Multi-Omics Approach Reveals Prebiotic and Potential Antioxidant Effects of Essential Oils from the Mediterranean Diet on Cardiometabolic Disorder Using Humanized Gnotobiotic Mice

Essential oils sourced from herbs commonly used in the Mediterranean diet have demonstrated advantageous attributes as nutraceuticals and prebiotics within a model of severe cardiometabolic disorder. The primary objective of this study was to assess the influences exerted by essential oils derived from thyme (Thymus vulgaris) and oregano (Origanum vulgare) via a comprehensive multi-omics approach within a gnotobiotic murine model featuring colonic microbiota acquired from patients diagnosed with coronary artery disease (CAD) and type-2 diabetes mellitus (T2DM). Our findings demonstrated prebiotic and potential antioxidant effects elicited by these essential oils. We observed a substantial increase in the relative abundance of the Lactobacillus genus in the gut microbiota, accompanied by higher levels of short-chain fatty acids and a reduction in trimethylamine N-oxide levels and protein oxidation in the plasma. Moreover, functional enrichment analysis of the cardiac tissue proteome unveiled an over-representation of pathways related to mitochondrial function, oxidative stress, and cardiac contraction. These findings provide compelling evidence of the prebiotic and antioxidant actions of thyme- and oregano-derived essential oils, which extend to cardiac function. These results encourage further investigation into the promising utility of essential oils derived from herbs commonly used in the Mediterranean diet as potential nutraceutical interventions for mitigating chronic diseases linked to CAD and T2DM.

[1]  A. Gasparotto Junior,et al.  Natural Products as Modulators of Mitochondrial Dysfunctions Associated with Cardiovascular Diseases: Advances and Opportunities. , 2023, Journal of medicinal food.

[2]  Xinchun Yang,et al.  Untargeted metabolomics unravel serum metabolic alterations in smokers with hypertension , 2023, Frontiers in Physiology.

[3]  E. Lucchi,et al.  Plant Essential Oils as Healthy Functional Ingredients of Nutraceuticals and Diet Supplements: A Review , 2023, Molecules.

[4]  C. Maack,et al.  Mitochondrial Effects of Common Cardiovascular Medications: The Good, the Bad and the Mixed , 2022, International journal of molecular sciences.

[5]  M. Queipo-Ortuño,et al.  Beneficial Effects of Essential Oils from the Mediterranean Diet on Gut Microbiota and Their Metabolites in Ischemic Heart Disease and Type-2 Diabetes Mellitus , 2022, Nutrients.

[6]  Xiangfang Yu,et al.  Perturbation on gut microbiota impedes the onset of obesity in high fat diet-induced mice , 2022, Frontiers in Endocrinology.

[7]  K. Liang,et al.  Lower All-Cause Mortality for Coronary Heart or Stroke Patients Who Adhere Better to Mediterranean Diet-An NHANES Analysis , 2022, Nutrients.

[8]  Xiaofang Jiang,et al.  Preclinical Studies of Natural Products Targeting the Gut Microbiota: Beneficial Effects on Diabetes. , 2022, Journal of agricultural and food chemistry.

[9]  J. Chalovich,et al.  Hypertrophic Cardiomyopathy Mutations of Troponin Reveal Details of Striated Muscle Regulation , 2022, Frontiers in Physiology.

[10]  G. Deco,et al.  Microbiota alterations in proline metabolism impact depression. , 2022, Cell metabolism.

[11]  I. Gould,et al.  Modulation of cardiac thin filament structure by phosphorylated troponin-I analyzed by protein-protein docking and molecular dynamics simulation. , 2022, Archives of biochemistry and biophysics.

[12]  Lanjuan Li,et al.  Akkermansia muciniphila Ameliorates Acetaminophen-Induced Liver Injury by Regulating Gut Microbial Composition and Metabolism , 2022, Microbiology spectrum.

[13]  S. Müller,et al.  SUMO-specific Isopeptidases Tuning Cardiac SUMOylation in Health and Disease , 2021, Frontiers in Molecular Biosciences.

[14]  R. Martínez,et al.  Protein carbonylation in food and nutrition: a concise update , 2021, Amino Acids.

