{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T08:35:30Z","timestamp":1775032530001,"version":"3.50.1"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"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:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Hyperbilirubinemia is among the most common conditions in neonates, and phototherapy is currently the most widely used treatment. However, it can induce side effects such as skin rashes, diarrhea, and gut microbiota dysbiosis, particularly affecting\n                      <jats:italic>Bifidobacterium<\/jats:italic>\n                      levels. This study aimed to investigate whether the supplementation of\n                      <jats:italic>Bifidobacterium<\/jats:italic>\n                      can alleviate dysbiosis and improve clinical outcomes in jaundiced neonates.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 79 jaundiced neonates were enrolled and divided into four groups: Phototherapy Control, M-16V, Bb-12, and the combined M-16V+Bb-12 group. Probiotics were administered until 30 days post-discharge, and neurodevelopment was assessed at 1.5\u20132 years using the Griffith Development Scales. Fecal samples collected before, during, and after treatment were analyzed using metagenomic sequencing and non-targeted metabolomics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Probiotic supplementation significantly increased daily defecation frequency, accelerated the reduction rate of transcutaneous bilirubin, and shortened hospital stays. Griffith scores indicated that Bb-12 supplementation improved scores in personal-social and performance domains. Metagenomic analysis revealed significant differences in beta diversity between the control and probiotic groups; specifically, M-16V and combined supplementation increased the abundance of\n                      <jats:italic>Bifidobacterium<\/jats:italic>\n                      breve. Pathway enrichment analysis showed up-regulation of pyrimidine-containing compound metabolic processes, intramolecular transferase activity, and DNA conformation change. Metabolomics further demonstrated that combined supplementation elevated levels of 5-methyltetrahydrofolate (linked to DNA synthesis), benzoic acid and indoleacetic acid (linked to growth and development), and the anti-inflammatory metabolite indole-3-lactic acid.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>For neonates receiving phototherapy, the addition of M-16 V + Bb-12 probiotics can improve the diversity of microflora, reduce the fixed value of harmful bacteria in the intestine, and enhance the excretion of bilirubin from the intestine, to improve the inflammatory damage and microbiota disorder caused by phototherapy, and achieve the effect of clinically improving jaundice, reducing bilirubin, shortening the length of hospitalization, and promoting neurodevelopment. It provides a safer and more effective treatment for neonatal jaundice.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1761245","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T05:42:09Z","timestamp":1775022129000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The enhancing therapeutic effect of neonatal jaundice by bifidobacterium through regulating inflammation and gut microbiota in combination with phototherapy\u2014a randomized controlled trial"],"prefix":"10.3389","volume":"17","author":[{"given":"Feng","family":"Zhang","sequence":"first","affiliation":[{"name":"College of Food Science and Technology, Shanghai Ocean University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiayi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, DiproX Medical Research Center","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanhan","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, DiproX Medical Research Center","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juanjuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, DiproX Medical Research Center","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Jiang","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology, Immunology, and Metabolism, Diprobio (Shanghai) Co, Limited","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiwei","family":"Xiang","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology, Immunology, and Metabolism, Diprobio (Shanghai) Co, Limited","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Na","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, DiproX Medical Research Center","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhimin","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, DiproX Medical Research Center","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sainan","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, DiproX Medical Research Center","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, DiproX Medical Research Center","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanan","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, DiproX Medical Research Center","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tianyu","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Food Science and Technology, Shanghai Ocean University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiahui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, DiproX Medical Research Center","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qinghua","family":"Yu","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology, Immunology, and Metabolism, Diprobio (Shanghai) Co, Limited","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, DiproX Medical Research Center","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,1]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"887","DOI":"10.3390\/metabo11120887","article-title":"Association of neonatal jaundice with gut dysbiosis characterized by decreased Bifidobacteriales","volume":"11","author":"Akagawa","year":"2021","journal-title":"Meta"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1159\/000496427","article-title":"Effect of delivery mode and nutrition on gut microbiota in neonates","volume":"74","author":"Akagawa","year":"2019","journal-title":"Ann. 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