{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T22:47:42Z","timestamp":1790290062903,"version":"4.1.0"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T00:00:00Z","timestamp":1736208000000},"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. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>This study aims to explore the therapeutic mechanism of Massa Medicata Fermentata (MMF) with different formulations on spleen deficiency constipation in mice by analyzing gastrointestinal hormones, D-xylose, intestinal microbiota, and intestinal enzyme activities.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A spleen deficiency constipation model was established using an oral administration of Sennae Folium decoction combined with controlled diet and water intake. After successful model establishment, the mice with spleen deficiency constipation were treated with MMF S1, S2, S3. Following the intervention, serum samples from each group of mice were collected to measure VIP, 5-HT, and D-xylose. Additionally, small intestine contents were analyzed for intestinal enzyme activity and subjected to 16S rRNA high-throughput sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Mice with spleen deficiency constipation showed significant decreases in body weight and fecal water content. In contrast, the body weight of the CS2 and CS3 groups returned to normal levels, and fecal water content in the CS2 and CS3 groups also returned to normal. The MMF S2 and S3 significantly increased protease and sucrase enzymes levels compared with CM group. Serum D-xylose levels were significantly reduced in the CM and CS2 group. VIP levels increased significantly in the CM group but decreased in the CS2 and CS3 groups. Additionally, 5-HT levels in the CM and CS1 groups decreased significantly, with the CS2 group returning to normal and the CS3 group showing significant increases. 16S rRNA sequencing analysis revealed that all three MMF formulations effectively restored the intestinal microbiota composition in mice. LEfSe analysis identified characteristic microbiota linked to different intervention groups. The CS3 group significantly upregulated the chloroalkane and chloroalkene degradation and vibrio cholerae pathogenic cycle pathways compared to the CM group. <jats:italic>Candidatus_Arthromitus<\/jats:italic> in the CS3 group and <jats:italic>Psychrobacter<\/jats:italic> in the CS2 group were positive and negative correlations with 5-HT and VIP, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The three formulations of MMF significantly alleviated spleen deficiency constipation symptoms by modulating intestinal enzyme activities, D-xylose, VIP, and 5-HT levels, and restoring intestinal microbiota balance. <jats:italic>Psychrobacter<\/jats:italic> and <jats:italic>Candidatus_Arthromitus<\/jats:italic> were identified as potential biomarkers for the treatment of spleen deficiency constipation. Different formulations of MMF have different mechanisms of regulating constipation through intestinal microbiota.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2024.1524327","type":"journal-article","created":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T06:46:57Z","timestamp":1736232417000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Study on the effects of Massa Medicata Fermentata with different formulations on the intestinal microbiota and enzyme activities in mice with spleen deficiency constipation"],"prefix":"10.3389","volume":"14","author":[{"given":"Xuejuan","family":"Liang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinliang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanmei","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linglong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,1,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2597","DOI":"10.5504\/BBEQ.2011.0085","article-title":"Effects of lactic acid bacteria (Lab) supplement on the growth rate and elimination of enteropathogenic bacteria in calves","volume":"25","author":"An","year":"2011","journal-title":"Biotechnol. Biotechnol. Equip."