Biology subjects

Rescigno, M.

Publications and source records attributed to Rescigno, M..

3 recordsLinked to original sources

bioRxiv2024

Lactobacillus paracasei CNCM I-5220-derived postbiotic counteracts skin inflammation and protects skin barrier integrity

IntroductionSkin inflammation and damage of skin barrier integrity contribute to the pathogenesis of inflammatory skin diseases such as psoriasis and atopic dermatitis. Nowadays, there is a growing interest in alternative and complementary strategies to counteract skin inflammation and treat dermatologic conditions. ObjectivesPostbiotics, metabolites released during bacterial fermentation, exert anti-inflammatory proprieties and contribute to the maintenance of epithelial barrier integrity. Therefore, we investigated the effect of LP-PBL, a novel Lactobacillus paracasei CNCM I-5220-derived postbiotic, in controlling skin inflammation and protecting the skin barrier. MethodsWe performed RNA-sequencing on Poly(I:C)-stimulated keratinocytes and investigated LP-PBL efficacy in regulating pro-inflammatory cytokine release. The production of most relevant cytokines was demonstrated by ELISA. Then, we tested postbiotic lenitive efficacy on healthy volunteers irritated skin. We compared the effect of a postbiotic-containing cream formulation versus placebo on sodium lauryl sulphate treated skin. ResultsWe demonstrate that LP-PBL has anti-inflammatory activity by modulating Poly(I:C)-dependent inflammatory pathways and pro-inflammatory cytokine release in keratinocytes. The postbiotic inhibited the upregulation of interleukin (IL)-23A, which is overexpressed in psoriatic skin, and of IL-33 and thymic stromal lymphopoietin (TSLP) that are upregulated in atopic dermatitis. Moreover, it increased filaggrin and zonula occludens (ZO)-1 expression in Poly(I:C)-stimulated keratinocytes, suggesting beneficial effects on inflamed and damaged skin. Consistently, a clinical test on healthy volunteers showed that topic LP-PBL treatment significantly reduced skin redness upon sodium lauryl sulphate challenge compared to placebo, leading to a rapid recovery of the irritated skin. ConclusionOverall, we demonstrated the protective role of LP-PBL on the skin, both in vitro and in the clinical test, suggesting that postbiotic topical application could represent an innovative and promising strategy to counteract skin inflammation and preserve skin barrier integrity.

microbiology↗

bioRxiv2023

Porphyromonas gingivalis fuels colorectal cancer through CHI3L1-mediated iNKT cell-driven immune evasion

The interaction between the gut microbiota and invariant Natural Killer T (iNKT) cells plays a pivotal role in colorectal cancer (CRC). Porphyromonas gingivalis is a keystone oral pathogen associated with CRC. The oral pathobiont Fusobacterium nucleatum influences the anti-tumour functions of CRC-infiltrating iNKT cells. However, the impact of other oral bacteria, like P. gingivalis, on their activation status remains unexplored. In this study, we demonstrate that mucosa-associated P. gingivalis induces a protumour phenotype in iNKT cells, subsequently influencing the composition of mononuclear-phagocyte cells within the tumour microenvironment in CRC. Mechanistically, in vivo and in vitro experiments show that P. gingivalis reduces the cytotoxic functions of iNKT cells, hampering the iNKT cell lytic machinery though increased expression of chitinase 3-like-1 protein (CHI3L1). Neutralization of CHI3L1 effectively restores iNKT cell cytotoxic functions suggesting a therapeutic potential to reactivate iNKT cell-mediated antitumour immunity. In conclusion, our data demonstrate how P. gingivalis accelerates CRC progression by inducing iNKT cells to upregulate CHI3L1, thus impairing iNKT cell cytotoxicity and promoting host tumour immune evasion.

immunology↗

bioRxiv2019

FxR-modulates the gut-vascular barrier by regulating the entry sites for bacterial translocation in experimental cirrhosis

Background and aimsPathological bacterial translocation (PBT) in liver cirrhosis (LC) is the hallmark for spontaneous bacterial infections increasing mortality several-fold. Factors known to contribute to PBT in LC are among others an increased intestinal permeability of which however, the mucus layer has not been addressed so far in detail. A clear route of translocation for luminal intestinal bacteria is yet to be defined but we hypothesize that the recently described gut vascular barrier (GVB) is impaired in experimental portal hypertension leading to increased accessibility of the vascular compartment for translocating bacteria.\n\nResultsHealthy and pre-hepatic portal-hypertensive (PPVL) mice lack translocation of FITC-dextran and GFP-Escherichia coli from the small intestine to the liver whereas bile-duct-ligated (BDL) and CCl4-induced cirrhotic mice demonstrate pathological translocation which is not altered by prior thoracic-duct ligation. Mucus layer is reduced in thickness with loss of goblet-cells and Muc2-staining and expression in cirrhotic but not PPVL-mice associated with bacterial overgrowth in inner mucus layer and pathological translocation of GFP-E.coli through the ileal epithelium. GVB is profoundly altered in BDL and CCl4-mice with Ileal extravasation of large-sized 150 kDa-FITC-dextran but only minor in PPVL-mice. This pathological endothelial permeability and accessibility in cirrhotic mice associates with an augmented expression of PV1 in intestinal vessels. OCA but not fexaramine stabilizes the GVB whereas both FXR-agonists ameliorate gut-liver-translocation of GFP-E.coli.\n\nConclusionsLiver cirrhosis but not portal hypertension per se grossly impairs the endothelial and muco-epithelial barriers promoting PBT to the portal-venous circulation. Both barriers appear FXR-modulated with -agonists reducing PBT via the portal-venous route.

physiology↗