Filipe Rosa Louisa, Gonda Steffen, Roese Nadine, Bischoff Stephan C
Institute of Nutritional Medicine, University of Hohenheim, Fruwirthstr. 12, 70599 Stuttgart, Germany.
MEDICE Arzneimittel Pütter GmbH & Co., KG, Kuhloweg 37, 58638 Iserlohn, Germany.
Pharmaceuticals (Basel). 2025 Aug 6;18(8):1167. doi: 10.3390/ph18081167.
: CNCM I-745, a probiotic yeast, is effectively used for the treatment of acute diarrhea as well as for the prevention and treatment of traveller's diarrhea and diarrhea under tube feeding. The underlying mechanisms are not fully elucidated. Both antitoxic and regulatory effects on the intestinal barrier, mediated either by the yeast or yeast-derived substrates, have been discussed. : To examine the effects of released substrates (S.b.S) on gastrointestinal (GI) barrier function, a murine small intestinal organoid cell model under stress was used. Stress was induced by lipopolysaccharide (LPS) exposure or withdrawal of growth factors from cell culture medium (GF). Stressed organoids were treated with S.b.S (200 µg/mL), and markers of GI barrier and inflammatory response were assessed. : GF-induced stress was characterized by disturbances in selected tight junction (TJ) ( < 0.05), adherent junction (AJ) ( < 0.001), and mucin () formation ( < 0.01), measured by gene expressions, whereby additional S.b.S treatment was found to reverse these effects by increasing (from 0.22 to 0.97-fold change, < 0.05), Occludin () (from 0.37 to 3.5-fold change, < 0.0001), and Claudin ()7 expression (from 0.13 ± 0.066-fold change, < 0.05) and by decreasing , , , and junctional adhesion molecule A () expression (all < 0.01). Further, S.b.S normalized expression of nucleotide binding oligomerization domain ()2- (from 44.5 to 0.51, < 0.0001) and matrix metalloproteinase ()7-dependent activation (from 28.3 to 0.02875 ± 0.0044 ** < 0.01) of antimicrobial peptide defense and reduced the expression of several inflammatory markers, such as myeloid differentiation primary response 88 () ( < 0.01), tumor necrosis factor α () ( < 0.01), interleukin ()-6 ( < 0.01), and ( < 0.001). : Our data provide new insights into the molecular mechanisms by which CNCM I-745-derived secretome attenuates inflammatory responses and restores GI barrier function in small intestinal organoids.
益生菌酵母CNCM I-745可有效用于治疗急性腹泻以及预防和治疗旅行者腹泻及管饲引起的腹泻。其潜在机制尚未完全阐明。已讨论了酵母或酵母衍生底物介导的对肠道屏障的抗毒和调节作用。：为了研究释放的底物（S.b.S）对胃肠道（GI）屏障功能的影响，使用了应激状态下的小鼠小肠类器官细胞模型。应激通过暴露于脂多糖（LPS）或从细胞培养基（GF）中去除生长因子来诱导。用S.b.S（200μg/mL）处理应激类器官，并评估GI屏障和炎症反应的标志物。：通过基因表达测量，GF诱导的应激表现为选定的紧密连接（TJ）（<0.05）、黏附连接（AJ）（<0.001）和黏蛋白（）形成（<0.01）的紊乱，由此发现额外的S.b.S处理通过增加（从0.22倍变化增加到0.97倍变化，<0.05）、闭合蛋白（）（从0.37倍变化增加到3.5倍变化，<0.0001）和Claudin（）7表达（从0.13±0.066倍变化增加，<0.05）以及降低、、和连接黏附分子A（）表达（均<0.01）来逆转这些影响。此外，S.b.S使核苷酸结合寡聚化结构域（）2-（从44.5降至0.51，<0.0001）的表达和抗菌肽防御的基质金属蛋白酶（）7依赖性激活（从28.3降至0.02875±0.0044**<0.01）正常化，并降低了几种炎症标志物的表达，如髓样分化初级反应88（）（<0.01）、肿瘤坏死因子α（）（<0.01）、白细胞介素（）-6（<0.01）和（<0.001）。：我们的数据为CNCM I-745衍生的分泌组减弱小肠类器官炎症反应并恢复GI屏障功能的分子机制提供了新的见解。
