Soluble peptidoglycan fragments produced by Limosilactobacillus fermentum with antiproliferative activity are suitable for potential therapeutic development: A preliminary report

Abstract

Currently, the use of probiotic strains and their products represents a promising innovative approach as an antagonist treatment against many human diseases. Previous studies showed that a strain of Limosilactobacillus fermentum (LAC92), previously defined as Lactobacillus fermentum, exhibited a suitable amensalistic property. The present study aimed to purify the active components from LAC92 to evaluate the biological properties of soluble peptidoglycan fragments (SPFs). The cell-free supernatant (CFS) and bacterial cells were separated after 48 h of growth in MRS medium broth and treated for isolation of SPFs. Antimicrobial activity and proliferation analysis on the human cell line HTC116 were performed using technologies such as xCELLigence, count and viability, and clonogenic analysis. MALDI-MS investigation and docking analysis were performed to determine the molecular structure and hypothetical mode of action, respectively. Our results showed that the antimicrobial activity was mainly due to SPFs. Moreover, the results obtained when investigating the SPF effect on the cell line HCT116 showed substantial preliminary evidence, suggesting their significant cytostatic and quite antiproliferative properties. Although MALDI was unable to identify the molecular structure, it was subsequently revealed by analysis of the bacterial genome. The amino acid structure is called peptide 92. Furthermore, we confirmed by molecular docking studies the interaction of peptide 92 with MDM2 protein, the negative regulator of p53. This study showed that SPFs from the LAC92 strain exerted anticancer effects on the human colon cancer HCT116 cell line via antiproliferation and inducing apoptosis. These findings indicated that this probiotic strain might be a potential candidate for applications in functional products in the future. Further examination is needed to understand the specific advantages of this probiotic strain and improve its functional features to confirm these data. Moreover, deeper research on peptide 92 could increase our knowledge and help us understand if it will be possible to apply to specific diseases such as CRC.

Putrescine Supplementation Limits the Expansion of pks+ Escherichia coli and Tumor Development in the Colon

“…Overall, we found that putrescine increased the Firmicutes / Bacteroidetes ratio, and a higher Firmicutes/Bacteroidetes ratio is linked to better survival in patients with colorectal cancer ( 51 ). In the phylum Firmicutes , we found an increase in the Limosilactobacillus genus in which Limosilactobacillus fermentum has been reported to produce peptidoglycan with anti-proliferative properties ( 52 ) and Limosilactobacillus reuteri has been shown to suppress colorectal tumorigenesis ( 53 ). Lachnospiraceae are known to produce SCFAs and to play a beneficial role in intestinal health.…”

Applications of Probiotics and Their Potential Health Benefits

“…gastric and colorectal cancers, and antibiotic-associated diarrhea have all been the subjects of extensive probiotic research [14]. Studies indicate that specific strains of probiotics could alleviate symptoms, reduce inflammation, and restore gut homeostasis in individuals suffering from these conditions.…”