Limosilactobacillus fermentum role in combination with human mesenchymal stem cell-derived secretome: A novel approach to alleviate inflammation in NASH pathogenesis.

BACKGROUND

Nonalcoholic steatohepatitis (NASH) is caused by the accumulation of excess fat in the liver, chronic inflammation, and cell death. The role of the secretome derived from Wharton's jelly and mesenchymal stem cells (WJ-MSC) in reducing inflammation and apoptosis has been investigated in several studies. Also, the strain Limosilactobacillus fermentum (L‌.‌fermentum) was identified as an antimicrobial and antioxidant probiotic. This study looked into the role of a combination of secretome and L.fermentum on cellular stress, apoptosis, and inflammation-related pathways in an NASH in-vitro model.

METHODS

Oil Red O staining confirmed the NASH model was induced using oleic acid and palmitic acid. Then, the 3 different groups were treated with two concentrations of WJ-MSCs-derived secretome, cell-free extract (CFE) of L.fermentum, and their combination. Oxidative stress was evaluated, and western blotting was used to identify the protein. Gene expression and protein quantity were assessed using real-time PCR and ELISA.

RESULT: The analysis revealed the secretome, L.fermentum, and their combination decreased oxidative stress. Additionally, the low levels of Caspase 3 and 9 led to a reduction in apoptosis. The combined treatment significantly impacted inflammation by increasing IL-10 and decreasing IL-6. The expression of STAT3 was also confirmed to be reduced using western blotting. Despite the significant modulation of TNF-alpha and STAT3 by L. fermentum at a high dose, the combined approach led to enhanced performance and restored the cell proliferation.

CONCLUSION

This enhancement has the potential to substantially influence the treatment of NASH disease by impacting inflammation, apoptosis, and oxidative stress, thereby revealing therapeutic potential for NASH disease.