Article Versions
Export Article
Cite this article
  • Normal Style
  • MLA Style
  • APA Style
  • Chicago Style
Case Report
Open Access Peer-reviewed

The Gut Feeling of the Heart: Pathophysiological Pathways in the Gut-heart Axis in Celiac Disease

Aaron Lerner , Jozélio Freire de Carvalho
International Journal of Celiac Disease. 2020, 8(4), 120-123. DOI: 10.12691/ijcd-8-4-2
Received September 09, 2020; Revised September 29, 2020; Accepted December 01, 2020

Abstract

The chain of events, starting from nutrients that change microbiome/dysbiome ratio followed by their secreted mobilome and ending with the leaky gut syndrome, can be applied for cardiovascular diseases. The Gut-heart axis is only one avenue where intestinal luminal eco-events induce remote organ's pathology. The present editorial highlights the mechanisms and potential pathways in the nutrients-microbiota-endocrine-cardiovascular axis that might affect human heart morbidity and mortality in celiac disease.

1. Introduction

The epidemiology of celiac disease (CD) is changing constantly and its incidence is surging in the last decades 1, 2, 3. Despite amelioration in cardiovascular diseases (CVD) therapy, their prevalence, morbidity and mortality are high 4. In fact, CVDs are the leading cause of mortality, responsible for 46% of non-communicable disease deaths.

More and more data are accumulating relaying heart diseases to nutrition, enteric luminal and mucosal eco-events, thus reinforcing the gut-heart axis 5, 6, 7. One of those axes is the gut-cardiovascular axis and with this regard, CD and CVDs are going to be the topic of the present editorial.

2. Potential Intestinal Mechanisms that Might Affect the Heart

2.1. Beneficial Nutrients vs. Harmful Nutrients or Diets

Understanding the basic mechanisms underlying specific nutrients' effects and the advances made in Nutrigenetics/Nutrigenomics allow the development of precision nutrition in various aspects of the metabolic syndrome and more specifically in CVDs 8. Western diet, overnutrition, junk food, industrial process food, unsaturated and trans fatty acids, simple sugars, salts and other harmful food additives are associated with CVDs 8, 9, 10, 11, 12. On the contrary, vegetarian, Mediterranean, high fiber and optimal omega 3/6 fatty acid diets are preventive and a better therapeutic option 13, 14, 15. Coming back to CD, gluten consumption and withdrawal might have some effects on heart morbidity and even on mortality 7, 11, 16.

2.2. Microbiome/dysbiome in CD and Potential Mobilome that Affects the CVD

Alterations in the microbial composition and diversity increase the risk of autoimmune diseases, including celiac disease 5, 6, 7, 17, 18, 19. Autoimmune and non-autoimmune heart diseases are not an exception. Notably, CVDs are associated with a luminal microbial imprint and its metabolic repertoire might play a crucial role in the induction and evolvement of those conditions 20, 21. The gut microbial metabolites that play a role in CVDs induction were summarized recently 22.

2.3. Posttranslational Modification of Proteins

This is a well-established enzyme-operated phenomenon that is quite frequent in the enteric gut compartment. The luminal and the mucosal transglutaminases are essential in breaking the tolerance to gluten and gliadin peptides, turning them immunogenic in CD 19, 23. Nonetheless, CVDs are also dependent on luminal enzymatic activity and heart diseases are highly connected to the gut microbiota/dysbiota ratio and their performances 24. It appears that some nutritional and microbial components that reside in the lumen, have cardiogenic, diabetogenic, atherosclerotic, coagulatory or hypertensive capacities (ex: choline, trimethylamine, betaine, carnitine, lipopolysaccharides). The posttranslational enzymatic modification of those molecules might contribute to cardiovascular pathology. Since choline and carnitine are major dietary precursors of trimethylamine in the human gut lumen, their enzymatic modifications are pivotal in driving cardiovascular pathology 25. The gut microbiota-dependent metabolite, namely, trimethylamine N-oxide, produced from choline and phosphatidylcholine, is a known detrimental molecule that enhances atherosclerosis and thrombosis and CVDs morbidity and outcome 26. It can be summarized that both CD and CVDs are highly dependent on nutrition, microbiome abnormalities and luminal enzymatic modification of foreign proteins.

2.4. Luminal Horizontal Gene Transfer

This is a very conserved prokaryotic genetic mechanism for microbial survival in the environment, including in the human gastrointestinal tract 27. In several minutes, adjacent bacteria can laterally transfer genetic material, helping them to overcome antibacterial drugs or to suppress local human immune systems. Antibiotic resistant genes and various additional hostile genes are some examples 27, 28. The potential connection to CVDs is the dysbiosis associated with CD and cardiovascular conditions.

