MS is a major disease that includes obesity, hyperlipidemia, and insulin resistance18. Recently, studies have confirmed that probiotic intervention is a novel strategy for alleviating MS19. Supplementation of probiotics in patients with MS, particularly those containing Lactobacillus or Bifidobacterium, appears to be a promising strategy for the prevention and treatment of MS20.
The regulatory effects of probiotics on lipid profile of host have been extensively studied. A recent study showed that lactobacillus strains significantly reduced serum levels of TC, TG, and LDL-C, while increased serum HDL-C level in rats fed with HFD21. Similarly, the results of the current study also showed that L. plantarum S9 not only reduced body weight gain, Lee’s index, and liver index in rats fed with HFD, but also reduced serum levels of TC, TG, and LDL-C. Furthermore, L. plantarum S9 treatment significantly increased serum HDL-C level. Nallala et al. reported similar results related to the influence of L. plantarum VJC38 on the increase of HDL concentration in Wistar albino rats22. Zhu et al. also recently reported that L. fermentum CQPC0 increased the level of HDL-C in both serum samples and liver tissue of obese rats fed with HFD23. One proposed mechanism to explain HDL increase after probiotic treatment was that the decrease of serum TG level may indirectly lead to the increase of serum HDL level. However, other studies have found that some strains or their fermented milk did not appear to affect HDL concentration24. These results suggested that probiotics could improve metabolic disorders related to strain specificity. However, these findings need to be further confirmed to clarify the role and mechanism of probiotics in improving metabolic disorders. In addition, liver is an organ of detoxification and lipid metabolism, and ALT and AST levels are important markers of liver injury. L. plantarum S9 could significantly reduce the ALT and AST levels, suggesting that L. Plantarum S9 has a protective effect on liver injury induced by HFD. Zhu et al. also reported that L. plantarum KFY04 mitigated HFD-induced increases of ALT and AST levels25.
Insulin resistance is a key factor in MS, and secondary hyperinsulinemia can induce a variety of metabolic disorders and cardiovascular diseases26. Recent studies showed that probiotics can effectively reduce insulin resistance and improve insulin sensitivity, which is an important strategy for improving MS. For instance, the administration of L. acidophilus combined with curcumin significantly improved insulin level and reduced insulin resistance in high-fructose-induced metabolic complex rats27. Another study demonstrated that oral administration of L. fermentum CQPC06 significantly decreased the blood glucose level and serum insulin level in NAFLD mice28. Similarly, Musso et al. reported that L. fermentum CRL1446 improved the HOMA index in mice with MS29. In the present study, it was found that after administration of L. plantarum S9 for 6 weeks, glucose metabolism of rats with MS was significantly improved, and glucose and insulin levels were significantly reduced, suggesting that L. plantarum S9 could effectively restore glucose metabolism and insulin resistance of rats with MS. The results of the current study are consistent with those reported previously, indicating that different strains of probiotics can reduce insulin resistance caused by various metabolic disorders in humans and animals.
MS is typically associated with systemic low-grade inflammation, and is characterized by activation of certain pro-inflammatory signaling pathways and elevated levels of pro-inflammatory cytokines, such as LPS, IL-1, IL-6, and TNF-α30. In the present study, LPS and TNF-α levels were significantly upregulated in HFD rats, indicating that the HFD model was in a low-grade inflammatory state. However, L. plantarum S9 significantly reduced the LPS and TNF-α levels, suggesting that L. plantarum S9 could reduce the inflammatory response in HFD-induced MS rats. It has been reported that elevated LPS, TNF-α and the release of pro-inflammatory cytokines are important triggers of diseases associated with metabolic disorders. L. pentosus S-PT84 prevents HFD/LPS-induced systemic inflammation by reducing the secretion of TNF-α and monocyte chemoattractant protein-1 (MCP-1)31. TLR4/NF-κB signaling pathway regulates the production of inflammatory cytokines. TLR4 is the receptor of bacterial LPS, which can rapidly transmit the signal of LPS transduction pathway into the nucleus and activate NF-κB located at the downstream hub32. The activated NF-κB enters the nucleus to promote the synthesis and release of inflammatory cytokines33. Previous studies have found that the expression level of TLR4 in the central nervous system was continuously elevated throughout the MS34. The results of the current study showed that the expression levels of TLR4 and NF-κB p65 significantly increased in the HFD model group. The expression level of NF-κB p65 increased, and the TNF-α content of NF-κB downstream inflammatory factor was elevated, suggesting that the activation of TLR4/NF-κB signaling pathway may be involved in the pathogenesis of MS. Inhibition of TLR4 signal transduction pathway on NF-κB activation is an effective method to ameliorate inflammation associated with MS. In this study, the expression levels of TLR4 and NF-κB p65 were significantly downregulated in HFD rats after receiving probiotics, and the nuclear expression of NF-κB p65 decreased, suggesting that L. plantarum S9 could inhibit the activation of the TLR4/NF-κB signaling pathway. Other probiotics, such as L. casei Lbs, L. freuteri V3401, L. rhamnosus GG, and Bifidobacterium bifidum have also been reported to ameliorate inflammation in MS patients35,36.
In summary, oral administration of L. plantarum S9 could reduce weight gain, and ameliorate lipid metabolism and insulin resistance. L. plantarum S9 was also shown to mitigate MS-associated inflammatory responses. L. plantarum S9 suppressed the expression levels of pro-inflammatory cytokines through the TLR4/NF-κB pathway, improving MS in rats fed with HFD. Therefore, L. plantarum S9 could alleviate HFD-induced MS by reducing hyperlipidemia, insulin resistance, and inflammation.