{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T02:55:56Z","timestamp":1790823356603,"version":"4.1.0"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T00:00:00Z","timestamp":1745971200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100024073","name":"Dr. Willmar Schwabe","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100024073","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Disruptions in the gut microbiota metabolism may contribute to the pathophysiology of gut\u2013brain interaction disorders, and correction of intestinal dysbiosis is considered a promising therapeutic approach. Menthacarin, a proprietary fixed combination of <jats:italic>Mentha x piperita L<\/jats:italic>. and <jats:italic>Carum carvi L.<\/jats:italic> essential oils, is used clinically for the treatment of functional dyspepsia and irritable bowel syndrome. Rodent model data indicate that treatment effects of Menthacarin on visceral hypersensitivity could be mediated <jats:italic>via<\/jats:italic> the normalization of gut dysbiosis. However, the impact of Menthacarin on human bacterial gut microbiota has not yet been studied.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>The aim of the present study was to assess whether Menthacarin affects the composition and metabolic activity of human fecal microbiota.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Fecal slurry samples from 10 healthy volunteers were cultivated for 36\u00a0h under anoxic conditions with and without Menthacarin. Relative bacterial abundance at the phylum and genus levels was evaluated using 16S rRNA metagenomic analysis. Short-chain fatty acids (SCFAs) in the supernatants were measured using the LC-MS technology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Menthacarin induced robust changes in microbial composition at both the phylum and genus levels among the 10 donor microbiomes. The relative abundance of <jats:italic>Firmicutes<\/jats:italic> (+13.6 \u00b1 8.6%) and <jats:italic>Actinobacteria<\/jats:italic> (+54.9 \u00b1 47.6%) significantly increased, whereas that of <jats:italic>Bacteroidetes<\/jats:italic> (\u221227.7% \u00b1 21.9%) and <jats:italic>Proteobacteria<\/jats:italic> (\u221225.7% \u00b1 12.3%) significantly decreased in the presence of Menthacarin. At the genus level, the most notable changes were significant increases in <jats:italic>Bifidobacterium<\/jats:italic> (+105.1 \u00b1 78.4%) and several SCFA-producing genera accompanied by a significant decrease in genera containing members involved in pro-inflammatory processes. In addition, Menthacarin significantly increased the levels of several SCFAs, namely, propionate, butyrate, isobutyrate, valerate, and isovalerate.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Menthacarin alters the microbiota composition and enhances SCFA production in human microbiota samples under <jats:italic>in vitro<\/jats:italic> conditions. These effects may contribute to the clinical benefits observed with Menthacarin treatment.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2025.1569052","type":"journal-article","created":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T07:25:58Z","timestamp":1745997958000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Menthacarin, a proprietary combination of peppermint and caraway oil, alters cultured human fecal microbiota composition, resulting in increased SCFA production"],"prefix":"10.3389","volume":"16","author":[{"given":"Martin D.","family":"Lehner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Ulsemer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Christochowitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1080\/00365520500206442","article-title":"A combination of peppermint oil and caraway oil attenuates the post-inflammatory visceral hyperalgesia in a rat model","volume":"41","author":"Adam","year":"2006","journal-title":"Scand. J. Gastroenterol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"153212","DOI":"10.1016\/j.phymed.2020.153212","article-title":"Menthacarin attenuates experimental colitis","volume":"77","author":"Alliger","year":"2020","journal-title":"Phytomedicine"},{"key":"B3","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1111\/j.1463-1318.2012.03152.x","article-title":"Microencapsulated sodium butyrate reduces the frequency of abdominal pain in patients with irritable bowel syndrome","volume":"15","author":"Banasiewicz","year":"2013","journal-title":"Colorectal Dis."},{"key":"B4","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: a practical and powerful approach to multiple testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. R. Stat. Soc. Ser. B Methodol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"e13299","DOI":"10.1111\/nmo.13299","article-title":"Reversal of visceral hypersensitivity in rat by Menthacarin(\u00ae), a proprietary combination of essential oils from peppermint and caraway, coincides with mycobiome modulation","volume":"30","author":"Botschuijver","year":"2018","journal-title":"Neurogastroenterol. Motil."