"},"reference-count":89,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T00:00:00Z","timestamp":1753056000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Resveratrol (RES) and \u03b2-hydroxy-\u03b2-methylbutyric acid (HMB) have been shown to improve growth performance in Tibetan sheep by regulating the gut microbiota. This study explored the effects of RES and HMB supplementation on the microbial composition and metabolite levels in the ileum of Tibetan sheep receiving diets with different protein levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In a 2 \u00d7 2 factorial arrangement, consisting of dietary protein levels (12% and 14%) and feed additive levels (no addition; and RES 1.50 g\/d and HMB 1.25 g\/d addition). A total of 120 healthy two-month-old male Tibetan lambs (16.87 \u00b1 0.31) were randomly divided into 4 groups (<jats:italic>n = 6<\/jats:italic>): 12% protein level group (L), the 12% protein level supplemented with RES and HMB group (L-RES-HMB); the 14% protein level group (H); and the 14% protein level supplemented with RES and HMB group (H-RES-HMB).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The results demonstrated that the activities of digestive enzymes (\u03b2-amylase, trypsin, lipase, and cellulase), the levels of antibodies (IgA and IgM), and the contents of short-chain fatty acid (SCFA) (butyric acid) were significantly increased in the H-RES-HMB group (<jats:italic>P<\/jats:italic> &amp;lt; 0.05). Additionally, RES and HMB supplementation affected the morphology of ileum tissue, improving the villus height, crypt depth, and mucosal thickness (<jats:italic>P<\/jats:italic> &amp;lt; 0.05). Microbial analysis revealed that compared with the L-RES-HMB group, the H-RES-HMB group had a higher abundance of <jats:italic>Planctomycetota<\/jats:italic>, <jats:italic>Solibacillus<\/jats:italic>, and <jats:italic>Paenibacillus<\/jats:italic> (<jats:italic>P<\/jats:italic> &amp;lt; 0.05). Metabolomics analysis revealed a total of 229 significantly different metabolites, of which Irinotecan, Erdosteine thioacid, 4,4\u2019-diaminodiphenylmethane, and Morphine N-oxide emerged as the key up-regulated metabolites. These differential metabolites were mainly enriched in pathways such as protein digestion and absorption, metabolic pathways, and mineral absorption.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Overall, when the dietary protein content was 14%, digestive enzyme activities, immune responses, and SCFAs levels in the ileum were improved, and the mucosal morphology of the ileum was enhanced. When the 14% protein diet was supplemented with RES and HMB, the concentration of butyric acid was increased. This increase was due to the regulation of the ileum microbiota (Firmicutes and <jats:italic>Clostridium_sensu_stricto_1<\/jats:italic>) and metabolites (xanthine and uric acid), which promoted the activities of digestive enzymes and immune responses and improved mucosal morphology in the ileum.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2025.1612170","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T10:17:20Z","timestamp":1753093040000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Exploring the effects of resveratrol and \u03b2-hydroxy-\u03b2-methylbutyric acid under different protein levels on the ileal health of tibetan sheep"],"prefix":"10.3389","volume":"16","author":[{"given":"Wei","family":"Gao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaina","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianhua","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geerli","family":"Saren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiacheng","family":"Gan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengzhen","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linsheng","family":"Gui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"625","DOI":"10.30466\/vrf.2023.560224.3650","article-title":"Effects of dietary resveratrol supplementation on digestive enzymes activities and serum biochemistry of rainbow trout (Oncorhynchus mykiss).","volume":"14","author":"Afzali-Kordmahalleh","year":"2023","journal-title":"Vet. Res. Forum."