{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T14:38:01Z","timestamp":1777905481531,"version":"3.51.4"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T00:00:00Z","timestamp":1748822400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014978","name":"Hunan University of Chinese Medicine","doi-asserted-by":"publisher","award":["202302"],"award-info":[{"award-number":["202302"]}],"id":[{"id":"10.13039\/501100014978","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009377","name":"Education Department of Hunan Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009377","id-type":"DOI","asserted-by":"publisher"}]}],"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 aimed to investigate the therapeutic effects of sodium propionate in combination with Sishen Pill in the treatment of diarrhea with kidney-yang deficiency syndrome in mice, with a focus on its influence on intestinal microbiota, enzyme activity, and associated therapeutic outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A model of diarrhea with kidney-yang deficiency syndrome was established via adenine combined with <jats:italic>Folium sennae<\/jats:italic> administration. The model group was randomly assigned to the following treatment groups: natural recovery group, 100% Sishen Pill group, 75% Sishen Pill + 60 mg\/kg sodium propionate group, 50% Sishen Pill + 120 mg\/kg sodium propionate group, 25% Sishen Pill + 240 mg\/kg sodium propionate group, and 480 mg\/kg sodium propionate group. A variety of parameters, including general symptoms, body weight, rectal temperature, intestinal microbiota composition, microbial activity, and enzyme activity, were assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared with natural recovery group, the 480 mg\/kg sodium propionate group presented significant improvements in mental state, anal temperature, fecal water content, the thymus index, and <jats:italic>Bifidobacterium<\/jats:italic> counts (<jats:italic>p<\/jats:italic> &amp;lt; 0.01). Compared with those in normal group, the fecal water content and <jats:italic>Escherichia coli<\/jats:italic> counts in the 100% Sishen Pill group were significantly different (<jats:italic>p<\/jats:italic> &amp;lt; 0.01), but no significant differences were observed compared with those in natural recovery group (<jats:italic>p<\/jats:italic> &amp;gt; 0.05). The 75% Sishen Pill + 60 mg\/kg sodium propionate group showed improvements in mental state, food and water intake, body weight, rectal temperature, fecal water content, spleen, and thymus index, <jats:italic>Bifidobacterium<\/jats:italic> counts, total bacterial count, <jats:italic>E. coli<\/jats:italic> count, microbial activity, and lactase activity, which were close to normal levels, and significant differences were observed when compared to the natural recovery group (<jats:italic>p<\/jats:italic> &amp;lt; 0.01). The 50% Sishen Pill + 120 mg\/kg sodium propionate group and 25% Sishen Pill + 240 mg\/kg sodium propionate group also exhibited significant differences in mental status, microbial activity, and Lactobacillus count relative to those of normal group (<jats:italic>p<\/jats:italic> &amp;lt; 0.01). Furthermore, the 50% Sishen Pill + 120 mg\/kg sodium propionate group presented significant changes in fecal water content (<jats:italic>p<\/jats:italic> &amp;lt; 0.01), whereas 25% Sishen Pill + 240 mg\/kg sodium propionate group presented significant differences in the spleen index, total bacterial count, <jats:italic>E. coli<\/jats:italic> count, protease activity, lactase activity, and xylanase activity compared with those of normal group (<jats:italic>p<\/jats:italic> &amp;lt; 0.01).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The 75% Sishen Pill + 60 mg\/kg sodium propionate can improve the symptoms of kidney-yang deficiency syndrome, promote the growth and development of mice, inhibit excessive bacterial proliferation, support the growth of beneficial bacteria, and enhance intestinal enzyme activity. Its effects are superior to the use of sodium propionate or Sishen Pill alone. These results suggest that this therapeutic ratio may optimize the efficacy of Sishen Pill in the treatment of diarrhea with kidney-yang deficiency syndrome. However, further research is necessary to confirm whether this combination represents the most effective treatment regimen for this condition in mice.