},{"key":"B6","doi-asserted-by":"publisher","first-page":"e14372","DOI":"10.1111\/nmo.14372","article-title":"Role of the duodenal microbiota in functional dyspepsia","volume":"34","author":"Brown","year":"2022","journal-title":"Neurogastroenterol. Motil."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1967","DOI":"10.3390\/nu16121967","article-title":"Effects of Bifidobacterium longum 35624 in children and adolescents with irritable bowel syndrome","volume":"16","author":"Cruchet Mu\u00f1oz","year":"2024","journal-title":"Nutrients"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1099","DOI":"10.3390\/biomedicines9091099","article-title":"Microbiome first medicine in health and safety","volume":"9","author":"Dietert","year":"2021","journal-title":"Biomedicines"},{"key":"B9","doi-asserted-by":"publisher","first-page":"672295","DOI":"10.1038\/s41587-020-0548-6","article-title":"PICRUSt2: an improved and customizable approach for metagenome inference","author":"Douglas","year":"2020","journal-title":"bioRxiv"},{"key":"B10","doi-asserted-by":"publisher","first-page":"e13983","DOI":"10.1111\/nmo.13983","article-title":"Changes in fecal short-chain fatty acids following fecal microbiota transplantation in patients with irritable bowel syndrome","volume":"33","author":"El-Salhy","year":"2021","journal-title":"Neurogastroenterol. Motil."},{"key":"B11","article-title":"ICH M12 Guideline on drug interaction studies - step 5","volume-title":"EMA\/CHMP\/ICH\/652460\/2022","year":"2022"},{"key":"B12","doi-asserted-by":"publisher","first-page":"559","DOI":"10.3390\/life14050559","article-title":"Short-chain fatty acids and human health: from metabolic pathways to current therapeutic implications","volume":"14","author":"Facchin","year":"2024","journal-title":"Life (Basel)"},{"key":"B13","doi-asserted-by":"publisher","first-page":"e13914","DOI":"10.1111\/nmo.13914","article-title":"Microbiota changes induced by microencapsulated sodium butyrate in patients with inflammatory bowel disease","volume":"32","author":"Facchin","year":"2020","journal-title":"Neurogastroenterol. Motil."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1357","DOI":"10.1111\/febs.17200","article-title":"The role of the gut microbiome in disorders of gut-brain interaction","volume":"292","author":"Gawey","year":"2024","journal-title":"Febs J."},{"key":"B15","article-title":"Measuring short-chain fatty acids in microbiome-derived samples by LC-MS\/MS","author":"Haidacher","year":"2020"},{"key":"B16","first-page":"380","article-title":"Essential oils in the treatment of intestinal dysbiosis: a preliminary in vitro study","volume":"14","author":"Hawrelak","year":"2009","journal-title":"Altern. Med. Rev."},{"key":"B17","doi-asserted-by":"publisher","first-page":"412","DOI":"10.3748\/wjg.v28.i4.412","article-title":"Gut bless you: the microbiota-gut-brain axis in irritable bowel syndrome","volume":"28","author":"Hillestad","year":"2022","journal-title":"World J. Gastroenterol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1078\/1433-187x-00310","article-title":"Effects of a fixed combination of peppermint oil and caraway oil on symptoms and quality of life in patients suffering from functional dyspepsia","volume":"10","author":"Holtmann","year":"2003","journal-title":"Phytomedicine"},{"key":"B19","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1038\/s41392-022-00974-4","article-title":"Microbiota in health and diseases","volume":"7","author":"Hou","year":"2022","journal-title":"Signal Transduct. Target Ther."},{"key":"B20","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1163\/18762891-bja00015","article-title":"Gut microbiome and symptoms in females with irritable bowel syndrome: a cross-sectional analysis","volume":"15","author":"Kamp","year":"2024","journal-title":"Benef. Microbes"},{"key":"B21","doi-asserted-by":"publisher","first-page":"e13748","DOI":"10.1111\/nmo.13748","article-title":"Peppermint and caraway oils have muscle inhibitory and pro-secretory activity in the human intestine in vitro","volume":"32","author":"Krueger","year":"2020","journal-title":"Neurogastroenterol. Motil."},{"key":"B22","doi-asserted-by":"publisher","first-page":"4146","DOI":"10.1038\/s41467-019-12087-8","article-title":"An in vitro model maintaining taxon-specific functional activities of the gut microbiome","volume":"10","author":"Li","year":"2019","journal-title":"Nat. Commun."},{"key":"B23","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1016\/j.dld.2017.01.142","article-title":"Altered molecular signature of intestinal microbiota in irritable bowel syndrome patients compared with healthy controls: a systematic review and meta-analysis","volume":"49","author":"Liu","year":"2017","journal-title":"Dig. Liver Dis."