},{"key":"B2","doi-asserted-by":"publisher","first-page":"114958","DOI":"10.1016\/j.anifeedsci.2021.114958","article-title":"Effects of three probiotic strains (Bacillus coagulans, B. licheniformis and Paenibacillus polymyxa) on growth, immune response, gut morphology and microbiota, and resistance against Vibrio harveyi of northern whitings, Sillago sihama Forssk\u00e1l (1775).","volume":"277","author":"Amoah","year":"2021","journal-title":"Anim. Feed Sci. Technol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"148","DOI":"10.3390\/antiox7100148","article-title":"A review of the effects of leucine metabolite (\u03b2-hydroxy-\u03b2-methylbutyrate) supplementation and resistance training on inflammatory markers: A new approach to oxidative stress and cardiovascular risk factors.","volume":"7","author":"Arazi","year":"2018","journal-title":"Antioxidants"},{"key":"B4","doi-asserted-by":"publisher","first-page":"e46231","DOI":"10.1371\/journal.pone.0046231","article-title":"Gut microbiota composition is correlated to grid floor induced stress and behavior in the BALB\/c mouse.","volume":"7","author":"Bangsgaard Bendtsen","year":"2012","journal-title":"PLoS One"},{"key":"B5","doi-asserted-by":"publisher","first-page":"2557","DOI":"10.1016\/j.bbadis.2018.05.003","article-title":"The role of xanthine oxidoreductase and uric acid in metabolic syndrome.","volume":"1864","author":"Battelli","year":"2018","journal-title":"Biochim. Biophys. Acta (BBA) Mol. Basis Dis."},{"key":"B6","doi-asserted-by":"publisher","first-page":"e15099","DOI":"10.1371\/journal.pone.0015099","article-title":"Anti-inflammatory effects of resveratrol, curcumin and simvastatin in acute small intestinal inflammation.","volume":"5","author":"Bereswill","year":"2010","journal-title":"PLoS One"},{"key":"B7","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/j.foodchem.2011.04.022","article-title":"Development of a headspace solid-phase microextraction gas chromatography\u2013mass spectrometric method for the determination of short-chain fatty acids from intestinal fermentation.","volume":"129","author":"Bianchi","year":"2011","journal-title":"Food Chem."},{"key":"B8","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1038\/nmeth.2276","article-title":"Quality-filtering vastly improves diversity estimates from Illumina amplicon sequencing.","volume":"10","author":"Bokulich","year":"2013","journal-title":"Nat. Methods"},{"key":"B9","doi-asserted-by":"publisher","first-page":"146063","DOI":"10.1016\/j.scitotenv.2021.146063","article-title":"The potential of outdoor environments to supply beneficial butyrate-producing bacteria to humans.","volume":"777","author":"Brame","year":"2021","journal-title":"Sci. Total Environ."},{"key":"B10","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1038\/nmeth.f.303","article-title":"QIIME allows analysis of high-throughput community sequencing data.","volume":"7","author":"Caporaso","year":"2010","journal-title":"Nat. Methods"},{"key":"B11","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1016\/j.aninu.2015.12.008","article-title":"Effects of mulberry leaf flavonoid and resveratrol on methane emission and nutrient digestion in sheep.","volume":"1","author":"Chen","year":"2015","journal-title":"Anim. Nutr."},{"key":"B12","doi-asserted-by":"publisher","first-page":"i884","DOI":"10.1093\/bioinformatics\/bty560","article-title":"fastp: An ultra-fast all-in-one FASTQ preprocessor.","volume":"34","author":"Chen","year":"2018","journal-title":"Bioinformatics"},{"key":"B13","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1080\/10495398.2019.1683022","article-title":"Effects of dietary resveratrol supplementation on immunity, antioxidative capacity and intestinal barrier function in weaning piglets.","volume":"32","author":"Chen","year":"2021","journal-title":"Anim. Biotechnol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"102415","DOI":"10.1016\/j.jtherbio.2019.102415","article-title":"Effects of resveratrol on intestinal oxidative status and inflammation in heat-stressed rats.","volume":"85","author":"Cheng","year":"","journal-title":"J. Thermal Biol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.jtherbio.2019.03.012","article-title":"Protective effect of resveratrol against hepatic damage induced by heat stress in a rat model is associated with the regulation of oxidative stress and inflammation.","volume":"82","author":"Cheng","year":"","journal-title":"J. Thermal Biol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"255","DOI":"10.3109\/08820139.2013.864667","article-title":"Pro-inflammatory effects of uric acid in the gastrointestinal tract.","volume":"43","author":"Crane","year":"2014","journal-title":"Immunol. Invest."