{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T12:47:55Z","timestamp":1793969275145,"version":"4.8.0"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,11,14]],"date-time":"2022-11-14T00:00:00Z","timestamp":1668384000000},"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. Endocrinol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Diarrhea-predominant irritable bowel syndrome (IBS-D) is a recurrent and common disease featuring dysbiotic intestinal microbiota, with limited treatments. Si-Jun-Zi Decoction (SJZD), a classic Chinese prescription, has been extensively used for IBS-D. This work aimed to explore the <jats:italic>ex vivo<\/jats:italic> interactions of SJZD and IBS-D\u2019s intestinal microbiota.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Five samples of intestinal microbiota collected from IBS-D volunteers and five age-matched healthy controls were recruited from the Affiliated Hospital, Chengdu University of Traditional Chinese Medicine (TCM). A representative mixture of intestinal microbiota was composed of an equal proportion of these fecal samples. To simulate the clinical interaction, this microbiota was cocultivated with SJZD at clinical dosage in an anaerobic incubator at 37\u00b0C for 35 h. Microbiota and metabolic alterations were assessed by 16S rRNA gene sequencing in the V3\/V4 regions and a nontargeted metabolome platform, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>After being cocultivated with SJZD, the dysbiotic intestine microbiota from IBS-D subjects was largely restored to those of the healthy controls. A total of 624 differentially expressed metabolites were detected by nontargeted metabolomics, of which 16 biomarkers were identified. These metabolites were then enriched into 11 pathways by KEGG, particularly those involved in neurotransmitter metabolism responses for the major symptom of IBS-D. Correlation analysis of bacterial metabolites demonstrated a synergistic pattern of neurotransmitter metabolism between <jats:italic>Streptococcus<\/jats:italic> and <jats:italic>E. Shigella.<\/jats:italic><\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:italic>SJZD<\/jats:italic> rescued the dysbiotic intestinal microbiota and ameliorated the dysfunctional neurotransmitter metabolism involved in IBS-D\u2019s major symptoms.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2022.1053103","type":"journal-article","created":{"date-parts":[[2022,11,14]],"date-time":"2022-11-14T04:58:52Z","timestamp":1668401932000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Cocultivation of Chinese prescription and intestine microbiota: SJZD alleviated the major symptoms of IBS-D subjects by tuning neurotransmitter metabolism"],"prefix":"10.3389","volume":"13","author":[{"given":"Xiuwen","family":"Xia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaoqiao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dou","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongqin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaji","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yili","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiumin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijun","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,11,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0000000000000714","article-title":"Epidemiology of irritable bowel syndrome in children and adolescents in Asia","volume":"60","author":"Devanarayana","year":"2015","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2005.11.061","article-title":"Functional bowel disorders","volume":"130","author":"Longstreth","year":"2006","journal-title":"Gastroenterology"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2005.40674.x","article-title":"Bowel habit subtypes and temporal patterns in irritable bowel syndrome: Systematic review","volume":"100","author":"Guilera","year":"2005","journal-title":"Am J Gastroenterol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s11894-005-0019-8","article-title":"New insights into the pathophysiology of irritable bowel syndrome: Implications for future treatments","volume":"7","author":"Crowell","year":"2005","journal-title":"Curr Gastroenterol Rep"},{"key":"B5","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.gtc.2010.12.004","article-title":"Traditional thoughts on the pathophysiology of irritable bowel syndrome","volume":"40","author":"Hasler","year":"2011","journal-title":"Gastroenterol Clin North Am"},{"key":"B6","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.gtc.2010.12.010","article-title":"Inflammation and microflora","volume":"40","author":"Pimentel","year":"2011","journal-title":"Gastroenterol Clin North Am"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-020-06109-5","article-title":"Microbiome and its role in irritable bowel syndrome","volume":"65","author":"Pimentel","year":"2020","journal-title":"Dig Dis Sci"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v22.i7.2219","article-title":"Gut microbiota role in irritable bowel syndrome: New therapeutic strategies","volume":"22","author":"Distrutti","year":"2016","journal-title":"World J Gastroenterol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1093\/nutrit\/nuy009","article-title":"Relationship between the gut microbiome and brain function","volume":"76","author":"Mohajeri","year":"2018","journal-title":"Nutr Rev"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1111\/apt.16625","article-title":"Review