},{"key":"B24","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1159\/000528553","article-title":"Menthacarin, a proprietary peppermint oil and caraway oil combination, improves multiple complaints in patients with functional gastrointestinal disorders: a systematic review and meta-analysis","volume":"41","author":"Madisch","year":"2023","journal-title":"Dig. Dis."},{"key":"B25","doi-asserted-by":"publisher","first-page":"925","DOI":"10.1055\/s-0031-1300528","article-title":"Treatment of functional dyspepsia with a fixed peppermint oil and caraway oil combination preparation as compared to cisapride. A multicenter, reference-controlled double-blind equivalence study","volume":"49","author":"Madisch","year":"1999","journal-title":"Arzneimittelforschung"},{"key":"B26","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1007\/s10354-018-0635-1","article-title":"Effectiveness of Menthacarin on symptoms of irritable bowel syndrome","volume":"169","author":"Madisch","year":"2019","journal-title":"Wien Med. Wochenschr"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1486","DOI":"10.1053\/j.gastro.2020.10.066","article-title":"The microbiota-gut-brain Axis: from motility to mood","volume":"160","author":"Margolis","year":"2021","journal-title":"Gastroenterology"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1671","DOI":"10.1046\/j.1365-2036.2000.00873.x","article-title":"Efficacy and tolerability of a fixed combination of peppermint oil and caraway oil in patients suffering from functional dyspepsia","volume":"14","author":"May","year":"2000","journal-title":"Aliment. Pharmacol. Ther."},{"key":"B29","doi-asserted-by":"publisher","first-page":"e61217","DOI":"10.1371\/journal.pone.0061217","article-title":"phyloseq: an R package for reproducible interactive analysis and graphics of microbiome census data","volume":"8","author":"Mcmurdie","year":"2013","journal-title":"PLoS One"},{"key":"B30","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1002\/(sici)1099-1573(200002)14:1<20::aid-ptr542>3.0.co;2-z","article-title":"Effects of peppermint oil and caraway oil on gastroduodenal motility","volume":"14","author":"Micklefield","year":"2000","journal-title":"Phytother. Res."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1191","DOI":"10.3390\/antibiotics12071191","article-title":"Antibacterial and antibiofilm effects of different samples of five commercially available essential oils","volume":"12","author":"Neagu","year":"2023","journal-title":"Antibiot. (Basel)"},{"key":"B32","unstructured":"Vegan: community ecology package\n          \n          \n            \n              Oksanen\n              J. S. G.\n            \n            \n              Blanchet\n              F. G.\n            \n          \n          \n          2022"},{"key":"B33","doi-asserted-by":"publisher","first-page":"e14760","DOI":"10.1111\/nmo.14760","article-title":"Menthacarin treatment attenuates nociception in models of visceral hypersensitivity","volume":"36","author":"Omoloye","year":"2024","journal-title":"Neurogastroenterol. Motil."},{"key":"B34","doi-asserted-by":"publisher","first-page":"6","DOI":"10.3390\/jcm7010006","article-title":"The gut-brain Axis and the microbiome: clues to pathophysiology and opportunities for novel management strategies in irritable bowel syndrome (IBS)","volume":"7","author":"Quigley","year":"2018","journal-title":"J. Clin. Med."},{"key":"B35","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1080\/15287394.2024.2375731","article-title":"Chemical composition, cytotoxicity, antimicrobial, antibiofilm, and anti-quorum sensing potential of Mentha Piperita essential oil against the oral pathogen Streptococcus mutans","volume":"87","author":"Quintana Soares Lopes","year":"2024","journal-title":"J. Toxicol. Environ. Health A"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.13132","article-title":"A randomized placebo-controlled trial on the effects of Menthacarin, a proprietary peppermint- and caraway-oil-preparation, on symptoms and quality of life in patients with functional dyspepsia","volume":"29","author":"Rich","year":"2017","journal-title":"Neurogastroenterol. Motil."},{"key":"B37","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1080\/09637486.2019.1580682","article-title":"The human-microbiome superorganism and its modulation to restore health","volume":"70","author":"Salvucci","year":"2019","journal-title":"Int. J. Food Sci. Nutr."},{"key":"B38","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1136\/gutjnl-2021-326158","article-title":"Alterations to the duodenal microbiota are linked to gastric emptying and symptoms in functional dyspepsia","volume":"72","author":"Shanahan","year":"2023","journal-title":"Gut"},{"key":"B39","doi-asserted-by":"publisher","first-page":"147","DOI":"10.4103\/0973-1296.66926","article-title":"Protective effects of bioactive phytochemicals from Mentha piperita with multiple health potentials","volume":"6","author":"Sharafi","year":"2010","journal-title":"Pharmacogn. Mag."