In addition to the trimethylamine/trimethylamine N-oxide, short-chain fatty acids primary and secondary bile acids pathways and metabolism independent processes, horizontal gene transfer of detrimental "cardiogenic" genes might drive or contribute to CVD pathogenesis 5, 6, 29.

2.5. Intestinal Permeability and the Leaky Gut

In many human chronic conditions, including metabolic, autoimmune, allergic, infectious, cancerous and geriatric diseases, intestinal tight junction functional integrity is compromised 30. Gluten/gliadins are known to enhance intestinal permeability in CD and in non-CD conditions and the permeability is increased in various CVDs, as well 5, 6, 7, 11, 31, 32, 33. The CD associate leaky gut can potentially irradiate microbial constituents and mobilome toward the cardiovascular organs 5, 6, 7, 31, 32, 33, 34. The following diets and nutrients were associated with enhanced enteric permeability: High fat diet, High carbohydrate/sugar diet, fructose, gluten, process food additives like salt, sugar, organic acids, emulsifiers and nanoparticles, medium chain fatty acids; capric acid, lauric acid, Acyl carnitines, Chitosan, Ethanol and Capsianoside 7, 11, 35, 36.

2.6. Cardiogenic Nutritional Deficiencies

An additional mechanism that can affect cardiovascular performances is a specific nutritional deficiency. vitamin A, C, D and E, creatine, coenzyme Q, potassium, calcium, magnesium, selenium, zinc, taurine, folic acid, B6 and B12 and iron are important for heart and vessels functionalities. Intriguingly, vitamin A, D and zinc deficiency and Glutamine deprivation were reported to increase intestinal permeability. However, despite their popular routine consumption as multi-vitamins and multi-minerals, no scientific evidence exists for their intake to prevent or treat CVDs, unless a specific deficiency is detected 37, 38, 39, 40, 41. In the present journal, Bohra and Shah reported on cardiomyopathy as a cardiac manifestation of CD 42 and Boutrid et al, in a corresponding editorial, highlighted carnitine deficiency as a potential contributor to the heart dysfunction 43. The interrelations between carnitine, cardiomyopathy and CD are well documented in the literature 44. Despite the endogenous synthesis, exogenous carnitine supply and absorption is pivotal for the body energy homeostasis and cardiac performances.

3. Potential Intestinal Pathways that Might Irradiate to the Heart

3.1. The Enteric-luminal Sensing Cells

The separation between commensal or pathogenic microorganisms and distinguishing between self and foreign luminal contents are essential for avoiding unnecessary immune stimulations and induce tolerance. In order to accomplish those tasks, sensing the luminal constituents and reporting on eco-events' consequences is indispensable, in order to transmit the messages to efferent systems, for adequate responses. Those enteric epithelial and subepithelial cells are: enterocytes, colonocytes, goblet, M, dendritic, enteroendocrine, enteric glial and Tuft cells. Following sensing and processing, several pathways exist to deliver the signals to remote organs, heart included 5, 6, 45, 46.

3.2. Gut-heart Blood Vasculature

Most probably the gut-originated blood vessels are the main avenue for systemic sharing of the informative luminal cargo. Mucosal committed immune cells, proinflammatory cytokines and lymphokines, post translation modified peptides, microbial processed constituents and mobilome, autoantibodies, antigen presenting cells and finally gluten/gliadin peptides can circulate via the blood vessels, to negatively impact the cardio-vascular domains 5, 6, 7.

3.3. Gut-heart Lymphatic Vessels

The lymphatic vasculature is a unidirectional conductive compartment that returns filtered interstitial fluid and peripheral tissue-originated molecules to the systemic blood circulation. The lymph is important for immune cell trafficking and surveillance, protective antibodies and lipid absorption 47. Recently, the role of lymphatics in organ regeneration and injury repair was unraveled, adding some new aspect for cardiac growth and regeneration and repair 48. The gut lymphatic vasculature might represent an additional door to door pathway in the gut -heart axis.

3.4. Enteric Nervous Inter-connections

The two intestinal mucosal neuronal plexuses and their close connections to the neuroendocrine, the vagal and autonomic nervous system were extensively described 45. Adding the sub-epithelial glial cells adjacent to the basement membrane, enterocyte mono layer, entero-chromatin and sub-epithelial dendritic cells and blood/ lymphatic vessels, those mucosal glial networks can potentially participate in gut lumen sensing and trafficking the messages and signals to the heart. Such an enteric mucosal-brain route was reported for alpha synuclein in Parkinson's disease 49. The question that arises if such a pathway can't operate between the gut and the heart? In summary, enteric nervous pathways in the gut-heart axis are presently suggested.

