{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T17:24:32Z","timestamp":1787073872691,"version":"build-2736575974"},"reference-count":34,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Changdu City Science and Technology Bureau","award":["CDKJ-2025QY001"],"award-info":[{"award-number":["CDKJ-2025QY001"]}]},{"award":["CDKJ-2025QY001"],"award-info":[{"award-number":["CDKJ-2025QY001"]}],"id":[{"id":"https:\/\/ror.org\/00xfea068","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vet. Sci.","Veterinary Sciences"],"abstract":"<jats:p>The ban on antibiotic growth promoters has created an urgent need for effective alternatives to maintain intestinal health and production performance. This exploratory study evaluated the effects of a novel antibiotic alternative additive at graded inclusion levels (control, 1%, 3%, 5%) on growth performance, intestinal histomorphology, gut microbiome ecology, and host metabolome in Tibetan pigs (n = 40). Forty Tibetan pigs were randomly assigned to four dietary treatment groups for a 21-day feeding trial. Growth performance, intestinal histopathology, metatranscriptomic sequencing (bacteria, viruses, fungi), and untargeted metabolomics were analyzed. Tibetan pigs fed the 3% additive diet exhibited the highest numerical average daily gain (0.197 vs. 0.148 kg\/d, +33.1%) and lowest feed conversion ratio (2.61 vs. 3.59, \u221227.3%), with overall treatment effects reaching statistical significance (ADG: p = 0.027; FCR: p = 0.023). Metatranscriptomic profiling revealed fundamentally distinct microbial communities between the duodenum and colon. Multi-omics integration identified 79 significant microbiome-pathology associations in the duodenum and 38 in the colon, with SCFA-producing bacteria positively correlated with mucosal architectural parameters. The multi-omics network revealed a core-periphery architecture with Eubacterium, Lactobacillus, and Escherichia as keystone hubs. Dietary supplementation at 3% showed the most favorable effects on growth performance and metabolic modulation without compromising intestinal structural integrity, supporting its potential as a viable antibiotic alternative.<\/jats:p>","DOI":"10.3390\/vetsci13080826","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T16:12:11Z","timestamp":1787069531000},"page":"826","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of an Antibiotic Alternative Additive on Growth Performance, Intestinal Histomorphology, Multi-Omics Profiles, and Microbiome\u2013Host Interactions in Tibetan Pigs"],"prefix":"10.3390","volume":"13","author":[{"given":"Zhaolong","family":"Li","sequence":"first","affiliation":[{"name":"Institute of Animal Husbandry and Veterinary Medicine, Fujian Academy of Agricultural Sciences, Fuzhou 350013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Changdu Animal Husbandry General Station, Changdu 854000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peimin","family":"Li","sequence":"additional","affiliation":[{"name":"Changdu Animal Husbandry General Station, Changdu 854000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Peng","sequence":"additional","affiliation":[{"name":"Institute of Animal Husbandry and Veterinary Medicine, Fujian Academy of Agricultural Sciences, Fuzhou 350013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junru","family":"Mo","sequence":"additional","affiliation":[{"name":"Institute of Animal Husbandry and Veterinary Medicine, Fujian Academy of Agricultural Sciences, Fuzhou 350013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guiheng","family":"Mei","sequence":"additional","affiliation":[{"name":"Institute of Animal Husbandry and Veterinary Medicine, Fujian Academy of Agricultural Sciences, Fuzhou 350013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiqin","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Animal Husbandry and Veterinary Medicine, Fujian Academy of Agricultural Sciences, Fuzhou 350013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengqiang","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Animal Husbandry and Veterinary Medicine, Fujian Academy of Agricultural Sciences, Fuzhou 350013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quanwang","family":"Wu","sequence":"additional","affiliation":[{"name":"Changdu Animal Husbandry General Station, Changdu 854000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Dexicuomu","sequence":"additional","affiliation":[{"name":"Changdu Animal Husbandry General Station, Changdu 854000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Danzengzhuoga","sequence":"additional","affiliation":[{"name":"Changdu Animal Husbandry General Station, Changdu 854000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Sangjiebazhu","sequence":"additional","affiliation":[{"name":"Changdu Animal Husbandry General Station, Changdu 854000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Pubuzhaxi","sequence":"additional","affiliation":[{"name":"Changdu Animal Husbandry General Station, Changdu 854000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Yang, S., Zhang, H., Mao, H., Yan, D., Lu, S., Lian, L., Zhao, G., and Zhang, M. (2011). The local origin of the Tibetan pig and additional insights into the origin of Asian pigs. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0028215"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Gan, M., Shen, L., Fan, Y., Guo, Z., Liu, B., Chen, L., Tang, G., Jiang, Y., Li, X., and Zhang, S. (2019). High altitude adaptability and meat quality in tibetan pigs: A reference for local pork processing and genetic improvement. Animals, 9.","DOI":"10.3390\/ani9121080"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Zhao, M., Zhao, H., Li, P., Peng, S., Lin, F., Wu, Q., Tashi, P., and Li, Z. (2026). Multi-Omics Analysis Reveals Age-Related Enhancements in Gut Morphology, Microbiome, and Metabolism of Tibetan Pigs. Microorganisms, 14.","DOI":"10.3390\/microorganisms14051162"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1038\/ng.2811","article-title":"Genomic analyses identify distinct patterns of selection in domesticated pigs and Tibetan wild boars","volume":"45","author":"Li","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1081\/ABIO-120005767","article-title":"Why and how antibiotics are used in swine production","volume":"13","author":"Cromwell","year":"2002","journal-title":"Anim. Biotechnol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5649","DOI":"10.1073\/pnas.1503141112","article-title":"Global trends in antimicrobial use in food animals","volume":"112","author":"Brower","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Loewenstein, F., Mascher, S., Frey, T., and Lechner, M. (2026). Feeding of Undocked Pigs: Effects of Feed Components and Feed Composition. Animals, 16.","DOI":"10.3390\/ani16081174"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/2049-1891-4-35","article-title":"Alternatives to antibiotics as growth promoters for use in swine production: A review","volume":"4","author":"Thacker","year":"2013","journal-title":"J. Anim. Sci. Biotechnol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.aninu.2018.01.007","article-title":"Non-antibiotic feed additives in diets for pigs: A review","volume":"4","author":"Liu","year":"2018","journal-title":"Anim. Nutr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/nrmicro2974","article-title":"The gut microbiota\u2014Masters of host development and physiology","volume":"11","author":"Sommer","year":"2013","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2369","DOI":"10.1056\/NEJMra1600266","article-title":"The human intestinal microbiome in health and disease","volume":"375","author":"Lynch","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.chom.2019.01.017","article-title":"Bacteriophages of the human gut: The \u201cknown unknown\u201d of the microbiome","volume":"25","author":"Shkoporov","year":"2019","journal-title":"Cell Host Microbe"},{"key":"ref_13","first-page":"331","article-title":"The gut mycobiota: Insights into analysis, environmental interactions and role in gastrointestinal diseases","volume":"16","author":"Richard","year":"2019","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1016\/j.cell.2016.05.041","article-title":"From dietary fiber to host physiology: Short-chain fatty acids as key bacterial metabolites","volume":"165","author":"Koh","year":"2016","journal-title":"Cell"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/j.chom.2018.05.012","article-title":"The impact of dietary fiber on gut microbiota in host health and disease","volume":"23","author":"Makki","year":"2018","journal-title":"Cell Host Microbe"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1186\/s13059-017-1215-1","article-title":"Multi-omics approaches to disease","volume":"18","author":"Hasin","year":"2017","journal-title":"Genome Biol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Lu, Z., Zhang, T., Zhao, Y., Pang, Y., Guo, M., Zhu, X., Li, Y., and Li, Z. (2024). The Influence of Host Genotype and Gut MicrobialInteractions on Feed Efficiency Traits in Pigs. Front. Microbiol., 15.","DOI":"10.3389\/fmicb.2024.1459773"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"van der Walt, S., Sch\u00f6nberger, J.L., Nunez-Iglesias, J., Boulogne, F., Warner, J.D., Yager, N., Gouillart, E., and Yu, T. (2014). Scikit-image: Image processing in Python. PeerJ, 2.","DOI":"10.7717\/peerj.453"},{"key":"ref_19","first-page":"291","article-title":"Quantification of histochemical staining by color deconvolution","volume":"23","author":"Ruifrok","year":"2001","journal-title":"Anal. Quant. Cytol. Histol."