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.

学界普遍认为，双歧杆菌（Bifidobacterium）对健康的有益功效源自其免疫调节能力，且这种能力很可能具有物种特异性，甚至菌株特异性。然而，双歧杆菌菌株通过哪些菌株特异性特征介导宿主直接与间接免疫调控，目前仍未得到充分阐明。本研究证实，分离自小鼠的假长双歧杆菌（B. pseudolongum）UMB-MBP-01菌株，在体内可抑制炎症反应并减轻纤维化程度。为明确该菌株发挥活性的分子机制，并验证其活性是否为UMB-MBP-01所特有，本研究将其与一株猪源假长双歧杆菌模式菌株ATCC25526进行了对比，实验手段涵盖体外（in vitro）与体内（in vivo）实验以及比较基因组学分析。尽管两株菌株具有诸多共有特征，但本研究证实二者在碳水化合物同化的遗传功能谱、先天免疫细胞的活化特征与细胞因子应答模式，以及淋巴结形态与局部、全身白细胞分布特征上均存在显著差异。尤为重要的是，分别施用这两株假长双歧杆菌后，宿主肠道菌群的结构、组成与功能均呈现出显著分化。与此同时，宿主肠道的转录活性也出现了显著差异的改变，这表明假长双歧杆菌菌株通过菌株特异性调控内源肠道菌群，是其介导免疫调控的关键途径。上述研究结果凸显了菌株特异性免疫调控在宿主-微生物互作中的重要性，并加深了我们对双歧杆菌与健康之间关联背后机制的理解。