Feed your microbiome and your heart: The gut-heart axis.

Cardiovascular and metabolic diseases are the leading causes of disability, morbidity, and mortality worldwide. Genetics plays an important role, but environmental factors change the game and hold the potential for prevention, reversibility, and applied therapy. Nutrition, phenotype, and behavior of microorganisms, intestinal eco-events, and intestinal permeability play a crucial role in the induction of diseases. The present mini-review summarizes nutrients, diets, microbial manipulations, and tight junction function modifiers that might prevent, modulate, or treat certain diseases.

Candida albicans in celiac disease: A wolf in sheep's clothing.

Candida albicans is a commensal fungus with a potential pathogenicity and celiac disease is an autoimmune condition. Both share multiple pathophysiological junctions, including serological markers against cell-wall proteins of Candida, anti-gliadin antibodies are positive in both entities, gluten and a candidal virulence factor share sequence similarity and the autoantigen of celiac disease, the tissue transglutaminase, is pivotal in Candida albicans commensalism and hostile behavior and its covalently cross linked products are stable and resistant to breakdown in the two entities. Those autoimmune/infectious cross roads are the basis for the hypothesis that Candida albicans is an additional environmental factor for celiac disease autoimmunogenesis.

Autoimmunity in celiac disease: Extra-intestinal manifestations.

Celiac disease is an autoimmune condition of the small intestine caused by prolamins in genetically susceptible individuals evoked by multiple environmental factors. The pathological luminal intricate eco-events produce multiple signals that irradiate the entire body, resulting in a plethora of extra-intestinal manifestations. Nutrients, dysbiosis, dysbiotic components and their mobilome, post-translational modification of naive proteins, inter-enterocyte's tight junction dysfunction resulting in a leaky gut, microbial lateral genetic transfer of virulent genes, the sensing network of the enteric nervous systems and the ensuing pro-inflammatory messengers are mutually orchestrating the autoimmune interplay. Genetic-environmental-luminal events-mucosal changes are driving centrifugally the remote organs autoimmunity, establishing extra-intestinal multi organ injury. Exploring the underlying intestinal eco-events, the sensing and the delivery pathways and mechanisms that induce the peripheral tissues' damages might unravel new therapeutical strategies to prevent and help the gluten affected patients.

Microbial transglutaminase: A new potential player in celiac disease.

Microbial transglutaminase is heavily used in the food processing industries to improve food qualities. Being a protein's glue, by cross-linking it creates neoepitope complexes that are immunogenic and potentially pathogenic in celiac disease. Despite low sequence identity, it imitates functionally its family member, the endogenous tissue transglutaminase, which is the autoantigen of celiac disease. The present comprehensive review highlights the enzyme characteristics, endogenous and exogenous intestinal sources, its cross-talks with gluten and gliadin, its immunogenicity and potential pathogenicity and risks for the gluten induced conditions. If substantiated, it might represent a new environmental inducer of celiac disease. The present findings might affect nutritional product labeling, processed food additive policies and consumer health education.

Microbial Transglutaminase Is Immunogenic and Potentially Pathogenic in Pediatric Celiac Disease.

The enzyme microbial transglutaminase is heavily used in the food processing industries to ameliorate food qualities and elongate the products' shelf life. As a protein's glue, it cross-links gliadin peptides, creating neo-complexes that are immunogenic and potentially pathogenic to celiac disease communities. Even lacking sequence identity, it imitates functionally the endogenous tissue transglutaminase, known to be the autoantigen of celiac disease and representing an undisputable key player in celiac disease initiation and progress. The present review expend on the enzyme characteristics, exogenous intestinal sources, its cross-linking avidity to gluten or gliadin, turning naïve protein to immunogenic ones. Several observation on microbial transglutaminase cross linked complexes immunogenicity in celiac patients are reviewed and its pathogenicity is summarized. Warnings on its potential risks for the gluten dependent conditions are highlighted. When substantiated, it might represent a new environmental factor of celiac disease genesis. It is hoped that the presented knowledge will encourage further research to explore the mechanism and the pathogenic pathways taken by the gliadin cross linked enzyme in driving celiac disease.

The last two millennias echo-catastrophes are the driving forces for the potential genetic advantage mechanisms in celiac disease.

Many human genes have adapted to the constant threat of exposure to changing environmental conditions. Balancing selection is the result of an initial stage of positive selection that favors the spread in a population of a new allele until selection opposes its fixation and balanced situation is established. It is suggested that the disadvantageous celiac patients survived the last two millennias echo-catastrophes by adapting to the extreme temperature changes and their consequences in Europe. Genetic selective diversity induced by changing environment, enabled the celiac population to survive. Such a genetic positive selection is represented by the HEF C282Y mutation of hemochromatosis, SH2B3 loci and the HLA celiac disease-associated repertoire, enabling the celiac to overcome iron deficiency anemia and micro pathogen richness, respectively. The increased incidence of those evolutionary events in the celiac patients is a recent phenomenon that occurred in the latest era of the modern human history. The present hypothesis can shed light on additional selective genetic adaptations, echo catastrophe-driven that are at the basis of autoimmune disease-affected population survival and current expansion.