Lactiplantibacillus plantarum from Thai fermented pork with inulin ameliorates metabolic disturbances through proteomic mechanisms

This study explored the molecular mechanisms through which Lactiplantibacillus plantarum strain P4, isolated from Thai fermented pork (Nham), modulates metabolic disturbances induced by a high-fat diet (HFD) in rats, both independently and in combination with the prebiotic inulin. Male Sprague-Dawley rats (n = 32; initial weight 204.12 ± 4.80 g) were randomly assigned to four groups (n = 8 per group): normal diet (N), high-fat diet (HF), high-fat diet supplemented with L. plantarum P4 (HFLac; 10⁹ CFU/g), and high-fat diet supplemented with both L. plantarum P4 and inulin (HFLacIn; 10⁹ CFU/g + 0.1% w/w inulin). After a 4-week intervention, lipid profiles, hepatic and renal function markers, and systemic inflammatory parameters were assessed. Proteomic profiling of liver tissues was performed using high-resolution mass spectrometry.The HF group exhibited significant alterations in hepatic protein expression compared to the N group, reflecting dysregulated fatty acid metabolism. Notably, the synbiotic intervention (HFLacIn) led to substantial improvements, including: (1) enhanced lipid profiles, characterized by elevated HDL-C (15.8%) and reduced LDL-C (9.5%) and VLDL (15.9%); (2) improved liver function, evidenced by decreased alkaline phosphatase (ALP) levels (3.4% reduction); and (3) attenuated inflammation, with reduced TNF-α (13.4%) and CRP (31.4%, p = 0.03). Proteomic analysis revealed upregulation of long-chain-fatty-acid-CoA ligase 1 (1.25-fold, p = 0.033), indicating enhanced fatty acid activation, and hemopexin (1.04-fold, p = 0.039), suggesting improved oxidative stress response. Additionally, inflammation-related proteins were modulated, and a pronounced increase in histone H2B type 1-A (2.82-fold, p = 0.002) implies epigenetic modulation associated with metabolic improvement.Collectively, these findings provide mechanistic insight into the metabolic benefits of L. plantarum P4, particularly when administered with inulin, highlighting the therapeutic potential of synbiotics derived from traditional fermented foods in managing diet-induced metabolic disorders.