[15]  L. Pieters,et al.  Natural Products as a Source of Inspiration for Novel Inhibitors of Advanced Glycation Endproducts (AGEs) Formation , 2021, Planta Medica.

[16]  J. Tanner,et al.  Structure, biochemistry, and gene expression patterns of the proline biosynthetic enzyme pyrroline-5-carboxylate reductase (PYCR), an emerging cancer therapy target , 2021, Amino Acids.

[17]  P. Kralickova,et al.  Gut Microbiota and NAFLD: Pathogenetic Mechanisms, Microbiota Signatures, and Therapeutic Interventions , 2021, Microorganisms.

[18]  Kathleen M. Jagodnik,et al.  Gene Set Knowledge Discovery with Enrichr , 2021, Current protocols.

[19]  C. Luna,et al.  Allysine and α-Aminoadipic Acid as Markers of the Glyco-Oxidative Damage to Human Serum Albumin under Pathological Glucose Concentrations , 2021, Antioxidants.

[20]  B. Udd,et al.  Panorama of the distal myopathies , 2020, Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology.

[21]  Xianwei Wang,et al.  ROS systems are a new integrated network for sensing homeostasis and alarming stresses in organelle metabolic processes , 2020, Redox biology.

[22]  Yuan Zhang,et al.  Gut microbiota from NLRP3-deficient mice ameliorates depressive-like behaviors by regulating astrocyte dysfunction via circHIPK2 , 2019, Microbiome.

[23]  E. Almogbel,et al.  Elevated Levels of Protein Carbonylation in Patients With Diabetic Nephropathy: Therapeutic and Diagnostic Prospects. , 2019, The American journal of the medical sciences.

[24]  Siyi Pan,et al.  Effects of orange essential oil on intestinal microflora in mice. , 2019, Journal of the science of food and agriculture.

[25]  Boris Lamp,et al.  The short-chain fatty acid pentanoate suppresses autoimmunity by modulating the metabolic-epigenetic crosstalk in lymphocytes , 2019, Nature Communications.

[26]  Elizabeth A. Kennedy,et al.  Mouse Microbiota Models: Comparing Germ-Free Mice and Antibiotics Treatment as Tools for Modifying Gut Bacteria , 2018, Front. Physiol..

[27]  F. Melchior,et al.  Control of SUMO and Ubiquitin by ROS: Signaling and disease implications. , 2018, Molecular aspects of medicine.

[28]  Amin Mousavi Khaneghah,et al.  The effects of food essential oils on cardiovascular diseases: A review , 2018, Critical reviews in food science and nutrition.

[29]  G. Corrêa Souza,et al.  Dietary Patterns in Secondary Prevention of Heart Failure: A Systematic Review , 2018, Nutrients.

[30]  M. Hernán,et al.  Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Supplemented with Extra‐Virgin Olive Oil or Nuts , 2018, The New England journal of medicine.

[31]  C. Alcántara,et al.  Shifts on Gut Microbiota Associated to Mediterranean Diet Adherence and Specific Dietary Intakes on General Adult Population , 2018, Front. Microbiol..

[32]  Benjamin M Hillmann,et al.  Fecal microbiota transplantation reverses antibiotic and chemotherapy-induced gut dysbiosis in mice , 2018, Scientific Reports.

[33]  M. Hecker,et al.  Role of protein carbonylation in diabetes , 2018, Journal of Inherited Metabolic Disease.

[34]  Jinlan Jiang,et al.  Sumoylation of SMAD 4 ameliorates the oxidative stress‐induced apoptosis in osteoblasts , 2017, Cytokine.

[35]  A. Barzegari,et al.  Myocardial infarction and gut microbiota: An incidental connection. , 2017, Pharmacological research.

[36]  I. Moreno-Indias,et al.  Role of Gut Microbiota on Cardio-Metabolic Parameters and Immunity in Coronary Artery Disease Patients with and without Type-2 Diabetes Mellitus , 2017, Front. Microbiol..

