Shin Yoon-Jung, Ma Xiaoyang, Joo Min-Kyung, Baek Ji-Su, Kim Dong-Hyun
Neurobiota Research Center, College of Pharmacy, Kyung Hee University, Seoul, 02447, Korea.
PBLbiolab, Inc., Seoul, 02374, Korea.
Sci Rep. 2024 Dec 30;14(1):31675. doi: 10.1038/s41598-024-81500-0.
To understand the action mechanism of probiotics against postmenopausal symptoms, we examined the effects of Lactococcus lactis P32 (P) and Bifidobacterium bifidum P45 (P), which suppressed interleukin (IL)-6 and receptor activator of nuclear factor-κB (RANK) ligand (RNAKL) expression in Gardnerella vaginalis (Gv)-stimulated macrophages, on vaginitis, osteoporosis, and depression/cognitive impairment (DC) in mice with vaginally infected Gv, ovariectomy (Ov), or Ov/Gv (oG). Oral administration of P or P decreased Gv-induced DC-like behavior and tumor necrosis factor (TNF)-α, IL-6, RANK, and/or RANKL expression in the vagina, bone, hypothalamus, hippocampus, and colon, while Gv-suppressed bone osteoprotegerin and brain serotonin and brain-derived neurotrophic factor (BDNF) levels increased. They partially shifted vaginal and gut dysbiosis in Gv-infected mice to the gut microbiota composition in normal control mice. In mice with oG, oral administration of P or P decreased oG-induced DC-like behavior and TNF-α, IL-6, RANK, and/or RANKL expression in the vagina, bone, brain, and colon, while oG-suppressed bone osteoprotegerin and brain serotonin and BDNF levels increased. They also alleviated oG-induced vaginal and gut dysbiosis: they decreased Proteobacteria population. P and P (4:1) mix (P) suppressed DC-like behavior in mice with Gv, Ov, or oG. P also suppressed TNF-α, IL-6, RANK, and/or RANKL expression in the vagina, bone, colon, and brain. P alleviated Gv-induced vaginal and gut dysbiosis: it decreased Proteobacteria population. These findings suggest that P and P, singly or together, can alleviate postmenopausal symptoms including vaginitis, colitis, osteoporosis, and DC by suppressing RANK/RANKL-mediated NF-κB activation and alleviating vaginal/gut microbiota dysbiosis.
为了解益生菌对抗绝经后症状的作用机制，我们检测了乳酸乳球菌P32（P32）和两歧双歧杆菌P45（P45）对阴道加德纳菌（Gv）感染、卵巢切除（Ov）或卵巢切除/阴道加德纳菌感染（oG）小鼠的阴道炎、骨质疏松症和抑郁/认知障碍（DC）的影响，这两种菌可抑制Gv刺激的巨噬细胞中白细胞介素（IL）-6和核因子-κB受体激活剂（RANK）配体（RANKL）的表达。口服P32或P45可降低Gv诱导的类似DC的行为以及阴道、骨骼、下丘脑、海马体和结肠中肿瘤坏死因子（TNF）-α、IL-6、RANK和/或RANKL的表达，而Gv抑制的骨保护素以及脑血清素和脑源性神经营养因子（BDNF）水平则升高。它们使Gv感染小鼠的阴道和肠道菌群失调部分转变为正常对照小鼠的肠道微生物群组成。在oG小鼠中，口服P32或P45可降低oG诱导的类似DC的行为以及阴道、骨骼、大脑和结肠中TNF-α、IL-6、RANK和/或RANKL的表达，而oG抑制的骨保护素以及脑血清素和BDNF水平升高。它们还减轻了oG诱导的阴道和肠道菌群失调：它们减少了变形菌门的数量。P32和P45（4:1）混合制剂（P）可抑制Gv、Ov或oG小鼠的类似DC的行为。P还可抑制阴道、骨骼、结肠和大脑中TNF-α、IL-6、RANK和/或RANKL的表达。P减轻了Gv诱导的阴道和肠道菌群失调：它减少了变形菌门的数量。这些发现表明，P32和P45单独或联合使用可通过抑制RANK/RANKL介导的NF-κB激活并减轻阴道/肠道微生物群失调来缓解包括阴道炎、结肠炎、骨质疏松症和DC在内的绝经后症状。