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2025.1608271","type":"journal-article","created":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T05:22:29Z","timestamp":1748841749000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Synergistic treatment of sodium propionate and Sishen Pill for diarrhea mice with kidney-yang deficiency syndrome"],"prefix":"10.3389","volume":"15","author":[{"given":"Meifang","family":"Guo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiaxin","family":"Di","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhijun","family":"Lei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"608","DOI":"10.3390\/nu14030608","article-title":"Different alterations in gut microbiota between bifidobacterium longum and fecal microbiota transplantation treatments in propionic acid rat model of autism","volume":"14","author":"Abujamel","year":"2022","journal-title":"Nutrients"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/9478630","article-title":"Probiotic species in the modulation of gut microbiota: an overview","volume":"2018","author":"Azad","year":"2018","journal-title":"BioMed. Res. Int."},{"key":"B3","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1016\/j.gtc.2021.02.008","article-title":"Small intestinal bacterial overgrowth","volume":"50","author":"Bushyhead","year":"2021","journal-title":"Gastroenterol. Clin. North Am."},{"key":"B4","doi-asserted-by":"publisher","first-page":"2082","DOI":"10.3390\/foods11142082","article-title":"Antidiarrheal effect of fermented millet bran on diarrhea induced by senna leaf in mice","volume":"11","author":"Chen","year":"2022","journal-title":"Foods"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1485","DOI":"10.12677\/acm.2024.1461939","article-title":"Advances in inflammatory mechanisms of neutrophils in UC","volume":"14","author":"Chen","year":"2024","journal-title":"Adv. Clin. Med."},{"key":"B6","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1079\/PNS2002213","article-title":"Motor effects of short-chain fatty acids and lactate in the gastrointestinal tract","volume":"62","author":"Cherbut","year":"2003","journal-title":"Proc. Nutr. Soc."},{"key":"B7","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1111\/j.1369-7625.2012.00794.x","article-title":"Views on traditional Chinese medicine amongst Chinese population: a systematic review of qualitative and quantitative studies","volume":"17","author":"Chung","year":"2014","journal-title":"Health Expect"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijfoodmicro.2019.108258","article-title":"The preservative propionic acid differentially affects survival of conidia and germ tubes of feed spoilage fungi","volume":"306","author":"Dijksterhuis","year":"2019","journal-title":"Int. J. Food Microbiol."},{"key":"B9","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":"2025","journal-title":"3 Biotech."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodres.2022.111754","article-title":"Stimulation of the intestinal microbiota with prebiotics enhances hepatic levels of dietary polyphenolic compounds, lipid metabolism and antioxidant status in healthy rats","volume":"160","author":"Fotschki","year":"2022","journal-title":"Food Res. Int."},{"key":"B11","first-page":"61","article-title":"The synergic effect of ultra-micro powder Qiweibaizhusan combined with yeast on dysbacteriotic diarrhea mice","volume":"21","author":"Guo","year":"2015","journal-title":"Chin. J. Appl. Environ. Biol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"7275","DOI":"10.2147\/JIR.S470254","article-title":"Decreasing of trimethylamine N-oxide by cecal microbiota and choline-trimethylamine lyase are associated with sishen pill on diarrhea with kidney-yang deficiency syndrome","volume":"17","author":"Guo","year":"2024","journal-title":"J. Inflammation Res."},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.livsci.2020.103940","article-title":"Effects of xylanase on growth performance, nutrients digestibility and intestinal health in weaned piglets","volume":"233","author":"He","year":"2020","journal-title":"Livestock Sci."},{"key":"B14","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1146\/annurev-med-042220-012821","article-title":"The gut microbiome: connecting diet, glucose homeostasis, and disease","volume":"73","author":"Howard","year":"2022","journal-title":"Annu. Rev. Med."},{"key":"B15","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1016\/j.canlet.2006.02.014","article-title":"Enhanced induction of mitochondrial damage and apoptosis in human leukemia HL-60 cells by the Ganoderma lucidum and Duchesnea chrysantha extracts","volume":"246","author":"Kim","year":"2007","journal-title":"Cancer Lett."