Recombinant Lactobacillus helveticus PJ4-Down Regulates TLR4 Mediated Inflammatory Responses in Sucrose Induced Diabetic Rats: A Novel Therapeutic Approach

Abstract

High sucrose diet (HSD) is known to induce type 2 diabetes. Recombinant Lactobacillus helveticus PJ4 was constructed to express the InuJ gene under the xylose promoter resulting in the secretion of inulosucrase enzyme in gastrointestinal tract which polymerizes the fructose moiety of sucrose to inulin type fructans. L. helveticus (pSLP-InuJ-Vhb) transformant (LHI) was intragastrically administered to rats fed with HSD diet. The composition of fecal microbiota and short-chain fatty acids (SCFA), oral glucose tolerance, blood, liver markers, serum and hepatic lipids profile and proinflammatory cytokines in serum were investigated. Additionally, the histopathological and expression of TLR2, TLR4 and NF-қB genes were also studied in liver, distal ileum and proximal colon. The levels of plasma glucose, liver injury markers, lipid profile in plasma and liver were significantly increased in high-sucrose-fed rats. However, after LHI feeding significantly ameliorated the elevated parameters. Feeding of LHI transformants enhanced the butyrate production compared to HSD group. The mRNA expression analysis revealed that the LHI administration restored the HSD-dysregulated TLR2, TLR4 and NF-кB toward a physiological level in liver, distal ileum, proximal colon and adipose tissue. The LHI significantly reduced the adverse effect of main regulators of inflammatory cytokines, i.e., IL6 and TNF-α in HSD rats. Besides that, it also reduces the other cytokines like MCP-1, INF-γ, and IL12p70. The LHI transformants was effective in reducing the severity of liver injury and insulin resistance, ameliorated hepatic steatosis associated with high sucrose intake, suggesting its possible therapeutic/preventive clinical utilization.

Keywords: Inulosucrase, Lactobacilli, probiotic, Toll like receptors, Cytokines, Insulin resistance

Cite this Article

Prasant Kumar Jena, Bhumika Prajapati, Nidhi Nagar et al. Recombinant Lactobacillus helveticus PJ4-Down Regulates TLR4 Mediated Inflammatory Responses in Sucrose Induced Diabetic Rats: A Novel Therapeutic Approach. Research & Reviews: A Journal of Immunology. 2017; 7(2): 44–65p.