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.