4. Conclusions

Collectively, through both nutrient metabolic processing and metabolism-independent mechanisms, the gut microbiome forms a largely overlooked dynamic yet resilient genetic, metabolic and endocrine organ that uptake nutritional hints, process and integrate them with the host, thus participating in the pathogenesis of CVDs and associated metabolic disorders 50. By secreting SCFAs and converting primary bile acids to secondary ones, the microbiota can increase energy expenditure and insulin sensitivity and suppress inflammation. On the contrary, by assisting trimethylamine-n-oxide liver production, they can enhance atherosclerotic changes and hypercoagulability, thus enhancing cardiac morbidity, inducing myocardial infarction, stroke and death 50. It seems that the nutrients-microbiota-endocrine-cardiovascular axis is a major pathway that determines human heart morbidity and mortality. Molecular mimicry between shared antigen present in both the myocardium and the small bowel may be responsible for cardiac injury. Interestingly, some reports on dilated cardiomyopathy, autoimmune myocarditis and recurrent pericarditis associated with CD were shown to improve to gluten withdrawal 51, 52, 53, 54. It is foreseeable that the CD cardiac manifestations like heart Failure, dilated cardiomyopathy, autoimmune myocarditis, recurrent pericarditis or arrhythmias can be prevented or improved by nutritional manipulations, microbiome rehabilitation, tight junction functional strengthening or quelling the leaky gut. Their exploration might bring new nutritional, microbial and metabolic therapeutic strategies to combat those prevalent heart diseases.

Abbreviations

CD- celiac disease, CVD-cardiovascular disease.

Conflicts of Interest

No conflict of interest and the manuscript was not granted.

Acknowledgments

The authors thank Mrs. Vered Raanan for the English revision of the manuscript.

References

[1]  Lerner A, Jeremias P, Matthias T. The world incidence of celiac disease is increasing: a review. Int J Recent Scient Res 2015; 7: 5491-6.
In article      
 
[2]  Lerner A, Jeremias P, Matthias T. The world incidence and prevalence of autoimmune diseases is increasing: a review. Int J Celiac Dis 2015; 3: 151-5.
In article      View Article
 
[3]  Lebwohl B, Green PHR. New Developments in Celiac Disease. Gastroenterol Clin North Am. 2019; 48: xv-xvi.
In article      View Article  PubMed
 
[4]  Noale M, Limongi F, Maggi S. Epidemiology of Cardiovascular Diseases in the Elderly. Adv Exp Med Biol. 2020; 1216: 29-38.
In article      View Article  PubMed
 
[5]  Lerner, A.; Matthias, T. Autoimmunity in celiac disease: extra- intestinal manifestations. Autoimm. Rev. 2019, 18, 241-246.
In article      View Article  PubMed
 
[6]  Lerner, A.; Matthias, T. GUT-the Trojan horse in remote organs’ autoimmunity. J of Clin & Cell Immunol. 2016; 7: 401.
In article      View Article
 
[7]  Lerner, A.; Shoenfeld, Y.; Matthias, T. A Review: Gluten ingestion side effects and withdrawal advantages in non-celiac autoimmune diseases. Nutritional rev. 2017, 75, 1046-1058.
In article      View Article  PubMed
 
[8]  de Toro-Martín J, Benoit J Arsenault BJ, Després J-P, Vohl M-C. Precision Nutrition: A Review of Personalized Nutritional Approaches for the Prevention and Management of Metabolic Syndrome. Nutrients 2017; 9: 913.
In article      View Article  PubMed
 
[9]  Simopoulos AP. The importance of the omega-6/omega-3 fatty acid ratio in cardiovascular disease and other chronic diseases. Exp Biol Med (Maywood). 2008; 233: 674-88.
In article      View Article  PubMed
 
[10]  Bechthold A, Boeing H, Schwedhelm C, Hoffmann G, Knüppel S, Iqbal K, et al. Food groups and risk of coronary heart disease, stroke and heart failure: A systematic review and dose-response meta-analysis of prospective studies. Crit Rev Food Sci Nutr. 2019; 59: 1071-1090.
In article      View Article  PubMed
 
[11]  Lerner A, Matthias T. Changes in intestinal tight junction permeability associated with industrial food additives explain the rising incidence of autoimmune disease. Autoimmun Rev. 2015; 14: 479-89.
In article      View Article  PubMed
 
[12]  Srour B, Fezeu LK, Kesse-Guyot E, Allès B, Méjean C, Andrianasolo RM, et al. Ultra-processed food intake and risk of cardiovascular disease prospective cohort study. (NutriNet-Santé). BMJ. 2019 May 29; 365: l1451.
In article      View Article  PubMed
 
[13]  Kahleova H, Levin S, Barnard ND. Vegetarian Dietary Patterns and Cardiovascular Disease. Prog Cardiovasc Dis. 2018; 61: 54-61.
In article      View Article  PubMed
 
[14]  Salas-Salvadó J, Becerra-Tomás N, García-Gavilán JF, Bulló M, Barrubés L. Mediterranean Diet and Cardiovascular Disease Prevention: What Do We Know? Prog Cardiovasc Dis. 2018; 61: 62-67.
In article      View Article  PubMed
 
