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Sabbatini, S.

Publications and source records attributed to Sabbatini, S..

2 recordsLinked to original sources
bioRxiv2024

Reduction of fungal dysbiosis is involved in the attenuation of Dextran Sodium Sulfate-Induced Mouse Colitis Mediated by GILZ protein and yeast extract compound

Inflammatory bowel diseases (IBD), such as Crohns disease and ulcerative colitis, have a complex and multifactorial pathogenesis that remains not fully elucidated. Recent research suggests that intestinal fungal dysbiosis may contribute to the development and persistence of IBD. In this study, we explored, for the first time, the effects of the glucocorticoid-induced leucine zipper (GILZ) protein, known to have protective effects on the gut mucosa in preclinical IBD models, in combination with a yeast extract, which supports the growth of beneficial microorganisms, in a mouse model of ulcerative colitis. The combined treatment produced significant protection against severe disease outcomes in the mice, including the restoration of intestinal barrier integrity and the reduction of pro-inflammatory cytokines. Specifically, GILZ primarily acted on the gut permeability, while the yeast extract mainly reduced pro-inflammatory cytokines. Notably, both treatments were effective in restoring the intestinal burden of clinically important Candida and former Candida species. Analysis of the intestinal fungal communities revealed that both treatments were able to reduce colitis-associated fungal dysbiosis, promoting a fungal composition similar to that of healthy mice. This effect was mainly the result of a decreased abundance of the Meyerozima genus, which was dominant in the colitic mice. Thus, combined treatment regimens with the GILZ protein and yeast extract could represent a new strategy for the treatment of inflammatory bowel diseases, by targeting multiple mechanisms at the basis of IBD, including the fungal dysbiosis. IMPORTANCEInflammatory bowel diseases (IBD), including Crohns disease and ulcerative colitis, are characterized by chronic inflammation and have a complex, multifactorial pathogenesis that is not yet fully understood. Currently, no established therapeutic strategy can consistently manage IBD effectively. Recent research indicates that intestinal fungal dysbiosis could potentially contribute to the development and persistence of chronic IBD, highlighting the importance of investigating alternative therapeutic strategies able to attenuate fungal dysbiosis in the context of intestinal inflammation. In this study, we demonstrate that a combination of a recombinant protein (GILZp) and a compound with prebiotic properties could represent a new therapeutic strategy for the treatment of IBD, as it not only decreases inflammation and restores the integrity of the epithelial barrier, but reduces fungal dysbiosis associated with DSS-induced colitis.

microbiology↗
bioRxiv2021

Discovery of a AhR flavonoid agonist that counter-regulates ACE2 expression in rodent models of inflammation and attenuates ACE2-SARS-CoV2 interaction in vitro

The severe acute respiratory syndrome (SARS)-CoV-2, a newly emerged coronavirus first identified in 2019, is the pathogenetic agent od Corona Virus Induced Disease (COVID)19. The virus enters the human cells after binding to the angiotensin converting enzyme (ACE) 2 receptor in target tissues. ACE2 expression is induced in response to inflammation. The colon expression of ACE2 is upregulated in patients with inflammatory bowel disease (IBD), highlighting a potential risk of intestinal inflammation in promoting viral entry in the human body. Because mechanisms that regulate ACE2 expression in the intestine are poorly understood and there is a need of anti-SARS-CoV2 therapies, we have settled to investigate whether natural flavonoids might regulate the expression of ACE2 in intestinal models of inflammation. The results of these studies demonstrated that pelargonidin, a natural flavonoid bind and activates the Aryl hydrocarbon Receptor (AhR) in vitro and reverses intestinal inflammation caused by chronic exposure to high fat diet or to the intestinal braking-barrier agent DSS in a AhR-dependent manner. In these two models, development of colon inflammation associated with upregulation of ACE2 mRNA expression. Colon levels of ACE2 mRNA were directly correlated with TNF mRNA levels. In contrast to ACE2 the angiotensin 1-7 receptor MAS was downregulated in the inflamed tissues. Molecular docking studies suggested that pelargonidin binds a fatty acid binding pocket on the receptor binding domain of SARS-CoV2 Spike protein. In vitro studies demonstrated that pelargonidin significantly reduces the binding of SARS-CoV2 Spike protein to ACE2 and reduces the SARS-CoV2 replication in a concentration-dependent manner. In summary, we have provided evidence that a natural flavonoid might hold potential in reducing intestinal inflammation and ACE2 induction in the inflamed colon in a AhR-dependent manner.

pharmacology and toxicology↗