Lactococcus lactis and Bifidobacterium bifidum alleviate postmenopausal symptoms by suppressing NF-κB signaling and microbiota dysbiosis

Abstract To understand the action mechanism of probiotics against postmenopausal symptoms, we examined the effects of Lactococcus lactis P32 (PL) and Bifidobacterium bifidum P45 (PB), which suppressed interleukin (IL)-6 and receptor activator of nuclear factor-κB (RANK) ligand (RNAKL) expression in...

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Main Authors: Yoon-Jung Shin, Xiaoyang Ma, Min-Kyung Joo, Ji-Su Baek, Dong-Hyun Kim
Format: Article
Language:English
Published: Nature Portfolio 2024-12-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-024-81500-0
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author Yoon-Jung Shin
Xiaoyang Ma
Min-Kyung Joo
Ji-Su Baek
Dong-Hyun Kim
author_facet Yoon-Jung Shin
Xiaoyang Ma
Min-Kyung Joo
Ji-Su Baek
Dong-Hyun Kim
author_sort Yoon-Jung Shin
collection DOAJ
description Abstract To understand the action mechanism of probiotics against postmenopausal symptoms, we examined the effects of Lactococcus lactis P32 (PL) and Bifidobacterium bifidum P45 (PB), 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 PL or PB 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 PL or PB 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. PL and PB (4:1) mix (PM) suppressed DC-like behavior in mice with Gv, Ov, or oG. PM also suppressed TNF-α, IL-6, RANK, and/or RANKL expression in the vagina, bone, colon, and brain. PM alleviated Gv-induced vaginal and gut dysbiosis: it decreased Proteobacteria population. These findings suggest that PL and PB, 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.
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spelling doaj-art-a607a01e11294b40a39ef0b52737afeb2025-01-05T12:29:13ZengNature PortfolioScientific Reports2045-23222024-12-0114111910.1038/s41598-024-81500-0Lactococcus lactis and Bifidobacterium bifidum alleviate postmenopausal symptoms by suppressing NF-κB signaling and microbiota dysbiosisYoon-Jung Shin0Xiaoyang Ma1Min-Kyung Joo2Ji-Su Baek3Dong-Hyun Kim4Neurobiota Research Center, College of Pharmacy, Kyung Hee UniversityNeurobiota Research Center, College of Pharmacy, Kyung Hee UniversityNeurobiota Research Center, College of Pharmacy, Kyung Hee UniversityNeurobiota Research Center, College of Pharmacy, Kyung Hee UniversityNeurobiota Research Center, College of Pharmacy, Kyung Hee UniversityAbstract To understand the action mechanism of probiotics against postmenopausal symptoms, we examined the effects of Lactococcus lactis P32 (PL) and Bifidobacterium bifidum P45 (PB), 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 PL or PB 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 PL or PB 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. PL and PB (4:1) mix (PM) suppressed DC-like behavior in mice with Gv, Ov, or oG. PM also suppressed TNF-α, IL-6, RANK, and/or RANKL expression in the vagina, bone, colon, and brain. PM alleviated Gv-induced vaginal and gut dysbiosis: it decreased Proteobacteria population. These findings suggest that PL and PB, 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.https://doi.org/10.1038/s41598-024-81500-0Menopausal symptomVaginitisOsteoporosisLactococcus lactisBifidobacterium bifidumGut microbiota
spellingShingle Yoon-Jung Shin
Xiaoyang Ma
Min-Kyung Joo
Ji-Su Baek
Dong-Hyun Kim
Lactococcus lactis and Bifidobacterium bifidum alleviate postmenopausal symptoms by suppressing NF-κB signaling and microbiota dysbiosis
Scientific Reports
Menopausal symptom
Vaginitis
Osteoporosis
Lactococcus lactis
Bifidobacterium bifidum
Gut microbiota
title Lactococcus lactis and Bifidobacterium bifidum alleviate postmenopausal symptoms by suppressing NF-κB signaling and microbiota dysbiosis
title_full Lactococcus lactis and Bifidobacterium bifidum alleviate postmenopausal symptoms by suppressing NF-κB signaling and microbiota dysbiosis
title_fullStr Lactococcus lactis and Bifidobacterium bifidum alleviate postmenopausal symptoms by suppressing NF-κB signaling and microbiota dysbiosis
title_full_unstemmed Lactococcus lactis and Bifidobacterium bifidum alleviate postmenopausal symptoms by suppressing NF-κB signaling and microbiota dysbiosis
title_short Lactococcus lactis and Bifidobacterium bifidum alleviate postmenopausal symptoms by suppressing NF-κB signaling and microbiota dysbiosis
title_sort lactococcus lactis and bifidobacterium bifidum alleviate postmenopausal symptoms by suppressing nf κb signaling and microbiota dysbiosis
topic Menopausal symptom
Vaginitis
Osteoporosis
Lactococcus lactis
Bifidobacterium bifidum
Gut microbiota
url https://doi.org/10.1038/s41598-024-81500-0
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