{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T05:44:42Z","timestamp":1788414282124,"version":"build-2803163510"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T00:00:00Z","timestamp":1751932800000},"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:p>Resveratrol (RES) and \u03b2-Hydroxy-\u03b2-methyl butyric acid (HMB) have been shown to exert antioxidant, anti-inflammatory effect as well as influence intestinal microbiota composition in monogastric animal. However, the mechanism by which RES and HMB regulate duodenal function in ruminants remains unclear. In this study, the effects of RES and HMB on the development and health of the duodenum in Tibetan sheep were investigated. A total of 120 early weaned Tibetan rams with similar initial body weight (15.5\u202f\u00b1\u202f0.14\u202fkg) were selected and randomly allocated into 4 groups. Each group received a basal diet supplemented with 1.5\u202fg RES\/d (RES group), 1.25\u202fg HMB\/d (HMB group), 1.5\u202fg RES\/d plus 1.25\u202fg HMB\/d (RES_HMB group), and without any additives (CON group). The results showed that RES and HMB supplementation significantly increased (<jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.05) the villus height and the ratio of villus height to crypt depth in the duodenum. Meanwhile, the concentrations of cellulase and trypsin were increased (<jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.05) when RES and HMB were supplemented in the basal diet. The RES group exhibited higher (<jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.05) levels of anti-inflammatory markers (IgG, IL-6, and IL-1\u03b2), while combined supplementation of RES and HMB promoted (<jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.05) the duodenal antioxidant capacity, as indicated by increased levels of GSH-Px and T-AOC. Furthermore, the RES group was characterized by a higher relative abundance of <jats:italic>Butyrivibrio<\/jats:italic>, while the HMB group was characterized by a higher relative abundance of <jats:italic>Aeromonas<\/jats:italic>, <jats:italic>Rummeliibacillus<\/jats:italic>, <jats:italic>UCG-002<\/jats:italic>, <jats:italic>Ralstonia<\/jats:italic> and <jats:italic>Stenotrophomonas<\/jats:italic> (<jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.05 and LDA\u202f&amp;gt;\u202f3.5). Metabolomics analysis showed that differential metabolites were significantly enriched (<jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.05) in the cyanoamino acid metabolism, biosynthesis of secondary metabolites, protein digestion and absorption and ABC transporters. These results indicated that RES and HMB can be used as feed additives to maintain intestinal health by enhancing duodenal development, promoting digestive enzyme secretion, and improving antioxidant and anti-inflammatory capacity in Tibetan sheep.<\/jats:p>","DOI":"10.3389\/fmicb.2025.1612102","type":"journal-article","created":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T05:28:34Z","timestamp":1751952514000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["The influence of resveratrol and \u03b2-Hydroxy-\u03b2-methyl butyric acid supplementation alone or in combination on the development and health of the duodenum in Tibetan sheep"],"prefix":"10.3389","volume":"16","author":[{"given":"Yu","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiurong","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linsheng","family":"Gui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kefyalew","family":"Gebeyew","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengzhen","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyou","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijuan","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,8]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1007\/s15010-010-0077-1","article-title":"Septic shock, pneumonia, and soft tissue infection due to Myroides odoratimimus: report of a case and review of Myroides infections","volume":"39","author":"Benedetti","year":"2011","journal-title":"Infection"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1038\/s41587-019-0209-9","article-title":"Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2","volume":"37","author":"Bolyen","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1002\/cem.1006","article-title":"OPLS discriminant analysis: combining the strengths of PLS-DA and SIMCA classification","volume":"20","author":"Bylesjo","year":"2006","journal-title":"J. Chemom."