Microbiome-driven cardiac allograft outcomes

The beneficial health effects attributed to Bifidobacterium are thought to arise from their immunomodulatory capabilities, which are likely to be species- and even strain-specific. However, the strain-specific characteristics through which Bifidobacterium strains elicit direct and indirect host immune modulation remain largely uncharacterized. We have shown that B. pseudolongum UMB-MBP-01, a murine isolate, is capable of suppressing inflammation and reducing fibrosis in vivo. To ascertain the mechanism driving this activity and to determine if it is specific to UMB-MBP-01, we compared it to B. pseudolongum type strain ATCC25526 of a porcine origin using a combination of in vitro and in vivo experimentation and comparative genomics approaches. Despites many shared features between the two strains, we demonstrate that each possesses a distinct genetic repertoire in carbohydrate assimilation, differential activation signatures and cytokine responses in innate immune cells, and differential lymph node morphology with unique local and systemic leukocyte distribution. Importantly, the administration of each B. pseudolongum strain resulted in outstanding divergence in the structure, composition, and function of gut microbiota. This was accompanied by markedly different changes in intestinal transcriptional activities, suggesting a strain-specific modulation of the endogenous gut microbiota as a key involvement in the immunomodulation of B. pseudolongum strains. These observations highlight the importance of strain-specific immunomodulation in host-microbe interactions, and advance our understanding of the mechanisms which drive the association between Bifidobacterium and health.

双歧杆菌（Bifidobacterium）所具备的健康获益效应，被认为源于其免疫调节能力，而这种能力很可能具有物种乃至菌株特异性。然而，双歧杆菌菌株引发宿主直接与间接免疫调节的菌株特异性特征，在很大程度上仍未被阐明。本研究证实，鼠源分离株假长双歧杆菌（B. pseudolongum）UMB-MBP-01能够在体内抑制炎症反应并减轻纤维化程度。为明确该活性的驱动机制，并验证其是否为UMB-MBP-01所特有，本研究结合体外实验、体内实验与比较基因组学策略，将该菌株与猪源假长双歧杆菌模式菌株ATCC25526进行了对比。尽管两株菌存在诸多共有特征，但本研究证实二者在碳水化合物同化相关遗传组分、先天免疫细胞的活化特征与细胞因子应答模式、淋巴结形态以及局部与系统性白细胞分布上均存在显著差异。重要的是，分别施用这两株假长双歧杆菌后，宿主肠道菌群的结构、组成与功能均呈现显著分化；同时肠道转录组活性也发生显著差异改变，这提示内源性肠道菌群的菌株特异性调控，是假长双歧杆菌发挥免疫调节作用的关键机制之一。上述研究结果凸显了宿主-微生物互作中菌株特异性免疫调节的重要性，并加深了我们对双歧杆菌与宿主健康关联背后机制的理解。