{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T17:03:33Z","timestamp":1789578213308,"version":"build-2803163510"},"reference-count":36,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Central Government Guides Local Science and Technology Development Fund Project","award":["264Z6601G"],"award-info":[{"award-number":["264Z6601G"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Balancing muscle growth and antioxidant\/anti-inflammatory homeostasis is a core requirement for modern beef production. This study investigated whether cysteamine hydrochloride (CSH) co-supplementation with guanidinoacetic acid (GAA) enhances growth and antioxidant status through fecal microbiome and serum metabolome modulation in Simmental beef cattle. A 60-day trial randomly assigned 45 10-month-old cattle to control (CON), GAA-supplemented, and GAA + CSH-supplemented groups (n = 15 per group). Growth performance was recorded throughout the trial. Fecal samples were collected for 16S rRNA sequencing, and serum samples for non-targeted metabolomics. Both GAA and GAA + CSH (GCSH) improved growth performance versus CON (p &lt; 0.05), with no differences between supplemented groups. However, GCSH uniquely elevated antioxidant enzymes and reduced malondialdehyde (p &lt; 0.05). GCSH treatment was associated with higher abundance of Adlercreutzia, Anaerofustis, and Monoglobus, alongside elevated indole-3-propionic acid and salicylsulfuric acid. In contrast, GAA reduced phenylacetyl-L-glutamine and indole-3-acetic acid. iCAMP analysis revealed that GCSH relieved homogenizing selection while enhancing heterogeneous selection, promoting beneficial taxa colonization. GAA primarily enhances nitrogen utilization, while CSH enriches beneficial microbiota and antioxidant metabolites. These findings suggest that GAA and CSH co-supplementation improves growth and antioxidant homeostasis through complementary mechanisms.<\/jats:p>","DOI":"10.3390\/antiox15091178","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T16:07:29Z","timestamp":1789574849000},"page":"1178","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Guanidinoacetic Acid and Cysteamine Hydrochloride Improve Beef Cattle Growth and Antioxidant Capacity via Fecal Microbiome and Serum Metabolome"],"prefix":"10.3390","volume":"15","author":[{"given":"Baoshan","family":"Feng","sequence":"first","affiliation":[{"name":"College of Animal Science and Technology, Hebei Agricultural University, Baoding 071001, 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China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Man","family":"Feng","sequence":"additional","affiliation":[{"name":"Chengde Academy of Agriculture and Forestry Sciences, Chengde 067000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Lianjie","family":"Song","sequence":"additional","affiliation":[{"name":"Chengde Academy of Agriculture and Forestry Sciences, Chengde 067000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Yinghao","family":"Zhou","sequence":"additional","affiliation":[{"name":"Chengde Academy of Agriculture and Forestry Sciences, Chengde 067000, 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(2025). Molecular and metabolic insights into muscle development and feed efficiency in beef cattle. Front. Anim. Sci., 6.","DOI":"10.3389\/fanim.2025.1613829"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Shimamoto, S., Nakamura, K., Tomonaga, S., Furukawa, S., Ohtsuka, A., and Ijiri, D. (2020). Effects of cyclic high ambient temperature and dietary supplementation of orotic acid, a pyrimidine precursor, on plasma and muscle metabolites in broiler chickens. Metabolites, 10.","DOI":"10.3390\/metabo10050189"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Zhang, S., Yimamu, M., Ma, C., Pan, J., Wang, C., Cai, W., and Yang, K. (2025). Dietary guanidinoacetic acid supplementation improves rumen metabolism, duodenal nutrient flux, and growth performance in lambs. Front. Vet. Sci., 12.","DOI":"10.3389\/fvets.2025.1528861"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Zhang, S., Zang, C., Pan, J., Ma, C., Wang, C., Li, X., Cai, W., and Yang, K. (2022). Effects of dietary guanidinoacetic acid on growth performance, guanidinoacetic acid absorption and creatine metabolism of lambs. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0264864"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"S\u00e1nchez-Moya, A., Balbuena-Pecino, S., V\u00e9lez, E.J., Perell\u00f3-Amor\u00f3s, M., Garc\u00eda-Meil\u00e1n, I., Fontanillas, R., Calduch-Giner, J.