Omics and Mastiha treatment in NAFLD – The EU Mast4Health program
C Amerikanou1, S Kanoni2, AC Kaliora1, A Barone3, M Bjelan4, G D’Auria5,6, A Gioxari1, MJ Gosalbes6,7, S Mouchti3, MG Stathopoulou8, B Soriano9, S Stojanoski4,10, R Banerjee3, M Halabalaki11, EV Mikropoulou11, A Kannt12-14, J Lamont15, C Llorens9, F Marascio16, M Marascio, FJ Roig9,17, I Smyrnioudis18, I Varlamis19, M Vukic20, N Milic4, M Medic-Stojanoska4,21, L Cesarini22, J Campolo23, A Gastaldelli24, P Deloukas2,25, MG Trivella23,24, MP Francino6,7, S Visvikis-Siest8 MAST4HEALTH consortium, George V Dedoussis1.
1Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece, 2William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK, 3Perspectum Ltd, Oxford, UK, 4Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia, 5Sequencing and Bioinformatics Service, Fundació per al Foment de la Investigació Sanitària i Biomèdica de la Comunitat Valenciana (FISABIO- Salut Pública), Avda. Catalunya 21, València, 46020, Spain, 6CIBER en Epidemiología y Salud Pública, Av. Monforte de Lemos 3-5, Madrid, 28029, Spain, 7Joint Research Unit in Genomics and Health, Fundació per al Foment de la Investigació Sanitària i Biomèdica de la Comunitat Valenciana (FISABIO) and Institut de Biologia Integrativa de Sistemes (Universitat de València / Consejo Superior de Investigaciones Científicas), Avda. Catalunya 21, València, 46020, Spain, 8UMR INSERM U1122; IGE-PCV, University of Loraine, Nancy, France, 9Biotechvana, Parc Científic, Universitat de València, Paterna, Valencia, Spain, 10Centre for Imaging Diagnostics, Oncology Insitute of Vojvodina, Sremska Kamenica, Serbia, 11Division of Pharmacognosy and Natural Products Chemistry, Department of Pharmacy, National and Kapodistrian University of Athens, Athens, Greece, 12Sanofi Research and Development, Industriepark Hoechst, Frankfurt, 65926, Germany, 13Institute of Clinical Pharmacology, Goethe University Frankfurt, Frankfurt, 60590, Germany, 14Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Frankfurt, 60596, Germany, 15Randox Laboratories Limited, Crumlin, Co. Antrim, Northern Ireland, UK, 16Marascio Fernando, Intervideo, Catanzaro, CZ, 88100, Italy, 17Facultad de Ciencias de la Salud, Universidad San Jorge, Zaragoza, 50830, Spain, 18Chios Mastic Gum Growers Association, Chios, Greece, 19Department of Informatics and Telematics, Harokopio University, Athens, Greece, 20Department of Food Technology, Faculty of Technology Zvornik, University of East Sarajevo, Zvornik, 75400, Bosnia and Herzegovina, 21Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Centre of Vojvodina, Novi Sad, Serbia, 22Division of Hepatology and Gastroenterology, Niguarda Ca’ Grande Hospital Milan, Italy, 23Institute of Clinical Physiology, CNR, Milan, Italy, Cardiometabolic Risk Unit, Institute of Clinical Physiology, CNR, Pisa, Italy 25Centre for Genomic Health, Life Sciences, Queen Mary University of London, London, UK.
Background: Nonalcoholic fatty liver disease (NAFLD) is a major public health concern in both industrialized and developing nations, with an estimated global incidence of 25% in the general population and with limited treatment approaches.
Objective: We investigated the effect of the nutraceutical Mastiha supplement (2.1 g/day for a total of 6-months) in the omics profile of patients with NAFLD.
Design: MAST4HEALTH was set on the concept of a multidisciplinary approach to assess a non-pharmacological nutraceutical intervention for managing NAFLD/NASH. Within a multicenter, randomized, double-blinded, and placebo-controlled clinical trial design MRI disease parameters, biochemical, and multi-omic analyses were performed.
Results: Improvement in liver inflammation and fibrosis was reported byMRI scanning and the use of the sensitive LiverMultiScan software. Post-treatment levels of both Liver Inflammation Fibrosis score (LIF) and iron-corrected T1 (cT1) were lower in Mastiha compared to the Placebo in BMI>35 kgm-2. The Bray-Curtis dissimilarity index between baseline and post-treatment bacterial communities was larger in Mastiha versus Placebo. Mastiha improved microbiota dysbiosis mainly through decreasing the abundance of inflammatory taxa. As intestinal microbiota dysbiosis is well-established in NAFLD pathogenesis, modification in microbiota composition is important in the resolution of the disease. The metabolomic analysis showed a significant reduction of Lysophosphatidylcholines and Lysophosphatidylethanolamines in the Mastiha group suggesting that Mastiha exhibits a beneficial effect in phospholipid homeostasis. A very significant post treatment increase in a Mastiha derived metabolite (sulpho-conjugated) within the Mastiha group compared to the Placebo has been detected and remained robust across the sensitivity analysis. Mastiha supplementation improved the TAS levels among NAFLD patients with severe obesity.
Conclusions: In conclusion, after six months of Mastiha supplementation, we observed a significant improvement on microbiota dysbiosis and lipid metabolite levels in patients with NAFLD. The beneficial effect on the microbiota parallel with a decrease in plasma cholic acid and phospholipids, may be attributed to the bioavailable triterpenic acids of Mastiha.
Acknowledgements: This project received funding from the European Union’s Horizon 2020 research and innovation program MAST4HEALTH under the Marie Skłodowska-Curie grant agreement no 691042.