Prolacta Bioscience, Duarte, CA 91010, USA.
Prolacta Bioscience, Duarte, CA 91010, USA; Department of Biostatistics, University of California Los Angeles, Fielding School of Public Health, Los Angeles, CA 90095, USA.
Cell Host Microbe. 2023 Sep 13;31(9):1523-1538.e10. doi: 10.1016/j.chom.2023.08.004. Epub 2023 Aug 31.
Manipulation of the gut microbiome using live biotherapeutic products shows promise for clinical applications but remains challenging to achieve. Here, we induced dysbiosis in 56 healthy volunteers using antibiotics to test a synbiotic comprising the infant gut microbe, Bifidobacterium longum subspecies infantis (B. infantis), and human milk oligosaccharides (HMOs). B. infantis engrafted in 76% of subjects in an HMO-dependent manner, reaching a relative abundance of up to 81%. Changes in microbiome composition and gut metabolites reflect altered recovery of engrafted subjects compared with controls. Engraftment associates with increases in lactate-consuming Veillonella, faster acetate recovery, and changes in indolelactate and p-cresol sulfate, metabolites that impact host inflammatory status. Furthermore, Veillonella co-cultured in vitro and in vivo with B. infantis and HMO converts lactate produced by B. infantis to propionate, an important mediator of host physiology. These results suggest that the synbiotic reproducibly and predictably modulates recovery of a dysbiotic microbiome.
使用活体生物治疗产品来操纵肠道微生物组在临床应用中显示出前景，但仍然具有挑战性。在这里，我们使用抗生素在 56 名健康志愿者中诱导肠道菌群失调，以测试一种包含婴儿肠道微生物双歧杆菌亚种婴儿（B. infantis）和人乳寡糖（HMOs）的共生体。双歧杆菌亚种婴儿以 HMO 依赖的方式定植于 76%的受试者中，相对丰度高达 81%。微生物组组成和肠道代谢物的变化反映了定植受试者与对照组相比的恢复情况。定植与乳酸消耗菌韦荣球菌的增加、乙酸盐恢复速度的加快以及吲哚乳酸和对甲酚硫酸盐的变化相关，这些代谢物影响宿主的炎症状态。此外，双歧杆菌亚种婴儿和 HMO 在体外和体内共培养的韦荣球菌将双歧杆菌亚种婴儿产生的乳酸转化为丙酸盐，丙酸盐是宿主生理学的重要介质。这些结果表明，共生体能有规律地、可预测地调节失调的微生物组的恢复。