},{"key":"B16","first-page":"74","article-title":"Research progress on establishment method and evaluation standard of animal model of kidney yang deficiency syndrome","volume":"52","author":"Li","year":"2021","journal-title":"Chiang-hsi Chung I Yao"},{"key":"B17","first-page":"1721","article-title":"Research progress on animal modeling methods and model evaluation of spleen-yang deficiency","volume":"17","author":"Li","year":"2015","journal-title":"Modernization Traditional Chin. Med. Materia Medica-World Sci. Technol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/j.psj.2020.10.009","article-title":"Propionate inhibits fat deposition via affecting feed intake and modulating gut microbiota in broilers","volume":"100","author":"Li","year":"2021","journal-title":"Poult Sci."},{"key":"B19","doi-asserted-by":"publisher","first-page":"4","DOI":"10.5152\/tjg.2022.211010","article-title":"Correlation between kidney function and intestinal biological characteristics of adenine and folium sennaeInduced diarrhea model in mice","volume":"34","author":"Li","year":"2023","journal-title":"Turkish J. Gastroenterol."},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.669561","article-title":"Commentary: focus on the gut-kidney axis in health and disease","volume":"8","author":"Li","year":"2021","journal-title":"Front. Med. (Lausanne)"},{"key":"B21","first-page":"78","article-title":"Development status and prospects of traditional Chinese medicine microecological regulators","volume":"25","author":"Liang","year":"2012","journal-title":"Traditional Chin. Medicinal Res."},{"key":"B22","doi-asserted-by":"publisher","first-page":"670","DOI":"10.16438\/j.0513-4870.2018-0920","article-title":"Experimental study on the effect of Sishen Wan on intestinal flora in rats with diarrhea-type irritable bowel syndrome","volume":"54","author":"Liu","year":"2019","journal-title":"Acta Pharm. Sin."},{"key":"B23","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1038\/nrrheum.2014.105","article-title":"TREG-cell therapies for autoimmune rheumatic diseases","volume":"10","author":"Miyara","year":"2014","journal-title":"Nat. Rev. Rheumatol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1016\/j.cgh.2016.11.012","article-title":"Colonic transit and bile acid synthesis or excretion in patients with irritable bowel syndrome-diarrhea without bile acid malabsorption","volume":"15","author":"Peleman","year":"2017","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"37","DOI":"10.16438\/j.0513-4870.2020-1246","article-title":"Strategy to delay the progression of chronic kidney disease by targeting gut microbiota and uremic toxins metabolism pathway","volume":"56","author":"Peng","year":"2021","journal-title":"Acta Pharm. Sin."},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.696810","article-title":"Low dietary fiber intake links development of obesity and lupus pathogenesis","volume":"12","author":"Schafer","year":"2021","journal-title":"Front. Immunol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"171","DOI":"10.12938\/bmfh.2024-078","article-title":"The effects of functional biscuits on intestinal mucosal microbiota composition, brain function, and antioxidant activity","volume":"44","author":"Shen","year":"2025","journal-title":"Biosci. Microbiota Food Health"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.202200164","article-title":"Roseburia hominis Alleviates Neuroinflammation via Short-Chain Fatty Acids through Histone Deacetylase Inhibition","volume":"66","author":"Song","year":"2022","journal-title":"Mol. Nutr. Food Res."},{"key":"B29","doi-asserted-by":"publisher","first-page":"e10446","DOI":"10.1002\/btm2.10446","article-title":"The efficacy of anti-proteolytic peptide R7I in intestinal inflammation, function, microbiota, and metabolites by multi-omics analysis in murine bacterial enteritis","volume":"8","author":"Sun","year":"2023","journal-title":"Bioeng. Transl. Med."},{"key":"B30","doi-asserted-by":"publisher","first-page":"17","DOI":"10.13381\/j.cnki.cjm.202001004","article-title":"Effect of Tongxieyaofang prescription on intestinal microbial activity in mice with Ganqichenpi diarrhea","volume":"32","author":"Tang","year":"2020","journal-title":"Chin. J. Microecol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"79","DOI":"10.13557\/j.cnki.issn1002-2813.2021.11.019","article-title":"Effect of ingredients compound of Mongolian veterinary medicine Babu-7 on intestinal barrier related factors in diarrhea mice","volume":"44","author":"Tian","year":"2021","journal-title":"Feed Res."},{"key":"B32","doi-asserted-by":"publisher","first-page":"461","DOI":"10.3390\/nu11020461","article-title":"Congenital lactase deficiency: mutations, functional and biochemical implications, and future perspectives","volume":"11","author":"Wanes","year":"2019","journal-title":"Nutrients"},{"key":"B33","doi-asserted-by":"publisher","first-page":"7145090","DOI":"10.1155\/2022\/7145090","article-title":"Dietary supplementation of crystalline amino acid improves growth performance and health of yellow catfish that reduced by plant proteins replacement of fishmeal","volume":"2022","author":"Wang","year":"2022","journal-title":"Aquaculture Nutr."