\u00c0., P\u00e9rez-S\u00e1nchez, J., Fern\u00e1ndez-Borr\u00e0s, J., and Blasco, J. (2023). Cysteamine improves growth and the GH\/IGF axis in gilthead sea bream (Sparus aurata): In vivo and in vitro approaches. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1211470"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Wu, Q., Chen, H., Zhang, F., Wang, W., Xiong, F., Liu, Y., Lv, L., Li, W., Bo, Y., and Yang, H. (2022). Cysteamine Supplementation In Vitro Remarkably Promoted Rumen Fermentation Efficiency towards Propionate Production via Prevotella Enrichment and Enhancing Antioxidant Capacity. Antioxidants, 11.","DOI":"10.3390\/antiox11112233"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4339","DOI":"10.1093\/jas\/sky292","article-title":"Dietary cysteamine hydrochloride protects against oxidation, inflammation, and mucosal barrier disruption of broiler chickens challenged with Clostridium perfringens","volume":"96","author":"Liu","year":"2018","journal-title":"J. Anim. Sci."},{"key":"ref_8","unstructured":"National Academies of Sciences, Engineering, and Medicine (2016). Nutrient Requirements of Beef Cattle, The National Academies Press. [8th ed.]."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3583","DOI":"10.3168\/jds.S0022-0302(91)78551-2","article-title":"Methods for dietary fiber, neutral detergent fiber, and nonstarch polysaccharides in relation to animal nutrition","volume":"74","author":"Robertson","year":"1991","journal-title":"J. Dairy Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"282","DOI":"10.2527\/jas1977.442282x","article-title":"Evaluation of acid-insoluble ash as a natural marker in ruminant digestibility studies","volume":"44","author":"Young","year":"1977","journal-title":"J. Anim. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1007\/s00253-015-7039-6","article-title":"Denitrifying sulfide removal process on high-salinity wastewaters in the presence of Halomonas sp.","volume":"100","author":"Liu","year":"2016","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_12","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_13","doi-asserted-by":"crossref","first-page":"2957","DOI":"10.1093\/bioinformatics\/btr507","article-title":"FLASH: Fast length adjustment of short reads to improve genome assemblies","volume":"27","author":"Salzberg","year":"2011","journal-title":"Bioinformatics"},{"key":"ref_14","doi-asserted-by":"crossref","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":"ref_15","doi-asserted-by":"crossref","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":"ref_16","doi-asserted-by":"crossref","first-page":"7537","DOI":"10.1128\/AEM.01541-09","article-title":"Introducing mothur: Open-source, platform-independent, community-supported software for describing and comparing microbial communities","volume":"75","author":"Schloss","year":"2009","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","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":"ref_18","doi-asserted-by":"crossref","unstructured":"O\u00f1ate, F.P., Chamignon, C., Burz, S.D., Lapaque, N., Monnoye, M., Philippe, C., Bredel, M., Ch\u00eane, L., Farin, W., and Paillarse, J.-M. (2023). Adlercreutzia equolifaciens Is an Anti-Inflammatory Commensal Bacterium with Decreased Abundance in Gut Microbiota of Patients with Metabolic Liver Disease. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241512232"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Zhang, X., Veliky, C.V., Birru, R.L., Barinas-Mitchell, E., Magnani, J.W., and Sekikawa, A. (2021). Potential Protective Effects of Equol (Soy Isoflavone Metabolite) on Coronary Heart Diseases\u2014From Molecular Mechanisms to Studies in Humans. Nutrients, 13.","DOI":"10.3390\/nu13113739"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2393270","DOI":"10.1080\/19490976.2024.2393270","article-title":"The interplay between gut microbiota, short-chain fatty acids, and implications for host health and disease","volume":"16","author":"Hays","year":"2024","journal-title":"Gut Microbes"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4863","DOI":"10.1111\/1462-2920.15269","article-title":"Unravelling lactate-acetate and sugar conversion into butyrate by intestinal Anaerobutyricum and Anaerostipes species by comparative proteogenomics","volume":"22","author":"Shetty","year":"2020","journal-title":"Environ. Microbiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1038\/s41396-019-0363-6","article-title":"Genomic insights from Monoglobus pectinilyticus: A pectin-degrading specialist bacterium in the human colon","volume":"13","author":"Kim","year":"2019","journal-title":"ISME J."