},{"key":"B2","doi-asserted-by":"publisher","first-page":"5028","DOI":"10.12659\/MSM.916526","article-title":"Efficacy of high specific volume polysaccharide \u2013 A new type of dietary fiber \u2013 on molecular mechanism of intestinal water metabolism in rats with constipation","volume":"25","author":"Cong","year":"2019","journal-title":"Med. Sci. Monit"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1285","DOI":"10.1038\/sj.bjp.0705762","article-title":"Role of serotonin in the pathophysiology of the irritable bowel syndrome","volume":"141","author":"Crowell","year":"2004","journal-title":"Br. J. Pharmacol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"484","DOI":"10.3945\/an.116.014407","article-title":"Mechanisms of action of probiotics and the gastrointestinal microbiota on gut motility and constipation","volume":"8","author":"Dimidi","year":"2017","journal-title":"Adv. Nutr."},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2023.1104759","article-title":"Fecal microbiota transplantation in Parkinson\u2019s disease\u2014A randomized repeat-dose, placebo-controlled clinical pilot study","volume":"14","author":"DuPont","year":"2023","journal-title":"Front. Neurol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1007\/s13205-024-04180-7","article-title":"Involvement of intestinal mucosal microbiota in adenine-induced liver function injury","volume":"15","author":"Fang","year":"2024","journal-title":"Biotech"},{"key":"B7","doi-asserted-by":"publisher","first-page":"6484","DOI":"10.1080\/21655979.2021.1973356","article-title":"The mechanism of intestinal flora dysregulation mediated by intestinal bacterial biofilm to induce constipation","volume":"12","author":"Fu","year":"2021","journal-title":"Bioengineered"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph18020667","article-title":"Exploring the association of autism spectrum disorders and constipation through analysis of the gut microbiome","volume":"18","author":"Fu","year":"2021","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"B9","doi-asserted-by":"publisher","first-page":"362","DOI":"10.13193\/j.issn.1673-7717.2016.02.031","article-title":"Effects of different Liushen Qu on digestive function in mice","volume":"34","author":"Gao","year":"2016","journal-title":"Chin. Arch. Tradit Chin. Med."},{"key":"B10","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1007\/s00253-021-11694-0","article-title":"Ligilactobacillus salivarius functionalities, applications, and manufacturing challenges","volume":"106","author":"Guerrero Sanchez","year":"2022","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2024.1354823","article-title":"Dysfunction of cecal microbiota and CutC activity in mice mediating diarrhea with kidney-yang deficiency syndrome","volume":"15","author":"Guo","year":"2024","journal-title":"Front. Microbiol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1191","DOI":"10.2217\/fmb-2016-0085","article-title":"Corynebacterium ulcerans, an emerging human pathogen","volume":"11","author":"Hacker","year":"2016","journal-title":"Future Microbiol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1513","DOI":"10.1039\/c9fo00132h","article-title":"Protective effect of mulberry (Morus atropurpurea) fruit against diphenoxylate-induced constipation in mice through the modulation of gut microbiota","volume":"10","author":"Hu","year":"2019","journal-title":"Food Funct."},{"key":"B14","doi-asserted-by":"publisher","first-page":"4","DOI":"10.4292\/wjgpt.v14.i2.4","article-title":"Cinnamic acid regulates the intestinal microbiome and short-chain fatty acids to treat slow transit constipation","volume":"14","author":"Jiang","year":"2023","journal-title":"World J. Gastrointest Pharmacol. Ther."},{"key":"B15","doi-asserted-by":"publisher","first-page":"2269","DOI":"10.7539\/j.issn.1672-2981.2023.09.001","article-title":"Effect of Guangdong Shenqu on the gastrointestinal motility, Cx43 and BDNF in mice with food stagnation","volume":"21","author":"Jiang","year":"2023","journal-title":"Cent. South Pharm."},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1163638","article-title":"Ginsenoside Rg1 can reverse fatigue behavior in CFS rats by regulating EGFR and affecting Taurine and Mannose 6-phosphate metabolism","volume":"14","author":"Lei","year":"2023","journal-title":"Front. Pharmacol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"4388","DOI":"10.1002\/fsn3.1736","article-title":"Gut microbiota is involved in the alleviation of loperamide-induced constipation by honey supplementation in mice","volume":"8","author":"Li","year":"2020","journal-title":"Food Sci. Nutr."