},{"key":"B34","doi-asserted-by":"publisher","first-page":"36","DOI":"10.13995\/j.cnki.11-1802\/ts.022133","article-title":"Study on microbial community structure in Sichuan traditional bacon","volume":"46","author":"Wen","year":"2020","journal-title":"Food Ferment. Ind."},{"key":"B35","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":"B36","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1007\/s13205-020-02597-4","article-title":"Characteristics of intestinal microbiota and enzyme activities in mice fed with lily bulb","volume":"11","author":"Wu","year":"2021","journal-title":"3 Biotech."},{"key":"B37","doi-asserted-by":"publisher","first-page":"e944185","DOI":"10.12659\/MSM.944185","article-title":"Targeting the gut-kidney axis in diarrhea with kidney-yang deficiency syndrome: the role of sishen pills in regulating TMAO-mediated inflammatory response","volume":"30","author":"Xie","year":"2024","journal-title":"Med. Sci. Monit."},{"key":"B38","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1186\/s40168-022-01390-0","article-title":"Beneficial effect of the short-chain fatty acid propionate on vascular calcification through intestinal microbiota remodelling","volume":"10","author":"Yan","year":"2022","journal-title":"Microbiome"},{"key":"B39","doi-asserted-by":"publisher","first-page":"319","DOI":"10.5246\/jcps.2021.04.026","article-title":"Changes in renal excretion pathways in rats with adenine-induced chronic renal failure","volume":"30","author":"Yanrong","year":"2021","journal-title":"J. Chin. Pharmaceutical Sci."},{"key":"B40","doi-asserted-by":"publisher","first-page":"33","DOI":"10.15979\/j.cnki.cn62-1064\/s.2019.05.010","article-title":"A review of research on Escherichia coli","volume":"49","author":"Yin","year":"2019","journal-title":"Gansu Anim. Husbandry Veterinar"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1159\/000510364","article-title":"Characteristics and contributing factors related to nonsteroidal anti-inflammatory drugs hypersensitivity","volume":"182","author":"Yuenyongviwat","year":"2021","journal-title":"Int Arch Allergy Immunol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1256","DOI":"10.13288\/j.11-2166\/r.2017.14.023","article-title":"Consensus expert opinions on traditional Chinese medicine diagnosis and treatment of diarrhea","volume":"58","author":"Zhang","year":"2017","journal-title":"Chin. J. Chin. Mater. Med."},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2024.155541","article-title":"Sishen Wan enhances intestinal barrier function via regulating endoplasmic reticulum stress to improve mice with diarrheal irritable bowel syndrome","volume":"129","author":"Zhao","year":"2024","journal-title":"Phytomedicine"},{"key":"B44","first-page":"61","article-title":"An overview of studies on the application of Sishen Pill in the treatment of gastrointestinal diseases","volume":"42","author":"Zhou","year":"2011","journal-title":"Chiang-hsi Chung I Yao"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2023.1157475","article-title":"Baohe pill decoction treats diarrhea induced by high-fat and high-protein diet by regulating lactase-producing bacteria in intestinal mucosa","volume":"14","author":"Zhou","year":"2023","journal-title":"Front. Microbiol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1007\/s00394-022-02958-0","article-title":"Bifico relieves irritable bowel syndrome by regulating gut microbiota dysbiosis and inflammatory cytokines","volume":"62","author":"Zhou","year":"2023","journal-title":"Eur. J. Nutr."},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e16166","article-title":"Intestinal mucosal flora of the intestine-kidney remediation process of diarrhea with deficiency kidney-yang syndrome in Sishen Pill treatment: Association with interactions between Lactobacillus johnsonii, Ca(2+)-Mg(2+)-ATP-ase, and Na(+)-K(+)-ATP-ase","volume":"9","author":"Zhu","year":"2023","journal-title":"Heliyon"}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2025.1608271\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T05:22:36Z","timestamp":1748841756000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2025.1608271\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,2]]},"references-count":47,"alternative-id":["10.3389\/fcimb.2025.1608271"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2025.1608271","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,2]]},"article-number":"1608271"}}