n-3 PUFA pork mitigates TMAO-exacerbated metabolic disorder, systemic inflammation and intestinal barrier dysfunction via gut microbiota

n-3 polyunsaturated fatty acids (PUFAs) exhibit critical regulatory functions in physiological metabolism, yet their concentrations in conventional pork remain scant. This study systematically investigated the comparative effects of long-term consumption of conventional pork (CP) versus n-3 PUFAs-rich pork (n-3 P) on metabolic homeostasis, employing a murine model to delineate mechanisms underlying lipid regulation, trimethylamine (TMA)/ trimethylamine N-oxide (TMAO) modulation, and gut microbiota restructuring. The results showed that, compared with the consumption of CP, n-3 P significantly inhibited the body weight gain (<em>P</em> &lt; 0.05). Moreover, n-3 P improved dyslipidemia by regulating signaling molecules such as peroxisome proliferator-activated receptor (PPAR)α/γ and fatty acid synthase (FAS), and restored bile acid metabolism disorders by regulating signaling molecules such as farnesoid x receptor (FXR) and cholesterol 7α-hydroxylase (CYP7A1). n-3 P could reduce the content of TMA/TMAO by regulating the choline-TMA-TMAO axis. 16S rRNA sequencing revealed n-3 P reshaped the gut microbiota, significantly increasing α and β diversities (<em>P</em> &lt; 0.05) and simultaneously reducing the abundances of <em>Lachnospiraceae</em> and <em>Lachnoclostridium</em>. These findings highlight the potential value of n-3 P in body weight control, prevention of metabolic disorders and inflammation, enhancement of intestinal barrier function, reduction of TMA/TMAO levels, and amelioration of gut microbiota.