},{"key":"ref_20","doi-asserted-by":"crossref","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":"ref_21","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.1923","article-title":"Fast gapped-read alignment with Bowtie 2","volume":"9","author":"Langmead","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1186\/s13059-019-1891-0","article-title":"Improved metagenomic analysis with Kraken 2","volume":"20","author":"Wood","year":"2019","journal-title":"Genome Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"E140","DOI":"10.2527\/jas.2007-0459","article-title":"Use of phytogenic products as feed additives for swine and poultry","volume":"86","author":"Windisch","year":"2008","journal-title":"J. Anim. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.aninu.2017.06.007","article-title":"Using probiotics to improve swine gut health and nutrient utilization","volume":"3","author":"Liao","year":"2017","journal-title":"Anim. Nutr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1080\/17450390903499915","article-title":"Effects of dose and formulation of carvacrol and thymol on bacteria and some functional traits of the gut in piglets after weaning","volume":"64","author":"Michiels","year":"2010","journal-title":"Arch. Anim. Nutr."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1038\/nri.2016.88","article-title":"Immunological aspects of intestinal mucus and mucins","volume":"16","author":"Johansson","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1136\/gut.46.2.218","article-title":"Mucin secretion is modulated by luminal factors in the isolated vascularly perfused rat colon","volume":"46","author":"Barcelo","year":"2000","journal-title":"Gut"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.vetmic.2011.05.021","article-title":"Longitudinal investigation of the age-related bacterial diversity in the feces of commercial pigs","volume":"153","author":"Kim","year":"2011","journal-title":"Vet. Microbiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"16161","DOI":"10.1038\/nmicrobiol.2016.161","article-title":"A reference gene catalogue of the pig gut microbiome","volume":"1","author":"Xiao","year":"2016","journal-title":"Nat. Microbiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1111\/j.1365-2036.2007.03562.x","article-title":"Review article: The role of butyrate on colonic function","volume":"27","author":"Hamer","year":"2008","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1186\/s40168-019-0713-7","article-title":"Dietary Fructose-Induced Gut Dysbiosis Promotes Mouse Hippocampal Neuroinflammation: A Benefit of Short-Chain Fatty Acids","volume":"7","author":"Li","year":"2019","journal-title":"Microbiome"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/nrmicro.2017.30","article-title":"M\u00e9nage \u00e0 trois in the human gut: Interactions between host, bacteria and phages","volume":"15","author":"Mirzaei","year":"2017","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.chom.2017.03.010","article-title":"The gut microbiome: Connecting spatial organization to function","volume":"21","author":"Tropini","year":"2017","journal-title":"Cell Host Microbe"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1186\/s40104-018-0275-8","article-title":"Effects of dietary Clostridium butyricum supplementation on growth performance, intestinal development, and immune response of weaned piglets","volume":"9","author":"Chen","year":"2018","journal-title":"J. Anim. Sci. Biotechnol."}],"container-title":["Veterinary Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2306-7381\/13\/8\/826\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T16:26:44Z","timestamp":1787070404000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2306-7381\/13\/8\/826"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,18]]},"references-count":34,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["vetsci13080826"],"URL":"https:\/\/doi.org\/10.3390\/vetsci13080826","relation":{},"ISSN":["2306-7381"],"issn-type":[{"value":"2306-7381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,18]]}}}