},{"key":"B40","doi-asserted-by":"publisher","first-page":"2338322","DOI":"10.1080\/19490976.2024.2338322","article-title":"A randomized double-blind, placebo-controlled trial to evaluate the safety and efficacy of live Bifidobacterium longum CECT 7347 (ES1) and heat-treated Bifidobacterium longum CECT 7347 (HT-ES1) in participants with diarrhea-predominant irritable bowel syndrome","volume":"16","author":"Srivastava","year":"2024","journal-title":"Gut Microbes"},{"key":"B41","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1055\/a-1823-1333","article-title":"Menthacarin for long-term treatment of functional dyspepsia - results from a clinical trial follow-up","volume":"61","author":"Storr","year":"2023","journal-title":"Z Gastroenterol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"109","DOI":"10.2147\/CEG.S451675","article-title":"A systematic review: fecal bacterial profile in patients with irritable bowel syndrome analyzed with the GA-map dysbiosis test based on the 16S rRNA Gene of bacterial species or groups","volume":"17","author":"Teige","year":"2024","journal-title":"Clin. Exp. Gastroenterol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"1131662","DOI":"10.3389\/fmicb.2023.1131662","article-title":"Bridging preclinical and clinical gut microbiota research using the ex vivo SIFR(\u00ae) technology","volume":"14","author":"Van Den Abbeele","year":"2023","journal-title":"Front. Microbiol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1080\/15366367.2019.1565254","article-title":"ggplot2: elegant graphics for data analysis (2nd ed.)","volume":"17","author":"Villanueva","year":"2019","journal-title":"Meas. Interdiscip. Res. Perspect."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1510","DOI":"10.1136\/gutjnl-2019-320204","article-title":"Interaction between drugs and the gut microbiome","volume":"69","author":"Weersma","year":"2020","journal-title":"Gut"},{"key":"B46","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.maturitas.2018.03.012","article-title":"Microbiota-drug interactions: impact on metabolism and efficacy of therapeutics","volume":"112","author":"Wilkinson","year":"2018","journal-title":"Maturitas"},{"key":"B47","doi-asserted-by":"publisher","first-page":"2863","DOI":"10.3390\/foods11182863","article-title":"Health benefits and side effects of short-chain fatty acids","volume":"11","author":"Xiong","year":"2022","journal-title":"Foods"},{"key":"B48","doi-asserted-by":"publisher","first-page":"goab046","DOI":"10.1093\/gastro\/goab046","article-title":"Microbiome therapeutics: exploring the present scenario and challenges","volume":"10","author":"Yadav","year":"2022","journal-title":"Gastroenterol. Rep. (Oxf)"},{"key":"B49","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1038\/s41467-023-44292-x","article-title":"Efficacy of Bifidobacterium animalis subsp. lactis BL-99 in the treatment of functional dyspepsia: a randomized placebo-controlled clinical trial","volume":"15","author":"Zhang","year":"","journal-title":"Nat. Commun."},{"key":"B50","doi-asserted-by":"publisher","first-page":"1409280","DOI":"10.3389\/fmicb.2024.1409280","article-title":"Duodenal microbiota dysbiosis in functional dyspepsia and its potential role of the duodenal microbiota in gut-brain axis interaction: a systematic review","volume":"15","author":"Zhang","year":"","journal-title":"Front. Microbiol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"3985","DOI":"10.3748\/wjg.v30.i35.3985","article-title":"Correlation between the neuroendocrine axis, microbial species, inflammatory response, and gastrointestinal symptoms in irritable bowel syndrome","volume":"30","author":"Zhang","year":"","journal-title":"World J. Gastroenterol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"910568","DOI":"10.3389\/fphys.2022.910568","article-title":"The role of gastrointestinal microbiota in functional dyspepsia: a review","volume":"13","author":"Zhou","year":"2022","journal-title":"Front. Physiol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"1600","DOI":"10.3389\/fmicb.2018.01600","article-title":"Fecal microbiota alterations associated with diarrhea-predominant irritable bowel syndrome","volume":"9","author":"Zhuang","year":"2018","journal-title":"Front. Microbiol."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1569052\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T07:26:01Z","timestamp":1745997961000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1569052\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,30]]},"references-count":53,"alternative-id":["10.3389\/fphar.2025.1569052"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2025.1569052","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,30]]},"article-number":"1569052"}}