article: Current and future treatment approaches for IBS with diarrhoea (IBS-d) and IBS mixed pattern (IBS-m)","author":"Nee","year":"2021","journal-title":"Aliment Pharmacol Ther"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.01210","article-title":"Synergistic effect of berberine-based Chinese medicine assembled nanostructures on diarrhea-predominant irritable bowel syndrome In vivo","volume":"11","author":"Li","year":"2020","journal-title":"Front Pharmacol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2020.109934","article-title":"Sanhuang shu\u2019ai decoction alleviates DSS-induced ulcerative colitis via regulation of gut microbiota, inflammatory mediators and cytokines","volume":"125","author":"Wu","year":"2020","journal-title":"BioMed Pharmacother"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.109252","article-title":"The interaction between the gut microbiota and herbal medicines","volume":"118","author":"An","year":"2019","journal-title":"BioMed Pharmacother"},{"key":"B14","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1152\/physrev.00045.2009","article-title":"Gut microbiota in health and disease","volume":"90","author":"Sekirov","year":"2010","journal-title":"Physiol Rev"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2015.12.031","article-title":"Could the gut microbiota reconcile the oral bioavailability conundrum of traditional herbs","volume":"179","author":"Chen","year":"2016","journal-title":"J Ethnopharmacol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.2590","article-title":"Traditional Chinese medicine: Balancing the gut ecosystem","volume":"23","author":"Li","year":"2009","journal-title":"Phytother Res"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0213869","article-title":"16S rRNA gene profiling and genome reconstruction reveal community metabolic interactions and prebiotic potential of medicinal herbs used in neurodegenerative disease and as nootropics","volume":"14","author":"Peterson","year":"2019","journal-title":"PloS One"},{"key":"B18","doi-asserted-by":"publisher","first-page":"16210","DOI":"10.1038\/s41598-021-94594-7","article-title":"Fermentation products of danshen relieved dextran sulfate sodium-induced experimental ulcerative colitis in mice","volume":"11","author":"Su","year":"2021","journal-title":"Sci Rep"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.00918","article-title":"Linggui zhugan formula improves glucose and lipid levels and alters gut microbiota in high-fat diet-induced diabetic mice","volume":"10","author":"Wu","year":"2019","journal-title":"Front Physiol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2505","article-title":"Gut microbiota: A potential new territory for drug targeting","volume":"7","author":"Jia","year":"2008","journal-title":"Nat Rev Drug Discovery"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2020.110380","article-title":"Chinese Herbal medicine baoyuan jiedu decoction inhibits the accumulation of myeloid derived suppressor cells in pre-metastatic niche of lung via TGF-\u03b2\/CCL9 pathway","volume":"129","author":"Tian","year":"2020","journal-title":"Biomed Pharmacother"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2011-301104","article-title":"Analysis of gut microbial regulation of host gene expression along the length of the gut and regulation of gut microbial ecology through MyD88","volume":"61","author":"Larsson","year":"2012","journal-title":"Gut"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1000352","article-title":"Statistical methods for detecting differentially abundant features in clinical metagenomic samples","volume":"5","author":"White","year":"2009","journal-title":"PloS Comput Biol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/srep21146","article-title":"BATMAN-TCM: A bioinformatics analysis tool for molecular mechANism of traditional Chinese medicine","volume":"6","author":"Liu","year":"2016","journal-title":"Sci Rep"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1002\/med.21431","article-title":"Understanding the molecular mechanisms of the interplay between herbal medicines and gut microbiota","volume":"37","author":"Xu","year":"2017","journal-title":"Med Res Rev"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2010.10.030","article-title":"Evidence for the complementary and synergistic effects of the three-alkaloid combination regimen containing berberine, hypaconitine and skimmianine on the ulcerative colitis rats induced by trinitrobenzene-sulfonic acid","volume":"651","author":"Zhang","year":"2011","journal-title":"Eur J Pharmacol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1053\/j.gastro.2019.03.049","article-title":"Gut microbiota in patients with irritable bowel syndrome-a systematic review","volume":"157","author":"Pittayanon","year":"2019","journal-title":"Gastroenterology"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v10.i12.1802","article-title":"Intestinal microecology and quality of life in irritable bowel syndrome patients","volume":"10","author":"Si","year":"2004","journal-title":"World J Gastroenterol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2015.0954","article-title":"Irritable bowel syndrome: A clinical review","volume":"313","author":"Chey","year":"2015","journal-title":"JAMA"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/9759138","article-title":"Research progress in fecal microbiota transplantation as treatment for irritable bowel