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1038\/nmeth.3869","article-title":"DADA2: high-resolution sample inference from Illumina amplicon data","volume":"13","author":"Callahan","year":"2016","journal-title":"Nat. Methods"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1651","DOI":"10.3390\/nu10111651","article-title":"Resveratrol, metabolic syndrome, and gut microbiota","volume":"10","author":"Chaplin","year":"2018","journal-title":"Nutrients"},{"key":"ref6","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":"ref7","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":"ref8","doi-asserted-by":"publisher","first-page":"253","DOI":"10.3390\/antiox13020253","article-title":"Maternal malic acid may ameliorate oxidative stress and inflammation in sows through modulating gut microbiota and host metabolic profiles during late pregnancy","volume":"13","author":"Chen","year":"2024","journal-title":"Antioxidants (Basel)"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1038\/s41587-020-0548-6","article-title":"PICRUSt2 for prediction of metagenome functions","volume":"38","author":"Douglas","year":"2020","journal-title":"Nat. Biotechnol."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1007\/s00726-015-2067-1","article-title":"The role of leucine and its metabolites in protein and energy metabolism","volume":"48","author":"Duan","year":"2016","journal-title":"Amino Acids"},{"key":"ref7001","doi-asserted-by":"publisher","first-page":"101677","DOI":"10.1016\/j.psj.2021.101677","article-title":"Effects of zinc and Bacillus subtilis on the reproductive performance, egg quality, nutrient digestion, intestinal morphology, and serum antioxidant capacity of geese breeders","volume":"101","author":"Fan","year":"2022","journal-title":"Poultry Sci."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"5952707","DOI":"10.1155\/2018\/5952707","article-title":"Effect of resveratrol dry suspension on immune function of piglets","volume":"2018","author":"Fu","year":"2018","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"ref12","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":"ref13","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.1038\/ni.3244","article-title":"Innate immunological function of TH2 cells in vivo","volume":"16","author":"Guo","year":"2015","journal-title":"Nat. Immunol."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1007\/978-1-4939-8728-3_8","article-title":"16S rRNA gene analysis with QIIME2","volume":"1849","author":"Hall","year":"2018","journal-title":"Methods Mol. Biol."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"msae058","DOI":"10.1093\/molbev\/msae058","article-title":"Multiomics analyses provide new insight into genetic variation of reproductive adaptability in Tibetan sheep","volume":"41","author":"Han","year":"2024","journal-title":"Mol. Biol. Evol."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1002\/jcsm.12208","article-title":"Beta-hydroxy-beta-methylbutyrate supplementation and skeletal muscle in healthy and muscle-wasting conditions","volume":"8","author":"Hole\u010dek","year":"2017","journal-title":"J. Cachexia. Sarcopenia Muscle"},{"key":"ref17","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":"2024","journal-title":"Antioxidants (Basel)"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1093\/nar\/28.1.27","article-title":"KEGG: Kyoto encyclopedia of genes and genomes","volume":"28","author":"Kanehisa","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"2013","DOI":"10.3389\/fmicb.2018.02013","article-title":"Effects of psychological, environmental and physical stressors on the gut microbiota","volume":"9","author":"Karl","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"2908","DOI":"10.1007\/s10620-016-4238-7","article-title":"Structural change in microbiota by a probiotic cocktail enhances the gut barrier and reduces Cancer via TLR2 signaling in a rat model of Colon Cancer","volume":"61","author":"Kuugbee","year":"2016","journal-title":"Dig. Dis. Sci."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"2427","DOI":"10.1038\/s44321-024-00129-8","article-title":"Multiomics reveals microbial metabolites as key actors in intestinal fibrosis in Crohn's disease","volume":"16","author":"Li","year":"2024","journal-title":"EMBO Mol. Med."},{"key":"ref22","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. (Berl.)"},{"key":"ref23","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":"Mago\u010d","year":"2011","journal-title":"Bioinformatics"},{"key":"ref24","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":"ref25","doi-asserted-by":"publisher","first-page":"83","DOI":"10.4141\/cjas87-010","article-title":"Nutritional performance and intestinal absorptive capacities of neonatal lambs fed milk replacer or dams milk, with or without access to creep feed","volume":"67","author":"Mir","year":"1987","journal-title":"Can. J. Anim. Sci."