[15]  Desnoyers M, Gilbert K, Madingou N, Gagné MA, Daneault C, Des Rosiers C, Rousseau G. A high omega-3 fatty acid diet rapidly changes the lipid composition of cardiac tissue and results in cardioprotection. Can J Physiol Pharmacol. 2018; 96: 916-921.
In article      View Article  PubMed
 
[16]  Lerner A, O'Bryan T, Matthias T. Navigating the Gluten-Free Boom: The Dark Side of Gluten Free Diet. Front Pediatr. 2019; 7: 414.
In article      View Article  PubMed
 
[17]  Krishnareddy S. The Microbiome in Celiac Disease. Gastroenterol Clin North Amer. 2019; 48: 115-126.
In article      View Article  PubMed
 
[18]  Valitutti F, Cucchiara S, Fasano A. Celiac Disease and the Microbiome Nutrients. 2019 Oct 8; 11(10): 2403.
In article      View Article  PubMed
 
[19]  Lerner A, Aminov R, Matthias T. Dysbiosis May Trigger Autoimmune Diseases via Inappropriate Post-Translational Modification of Host Proteins. Front Microbiol. 2016; 7: 84.
In article      View Article  PubMed
 
[20]  Peng J, Xiao X, Hu M, Zhang X. Interaction between gut microbiome and cardiovascular disease. Life Sci. 2018 Dec 1; 214: 153-157.
In article      View Article  PubMed
 
[21]  Jovanovich A, Isakova T, Stubbs J. Microbiome and Cardiovascular Disease in CKD. Clin J Am Soc Nephrol. 2018; 13: 1598-1604.
In article      View Article  PubMed
 
[22]  Zhu Y, Shui X, Liang Z, Huang Z, Qi Y, He Y, et al. Gut microbiota metabolites as integral mediators in cardiovascular diseases (Review). Int J Mol Med. 2020; 46: 936-948.
In article      View Article  PubMed
 
[23]  Lerner A, Aminov R, Matthias T. Transglutaminases in Dysbiosis As Potential Environmental Drivers of Autoimmunity. Front Microbiol. 2017. 8: 66.
In article      View Article
 
[24]  Xu H, Wang X, Feng W, Liu Q, Zhou S, Liu Q, Cai L. The gut microbiota and Its interactions with cardiovascular disease. Microb Biotechnol. 13: 637-656. 2020.
In article      View Article  PubMed
 
[25]  Jameson E, Quareshy M, Chen Y: Methodological considerations for the identification of choline and carnitine-degrading bacteria in the gut. Methods. 2018; 149: 42-48.
In article      View Article  PubMed
 
[26]  Kanitsoraphan C, Rattanawong P, Charoensri S, Senthong V. Trimethylamine N-Oxide and Risk of Cardiovascular Disease and Mortality. Curr Nutr Rep. 2018; 7: 207-213.
In article      View Article  PubMed
 
[27]  Lerner A, Matthias T, Aminov R. Potential Effects of Horizontal Gene Exchange in the Human Gut. Front. Immunol. 2017; 8; article 1630.
In article      View Article  PubMed
 
[28]  Lin J, Nishino K, Roberts MC, Tolmasky M, Aminov RI and Zhang L. Mechanisms of antibiotic resistance. Front. Microbiol. 2015; 6: article 34.
In article      View Article
 
[29]  Tang WHW, Kitai T, Haze SL. Gut Microbiota in Cardiovascular Health and Disease. Circ Res. 2017 Mar 31; 120: 1183-1196.
In article      View Article  PubMed
 
[30]  Bischoff SC, Barbara G, Buurman W, Ockhuizen T, Schulzke J-D, Serino M, et al. Intestinal permeability – a new target for disease prevention and therapy. BMC Gastroenterol. 2014; 14: 189.
In article      View Article  PubMed
 
[31]  Chakaroun RM, Massier L, Kovacs P. Gut Microbiome, Intestinal Permeability, and Tissue Bacteria in Metabolic Disease: Perpetrators or Bystanders? Nutrients. 2020; 12: 1082.
In article      View Article  PubMed
 
[32]  Fukui H. Increased Intestinal Permeability and Decreased Barrier Function: Does It Really Influence the Risk of Inflammation? Inflamm Intest Dis. 2016; 1: 135-145.
In article      View Article  PubMed
 
[33]  Forkosh E, Ilan Y. The heart-gut axis: new target for atherosclerosis and congestive heart failure therapy. Open Heart. 2019; 6: e000993.
In article      View Article  PubMed
 
[34]  Kazemian, N., Mahmoudi, M., Halperin, F. et al. Gut microbiota and cardiovascular disease: opportunities and challenges. Microbiome. 8: 36; 2020.
In article      View Article  PubMed
 
