Bifidobacterium breve reduces apoptotic epithelial cell shedding in an exopolysaccharide and MyD88-dependent manner.
Bifidobacterium breve reduces apoptotic epithelial cell shedding in an exopolysaccharide and MyD88-dependent manner.
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DOI：
10.1098/rsob.160155
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发表时间：
2017-01
期刊：
影响因子：
5.8
通讯作者：
Hall LJ
中科院分区：
文献类型：
--
作者：
Hughes KR;Harnisch LC;Alcon-Giner C;Mitra S;Wright CJ;Ketskemety J;van Sinderen D;Watson AJ;Hall LJ
双歧杆菌属微生物群的某些成员已知会对宿主的福祉产生积极影响。重要的是，双歧杆菌水平降低与炎症性肠病(IBD)患者相关，这些患者也有上皮屏障功能受损，包括从绒毛中排出小肠上皮细胞(IECS)的凋亡率增加-这一过程被称为“细胞脱落”。使用病理性细胞脱落的小鼠模型，我们发现接受短双歧杆菌UCC2003的小鼠的小IEC脱落率显著降低。双歧杆菌诱导的保护作用似乎是由特定的双歧杆菌表面胞外多糖介导的，并与宿主MyD88相互作用，导致内源性和外源性凋亡反应下调，从而在高度炎症条件下保护上皮细胞。我们的结果揭示了B.breve在通过细菌和宿主依赖因子积极调节上皮细胞脱落结果方面的重要作用，支持了微生物区系的操纵影响肠道疾病结果的概念。
Certain members of the microbiota genus Bifidobacterium are known to positively influence host well-being. Importantly, reduced bifidobacterial levels are associated with inflammatory bowel disease (IBD) patients, who also have impaired epithelial barrier function, including elevated rates of apoptotic extrusion of small intestinal epithelial cells (IECs) from villi—a process termed ‘cell shedding’. Using a mouse model of pathological cell shedding, we show that mice receiving Bifidobacterium breve UCC2003 exhibit significantly reduced rates of small IEC shedding. Bifidobacterial-induced protection appears to be mediated by a specific bifidobacterial surface exopolysaccharide and interactions with host MyD88 resulting in downregulation of intrinsic and extrinsic apoptotic responses to protect epithelial cells under highly inflammatory conditions. Our results reveal an important and previously undescribed role for B. breve, in positively modulating epithelial cell shedding outcomes via bacterial- and host-dependent factors, supporting the notion that manipulation of the microbiota affects intestinal disease outcomes.