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.anifeedsci.2014.03.001","article-title":"Starch digestion in the rumen, small intestine, and hind gut of dairy cows \u2013 a meta-analysis","volume":"192","author":"Moharrery","year":"2014","journal-title":"Anim. Feed Sci. Technol."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1093\/nar\/27.1.29","article-title":"KEGG: Kyoto encyclopedia of genes and genomes","volume":"27","author":"Ogata","year":"1999","journal-title":"Nucleic Acids Res."},{"key":"ref7002","doi-asserted-by":"publisher","first-page":"3123","DOI":"10.1093\/bioinformatics\/btu494","article-title":"STAMP: statistical analysis of taxonomic and functional profiles","volume":"30","author":"Parks","year":"2014","journal-title":"Bioinformatics."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"s399","DOI":"10.1017\/s1751731118001921","article-title":"Review: enhancing gastrointestinal health in dairy cows","volume":"12","author":"Plaizier","year":"2018","journal-title":"Animal"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"D590","DOI":"10.1093\/nar\/gks1219","article-title":"The SILVA ribosomal RNA gene database project: improved data processing and web-based tools","volume":"41","author":"Quast","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1186\/s42523-022-00206-8","article-title":"Enteroendocrine peptides, growth, and the microbiome during the porcine weaning transition","volume":"4","author":"Ramsay","year":"2022","journal-title":"Anim. Microbiome"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"e000216","DOI":"10.1099\/mgen.0.000216","article-title":"The first complete genomic structure of Butyrivibrio fibrisolvens and its chromid","volume":"4","author":"Rodr\u00edguez Hern\u00e1ez","year":"2018","journal-title":"Microb. Genom."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"e2584","DOI":"10.7717\/peerj.2584","article-title":"VSEARCH: a versatile open source tool for metagenomics","volume":"4","author":"Rognes","year":"2016","journal-title":"PeerJ"},{"key":"ref33","doi-asserted-by":"crossref","DOI":"10.1007\/978-981-33-4343-6_3","article-title":"Goat and sheep farming","volume-title":"Sustainability in Ruminant Livestock","author":"Rout","year":"2021"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1016\/B978-0-323-40232-3.00068-6","article-title":"Anatomy and physiology of the duodenum","volume-title":"Shackelford's surgery of the alimentary tract","author":"Shames","year":"2019"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"149205","DOI":"10.1016\/j.scitotenv.2021.149205","article-title":"A systematic review on antibiotics misuse in livestock and aquaculture and regulation implications in China","volume":"798","author":"Shao","year":"2021","journal-title":"Sci. Total Environ."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"e14069","DOI":"10.1111\/jfbc.14069","article-title":"Gibberellic acid-induced Hepatorenal dysfunction and oxidative stress: mitigation by quercetin through modulation of antioxidant, anti-inflammatory, and Antiapoptotic activities","volume":"46","author":"Soliman","year":"2022","journal-title":"J. Food Biochem."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"37","DOI":"10.5751\/es-15717-290437","article-title":"Overcoming collapse of farming systems: shifting from vicious to virtuous circles in the extensive sheep farming system in Huesca (Spain)","volume":"29","author":"Soriano","year":"2024","journal-title":"Ecol. Soc."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1016\/j.fsi.2019.06.027","article-title":"Improvements in the growth performance, immunity, disease resistance, and gut microbiota by the probiotic Rummeliibacillus Stabekisii in Nile Tilapia (oreochromis Niloticus)","volume":"92","author":"Tan","year":"2019","journal-title":"Fish Shellfish Immunol."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/b978-0-12-800100-4.00003-9","article-title":"The role of short-chain fatty acids in health and disease","volume":"121","author":"Tan","year":"2014","journal-title":"Adv. Immunol."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"107","DOI":"10.3390\/antiox14010107","article-title":"Reduced glutathione promoted growth performance by improving the Jejunal barrier, antioxidant function, and altering proteomics of weaned piglets","volume":"14","author":"Tian","year":"2025","journal-title":"Antioxidants"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"1392","DOI":"10.1002\/jsfa.10152","article-title":"Resveratrol: a review of plant sources, synthesis, stability, modification and food application","volume":"100","author":"Tian","year":"2019","journal-title":"J. Sci. Food Agric."