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Li, Z., Liang, H., Xin, J., Xu, L., Li, M., Yu, H., Zhang, W., Ge, Y., Li, Y., and Qu, M. (2021). Effects of dietary guanidinoacetic acid on the feed efficiency, blood measures, and meat quality of Jinjiang bulls. Front. Vet. Sci., 8.","DOI":"10.3389\/fvets.2021.684295"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Zhu, W., Guo, J., Li, X., Li, Y., Song, L., Li, Y., Feng, B., Bao, X., Li, J., and Gao, Y. (2025). Effects of Gallic Acid on In Vitro Ruminal Fermentation, Methane Emission, Microbial Composition, and Metabolic Functions. Animals, 15.","DOI":"10.3390\/ani15131959"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.cmet.2024.09.011","article-title":"Lighting up arginine metabolism reveals its functional diversity in physiology and pathology","volume":"37","author":"Li","year":"2025","journal-title":"Cell Metab."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Zhu, W., Tian, C., Zeng, W., Chen, Y., and Liu, M. (2026). Rumen-protected guanidinoacetic acid is associated with improved growth performance and altered portal nutrient and hepatic IGF-1 indices in Hu sheep. Front. Vet. Sci., 13.","DOI":"10.3389\/fvets.2026.1832720"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Ren, J., Ma, C., Yang, K., Li, X., Yang, F., Guo, X., Yao, X., and Wang, C. (2026). Effects of Dietary Zinc Cysteamine Supplementation on Growth Performance, Physiological Responses, and Fecal Microbiota in Weaned Foals. Animals, 16.","DOI":"10.3390\/ani16101568"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e13997","DOI":"10.1111\/asj.13997","article-title":"Effects of various levels of coated cysteamine hydrochloride in the diet on feed intake, digestibility, ruminal fermentation, and blood metabolites in growing Charolais crossbred cattle","volume":"95","author":"Meenongyai","year":"2024","journal-title":"Anim. Sci. J."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Kalinina, E. (2026). GSH-Related Enzymes GPx4, Chac1, and GSTs and Redox Regulation of Ferroptosis in Cancer. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27146353"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1186\/s40168-023-01661-4","article-title":"Integrated multi-omics analysis reveals the positive leverage of citrus flavonoids on hindgut microbiota and host homeostasis by modulating sphingolipid metabolism in mid-lactation dairy cows consuming a high-starch diet","volume":"11","author":"Zhao","year":"2023","journal-title":"Microbiome"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"10-1128","DOI":"10.1128\/MMBR.00002-17","article-title":"Stochastic Community Assembly: Does It Matter in Microbial Ecology?","volume":"81","author":"Zhou","year":"2017","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2069","DOI":"10.1038\/ismej.2013.93","article-title":"Quantifying community assembly processes and identifying features that impose them","volume":"7","author":"Stegen","year":"2013","journal-title":"ISME J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1186\/s40168-024-01802-3","article-title":"Synthesis of recovery patterns in microbial communities across environments","volume":"12","author":"Jurburg","year":"2024","journal-title":"Microbiome"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"G696","DOI":"10.1152\/ajpgi.00256.2024","article-title":"Indole-3-propionic acid protects medium-diversity colitic mice via barrier enhancement preferentially over anti-inflammatory effects","volume":"328","author":"Nieves","year":"2025","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.ymgme.2017.08.011","article-title":"Quantitation of phenylbutyrate metabolites by UPLC-MS\/MS demonstrates inverse correlation of phenylacetate:phenylacetylglutamine ratio with plasma glutamine levels","volume":"122","author":"Jiang","year":"2017","journal-title":"Mol. Genet. Metab."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Valgimigli, L. (2023). Lipid Peroxidation and Antioxidant Protection. Biomolecules, 13.","DOI":"10.3390\/biom13091291"}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/15\/9\/1178\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T16:22:48Z","timestamp":1789575768000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/15\/9\/1178"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,16]]},"references-count":36,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["antiox15091178"],"URL":"https:\/\/doi.org\/10.3390\/antiox15091178","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,16]]}}}