[35]  Vancamelbeke M, Vermeire S: The intestinal barrier: a fundamental role in health and disease. Expert Rev Gastroenterol Hepatol. 2017; 11: 821-834.
In article      View Article  PubMed
 
[36]  De Santis S, Cavalcanti E, Mastronardi M, Jirillo E, Chieppa M. Nutritional Keys for Intestinal Barrier Modulation. Front Immunol. 2015; 6: 612.
In article      View Article  PubMed
 
[37]  Ingles DP, Rodriguez JBC, Garcia H. Supplemental Vitamins and Minerals for Cardiovascular Disease Prevention and Treatment. Review Curr Cardiol Rep. 2020; 22:22.
In article      View Article  PubMed
 
[38]  Marinescu V, McCullough PA. Nutritional and micronutrient determinants of idiopathic dilated cardiomyopathy: diagnostic and therapeutic implications. Expert Rev Cardiovasc Ther. 2011; 9: 1161-70.
In article      View Article  PubMed
 
[39]  Allard ML, Jeejeebhoy KN, Sole MJ. The management of conditioned nutritional requirements in heart failure. Heart Fail Rev. 2006; 11: 75-82.
In article      View Article  PubMed
 
[40]  Frustaci A, Sabbioni E, Fortaner S, Farina M, del Torchio R, Tafani M, et al. Selenium- and zinc-deficient cardiomyopathy in human intestinal malabsorption: preliminary results of selenium/zinc infusion. Eur J Heart Fail. 2012; 14: 202-10.
In article      View Article  PubMed
 
[41]  Lerner A, Matthias T. Celiac Disease: Intestinal, Heart and Skin Inter connections. Internat J of Celiac Dis. 2015; 3: 28-30.
In article      View Article
 
[42]  Bohra S, Shah A. Celiac Disease Presenting as Cardiomyopathy -A Rare Extra Intestinal Manifestation. Internat J of Celiac Dis, 2020; 8: 56-57..
In article      
 
[43]  Boutrid N, Rahmoun H, Amrane M. Cardiomyopathy in Celiac Disease: Carnitine Behind? Internat J of Celiac Dis, 2020; 8: x-y.
In article      
 
[44]  Uslu N, Demir H, Karagöz T, Saltik-Temizel IN. Dilated cardiomyopathy in celiac disease: role of carnitine deficiency. Acta Gastroenterol Belg. 73: 530-1; 2010.
In article      
 
[45]  Lerner A, Neidhöfer S, Matthias T. The Gut Microbiome Feelings of the Brain: A Perspective for Non-Microbiologist. Microorganisms 2017, 5, 66.
In article      View Article  PubMed
 
[46]  Lerner A, Wusterhausen P, Ramesh A, Lopez F, Matthias T. The Gut Feeling of the Joints: Celiac Disease and Rheumatoid Arthritis Are Related. Internat J of Celiac Dis, 2019;7: 21-25.
In article      
 
[47]  Oliver G, Kipnis J, Randolph GJ, Harvey NL. The Lymphatic Vasculature in the 21 st Century: Novel Functional Roles in Homeostasis and Disease. Cell 182: 270-296; 2020.
In article      View Article  PubMed
 
[48]  Gancz D, Raftrey BC, Perlmoter G, Marín-Juez R, Semo J, Matsuoka RL, et al. Distinct origins and molecular mechanisms contribute to lymphatic formation during cardiac growth and regeneration. Elife. 2019; 8: e44153.
In article      View Article  PubMed
 
[49]  Harsanyiova J, Buday T, Kralova Trancikova A. Parkinson's Disease and the Gut: Future Perspectives for Early Diagnosis. Front Neurosci. 2020; 14: 626.
In article      View Article  PubMed
 
[50]  Brown JM, Hazen SL. The gut microbial endocrine organ: bacterially derived signals driving cardiometabolic diseases. Annu Rev Med.2015; 66: 343-59.
In article      View Article  PubMed
 
[51]  Curione M, Barbato M, Viola F, Francia P, De Biase L, Cucchiara S. Idiopathic dilated cardiomyopathy associated with celiac disease: the effect of a gluten-free diet on cardiac performance. Dig Liver Dis. 2002; 34: 866-9.
In article      View Article
 
[52]  Frustaci A, Cuoco L, Chimenti C, et al. Celiac disease associated with autoimmune myocarditis. Circulation. 2002; 105: 2611-2618.
In article      View Article  PubMed
 
[53]  Faizallah R, Costello FC, Lee FI, Walker R. Adult celiac disease and recurrent pericarditis. Dig Dis Sci. 1982; 27: 728-730.
In article      View Article  PubMed
 