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"461","DOI":"10.5507\/bp.2016.052","article-title":"Nutrition, oxidative stress and intestinal dysbiosis: influence of diet on gut microbiota in inflammatory bowel diseases","volume":"160","author":"Tomasello","year":"2016","journal-title":"Biomed. Pap. Med. Fac. Univ. Palacky Olomouc Czech Repub."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"87","DOI":"10.2478\/aoas-2021-0079","article-title":"The effect of supplementation with \u0392-hydroxy-\u03b2-methylbutyric acid (HMB) to pregnant sows on the mucosal structure, immunolocalization of intestinal barrier proteins, VIP and leptin in the large intestine in their offspring","volume":"23","author":"Tomaszewska","year":"2023","journal-title":"Ann. Anim. Sci."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1002\/biof.1399","article-title":"Role of resveratrol in regulation of cellular defense systems against oxidative stress","volume":"44","author":"Truong","year":"2018","journal-title":"Biofactors"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"2769","DOI":"10.3390\/ani13172769","article-title":"Stress factors and their effects on productivity in sheep","volume":"13","author":"Tufekci","year":"2023","journal-title":"Animals"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1079\/9781845931803.0029","article-title":"Early development of small intestinal function","volume-title":"Avian gut function in health and disease","author":"Uni","year":"2006"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1080\/17474124.2017.1343143","article-title":"The intestinal barrier: a fundamental role in health and disease","volume":"11","author":"Vancamelbeke","year":"2017","journal-title":"Expert Rev. Gastroenterol. Hepatol."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"1551327","DOI":"10.3389\/fvets.2025.1551327","article-title":"Temporal modulation of duodenal microbiota in dairy cows: effects of dietary shift from high forage to high concentration","volume":"12","author":"Wang","year":"2025","journal-title":"Front. Vet. Sci."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1186\/s40168-024-02013-6","article-title":"Ningxiang pig-derived lactobacillus reuteri modulates host intramuscular fat deposition via branched-chain amino acid metabolism","volume":"13","author":"Yang","year":"2025","journal-title":"Microbiome"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"1745","DOI":"10.1093\/jas\/skz057","article-title":"Long-term dietary resveratrol supplementation decreased serum lipids levels, improved intramuscular fat content, and changed the expression of several lipid metabolism-related Mirnas and genes in growing-finishing Pigs1","volume":"97","author":"Zhang","year":"2019","journal-title":"J. Anim. Sci."},{"key":"ref51","doi-asserted-by":"publisher","first-page":"915558","DOI":"10.3389\/fnut.2022.915558","article-title":"Metabolomics approach reveals high energy diet improves the quality and enhances the flavor of black Tibetan sheep meat by altering the composition of rumen microbiota","volume":"9","author":"Zhang","year":"2022","journal-title":"Front. Nutr."},{"key":"ref52","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":"Anim. Feed Sci. Technol."},{"key":"ref53","doi-asserted-by":"publisher","first-page":"1533","DOI":"10.3390\/ani14111533","article-title":"Changes in rumen microbiology and metabolism of Tibetan sheep with different Lys\/met ratios in low-protein diets","volume":"14","author":"Zhang","year":"2024","journal-title":"Animals"},{"key":"ref54","doi-asserted-by":"publisher","first-page":"971496","DOI":"10.3389\/fnut.2022.971496","article-title":"Maternal resveratrol regulates the growth performance, antioxidant capacity, and intestinal health of suckling piglets through intestinal microorganisms at high summer temperatures","volume":"9","author":"Zhao","year":"2022","journal-title":"Front. Nutr."},{"key":"ref55","doi-asserted-by":"publisher","first-page":"110839","DOI":"10.1016\/j.nut.2020.110839","article-title":"Dietary \u0392-Hydroxy-\u03b2-methylbutyrate improves intestinal function in weaned piglets after lipopolysaccharide challenge","volume":"78","author":"Zheng","year":"2020","journal-title":"Nutrition"}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2025.1612102\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T05:28:37Z","timestamp":1751952517000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2025.1612102\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,8]]},"references-count":57,"alternative-id":["10.3389\/fmicb.2025.1612102"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2025.1612102","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,8]]},"article-number":"1612102"}}