{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T06:04:13Z","timestamp":1789365853502,"version":"build-2803163510"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"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>\n                    High stocking density can impair broiler growth and is associated with alterations in intestinal microbial ecology and neuroendocrine regulation of feeding. Chlorogenic acid (CGA) has antioxidant, anti-inflammatory, and microbiota-modulating properties. This study evaluated dietary CGA in a 2\u202f\u00d7\u202f2 experimental arrangement defined by stocking density (normal vs. high) and CGA supplementation (0 vs. 1\u202fg\/kg). Two hundred and sixteen one-day-old male Arbor Acres (AA) broilers were assigned to ND (14 birds\/m\n                    <jats:sup>2<\/jats:sup>\n                    ), HD (22 birds\/m\n                    <jats:sup>2<\/jats:sup>\n                    ), NDCGA (14 birds\/m\n                    <jats:sup>2<\/jats:sup>\n                    \u202f+\u202f1\u202fg\/kg CGA), or HDCGA (22 birds\/m\n                    <jats:sup>2<\/jats:sup>\n                    \u202f+\u202f1\u202fg\/kg CGA), with six replicate pens per treatment. High stocking density was associated with poorer late-stage growth performance, age-dependent alterations in circulating cytokines, changes in jejunal microbial composition, lower concentrations of several jejunal short-chain fatty acids (SCFAs), and altered hypothalamic inflammatory- and appetite-related transcripts. Factorial analysis of growth-performance and serum-cytokine endpoints identified prominent stocking-density effects, whereas density \u00d7 CGA interactions were limited to selected growth variables and were not consistently detected across outcomes. Accordingly, isolated HD\u2013HDCGA pairwise differences were interpreted as treatment-combination differences unless supported by a significant interaction. Jejunal propionate and butyrate showed numerical upward trends in HDCGA compared with HD, but the pairwise differences were not significant. The transcriptional findings are consistent with possible involvement of AMPK\/NF-\u03baB- and MAPK-related regulation; however, direct pathway activation was not demonstrated. Collectively, these findings support coordinated associations among stocking density, dietary CGA, jejunal microbial ecology, local SCFA profiles, and hypothalamic transcription without establishing a causal microbiota\u2013gut\u2013brain signaling mechanism.\n                  <\/jats:p>","DOI":"10.3389\/fmicb.2026.1940516","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T05:38:56Z","timestamp":1789364336000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Dietary chlorogenic acid modulates jejunal microbiota, short-chain fatty acids, and hypothalamic gene expression in broilers under high stocking density"],"prefix":"10.3389","volume":"17","author":[{"given":"Dongying","family":"Bai","sequence":"first","affiliation":[{"name":"Department of Animal Physiology, College of Animal Science and Technology, Henan University of Science and Technology","place":["Luoyang, China"]},{"name":"Henan International Joint Laboratory of Animal Welfare and Health Breeding, College of Animal Science and Technology, Henan University of Science and Technology","place":["Luoyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Animal Physiology, College of Animal Science and Technology, Henan University of Science and Technology","place":["Luoyang, China"]},{"name":"Henan International Joint Laboratory of Animal Welfare and Health Breeding, College of Animal Science and Technology, Henan University of Science and Technology","place":["Luoyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanli","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Animal Physiology, College of Animal Science and Technology, Henan University of Science and Technology","place":["Luoyang, China"]},{"name":"Henan International Joint Laboratory of Animal Welfare and Health Breeding, College of Animal Science and Technology, Henan University of Science and Technology","place":["Luoyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangshen","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Animal Physiology, College of Animal Science and Technology, Henan University of Science and Technology","place":["Luoyang, China"]},{"name":"Henan International Joint Laboratory of Animal Welfare and Health Breeding, College of Animal Science and Technology, Henan University of Science and Technology","place":["Luoyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenrui","family":"Zhen","sequence":"additional","affiliation":[{"name":"Department of Animal Physiology, College of Animal Science and Technology, Henan University of Science and Technology","place":["Luoyang, China"]},{"name":"Henan International Joint Laboratory of Animal Welfare and Health Breeding, College of Animal Science and Technology, Henan University of Science and Technology","place":["Luoyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyue","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Animal Physiology, College of Animal Science and Technology, Henan University of Science and Technology","place":["Luoyang, China"]},{"name":"Innovative Research Team of Livestock Intelligent Breeding and Equipment, Science & Technology Innovation Center for Completed Set Equipment, Longmen Laboratory","place":["Luoyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keyuan","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of Animal Physiology, College of Animal Science and Technology, Henan University of Science and Technology","place":["Luoyang, China"]},{"name":"Innovative Research Team of Livestock Intelligent Breeding and Equipment, Science & Technology Innovation Center for Completed Set Equipment, Longmen Laboratory","place":["Luoyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenjie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Animal Physiology, College of Animal Science and Technology, Henan University of Science and Technology","place":["Luoyang, China"]},{"name":"Innovative Research Team of Livestock Intelligent Breeding and Equipment, Science & Technology Innovation Center for Completed Set Equipment, Longmen Laboratory","place":["Luoyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cai","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Animal Physiology, College of Animal Science and Technology, Henan University of Science and Technology","place":["Luoyang, China"]},{"name":"Henan International Joint Laboratory of Animal Welfare and Health Breeding, College of Animal Science and Technology, Henan University of Science and Technology","place":["Luoyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yushu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Agriculture, Graduate School of Science and Technology, Shinshu University","place":["Matsumoto, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingkun","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition, Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, China Agricultural University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanbo","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Animal Physiology, College of Animal Science and Technology, Henan University of Science and Technology","place":["Luoyang, China"]},{"name":"Henan International Joint Laboratory of Animal Welfare and Health Breeding, College of Animal Science and Technology, Henan University of Science and Technology","place":["Luoyang, China"]},{"name":"Innovative Research Team of Livestock Intelligent Breeding and Equipment, Science & Technology Innovation Center for Completed Set Equipment, Longmen Laboratory","place":["Luoyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,14]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"582","DOI":"10.3390\/vetsci9100582","article-title":"Effect of dietary chlorogenic acid on growth performance, antioxidant function, and immune response of broiler breeders under immune stress and stocking density stress","volume":"9","author":"Bai","year":"2022","journal-title":"Vet. Sci."