},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1101\/672295","article-title":"PICRUSt2: An improved and extensible approach for metagenome inference.","author":"Douglas","year":"2019","journal-title":"BioRxiv [PrePrint]"},{"key":"B18","doi-asserted-by":"publisher","first-page":"10019","DOI":"10.1096\/fj.201900665RR","article-title":"Gut microbiota mediates the protective effects of dietary \u03b2\u2212hydroxy\u2212\u03b2\u2212methylbutyrate (HMB) against obesity induced by high-fat diets.","volume":"33","author":"Duan","year":"2019","journal-title":"FASEB J."},{"key":"B19","doi-asserted-by":"publisher","first-page":"2460","DOI":"10.1093\/bioinformatics\/btq461","article-title":"Search and clustering orders of magnitude faster than BLAST.","volume":"26","author":"Edgar","year":"2010","journal-title":"Bioinformatics"},{"key":"B20","doi-asserted-by":"publisher","first-page":"2194","DOI":"10.1093\/bioinformatics\/btr381","article-title":"UCHIME improves sensitivity and speed of chimera detection.","volume":"27","author":"Edgar","year":"2011","journal-title":"Bioinformatics"},{"key":"B21","doi-asserted-by":"publisher","first-page":"3152","DOI":"10.2174\/092986709788803024","article-title":"TNF-alpha as a therapeutic target in inflammatory diseases, ischemia-reperfusion injury and trauma.","volume":"16","author":"Esposito","year":"2009","journal-title":"Curr. Med. Chem."},{"key":"B22","doi-asserted-by":"publisher","first-page":"960","DOI":"10.1016\/j.jnutbio.2012.06.019","article-title":"Resveratrol attenuates oxidative stress and prevents steatosis and hypertension in obese rats programmed by early weaning.","volume":"24","author":"Franco","year":"2013","journal-title":"J. Nutr. Biochem."},{"key":"B23","doi-asserted-by":"publisher","first-page":"2336","DOI":"10.1016\/j.immuni.2022.11.002","article-title":"B cell expansion hinders the stroma-epithelium regenerative cross talk during mucosal healing.","volume":"55","author":"Frede","year":"2022","journal-title":"Immunity"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1470992","DOI":"10.3389\/fvets.2024.1470992","article-title":"Resveratrol and \u03b2-hydroxy-\u03b2-methylbutyric acid supplementation promotes ileal development and digestive function by altering microbial community abundance and metabolites in Tibetan sheep.","volume":"11","author":"Gan","year":"2024","journal-title":"Front. Vet. Sci."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1220","DOI":"10.3390\/molecules24071220","article-title":"Curcumin and resveratrol regulate intestinal bacteria and alleviate intestinal inflammation in weaned piglets.","volume":"24","author":"Gan","year":"2019","journal-title":"Molecules"},{"key":"B26","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1038\/s41575-018-0081-y","article-title":"Tales from the crypt: New insights into intestinal stem cells.","volume":"16","author":"Gehart","year":"2019","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1471-230X-4-1","article-title":"Mobilization of xanthine oxidase from the gastrointestinal tract in acute pancreatitis.","volume":"4","author":"Granell","year":"2004","journal-title":"BMC Gastroenterol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.aqrep.2016.07.002","article-title":"Paenibacillus polymyxa as a water additive improved immune response of Cyprinus carpio and disease resistance against Aeromonas hydrophila.","volume":"4","author":"Gupta","year":"2016","journal-title":"Aquacult. Rep."},{"key":"B29","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1038\/s41598-017-18298-7","article-title":"Characterizing the bacterial microbiota in different gastrointestinal tract segments of the Bactrian camel.","volume":"8","author":"He","year":"2018","journal-title":"Sci. Rep."},{"key":"B30","doi-asserted-by":"publisher","first-page":"347","DOI":"10.2337\/db09-0016","article-title":"Depletion of liver Kupffer cells prevents the development of diet-induced hepatic steatosis and insulin resistance.","volume":"59","author":"Huang","year":"2010","journal-title":"Diabetes"},{"key":"B31","doi-asserted-by":"publisher","first-page":"3329","DOI":"10.2147\/NDT.S188340","article-title":"Possible association of Firmicutes in the gut microbiota of patients with major depressive disorder.","volume":"14","author":"Huang","year":"2018","journal-title":"Neuropsychiatric Dis. Treat."