Hughes K R, Harnisch L C, Alcon-Giner C, Mitra S, Wright C J, Ketskemety J, van Sinderen D, Watson A J M, Hall L J
The Gut Health and Food Safety Programme, Institute of Food Research, Norwich Research Park, Colney, Norwich NR4 7UA, UK
Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich NR4 7UQ, UK.
Open Biol. 2017 Jan;7(1). doi: 10.1098/rsob.160155.
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.
已知双歧杆菌属的某些微生物成员对宿主健康有积极影响。重要的是，双歧杆菌水平降低与炎症性肠病（IBD）患者有关，这些患者的上皮屏障功能也受损，包括小肠上皮细胞（IECs）从绒毛凋亡性挤出的速率升高——这一过程称为“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的小鼠小肠IEC脱落速率显著降低。双歧杆菌诱导的保护作用似乎由特定的双歧杆菌表面胞外多糖介导，并与宿主髓样分化因子88（MyD88）相互作用，导致内在和外在凋亡反应下调，从而在高度炎症条件下保护上皮细胞。我们的结果揭示了短双歧杆菌通过细菌和宿主依赖因子对上皮细胞脱落结果进行正向调节的重要且此前未被描述的作用，支持了微生物群的调控会影响肠道疾病结果这一观点。