},{"key":"B18","doi-asserted-by":"publisher","first-page":"437","DOI":"10.3724\/SP.J.1145.2015.08018","article-title":"The effects of spleen-deficient constipation model construction on the intestinal bacterial diversity in mice","volume":"22","author":"Li","year":"2016","journal-title":"Chin. J. Appl. Environ. Biol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1186\/s12866-023-02896-9","article-title":"Diarrhea accompanies intestinal inflammation and intestinal mucosal microbiota dysbiosis during fatigue combined with a high-fat diet","volume":"23","author":"Liu","year":"2023","journal-title":"BMC Microbiol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.16333\/j.1001-6880.2017.6.020","article-title":"Effects of Dendrobium candidum polysaccharide on immunity, intestinal microbiota and enzyme activity in mice with spleen deficiency constipation","volume":"29","author":"Long","year":"2017","journal-title":"Nat. Prod Res. Dev."},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000034703","article-title":"Intestinal flora in the constipation patients before versus after lactulose intervention","volume":"102","author":"Ma","year":"2023","journal-title":"Med. (Baltimore)"},{"key":"B22","doi-asserted-by":"publisher","first-page":"121","DOI":"10.15912\/j.cnki.gocm.2023.26.014","article-title":"Clinical Effect of Shenqu Xiaoshi oral liquid plus intestinal probiotics on the treatment of infantile function constipation","volume":"21","author":"Mu","year":"2023","journal-title":"China Med. Guide"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2023.1214577","article-title":"Zhishi Daozhi decoction alleviates constipation induced by a high-fat and high-protein diet via regulating intestinal mucosal microbiota and oxidative stress","volume":"14","author":"Peng","year":"2023","journal-title":"Front. Microbiol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1007\/s13205-024-04045-z","article-title":"Shenling Baizhu powder attenuates lard diet in a fatigued state-induced diarrhea via targeting microbial metabolites short chain fatty acids-mediated lipid metabolism","volume":"14","author":"Qiao","year":"2024","journal-title":"3 Biotech."},{"key":"B25","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1111\/j.1574-6941.2007.00375.x","article-title":"Multivariate analyses in microbial ecology","volume":"62","author":"Ramette","year":"2007","journal-title":"FEMS Microbiol. Ecol."},{"key":"B26","doi-asserted-by":"publisher","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":"B27","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2024.1502373","article-title":"Chinese herbal medicine, Tongxieyaofang, alleviates diarrhea via gut microbiota remodeling: evidence from network pharmacology and full-length 16S rRNA gene sequencing","volume":"14","author":"Shao","year":"2024","journal-title":"Front. Cell Infect. Microbiol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1039\/d3fo03259k","article-title":"Ligilactobacillus acidipiscis YJ5 modulates the gut microbiota and produces beneficial metabolites to relieve constipation by enhancing the mucosal barrier","volume":"15","author":"Shen","year":"2024","journal-title":"Food Funct."},{"key":"B29","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1080\/13880209.2021.2019283","article-title":"A comprehensive study on the relieving effect of Lilium brownii on the intestinal flora and metabolic disorder in p-chlorphenylalanine induced insomnia rats","volume":"60","author":"Si","year":"2022","journal-title":"Pharm. Biol."},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.654074","article-title":"Intestinal microbiota mediates high-fructose and high-fat diets to induce chronic intestinal inflammation","volume":"11","author":"Tan","year":"2021","journal-title":"Front. Cell Infect. Microbiol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/j.jad.2023.10.072","article-title":"TGR5 deficiency-induced anxiety and depression-like behaviors: The role of gut microbiota dysbiosis","volume":"344","author":"Tao","year":"2024","journal-title":"J.\u00a0Affect. Disord."},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1359954","article-title":"The effects of Massa Medicata Fermentata on the digestive function and intestinal flora of mice with functional dyspepsia","volume":"15","author":"Wang","year":"2024","journal-title":"Front. Pharmacol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1026","DOI":"10.13381\/j.cnki.cjm.202309006","article-title":"Effect of Dendrobium officinale on the diversity of intestinal microbiota in mice with spleen deficiency constipation","volume":"35","author":"Wu","year":"2023","journal-title":"Chin. J. Microecol."