},{"key":"B32","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1186\/s12864-024-10480-2","article-title":"Effect of supplementing lysins and methionine to low-protein diets on growth performance, hepatic antioxidant capacity, immune status, and glycolytic activity of tibetan sheep.","volume":"25","author":"Ji","year":"","journal-title":"BMC Genomics"},{"key":"B33","doi-asserted-by":"publisher","first-page":"892","DOI":"10.3390\/antiox13080892","article-title":"Multi-omics revealed resveratrol and \u03b2-Hydroxy-\u03b2-methyl butyric acid alone or in combination improved the jejunal function in tibetan sheep.","volume":"13","author":"Ji","year":"","journal-title":"Antioxidants"},{"key":"B34","doi-asserted-by":"publisher","first-page":"908015","DOI":"10.3389\/fimmu.2022.908015","article-title":"Oregano essential oils mediated intestinal microbiota and metabolites and improved growth performance and intestinal barrier function in sheep.","volume":"13","author":"Jia","year":"2022","journal-title":"Front. Immunol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"343","DOI":"10.4162\/nrp.2015.9.4.343","article-title":"Butyrate modulates bacterial adherence on LS174T human colorectal cells by stimulating mucin secretion and MAPK signaling pathway.","volume":"9","author":"Jung","year":"2015","journal-title":"Nutr. Res. Pract."},{"key":"B36","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1111\/j.0105-2896.2005.00278.x","article-title":"The polymeric immunoglobulin receptor: Bridging innate and adaptive immune responses at mucosal surfaces.","volume":"206","author":"Kaetzel","year":"2005","journal-title":"Immunol. Rev."},{"key":"B37","doi-asserted-by":"publisher","first-page":"53","DOI":"10.3390\/antib9040053","article-title":"Structure, function, and therapeutic use of IgM antibodies.","volume":"9","author":"Keyt","year":"2020","journal-title":"Antibodies"},{"key":"B38","doi-asserted-by":"publisher","first-page":"1450","DOI":"10.1002\/jsfa.13023","article-title":"Beta-hydroxy\u2212\u03b2\u2212methyl butyrate-supplemented diet for broiler chickens is more conducive to dietary protein reduction than a leucine-supplemented diet until 21 days old.","volume":"104","author":"Kop Bozbay","year":"2024","journal-title":"J. Sci. Food Agric."},{"key":"B39","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1016\/j.bbamcr.2008.12.017","article-title":"\u03b2-hydroxy-\u03b2-methylbutyrate (HMB) stimulates myogenic cell proliferation, differentiation and survival via the MAPK\/ERK and PI3K\/Akt pathways.","volume":"1793","author":"Kornasio","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"B40","doi-asserted-by":"publisher","first-page":"11070","DOI":"10.1073\/pnas.0504978102","article-title":"Obesity alters gut microbial ecology.","volume":"102","author":"Ley","year":"2005","journal-title":"Proc. Natl. Acad. Sci. U S A."},{"key":"B41","doi-asserted-by":"publisher","first-page":"114568","DOI":"10.1016\/j.biopha.2023.114568","article-title":"Protective effect of sodium butyrate on intestinal barrier damage and uric acid reduction in hyperuricemia mice.","volume":"161","author":"Li","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"B42","doi-asserted-by":"publisher","first-page":"5555","DOI":"10.1007\/s00216-017-0493-5","article-title":"Development of a fast and cost-effective gas chromatography\u2013mass spectrometry method for the quantification of short-chain and medium-chain fatty acids in human biofluids.","volume":"409","author":"Lotti","year":"2017","journal-title":"Anal. Bioanal. Chem."},{"key":"B43","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1574-6968.2009.01514.x","article-title":"Diversity, metabolism and microbial ecology of butyrate-producing bacteria from the human large intestine.","volume":"294","author":"Louis","year":"2009","journal-title":"FEMS Microbiol. Lett."},{"key":"B44","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1111\/jpn.12264","article-title":"Effect of dietary supplementation with resveratrol on nutrient digestibility, methanogenesis and ruminal microbial flora in sheep.","volume":"99","author":"Ma","year":"2015","journal-title":"J. Anim. Physiol. Anim. Nutr."},{"key":"B45","doi-asserted-by":"publisher","first-page":"3516","DOI":"10.1002\/fsn3.3340","article-title":"Exploring the effects of palm kernel meal feeding on the meat quality and rumen microorganisms of Qinghai Tibetan sheep.","volume":"11","author":"Ma","year":"2023","journal-title":"Food Sci. Nutr."