[54]  Dawes PT, Atherton ST. Coeliac disease presenting as recurrent pericarditis. Lancet. 1981; 1(8228): 1021-1022.
In article      View Article
 

Published with license by Science and Education Publishing, Copyright © 2020 Aaron Lerner and Jozélio Freire de Carvalho

Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

Cite this article:

Normal Style
Aaron Lerner, Jozélio Freire de Carvalho. The Gut Feeling of the Heart: Pathophysiological Pathways in the Gut-heart Axis in Celiac Disease. International Journal of Celiac Disease. Vol. 8, No. 4, 2020, pp 120-123. http://pubs.sciepub.com/ijcd/8/4/2
MLA Style
Lerner, Aaron, and Jozélio Freire de Carvalho. "The Gut Feeling of the Heart: Pathophysiological Pathways in the Gut-heart Axis in Celiac Disease." International Journal of Celiac Disease 8.4 (2020): 120-123.
APA Style
Lerner, A. , & Carvalho, J. F. D. (2020). The Gut Feeling of the Heart: Pathophysiological Pathways in the Gut-heart Axis in Celiac Disease. International Journal of Celiac Disease, 8(4), 120-123.
Chicago Style
Lerner, Aaron, and Jozélio Freire de Carvalho. "The Gut Feeling of the Heart: Pathophysiological Pathways in the Gut-heart Axis in Celiac Disease." International Journal of Celiac Disease 8, no. 4 (2020): 120-123.
Share
[1]  Lerner A, Jeremias P, Matthias T. The world incidence of celiac disease is increasing: a review. Int J Recent Scient Res 2015; 7: 5491-6.
In article      
 
[2]  Lerner A, Jeremias P, Matthias T. The world incidence and prevalence of autoimmune diseases is increasing: a review. Int J Celiac Dis 2015; 3: 151-5.
In article      View Article
 
[3]  Lebwohl B, Green PHR. New Developments in Celiac Disease. Gastroenterol Clin North Am. 2019; 48: xv-xvi.
In article      View Article  PubMed
 
[4]  Noale M, Limongi F, Maggi S. Epidemiology of Cardiovascular Diseases in the Elderly. Adv Exp Med Biol. 2020; 1216: 29-38.
In article      View Article  PubMed
 
[5]  Lerner, A.; Matthias, T. Autoimmunity in celiac disease: extra- intestinal manifestations. Autoimm. Rev. 2019, 18, 241-246.
In article      View Article  PubMed
 
[6]  Lerner, A.; Matthias, T. GUT-the Trojan horse in remote organs’ autoimmunity. J of Clin & Cell Immunol. 2016; 7: 401.
In article      View Article
 
[7]  Lerner, A.; Shoenfeld, Y.; Matthias, T. A Review: Gluten ingestion side effects and withdrawal advantages in non-celiac autoimmune diseases. Nutritional rev. 2017, 75, 1046-1058.
In article      View Article  PubMed
 
[8]  de Toro-Martín J, Benoit J Arsenault BJ, Després J-P, Vohl M-C. Precision Nutrition: A Review of Personalized Nutritional Approaches for the Prevention and Management of Metabolic Syndrome. Nutrients 2017; 9: 913.
In article      View Article  PubMed
 
[9]  Simopoulos AP. The importance of the omega-6/omega-3 fatty acid ratio in cardiovascular disease and other chronic diseases. Exp Biol Med (Maywood). 2008; 233: 674-88.
In article      View Article  PubMed
 
[10]  Bechthold A, Boeing H, Schwedhelm C, Hoffmann G, Knüppel S, Iqbal K, et al. Food groups and risk of coronary heart disease, stroke and heart failure: A systematic review and dose-response meta-analysis of prospective studies. Crit Rev Food Sci Nutr. 2019; 59: 1071-1090.
In article      View Article  PubMed
 
[11]  Lerner A, Matthias T. Changes in intestinal tight junction permeability associated with industrial food additives explain the rising incidence of autoimmune disease. Autoimmun Rev. 2015; 14: 479-89.
In article      View Article  PubMed
 
[12]  Srour B, Fezeu LK, Kesse-Guyot E, Allès B, Méjean C, Andrianasolo RM, et al. Ultra-processed food intake and risk of cardiovascular disease prospective cohort study. (NutriNet-Santé). BMJ. 2019 May 29; 365: l1451.
In article      View Article  PubMed
 
[13]  Kahleova H, Levin S, Barnard ND. Vegetarian Dietary Patterns and Cardiovascular Disease. Prog Cardiovasc Dis. 2018; 61: 54-61.
In article      View Article  PubMed
 
[14]  Salas-Salvadó J, Becerra-Tomás N, García-Gavilán JF, Bulló M, Barrubés L. Mediterranean Diet and Cardiovascular Disease Prevention: What Do We Know? Prog Cardiovasc Dis. 2018; 61: 62-67.
In article      View Article  PubMed
 
