The serum metabolic profile plays a role in mediating the regulatory impact of gut microbiota and its metabolites on susceptibility to obesity in mice

Abstract Obesity is a multifaceted health concern that is impacted by genetic, environmental, and behavioral factors, with varying levels of individual susceptibility. Research has identified distinct physiological characteristics among individuals with differing susceptibilities to obesity. Prior research has demonstrated notable variances in gut microbiota and gut metabolites between obesity-prone (OP) individuals and those obesity-resistance (OR). However, the potential impact of these differences on serum metabolites remains uncertain, as does the potential role of serum metabolite changes in influencing susceptibility to obesity. We performed non-targeted metabolomic analysis on serum samples from OP and OR mice. Subsequently, correlation analysis was conducted on the data pertaining to serum metabolites, gut microbiota, gut metabolites, obesity-related physiological indicators, among other factors. This study aimed to investigate the association between alterations in serum metabolites and gut microbiota and metabolites in OP and OR mice, as well as to examine the impact of serum metabolites on susceptibility to obesity. Our research demonstrates that following HFD, gut 8Z,11Z,14Z-Eicosatrienoic acid (ESA) and gut Eicosapentaenoic acid (EPA) can impact lipid levels through the regulation of serum Arachidonic acid (AA) and serum EPA. EPA also influences the abundance of Lachnospiraceae_NK4A136_group, resulting in increased lipid accumulation. Moreover, Ruminiclostridium_9 exacerbates levels of serum saturated fatty acids and serum AA by decreasing EPA. Additionally, gut Hydroxybenzoic acid influences susceptibility to lipid accumulation by elevating serum Choline levels. These alterations contribute to the development of susceptibility to obesity, indicating that variations in serum metabolites play a significant role in susceptibility disparities, with the serum metabolites being influenced by gut microbiota and gut metabolites.