},{"key":"B46","doi-asserted-by":"publisher","first-page":"2957","DOI":"10.1093\/bioinformatics\/btr507","article-title":"FLASH: Fast length adjustment of short reads to improve genome assemblies.","volume":"27","author":"Magoc","year":"2011","journal-title":"Bioinformatics"},{"key":"B47","doi-asserted-by":"publisher","first-page":"946","DOI":"10.3390\/nu11050946","article-title":"Influence of resveratrol on the immune response.","volume":"11","author":"Malaguarnera","year":"2019","journal-title":"Nutrients"},{"key":"B48","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1210\/er.2009-0030","article-title":"Gut microbiota, lipopolysaccharides, and innate immunity in the pathogenesis of obesity and cardiovascular risk.","volume":"31","author":"Manco","year":"2010","journal-title":"Endocrine Rev."},{"key":"B49","doi-asserted-by":"publisher","first-page":"964","DOI":"10.1161\/CIRCULATIONAHA.116.024545","article-title":"High-fiber diet and acetate supplementation change the gut microbiota and prevent the development of hypertension and heart failure in hypertensive mice.","volume":"135","author":"Marques","year":"2017","journal-title":"Circulation"},{"key":"B50","doi-asserted-by":"publisher","first-page":"12666","DOI":"10.1021\/acs.jafc.8b04138","article-title":"Resveratrol ameliorates intestinal barrier defects and inflammation in colitic mice and intestinal cells.","volume":"66","author":"Mayangsari","year":"","journal-title":"Journal of Agricultural and Food Chemistry"},{"key":"B51","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.jff.2018.10.009","article-title":"Resveratrol enhances intestinal barrier function by ameliorating barrier disruption in Caco-2 cell monolayers.","volume":"51","author":"Mayangsari","year":"","journal-title":"J. Funct. Foods"},{"key":"B52","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/s40104-022-00822-z","article-title":"Biological function of resveratrol and its application in animal production: A review.","volume":"14","author":"Meng","year":"2023","journal-title":"J. Anim. Sci. Biotechnol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1080\/19490976.2015.1134082","article-title":"Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism.","volume":"7","author":"Morrison","year":"2016","journal-title":"Gut Microbes"},{"key":"B54","doi-asserted-by":"publisher","first-page":"1262","DOI":"10.1126\/science.1223813","article-title":"Host-gut microbiota metabolic interactions.","volume":"336","author":"Nicholson","year":"2012","journal-title":"Science"},{"key":"B55","doi-asserted-by":"publisher","first-page":"294","DOI":"10.3390\/life12020294","article-title":"resveratrol and reproductive health.","volume":"12","author":"Novakovic","year":"2022","journal-title":"Life"},{"key":"B56","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1017\/S095442241700021X","article-title":"Resveratrol and inflammatory bowel disease: The evidence so far.","volume":"31","author":"Nunes","year":"2018","journal-title":"Nutr. Res. Rev."},{"key":"B57","author":"Oksanen","year":"2019","journal-title":"vegan: Community Ecology Package. R Package Version 2.5-6."},{"key":"B58","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1159\/000442020","article-title":"The impact of resveratrol on oxidative stress induced by methotrexate in rat ileum tissue: Evaluation of biochemical and histopathological features and analysis of gene expression.","volume":"25","author":"Ozcicek","year":"2016","journal-title":"Med. Princ. Pract."},{"key":"B59","doi-asserted-by":"publisher","first-page":"4554","DOI":"10.3390\/molecules25194554","article-title":"The role of resveratrol in mammalian reproduction.","volume":"25","author":"Pasquariello","year":"2020","journal-title":"Molecules"},{"key":"B60","doi-asserted-by":"publisher","first-page":"skae077","DOI":"10.1093\/jas\/skae077","article-title":"Effects of dietary protein level on intestinal function and inflammation in nursery pigs.","volume":"102","author":"Pearce","year":"2024","journal-title":"J. Anim. Sci."},{"key":"B61","doi-asserted-by":"publisher","first-page":"1619","DOI":"10.3945\/jn.109.104638","article-title":"Butyrate enhances the intestinal barrier by facilitating tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers.","volume":"139","author":"Peng","year":"2009","journal-title":"J. Nutr."},{"key":"B62","doi-asserted-by":"publisher","first-page":"185","DOI":"10.3389\/fmicb.2016.00185","article-title":"Intestinal short chain fatty acids and their link with diet and human health.","volume":"7","author":"R\u00edos-Covi\u00e1n","year":"2016","journal-title":"Front. Microbiol."