Department of Biology, University of British Columbia, Syilx Okanagan Nation Territory, Kelowna, BC V1V1V7, Canada.
Department of Chemistry, University of British Columbia, Syilx Okanagan Nation Territory, Kelowna, BC V1V1V7, Canada.
Biomolecules. 2021 May 15;11(5):738. doi: 10.3390/biom11050738.
The use of live biotherapeutic products (LBPs), including single strains of beneficial probiotic bacteria or consortiums, is gaining traction as a viable option to treat inflammatory-mediated diseases like inflammatory bowel disease (IBD). However, LBPs' persistence in the intestine is heterogeneous since many beneficial bacteria lack mechanisms to tolerate the inflammation and the oxidative stress associated with IBD. We rationalized that optimizing LBPs with enhanced colonization and persistence in the inflamed intestine would help beneficial bacteria increase their bioavailability and sustain their beneficial responses. Our lab developed two bioengineered LBPs (SBT001/BioPersist and SBT002/BioColoniz) modified to enhance colonization or persistence in the inflamed intestine. In this study, we examined colon-derived metabolites via ultra-high performance liquid chromatography-mass spectrometry in colitic mice treated with either BioPersist or BioColoniz as compared to their unmodified parent strains ( Nissle 1917 [EcN] and , respectively) or to each other. BioPersist administration resulted in lowered concentrations of inflammatory prostaglandins, decreased stress hormones such as adrenaline and corticosterone, increased serotonin, and decreased bile acid in comparison to EcN. In comparison to BioColoniz, BioPersist increased serotonin and antioxidant production, limited bile acid accumulation, and enhanced tissue restoration via activated purine and pyrimidine metabolism. These data generated several novel hypotheses for the beneficial roles that LBPs may play during colitis.
使用活菌治疗产品（LBPs），包括单一菌株的有益益生菌或联合体，作为治疗炎症性疾病（如炎症性肠病（IBD））的可行选择正在受到关注。然而，LBPs 在肠道中的持久性存在异质性，因为许多有益细菌缺乏耐受与 IBD 相关的炎症和氧化应激的机制。我们推断，优化具有增强的定植和在炎症肠道中持久性的 LBPs 将有助于有益细菌增加其生物利用度并维持其有益反应。我们的实验室开发了两种经过生物工程改造的 LBPs（SBT001/BioPersist 和 SBT002/BioColoniz），经过修饰可增强在炎症肠道中的定植或持久性。在这项研究中，我们通过超高效液相色谱-质谱法检测了溃疡性结肠炎小鼠的结肠衍生代谢物，与未修饰的亲本菌株（分别为 Nissle 1917 [EcN] 和 ）或彼此相比，用 BioPersist 或 BioColoniz 治疗的小鼠。与 EcN 相比，BioPersist 给药导致炎症性前列腺素的浓度降低，应激激素如肾上腺素和皮质酮减少，血清素增加，胆汁酸减少。与 BioColoniz 相比，BioPersist 增加了血清素和抗氧化剂的产生，限制了胆汁酸的积累，并通过激活嘌呤和嘧啶代谢促进组织修复。这些数据为 LBPs 在结肠炎中可能发挥的有益作用提出了几个新的假设。
