Abstract: Over the past decade, the gut microbiota (GM), often known as the "shadow metabolic organ", has undergone a revolutionary metamorphosis from the exploration of a "New Frontier" to the establishment of a "New Paradigm". This complex microbial ecosystem regulates critical host functions, energy balance, immune homeostasis and endocrine signaling through dynamic microbiome⁃host crosstalk. GM dysbiosis is now firmly implicated in the pathogenesis of metabolic disease, including obesity, type 2 diabetes and metabolic dysfunction⁃associated steatotic liver disease (MASLD). In this Review, we discuss state of the art for gut microbiote in metabolic disease. We introduce the evolving mechanistic understanding of how GM may link to the pathogenesis of common metabolic diseases, and explore the microbiota⁃targeted interventions to optimize metabolic health, which provides perspectives for future basic and translational investigations within the metabolic diseases field.

Key words: gut microbiota, metabolic disease, multi?omics, precision therapy