},{"key":"B63","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1007\/s40200-019-00456-5","article-title":"Anti-hyperglycemic and ameliorative effect of concentrated hot water-infusion of Phragmanthera incana leaves on type 2 diabetes and indices of complications in diabetic rats.","volume":"18","author":"Sanni","year":"2019","journal-title":"J. Diabetes Metab. Disord."},{"key":"B64","doi-asserted-by":"publisher","first-page":"R60","DOI":"10.1186\/gb-2011-12-6-r60","article-title":"Metagenomic biomarker discovery and explanation.","volume":"12","author":"Segata","year":"2011","journal-title":"Genome Biol."},{"key":"B65","doi-asserted-by":"publisher","first-page":"12430","DOI":"10.3390\/ijms232012430","article-title":"Response of ruminal microbiota\u2013host gene interaction to high-altitude environments in Tibetan sheep.","volume":"23","author":"Sha","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B66","doi-asserted-by":"publisher","first-page":"3791","DOI":"10.1038\/s41598-020-60185-1","article-title":"Resveratrol alleviates obesity-induced skeletal muscle inflammation via decreasing M1 macrophage polarization and increasing the regulatory T cell population.","volume":"10","author":"Shabani","year":"2020","journal-title":"Sci. Rep."},{"key":"B67","doi-asserted-by":"publisher","first-page":"13539","DOI":"10.3390\/ijms222413539","article-title":"Separation and identification of resveratrol butyrate ester complexes and their bioactivity in HepG2 cell models.","volume":"22","author":"Shih","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B68","doi-asserted-by":"publisher","first-page":"105","DOI":"10.2165\/00007256-200030020-00004","article-title":"\u03b2-hydroxy-\u03b2-methylbutyrate (HMB) supplementation and the promotion of muscle growth and strength.","volume":"30","author":"Slater","year":"2000","journal-title":"Sports Med."},{"key":"B69","doi-asserted-by":"publisher","first-page":"4199","DOI":"10.3390\/molecules25184199","article-title":"Synthesis and characterization of novel resveratrol butyrate esters that have the ability to prevent fat accumulation in a liver cell culture model.","volume":"25","author":"Tain","year":"2020","journal-title":"Molecules"},{"key":"B70","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1021\/acs.jproteome.5b00354","volume":"1","author":"Thevenot","year":"2016","journal-title":"PCA, PLS (-DA) and OPLS (-DA) for Multivariate Analysis and Feature Selection of Omics Data."},{"key":"B71","doi-asserted-by":"publisher","first-page":"1427","DOI":"10.3390\/ani11051427","article-title":"Effects of resveratrol on growth performance, intestinal development, and antioxidant status of broilers under heat stress.","volume":"11","author":"Wang","year":"2021","journal-title":"Animals"},{"key":"B72","doi-asserted-by":"publisher","first-page":"695445","DOI":"10.3389\/fmicb.2021.695445","article-title":"Effects of dietary energy levels on rumen fermentation, gastrointestinal tract histology, and bacterial community diversity in fattening male Hu lambs.","volume":"12","author":"Wang","year":"2021","journal-title":"Front. Microbiol."},{"key":"B73","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1002\/wics.147","article-title":"ggplot2.","volume":"3","author":"Wickham","year":"2011","journal-title":"Wiley Interdiscipl. Rev. Comput. Stat."},{"key":"B74","doi-asserted-by":"publisher","first-page":"10665","DOI":"10.7150\/thno.43528","article-title":"Rhein modulates host purine metabolism in intestine through gut microbiota and ameliorates experimental colitis.","volume":"10","author":"Wu","year":"2020","journal-title":"Theranostics"},{"key":"B75","doi-asserted-by":"publisher","first-page":"1250914","DOI":"10.3389\/fmed.2023.1250914","article-title":"Resveratrol regulates macrophage recruitment and M1 macrophage polarization and prevents corneal allograft rejection in rats.","volume":"10","author":"Xu","year":"2023","journal-title":"Front. Med."},{"key":"B76","doi-asserted-by":"publisher","first-page":"229","DOI":"10.2141\/jpsa.39.229","article-title":"Review on chicken intestinal villus histological alterations related with intestinal function.","volume":"39","author":"Yamauchi","year":"2002","journal-title":"J. Poultry Sci."