{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T05:28:50Z","timestamp":1786685330643,"version":"build-2736575974"},"reference-count":31,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Physiological Reports"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Breast milk proteins may regulate gut function and defecation frequency; however, their specific roles in these processes remain poorly understood. We hypothesized that variations in specific human milk proteins are associated with differences in stool frequency among exclusively breastfed infants. Infants were categorized into three groups based on defecation frequency: Group A (normal, 1\u20133 times per day), Group B (frequent, &gt;3 times per day), and Group C (infrequent, \u22641 time every 3\u20134\u2009days). Each group consisted of three biological replicates (total\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u20099). This study was an exploratory pilot study. Breast\u2010milk samples were analyzed using tandem mass tag (TMT)\u2010based proteomics to identify differentially expressed proteins across groups. Gene Ontology (GO), KEGG pathway enrichment, and protein\u2013protein interaction (PPI) analyses were conducted to explore functional pathways. A total of 2563 proteins were identified; \u03b2\u2010casein, \u03b1\n                    <jats:sub>s1<\/jats:sub>\n                    \u2010casein, and \u03ba\u2010casein were significantly downregulated in infants with lower defecation frequency (Group C vs. Group A; fold change &lt;0.6,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). \u03b2\u2010casein showed the most significant difference (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0003). Enrichment analysis revealed pathways related to glycolipid metabolism, fibroblast proliferation, and coagulation cascades, while PPI analysis identified fibrinogen\u2010related proteins as key interaction nodes. These findings suggest that \u03b2\u2010casein levels in breast milk are associated with infant stool frequency. This may help clarify the association between constipation, diarrhea, and breastfeeding in infants and young children and may provide a theoretical reference for the subsequent development of targeted breast milk fortifiers and improvements in the intestinal environment in infants.\n                  <\/jats:p>","DOI":"10.14814\/phy2.71027","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T07:40:14Z","timestamp":1785915614000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Beta\u2010casein in human milk is associated with infant stool frequency: A pilot proteomics study"],"prefix":"10.14814","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6843-2219","authenticated-orcid":false,"given":"Zhan\u2010Hua","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pediatrics The First Affiliated Hospital of Kunming Medical University  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen\u2010Rong","family":"Xie","sequence":"additional","affiliation":[{"name":"The Medical Biobank The First Affiliated Hospital of Kunming Medical University  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Li","sequence":"additional","affiliation":[{"name":"Yunnan Key Laboratory of Clinical Medicine  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing\u2010Jing","family":"Xiong","sequence":"additional","affiliation":[{"name":"Yunnan Key Laboratory of Clinical Medicine  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics The First Affiliated Hospital of Kunming Medical University  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0157-8138","authenticated-orcid":false,"given":"Yong\u2010Kun","family":"Huang","sequence":"additional","affiliation":[{"name":"Yunnan Key Laboratory of Clinical Medicine  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.3945\/an.116.013953"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.mpg.0000232019.79025.8f"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu12092591"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0205987"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/14789450.2022.2070477"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.0c00816"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22158140"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.1c05435"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/apa.16736"},{"issue":"1","key":"e_1_2_13_11_1","first-page":"4","article-title":"Rome IVCriteria for pediatric functional gastrointestinal disorders","volume":"55","author":"Geng L. L.","year":"2017","journal-title":"Chinese Journal of Pediatrics"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12887-021-02610-6"},{"issue":"3","key":"e_1_2_13_13_1","first-page":"252","article-title":"Human milk proteome: what's new?","volume":"24","author":"Kelly A.","year":"2021","journal-title":"Current Opinion in Clinical Nutrition and Metabolic Care"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu11071688"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.6133\/apjcn.201912_28(4).0017"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2022.970685"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1039\/D4FO05556J"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/77.6.1537S"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu12041039"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10534\u2010014\u20109762\u20103"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu15061313"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu15061313"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/apa.14620"},{"issue":"2","key":"e_1_2_13_24_1","first-page":"198","article-title":"Beta\u2010casein proteins and infant growth and development","volume":"32","author":"Sadler M. J.","year":"2014","journal-title":"Clinical Pediatric Journal"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(22)00687\u20100"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1080\/17474124.2023.2242255"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1001461"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/prca.201800024"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2023.1239501"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.203095"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.TIR119.001385"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1039\/c9fo01591d"}],"container-title":["Physiological Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.14814\/phy2.71027","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/full-xml\/10.14814\/phy2.71027","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.14814\/phy2.71027","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T05:09:25Z","timestamp":1786684165000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.14814\/phy2.71027"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":31,"journal-issue":{"issue":"15","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.14814\/phy2.71027"],"URL":"https:\/\/doi.org\/10.14814\/phy2.71027","archive":["Portico"],"relation":{},"ISSN":["2051-817X","2051-817X"],"issn-type":[{"value":"2051-817X","type":"print"},{"value":"2051-817X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8]]},"assertion":[{"value":"2026-02-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e71027"}}