In this paper, we demonstrate that the antimicrobial activity of L. plantarum PBS067 strain against antagonist microorganisms was mediated by the production of a bacteriocin-like compound secreted at the stationary phase of the growth. The novel bacteriocin-like compound, designed plantaricin P1053, was identified by using sorption–desorption method, butanol extraction and SEC-HPLC. The molecular mass of plantaricin P1053 was shown to be 1053 Da by ESI-MS analysis. Plantaricin P1053 exhibited a broad-spectrum antimicrobial activity against Gram-positive bacteria as S. aureus and Gram-negative bacteria as E. coli. In addition to the antimicrobial activity, the isolated bacteriocin-like compound showed effects on normal and cancerogenic epithelial intestinal cell lines through an enhancing of viability of healthy cells and a proliferation reduction of cancer cells. Moreover, in this paper we demonstrate that the isolated bacteriocin-like compound acts on healthy cells through the epidermal growth factor receptor (EGFR) pathways. In conclusion, plantaricin P1053 isolated from L. plantarum PBS067 strain could represent one of the first multifunctional bacteriocin-like compound acting on human epithelial intestinal cells.

The epidermal growth factor receptor (EGFR), through the MAP kinase and PI3K-Akt-mTOR axis, plays a pivotal role in colorectal cancer (CRC) pathogenesis. The membrane-associated NEU3 sialidase interacts with and desialylates EGFR by promoting its dimerization and downstream effectors’ activation. Among the targeted therapies against EGFR, the monoclonal antibody cetuximab is active only in a subgroup of patients not carrying mutations in the MAP kinase pathway. In order to better understand the EGFR-NEU3 interplay and the mechanisms of pharmacological resistance, we investigated the role of NEU3 deregulation in cetuximab-treated CRC cell lines transiently transfected with NEU3 using Western blot analysis. Our results indicate that NEU3 overexpression can enhance EGFR activation only if EGFR is overexpressed, indicating the existence of a threshold for NEU3-mediated EGFR activation. This enhancement mainly leads to the constitutive activation of the MAP kinase pathway. Consequently, we suggest that the evaluation of NEU3 expression cannot entirely substitute the evaluation of EGFR because EGFR-negative cases cannot be stimulated by NEU3. Furthermore, NEU3-mediated hyperactivation of EGFR is counterbalanced by the administration of cetuximab, hypothesizing that a combined treatment of NEU3- and EGFR-targeted therapies may represent a valid option for CRC patients, which must be investigated in the future.

Maitake (Grifola frondosa) is a medicinal mushroom known for its peculiar biological activities due to the presence of functional components, including dietary fibers and glucans, that can improve human health through the modulation of the gut microbiota. In this paper, a Maitake ethanol/water extract was prepared and characterized through enzymatic and chemical assays. The prebiotic potential of the extract was evaluated by the growth of some probiotic strains and of a selected probiotic consortium. The results revealed the prebiotic properties due to the stimulation of the growth of the probiotic strains, also in consortium, leading to the production of SCFAs, including lactic, succinic, and valeric acid analyzed via GC-MSD. Then, their beneficials effect were employed in evaluating the vitality of three different healthy and tumoral colorectal cell lines (CCD841, CACO-2, and HT-29) and the viability rescue after co-exposure to different stressor agents and the probiotic consortium secondary metabolites. These metabolites exerted positive effects on colorectal cell lines, in particular in protection from reactive oxygen species.

Oxidative stress caused by reactive oxygen species (ROS) affects the aging process and increases the likelihood of several diseases. A new frontier in its prevention includes bioactive foods and natural extracts that can be introduced by the diet in combination with specific probiotics. Among the natural compounds that we can introduce by the diet, Panax ginseng extract is one of the most utilized since it contains a vast number of bioactive molecules such as phenolic acids, flavonoids, and polysaccharides that have been shown to possess antioxidant, anti-ageing, anti-cancer, and immunomodulatory activity. In this work, the ability of a P. ginseng extract in combination with a probiotic formulation was taken into consideration to evaluate its effects on the modulation of in vitro reconstructed human gut microbiota (HGM). After evaluating the growth of the individual strains on the ginseng extract, we tested the in vitro reconstructed HGM setup (probiotics, minimal core, and whole community) using 2% w/v ginseng as the only carbon and energy source. The probiotic strains reached the highest growth, while the minimal core and the whole community showed almost the same growth. Specifically, the presence of the ginseng extract favors L. plantarum and B. animalis subsp. lactis among the probiotics, while B. cellulosilyticus prevails over the other strains in the minimal core condition. In the presence of both probiotics and minimal core strains, L. plantarum, B. animalis subsp. lactis, and B. cellulosilyticus reach the highest growth values. The bacterial metabolites produced during ginseng extract fermentation in the three conditions were administered to human intestinal epithelial cells (HT-29) to investigate a potential antioxidant effect. Remarkably, our results highlighted a significant reduction in the total ROS and a slightly reduction in the cytosolic superoxide anion content in HT-29 cells treated with bacterial metabolites deriving from ginseng extract fermentation by the whole community.