},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2022.964847","article-title":"Sex hormones influence the intestinal microbiota composition in mice","volume":"13","author":"Wu","year":"2022","journal-title":"Front. Microbiol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"20","DOI":"10.13412\/j.cnki.zyyl.20230423.004","article-title":"Detection method study of enzyme activity potency of Massa Medicata Fermentata based on in vitro and in vivo correlation","volume":"39","author":"Yang","year":"2023","journal-title":"Pharmacol. Clin. Chin. Mater Med."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.3969\/j.issn.0253-9926.2023.13.015","article-title":"Effects of different processing techniques and tasteless Divine Massa Medicata Fermentataon digestive function","volume":"52","author":"Yang","year":"2023","journal-title":"Shanxi Med. J."},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2023.1090302","article-title":"Simo decoction curing spleen deficiency constipation was associated with brain-bacteria-gut axis by intestinal mucosal microbiota","volume":"14","author":"Yi","year":"2023","journal-title":"Front. Microbiol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1007\/s13205-023-03580-5","article-title":"Brain-bacteria-gut axis and oxidative stress mediated by intestinal mucosal microbiota might be an important mechanism for constipation in mice","volume":"13","author":"Yi","year":"2023","journal-title":"3 Biotech."},{"key":"B39","doi-asserted-by":"publisher","first-page":"186","DOI":"10.11954\/ytctyy.202101057","article-title":"Analysis of the process evolution and modern research progress of Massa Medicata Fermentata","volume":"17","author":"Yin","year":"2021","journal-title":"Asia-Pacific Tradit Med."},{"key":"B40","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1186\/s13020-020-00394-y","article-title":"Shengmai Yin formula modulates the gut microbiota of spleen-deficiency rats","volume":"15","author":"You","year":"2020","journal-title":"Chin. Med."},{"key":"B41","doi-asserted-by":"publisher","first-page":"353","DOI":"10.19852\/j.cnki.jtcm.20220408.002","article-title":"Correlation between slow transit constipation and spleen Qi deficiency, and gut microbiota: a pilot study","volume":"42","author":"Yu","year":"2022","journal-title":"J.\u00a0Tradit Chin. Med."},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2024.1376232","article-title":"Assessing the causal effects of Eubacterium and Rumphococcus on constipation: a Mendelian randomized study","volume":"15","author":"Zhang","year":"2024","journal-title":"Front. Microbiol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.13288\/j.11-2166\/r.2017.15.023","article-title":"Expert consensus on traditional Chinese medicine diagnosis and Treatment of Constipatio","volume":"58","author":"Zhang","year":"2017","journal-title":"J. Tradit Chin. Med."},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2022.956438","article-title":"Alleviating effects of gut micro-ecologically regulatory treatments on mice with constipation","volume":"13","author":"Zhao","year":"2022","journal-title":"Front. Microbiol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1007\/s13205-024-03959-y","article-title":"Adenine\u2019s impact on mice\u2019s gut and kidney varies with the dosage administered and relates to intestinal microorganisms and enzyme activities","volume":"14","author":"Zhou","year":"2024","journal-title":"3 Biotech."},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2023.1324938","article-title":"The dysfunction in intestinal microorganisms and enzyme activity as significant contributors to diarrhea with kidney-yang deficiency syndrome","volume":"14","author":"Zhou","year":"2023","journal-title":"Front. Microbiol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"18","DOI":"10.13381\/j.cnki.cjm.202201004","article-title":"Effect of Yangwei Sijunzi Tea\u00a0on intestinal microorganisms, enzyme activity, and gastric motility in mice with spleen deficiency-type constipation","volume":"34","author":"Zhu","year":"2022","journal-title":"Chin. J. Microecol."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2024.1524327\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T06:47:08Z","timestamp":1736232428000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2024.1524327\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,7]]},"references-count":47,"alternative-id":["10.3389\/fcimb.2024.1524327"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2024.1524327","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,7]]},"article-number":"1524327"}}