[15]  Desnoyers M, Gilbert K, Madingou N, Gagné MA, Daneault C, Des Rosiers C, Rousseau G. A high omega-3 fatty acid diet rapidly changes the lipid composition of cardiac tissue and results in cardioprotection. Can J Physiol Pharmacol. 2018; 96: 916-921.
In article      View Article  PubMed
 
[16]  Lerner A, O'Bryan T, Matthias T. Navigating the Gluten-Free Boom: The Dark Side of Gluten Free Diet. Front Pediatr. 2019; 7: 414.
In article      View Article  PubMed
 
[17]  Krishnareddy S. The Microbiome in Celiac Disease. Gastroenterol Clin North Amer. 2019; 48: 115-126.
In article      View Article  PubMed
 
[18]  Valitutti F, Cucchiara S, Fasano A. Celiac Disease and the Microbiome Nutrients. 2019 Oct 8; 11(10): 2403.
In article      View Article  PubMed
 
[19]  Lerner A, Aminov R, Matthias T. Dysbiosis May Trigger Autoimmune Diseases via Inappropriate Post-Translational Modification of Host Proteins. Front Microbiol. 2016; 7: 84.
In article      View Article  PubMed
 
[20]  Peng J, Xiao X, Hu M, Zhang X. Interaction between gut microbiome and cardiovascular disease. Life Sci. 2018 Dec 1; 214: 153-157.
In article      View Article  PubMed
 
[21]  Jovanovich A, Isakova T, Stubbs J. Microbiome and Cardiovascular Disease in CKD. Clin J Am Soc Nephrol. 2018; 13: 1598-1604.
In article      View Article  PubMed
 
[22]  Zhu Y, Shui X, Liang Z, Huang Z, Qi Y, He Y, et al. Gut microbiota metabolites as integral mediators in cardiovascular diseases (Review). Int J Mol Med. 2020; 46: 936-948.
In article      View Article  PubMed
 
[23]  Lerner A, Aminov R, Matthias T. Transglutaminases in Dysbiosis As Potential Environmental Drivers of Autoimmunity. Front Microbiol. 2017. 8: 66.
In article      View Article
 
[24]  Xu H, Wang X, Feng W, Liu Q, Zhou S, Liu Q, Cai L. The gut microbiota and Its interactions with cardiovascular disease. Microb Biotechnol. 13: 637-656. 2020.
In article      View Article  PubMed
 
[25]  Jameson E, Quareshy M, Chen Y: Methodological considerations for the identification of choline and carnitine-degrading bacteria in the gut. Methods. 2018; 149: 42-48.
In article      View Article  PubMed
 
[26]  Kanitsoraphan C, Rattanawong P, Charoensri S, Senthong V. Trimethylamine N-Oxide and Risk of Cardiovascular Disease and Mortality. Curr Nutr Rep. 2018; 7: 207-213.
In article      View Article  PubMed
 
[27]  Lerner A, Matthias T, Aminov R. Potential Effects of Horizontal Gene Exchange in the Human Gut. Front. Immunol. 2017; 8; article 1630.
In article      View Article  PubMed
 
[28]  Lin J, Nishino K, Roberts MC, Tolmasky M, Aminov RI and Zhang L. Mechanisms of antibiotic resistance. Front. Microbiol. 2015; 6: article 34.
In article      View Article
 
[29]  Tang WHW, Kitai T, Haze SL. Gut Microbiota in Cardiovascular Health and Disease. Circ Res. 2017 Mar 31; 120: 1183-1196.
In article      View Article  PubMed
 
[30]  Bischoff SC, Barbara G, Buurman W, Ockhuizen T, Schulzke J-D, Serino M, et al. Intestinal permeability – a new target for disease prevention and therapy. BMC Gastroenterol. 2014; 14: 189.
In article      View Article  PubMed
 
[31]  Chakaroun RM, Massier L, Kovacs P. Gut Microbiome, Intestinal Permeability, and Tissue Bacteria in Metabolic Disease: Perpetrators or Bystanders? Nutrients. 2020; 12: 1082.
In article      View Article  PubMed
 
[32]  Fukui H. Increased Intestinal Permeability and Decreased Barrier Function: Does It Really Influence the Risk of Inflammation? Inflamm Intest Dis. 2016; 1: 135-145.
In article      View Article  PubMed
 
[33]  Forkosh E, Ilan Y. The heart-gut axis: new target for atherosclerosis and congestive heart failure therapy. Open Heart. 2019; 6: e000993.
In article      View Article  PubMed
 
[34]  Kazemian, N., Mahmoudi, M., Halperin, F. et al. Gut microbiota and cardiovascular disease: opportunities and challenges. Microbiome. 8: 36; 2020.
In article      View Article  PubMed
 
