Reversal of visceral hypersensitivity in rat by Menthacarin®, a proprietary combination of essential oils from peppermint and caraway, coincides with mycobiome modulation

Neurogastroenterology and Motility - Tập 30 Số 6 - 2018
Sara Botschuijver1, Olaf Welting1, Evgeni Levin2,3, Daniele Maria-Ferreira4,5,1, E Koch6, R.C. Montijn7, Jurgen Seppen1, Theodorus B. M. Hakvoort1, Frank Schuren7, Wouter J. de Jonge1, René M. van den Wijngaard1
1Department of Gastroenterology and Hepatology, Academic Medical Center, Tytgat Institute for Liver and Intestinal Research, Amsterdam, The Netherlands
2Department of Experimental Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands
3HorAIzon BV, Rotterdam, the Netherlands
4Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, PR, Brazil
5Departamento de Farmacologia, Setor de Ciências Biológicas, Universidade Federal do Paraná, Curitiba, PR, Brazil
6Dr. Willmar Schwabe Pharmaceuticals, Karlsruhe, Germany
7Microbiology and Systems Biology, The Netherlands Organization for Applied Scientific Research (TNO), Zeist, The Netherlands

Tóm tắt

AbstractBackgroundIrritable bowel syndrome (IBS) is a common gastrointestinal disorder associated with altered gastrointestinal microflora and increased nociception to colonic distension. This visceral hypersensitivity can be reversed in our rat maternal separation model by fungicides. Menthacarin® is a proprietary combination of essential oils from Mentha x piperita L. and Carum carvi. Because these oils exhibit antifungal and antibacterial properties, we investigated whether Menthacarin® can reverse existing visceral hypersensitivity in maternally separated rats.MethodsIn non‐handled and maternally separated rats, we used the visceromotor responses to colorectal distension as measure for visceral sensitivity. We evaluated this response before and 24 hours after water‐avoidance stress and after 7 days treatment with Menthacarin® or control. The pre‐ and post‐treatment mycobiome and microbiome were characterized by sequencing of fungal internal transcribed spacer 1 (ITS‐1) and bacterial 16s rDNA regions. In vitro antifungal and antimicrobial properties of Menthacarin® were studied with radial diffusion assay.Key ResultsMenthacarin® inhibited in vitro growth of yeast and bacteria. Water‐avoidance caused visceral hypersensitivity in maternally separated rats, and this was reversed by treatment. Multivariate analyses of ITS‐1 and 16S high throughput data showed that maternal separation, induced changes in the myco‐ and microbiome. Menthacarin® treatment of non‐handled and maternally separated rats shifted the mycobiomes to more similar compositions.Conclusions & InferencesThe development of visceral hypersensitivity in maternally separated rats and the Menthacarin®‐mediated reversal of hypersensitivity is associated with changes in the mycobiome. Therefore, Menthacarin® may be a safe and effective treatment option that should be tested for IBS.

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