Lipid droplet levels vary heterogeneously in response to simulated gastrointestinal stresses in different probiotic Saccharomyces cerevisiae strains

AbstractTo exert their therapeutic action, probiotic Saccharomyces cerevisiae strains must survive harsh digestive environments. Lipid droplets accumulate in cells which undergo stress-inducing situations, supposedly having a protective role. We assessed lipid droplet levels, either naturally accumulated or induced in response to digestive challenges, of probiotic strains S. boulardii, S. cerevisiae A-905, S. cerevisiae Sc47 and S. cerevisiae L11, and of non-probiotic strains S. cerevisiae BY4741 and S. cerevisiae BY4743. Strains 905 and Sc47 had lower and higher lipid droplet levels, respectively, when compared to the remaining strains, showing that higher accumulationof these neutral lipids is not a feature shared by all probiotic Saccharomyces strains. When submitted to simulated gastric or bile salts environments, lipid droplet levels increase in all tested probiotic strains, at least for one to the induced stresses, suggesting that lipid droplets participate in the protective mechanisms against gastrointestinal stresses in probiotic Saccharomyces yeasts

Immune determinants of Barrett’s progression to esophageal adenocarcinoma

Esophageal adenocarcinoma (EAC) develops from Barrett’s esophagus (BE), a chronic inflammatory state that can progress through a series of transformative dysplastic states before tumor development. While molecular and genetic changes of EAC tumors have been studied, immune microenvironment changes during Barrett’s progression to EAC remain poorly understood. In this study, we identify potential immunologic changes that can occur during BE-to-EAC progression. RNA sequencing (RNA-Seq) analysis on tissue samples from EAC patients undergoing surgical resection demonstrated that a subset of chemokines and cytokines, most notably IL6 and CXCL8, increased during BE progression to EAC. xCell deconvolution analysis investigating immune cell population changes demonstrated that the largest changes in expression during BE progression occurred in M2 macrophages, pro–B cells, and eosinophils. Multiplex immunohistochemical staining of tissue microarrays showed increased immune cell populations during Barrett’s progression to high-grade dysplasia. In contrast, EAC tumor sections were relatively immune poor, with a rise in PD-L1 expression and loss of CD8+ T cells. These data demonstrate that the EAC microenvironment is characterized by poor cytotoxic effector cell infiltration and increased immune inhibitory signaling. These findings suggest an immunosuppressive microenvironment, highlighting the need for further studies to explore immune modulatory therapy in EAC