[35]  Vancamelbeke M, Vermeire S: The intestinal barrier: a fundamental role in health and disease. Expert Rev Gastroenterol Hepatol. 2017; 11: 821-834.
In article      View Article  PubMed
 
[36]  De Santis S, Cavalcanti E, Mastronardi M, Jirillo E, Chieppa M. Nutritional Keys for Intestinal Barrier Modulation. Front Immunol. 2015; 6: 612.
In article      View Article  PubMed
 
[37]  Ingles DP, Rodriguez JBC, Garcia H. Supplemental Vitamins and Minerals for Cardiovascular Disease Prevention and Treatment. Review Curr Cardiol Rep. 2020; 22:22.
In article      View Article  PubMed
 
[38]  Marinescu V, McCullough PA. Nutritional and micronutrient determinants of idiopathic dilated cardiomyopathy: diagnostic and therapeutic implications. Expert Rev Cardiovasc Ther. 2011; 9: 1161-70.
In article      View Article  PubMed
 
[39]  Allard ML, Jeejeebhoy KN, Sole MJ. The management of conditioned nutritional requirements in heart failure. Heart Fail Rev. 2006; 11: 75-82.
In article      View Article  PubMed
 
[40]  Frustaci A, Sabbioni E, Fortaner S, Farina M, del Torchio R, Tafani M, et al. Selenium- and zinc-deficient cardiomyopathy in human intestinal malabsorption: preliminary results of selenium/zinc infusion. Eur J Heart Fail. 2012; 14: 202-10.
In article      View Article  PubMed
 
[41]  Lerner A, Matthias T. Celiac Disease: Intestinal, Heart and Skin Inter connections. Internat J of Celiac Dis. 2015; 3: 28-30.
In article      View Article
 
[42]  Bohra S, Shah A. Celiac Disease Presenting as Cardiomyopathy -A Rare Extra Intestinal Manifestation. Internat J of Celiac Dis, 2020; 8: 56-57..
In article      
 
[43]  Boutrid N, Rahmoun H, Amrane M. Cardiomyopathy in Celiac Disease: Carnitine Behind? Internat J of Celiac Dis, 2020; 8: x-y.
In article      
 
[44]  Uslu N, Demir H, Karagöz T, Saltik-Temizel IN. Dilated cardiomyopathy in celiac disease: role of carnitine deficiency. Acta Gastroenterol Belg. 73: 530-1; 2010.
In article      
 
[45]  Lerner A, Neidhöfer S, Matthias T. The Gut Microbiome Feelings of the Brain: A Perspective for Non-Microbiologist. Microorganisms 2017, 5, 66.
In article      View Article  PubMed
 
[46]  Lerner A, Wusterhausen P, Ramesh A, Lopez F, Matthias T. The Gut Feeling of the Joints: Celiac Disease and Rheumatoid Arthritis Are Related. Internat J of Celiac Dis, 2019;7: 21-25.
In article      
 
[47]  Oliver G, Kipnis J, Randolph GJ, Harvey NL. The Lymphatic Vasculature in the 21 st Century: Novel Functional Roles in Homeostasis and Disease. Cell 182: 270-296; 2020.
In article      View Article  PubMed
 
[48]  Gancz D, Raftrey BC, Perlmoter G, Marín-Juez R, Semo J, Matsuoka RL, et al. Distinct origins and molecular mechanisms contribute to lymphatic formation during cardiac growth and regeneration. Elife. 2019; 8: e44153.
In article      View Article  PubMed
 
[49]  Harsanyiova J, Buday T, Kralova Trancikova A. Parkinson's Disease and the Gut: Future Perspectives for Early Diagnosis. Front Neurosci. 2020; 14: 626.
In article      View Article  PubMed
 
[50]  Brown JM, Hazen SL. The gut microbial endocrine organ: bacterially derived signals driving cardiometabolic diseases. Annu Rev Med.2015; 66: 343-59.
In article      View Article  PubMed
 
[51]  Curione M, Barbato M, Viola F, Francia P, De Biase L, Cucchiara S. Idiopathic dilated cardiomyopathy associated with celiac disease: the effect of a gluten-free diet on cardiac performance. Dig Liver Dis. 2002; 34: 866-9.
In article      View Article
 
[52]  Frustaci A, Cuoco L, Chimenti C, et al. Celiac disease associated with autoimmune myocarditis. Circulation. 2002; 105: 2611-2618.
In article      View Article  PubMed
 
[53]  Faizallah R, Costello FC, Lee FI, Walker R. Adult celiac disease and recurrent pericarditis. Dig Dis Sci. 1982; 27: 728-730.
In article      View Article  PubMed
 
[54]  Dawes PT, Atherton ST. Coeliac disease presenting as recurrent pericarditis. Lancet. 1981; 1(8228): 1021-1022.
In article      View Article