Systemic inflammation is a common denominator to a variety of cardiovascular (CV) and non-CV
diseases and relative risk factors, including hypertension and its control, metabolic diseases, rheumatic disorders,
and those affecting the gastrointestinal tract. Besides medications, a non-pharmacological approach encompassing
lifestyle changes and other complementary measures is mentioned in several updated guidelines on the management
of these conditions. We performed an updated narrative review on the mechanisms behind the systemic
impact of inflammation and the role of non-pharmacological, complementary measures centered on lowering
systemic phlogosis for preserving or restoring a good global health. The central role of genetics in shaping the
immune response is discussed in conjunction with that of the microbiome, highlighting the interdependence and
mutual influences between the human genome and microbial integrity, diversity, and functions. Several plausible
strategies to modulate inflammation and restore balanced crosstalk between the human genome and the microbiome
are then recapitulated, including dietary measures, active lifestyle, and other potential approaches to manipulate
the resident microbial community. To date, evidence from high-quality human studies is sparse to allow
the unconditioned inclusion of understudied, though plausible solutions against inflammation into public health
strategies for global wellness. This gap claims further focused, well-designed research targeted at unravelling the
mechanisms behind future personalized medicine.