Obesity and Cardiometabolic Diseases: A Gut Microbiota Centered Perspective

Review Article

Abstract

The escalating trajectory of obesity worldwide constitutes a severe public health crisis, intimately linked to elevated rates of death and chronic disease burden. Contemporary medical understanding has shifted from viewing obesity solely as a caloric equilibrium issue to recognizing it as a complex, multifactorial pathology driven by neurohormonal disruptions, metabolic dysregulation, and inflammatory cascades. Adipose tissue is no longer regarded merely as an energy depot; it is an active endocrine organ where cellular expansion and hypoxia precipitate chronic low-grade inflammation, a precursor to insulin insensitivity and metabolic breakdown. Recently, the intestinal ecosystem has been identified as a central architect in the development of metabolic syndrome and cardiovascular impairments. Individuals with obesity typically exhibit a distinct microbial signature characterized by diminished diversity and dysbiosis. Mechanistically, the gut flora dictates host metabolic health by modulating lipid profiles, energy harvesting, and immune responses via several pathways, including the fermentation of fibers into short-chain fatty acids, the regulation of bile acid signaling, the modulation of metabolic endotoxemia, and the inhibition of FIAF. Of particular concern is the synthesis of trimethylamine-N-oxide (TMAO) by gut bacteria, which directly exacerbates atherosclerotic plaque progression and heightens platelet reactivity. Furthermore, the bidirectional communication via the gut-brain axis plays a pivotal role in regulating satiety and dietary choices. In light of these associations, therapeutic strategies that reshape the microbial landscape—ranging from probiotic and prebiotic administration to fecal microbiota transplantation and novel pharmacological modulators—hold significant promise for mitigating the cardiometabolic risks associated with obesity.