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"38","DOI":"10.3390\/agriculture16010038","article-title":"Aspirin eugenol ester ameliorates hypothalamic neuroinflammation and improves growth performance in high-density-raised broilers","volume":"16","author":"Bai","year":"2026","journal-title":"Agriculture"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"5540","DOI":"10.3390\/molecules28145540","article-title":"Risk assessment of chlorogenic and isochlorogenic acids in coffee by-products","volume":"28","author":"Behne","year":"2023","journal-title":"Molecules"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"106574","DOI":"10.1016\/j.prostaglandins.2021.106574","article-title":"Prostaglandin E2-induced anorexia involves hypothalamic brain-derived neurotrophic factor and ghrelin in chicks","volume":"156","author":"Cao","year":"2021","journal-title":"Prostaglandins Other Lipid Mediat."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"8157","DOI":"10.1007\/s00253-019-10025-8","article-title":"Changes of porcine gut microbiota in response to dietary chlorogenic acid supplementation","volume":"103","author":"Chen","year":"2019","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref6","first-page":"19","article-title":"Council directive 2007\/43\/EC of 28 June 2007 laying down minimum rules for the protection of chickens kept for meat production","year":"2007","journal-title":"Off. J. Eur. Union"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"5617","DOI":"10.1038\/s41467-022-33313-w","article-title":"Lactobacillus supports Clostridiales to restrict gut colonization by multidrug-resistant Enterobacteriaceae","volume":"13","author":"Djukovic","year":"2022","journal-title":"Nat. Commun."},{"key":"ref8","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1093\/ps\/84.8.1332","article-title":"Stocking density on growth performance and processing yields of heavy broilers","volume":"84","author":"Dozier","year":"2005","journal-title":"Poult. Sci."},{"key":"ref9","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1093\/ps\/85.2.344","article-title":"Stocking density effects on male broilers grown to 1.8 kilograms of BW","volume":"85","author":"Dozier","year":"2006","journal-title":"Poult. Sci."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"7379","DOI":"10.3390\/ijms25137379","article-title":"The role of short chain fatty acids in inflammation and body health","volume":"25","author":"Du","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"2309","DOI":"10.3945\/jn.108.095554","article-title":"Chlorogenic acids from green coffee extract are highly bioavailable in humans","volume":"138","author":"Farah","year":"2008","journal-title":"J. Nutr."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1853","DOI":"10.1093\/jn\/133.6.1853","article-title":"Chlorogenic acid bioavailability largely depends on its metabolism by the gut microflora in rats","volume":"133","author":"Gonthier","year":"2003","journal-title":"J. Nutr."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"160014","DOI":"10.1016\/j.scitotenv.2022.160014","article-title":"Intensive poultry farming: a review of the impact on the environment and human health","volume":"858","author":"Gr\u017eini\u0107","year":"2023","journal-title":"Sci. Total Environ."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"1877","DOI":"10.3390\/ijms26051877","article-title":"Aspirin eugenol ester alleviates energy metabolism disorders by reducing oxidative damage and inflammation in the livers of broilers under high-stocking-density stress","volume":"26","author":"Guo","year":"2025","journal-title":"Int. J. Mol. Sci."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"2164","DOI":"10.2337\/db13-0368","article-title":"AMPK: a target for drugs and natural products with effects on both diabetes and cancer","volume":"62","author":"Hardie","year":"2013","journal-title":"Diabetes"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1179\/1476830514y.0000000146","article-title":"Cognitive and neuroprotective effects of chlorogenic acid","volume":"20","author":"Heitman","year":"2017","journal-title":"Nutr. Neurosci."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1016\/j.bbadis.2009.12.009","article-title":"Pathological roles of MAPK signaling pathways in human diseases","volume":"1802","author":"Kim","year":"2010","journal-title":"Biochim. Biophys. 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Sci."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"103586","DOI":"10.1016\/j.psj.2024.103586","article-title":"Chlorogenic acid ameliorates intestinal inflammation by inhibiting NF-\u03baB and endoplasmic reticulum stress in lipopolysaccharide-challenged broilers","volume":"103","author":"Liu","year":"2024","journal-title":"Poult. Sci."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"2333","DOI":"10.1016\/j.clnu.2022.08.029","article-title":"Recent findings in Akkermansia muciniphila-regulated metabolism and its role in intestinal diseases","volume":"41","author":"Liu","year":"2022","journal-title":"Clin. 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Lett."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"1517142","DOI":"10.3389\/fvets.2025.1517142","article-title":"Growth performance, behavior, gene expression, carcass characteristics, stress indicators, and economical parameters of avian 48 broiler chickens raised under three different stocking density","volume":"12","author":"Sakr","year":"2025","journal-title":"Front. Vet. Sci."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"254","DOI":"10.3389\/fvets.2018.00254","article-title":"Chicken gut microbiota: importance and detection technology","volume":"5","author":"Shang","year":"2018","journal-title":"Front. Vet. Sci."},{"key":"ref27","first-page":"e00114","article-title":"Activation of NF-\u03baB mediates up-regulation of cerebellar and hypothalamic pro-inflammatory chemokines and cytokines in acute edible camphor administration","volume":"5","author":"Somade","year":"2019","journal-title":"Sci. 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