Table 3 Identifiable probiotic species in kefir with osteoprotective potential and major findings in related intervention studies
From: Potential of Kefir-Derived Peptides, Probiotics, and Exopolysaccharides for Osteoporosis Management
Probiotics (strains) | Intervention regimens (oral route) | Major findings |
|---|---|---|
Lactobacillus acidophilus (ATCC4356 [53], LA-02 [54], GDMCC1.412 [55]) | 1. 2 × 108 CFU/day for 6 weeks in OVX mice [53] 2. 2 × 107 CFU/10 g BW/day for 2 weeks in OVX mice [54] 3. 109 CFU/ml in drinking water for 2 weeks in mice prior to OVX operation [55] | 1. These studies showed that administration of L. acidophilus reduced OVX-induced bone loss and enhanced trabecular and cortical bone microarchitecture [53,54,55] 2. The treatments skewed Treg/Th17 cell balance by inhibiting osteoclastogenic Th17 cells (↓IL-1β, IL-6, and TNF-α) and promoting anti-osteoclastogenic Treg cells (↑IL-10 and IFN-γ) [53, 54] 3. The treatment enhanced intestinal barrier permeability and reduced RANKL production in B cells of OVX mice [51] 4. The treatment modulated the gut microbiota and altered certain microorganism abundances, which led to an attenuation of bone loss [55] |
Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus reuteri [56, 57], and the combination of 3 strains [58] | 1. 109 CFU/day for 4 weeks in OVX rats [56, 57] 2. 109 CFU/strain/day for 4 weeks in OVX rats [58] | 1. All the treatments with single strain exerted osteoprotective effects in OVX rats, in terms of BMD, bone marrow concentration, bone area, and biochemical parameters [56] 2. Treatments with the postbiotics from these bacteria also ameliorated OVX-induced bone loss [57] 3. The treatment with a combination of 3 strains showed significant enhancement in OVX rats in terms of BMD and bone mineral content [58] |
Lactobacillus fermentum SRK414 [59] | 4 × 109 CFU/capsule, twice a day for 6 months in postmenopausal osteoporosis women who are not on osteoporosis medications | The treatment was found to maintain OC levels and increase femur neck BMD during a 6-month trial in postmenopausal women but not in the placebo-treated group |
108–109 CFU/day for 16 weeks in OVX rats | The treatments attenuated bone remodeling and consequently improved bone health in OVX rats by increasing bone formation (↑BMP-2, RUNX2, OC, BMD, BV/TV, Tb.Th) along with bone resorption reduction (↓CTX, Tb.Sp, porosity) | |
Lactobacillus plantarum GKM3, Lactobacillus paracasei GKS6 [62] | 109 CFU/day for 4 weeks in OVX mice | 1. Both strains showed anti-osteoporosis effects in OVX mice, with GKS6 outperforming GKM3 2. In vitro, the treatments upregulated osteoblastic marker genes (↑BMP-2, ALP, and OC) while downregulating osteoclastic marker genes (↓RANK, c-Fos, and TRAP), suggesting its anti-osteoporosis benefit |
Lactobacillus paracasei (DSM13434) and Lactobacillus plantarum (DSM15312, DSM 15313) mix [63, 64] | 1. 109 CFU/ml in drinking water, average 4.5 ml/day for 2 weeks in ♀ mice before OVX surgery [63] 2. 1010 CFU/day for 1 year in early postmenopausal women [64] | 1. The treatment prevented OVX-induced cortical bone loss and altered the immune status in bone by reducing TNF-α and IL-1β and increasing OPG expression, resulting in attenuated bone resorption in OVX mice [63] 2. The probiotic treatment significantly reduced lumbar spine bone loss compared with placebo in postmenopausal women [64] |
1. 5 × 108 CFU/mice, twice a week for 8 weeks in tenofovir disoproxil fumarate (TDF)-treated mice [65] 2. 4 × 108 CFU/day for 6 weeks in OVX mice [66] 3. 109 CFU/mice, 5 times a week for 4 weeks in ♀ C57BL/6, TCRβ−/−, OT-1, and DEREG mice [67] | 1. The osteoprotective effects of L. rhamnosus were largely determined by activities to balance the Treg/Th17 cell ratio (↑Treg, ↓Th17) in the bone marrow, spleen, and gut of mice [65,66,67], which may reduce serum osteoclastogenic cytokines (IL-6, IL-17, TNF-α) while increasing anti-osteoclastogenic cytokines (IL-4, IL-10, IFN-γ) [65, 66], along with the upregulation of Wnt10b expression by CD8+ T cells, which in turn activate Wnt signaling in osteoblasts to stimulate bone formation [67] 2. The concentration of butyrate produced in the gut following LGG administration is linked with the regulation of bone anabolism via Treg cell-mediated CD8+ T cell Wnt10b production [67] | |
Bifidobacterium bifidum FL228.1, Bifidobacterium animalis subsp. Lactis F1-7 [68] | 109 CFU/day for 10 weeks in OVX mice | 1. Both strains prevented OVX-induced bone loss in mice by the mechanisms to protect gut mucosal barrier and reduce pro-inflammatory M1 macrophage growth, thus suppressing excessive osteoclast generation 2. FL228.1 increased the abundance of beneficial bacteria in the colon, including Lactobacillus and Colidextribacter, while F1-7 increased the abundance of Bifidobacterium and decreased the abundance of Desulfovibrio and Ruminococcus in the colon |
Bacillus clausii (commercial spores) [69] | 2 × 108 CFU/day for 6 weeks in OVX mice | The treatment prevented bone loss by skewing Treg/Th17 cell balance (↑Treg, ↓Th17) in the bone marrow and spleen of OVX mice, which resulted in the reduction of proinflammatory cytokines (IL-6, IL-17, IFN-γ, and TNF-α) and increased levels of anti-inflammatory cytokine (IL-10) |
Bacillus subtilis C-3102 [70] | 3.4 × 109 CFU/day for 24 weeks in postmenopausal women without diagnosis of osteoporosis | 1. Compared with placebo, the probiotic treatment lowered urinary NTX and serum TRAP levels at 12 weeks of treatment and increased total hip BMD at the end of 24 weeks of treatment in postmenopausal women 2. The probiotic treatment was shown to modulate gut microbiota by increasing Bifidobacterium and decreasing Fusobacterium abundances |