},{"key":"B77","doi-asserted-by":"publisher","first-page":"11977","DOI":"10.3390\/ijms231911977","article-title":"Resveratrol improves the Digestive ability and the Intestinal Health of Siberian Sturgeon.","volume":"23","author":"Yang","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B78","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1186\/s12882-019-1506-8","article-title":"Uric acid regulates NLRP3\/IL-1\u03b2 signaling pathway and further induces vascular endothelial cells injury in early CKD through ROS activation and K+ efflux.","volume":"20","author":"Yin","year":"2019","journal-title":"BMC Nephrol."},{"key":"B79","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1080\/1745039X.2019.1614849","article-title":"Effects of low-protein diet on the intestinal morphology, digestive enzyme activity, blood urea nitrogen, and gut microbiota and metabolites in weaned pigs.","volume":"73","author":"Yu","year":"2019","journal-title":"Arch. Animal Nutr."},{"key":"B80","doi-asserted-by":"publisher","first-page":"247","DOI":"10.14943\/jjvr.64.4.247","article-title":"Effect of \u03b2-hydroxy-\u03b2-methylbutyrate acid on meat performance traits and selected indicators of humoral immunity in goats.","volume":"64","author":"Z\u0105bek","year":"2016","journal-title":"Jpn. J. Vet. Res."},{"key":"B81","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1007\/s00726-019-02709-2","article-title":"Regulation of protein synthesis in porcine mammary epithelial cells by L-valine.","volume":"51","author":"Zhang","year":"2019","journal-title":"Amino Acids"},{"key":"B82","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.anifeedsci.2019.03.004","article-title":"Sanguinarine and resveratrol affected rumen fermentation parameters and bacterial community in calves.","volume":"251","author":"Zhang","year":"2019","journal-title":"Animal Feed Sci. Technol."},{"key":"B83","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/j.cbi.2010.03.035","article-title":"Butyrate induces cell apoptosis through activation of JNK MAP kinase pathway in human colon cancer RKO cells.","volume":"185","author":"Zhang","year":"2010","journal-title":"Chemico Biol. Interactions"},{"key":"B84","doi-asserted-by":"publisher","first-page":"1540","DOI":"10.5713\/ajas.18.0901","article-title":"Effect of tannins and cellulase on growth performance, nutrients digestibility, blood profiles, intestinal morphology and carcass characteristics in Hu sheep.","volume":"32","author":"Zhao","year":"2019","journal-title":"Asian Australasian J. Animal Sci."},{"key":"B85","doi-asserted-by":"publisher","first-page":"6158671","DOI":"10.1155\/2018\/6158671","article-title":"Resveratrol suppresses gut-derived NLRP3 inflammasome partly through stabilizing mast cells in a rat model.","volume":"2018","author":"Zhao","year":"2018","journal-title":"Mediators Inflammation"},{"key":"B86","doi-asserted-by":"publisher","first-page":"110839","DOI":"10.1016\/j.nut.2020.110839","article-title":"Dietary \u03b2-hydroxy-\u03b2-methylbutyrate improves intestinal function in weaned piglets after lipopolysaccharide challenge.","volume":"78","author":"Zheng","year":"2020","journal-title":"Nutrition"},{"key":"B87","doi-asserted-by":"publisher","first-page":"444","DOI":"10.3390\/ijms24010444","article-title":"\u03b2-Hydroxy-\u03b2-methylbutyric acid promotes repair of sheep myoblast injury by inhibiting IL-17\/NF-\u03baB signaling.","volume":"24","author":"Zheng","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B88","doi-asserted-by":"publisher","first-page":"936","DOI":"10.3390\/agriculture14060936","article-title":"The Effects of dietary resveratrol and \u03b2-Hydroxy-\u03b2-Methylbutyric acid supplementation at two protein levels on the ruminal microbiome and metabolome of tibetan sheep.","volume":"14","author":"Zhu","year":"2024","journal-title":"Agriculture"},{"key":"B89","doi-asserted-by":"publisher","first-page":"e27081","DOI":"10.1371\/journal.pone.0027081","article-title":"Activation of Sirt1 by resveratrol inhibits TNF-\u03b1 induced inflammation in fibroblasts.","volume":"6","author":"Zhu","year":"2011","journal-title":"PLoS One"}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2025.1612170\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T10:17:21Z","timestamp":1753093041000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2025.1612170\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,21]]},"references-count":89,"alternative-id":["10.3389\/fmicb.2025.1612170"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2025.1612170","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,21]]},"article-number":"1612170"}}