syndrome","volume":"2019","author":"Wang","year":"2019","journal-title":"Gastroenterol Res Pract"},{"key":"B31","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1053\/j.gastro.2007.04.005","article-title":"The fecal microbiota of irritable bowel syndrome patients differs significantly from that of healthy subjects","volume":"133","author":"Kassinen","year":"2007","journal-title":"Gastroenterology"},{"key":"B32","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1038\/nature08821","article-title":"A human gut microbial gene catalogue established by metagenomic sequencing","volume":"464","author":"Qin","year":"2010","journal-title":"Nature"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2982.2011.01803.x","article-title":"Distinct microbial populations exist in the mucosa-associated microbiota of sub-groups of irritable bowel syndrome","volume":"24","author":"Parkes","year":"2012","journal-title":"Neurogastroenterol Motil"},{"key":"B34","doi-asserted-by":"publisher","first-page":"E1159","DOI":"10.3390\/nu12041159","article-title":"Efficacy of lactobacillus paracasei HA-196 and bifidobacterium longum R0175 in alleviating symptoms of irritable bowel syndrome (IBS): A randomized, placebo-controlled study","volume":"12","author":"Lewis","year":"2020","journal-title":"Nutrients"},{"key":"B35","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1159\/000512167","article-title":"Mucosa-associated microbiota in patients with irritable bowel syndrome: A comparison of subtypes","volume":"102","author":"Matsumoto","year":"2021","journal-title":"Digestion"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.14309\/ctg.0000000000000146","article-title":"Increased ileal immunoglobulin a production and immunoglobulin a-coated bacteria in diarrhea-predominant irritable bowel syndrome","volume":"11","author":"Liu","year":"2020","journal-title":"Clin Transl Gastroenterol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2018.01110","article-title":"Tong-Xie-Yao-Fang regulates 5-HT level in diarrhea predominant irritable bowel syndrome through gut microbiota modulation","volume":"9","author":"Li","year":"2018","journal-title":"Front Pharmacol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1111\/j.1365-2982.2012.01891.x","article-title":"Alterations in composition and diversity of the intestinal microbiota in patients with diarrhea-predominant irritable bowel syndrome","volume":"24","author":"Carroll","year":"2012","journal-title":"Neurogastroenterol Motil"},{"key":"B39","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1016\/j.chom.2020.03.007","article-title":"Genome-wide CRISPR screen identifies semaphorin 6A and 6B as receptors for paeniclostridium sordellii toxin TcsL","volume":"27","author":"Tian","year":"2020","journal-title":"Cell Host Microbe"},{"key":"B40","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.coph.2019.04.007","article-title":"The gut microbiome and pharmacology: A prescription for therapeutic targeting of the gut-brain axis","volume":"49","author":"Leprun","year":"2019","journal-title":"Curr Opin Pharmacol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2018.00013","article-title":"Impact of the gut microbiota on intestinal immunity mediated by tryptophan metabolism","volume":"8","author":"Gao","year":"2018","journal-title":"Front Cell Infect Microbiol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.13178","article-title":"Microbiota-derived tryptophan indoles increase after gastric bypass surgery and reduce intestinal permeability in vitro and in vivo","volume":"30","author":"Jennis","year":"2018","journal-title":"Neurogastroenterol Motil"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706948","article-title":"Trace amine-associated receptors and their ligands","volume":"149","author":"Zucchi","year":"2006","journal-title":"Br J Pharmacol"},{"key":"B44","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1016\/j.chom.2014.09.001","article-title":"Discovery and characterization of gut microbiota decarboxylases that can produce the neurotransmitter tryptamine","volume":"16","author":"Williams","year":"2014","journal-title":"Cell Host Microbe"},{"key":"B45","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1016\/j.chom.2018.05.004","article-title":"Gut microbiota-produced tryptamine activates an epithelial G-Protein-Coupled receptor to increase colonic secretion","volume":"23","author":"Bhattarai","year":"2018","journal-title":"Cell Host Microbe"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1155\/1999\/598659","article-title":"Role of opioid ligands in the irritable bowel syndrome","author":"Corazziari","year":"1999","journal-title":"Can J Gastroenterol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1039\/d0fo02682d","article-title":"Effect of konjac glucomannan on metabolites in the stomach, small intestine and large intestine of constipated mice and prediction of the KEGG pathway","volume":"12","author":"Zhang","year":"2021","journal-title":"Food Funct"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.1053103\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,14]],"date-time":"2022-11-14T04:58:54Z","timestamp":1668401934000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.1053103\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,14]]},"references-count":47,"alternative-id":["10.3389\/fendo.2022.1053103"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2022.1053103","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,14]]},"article-number":"1053103"}}