[37]  J. Peng,et al.  A carvacrol-thymol blend decreased intestinal oxidative stress and influenced selected microbes without changing the messenger RNA levels of tight junction proteins in jejunal mucosa of weaning piglets. , 2017, Animal : an international journal of animal bioscience.

[38]  Andrew D. Rouillard,et al.  Enrichr: a comprehensive gene set enrichment analysis web server 2016 update , 2016, Nucleic Acids Res..

[39]  Chi-Tang Ho,et al.  Dietary allicin reduces transformation of L-carnitine to TMAO through impact on gut microbiota , 2015 .

[40]  H. Godoy,et al.  Microencapsulated eucalyptol and eugenol as growth promoters in broilers. , 2014 .

[41]  M. Blüher,et al.  Carbonylated plasma proteins as potential biomarkers of obesity induced type 2 diabetes mellitus. , 2014, Journal of proteome research.

[42]  T. Wolever,et al.  Adiposity, gut microbiota and faecal short chain fatty acids are linked in adult humans , 2014, Nutrition & Diabetes.

[43]  H. Tilg,et al.  Microbiota and diabetes: an evolving relationship , 2014, Gut.

[44]  X. Cai,et al.  Regulation of N-acetyl cysteine on gut redox status and major microbiota in weaned piglets. , 2014, Journal of animal science.

[45]  H. Ping,et al.  Essential Oils, A New Horizon in Combating Bacterial Antibiotic Resistance , 2014, The open microbiology journal.

[46]  A. Golian,et al.  Effect of thymol and carvacrol feed supplementation on performance, antioxidant enzyme activities, fatty acid composition, digestive enzyme activities, and immune response in broiler chickens. , 2013, Poultry science.

[47]  Edward Y. Chen,et al.  Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool , 2013, BMC Bioinformatics.

[48]  Nora C. Toussaint,et al.  Intestinal Microbiota Containing Barnesiella Species Cures Vancomycin-Resistant Enterococcus faecium Colonization , 2013, Infection and Immunity.

[49]  P. Ray,et al.  Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. , 2012, Cellular signalling.

[50]  S. Y. Li,et al.  The effect of essential oils on performance, immunity and gut microbial population in weaner pigs , 2012 .

[51]  M. Estévez,et al.  Fluorescent HPLC for the detection of specific protein oxidation carbonyls - α-aminoadipic and γ-glutamic semialdehydes - in meat systems. , 2011, Meat science.

[52]  Arthur Kaser,et al.  Gut microbiome, obesity, and metabolic dysfunction. , 2011, The Journal of clinical investigation.

[53]  L. Meza-Zepeda,et al.  Depletion of Murine Intestinal Microbiota: Effects on Gut Mucosa and Epithelial Gene Expression , 2011, PloS one.

[54]  Jin Sun,et al.  Lactobacilli prevent hydroxy radical production and inhibit Escherichia coli and Enterococcus growth in system mimicking colon fermentation , 2010, Letters in applied microbiology.

[55]  V. Monnier,et al.  2-aminoadipic acid is a marker of protein carbonyl oxidation in the aging human skin: effects of diabetes, renal failure and sepsis. , 2007, The Biochemical journal.

[56]  G. Macfarlane,et al.  Regulation of short-chain fatty acid production , 2003, Proceedings of the Nutrition Society.

[57]  T. Miller,et al.  Pathways of acetate, propionate, and butyrate formation by the human fecal microbial flora , 1996, Applied and environmental microbiology.

[58]  S. Chung,et al.  Tissue-specific expression of two aldose reductase-like genes in mice: abundant expression of mouse vas deferens protein and fibroblast growth factor-regulated protein in the adrenal gland. , 1995, The Biochemical journal.

[59]  S. Lacroix,et al.  Contemporary issues regarding nutrition in cardiovascular rehabilitation. , 2017, Annals of physical and rehabilitation medicine.

[60]  M. Alagawany Biological Effects and Modes of Action of Carvacrol in Animal and Poultry Production and Health - A Review , 2015 .

[61]  J. Lovegrove,et al.  The gut microbiota and lipid metabolism: implications for human health and coronary heart disease. , 2006, Current medicinal chemistry.