Mild stimulatory effect of a probiotic mix on bone mass when treatment is initiated 1.5 weeks after ovariectomy in mice

Abstract

Studies in humans and rodents show that probiotic bacteria can protect from bone loss caused by sex-steroid deficiency. We showed earlier that a mixture of three probiotic bacteria, Lacticaseibacillus paracasei DSM13434, Lactiplantibacillus plantarum DSM 15312 and DSM 15313 (L. Mix) protects mice from ovariectomy (ovx)-induced bone loss when treatment was started two weeks before sham and ovx surgery. In addition, the same probiotic treatment protected against lumbar spine bone loss in early postmenopausal women. In the present study we wanted to evaluate the therapeutic potential of L. Mix by starting treatment 1.5 weeks after ovx when most of the rapid bone loss as a result of estrogen deficiency, has already occurred. Treatment with L. Mix for 5.5 weeks increased the trabecular thickness but not the trabecular number in the proximal metaphyseal region of tibia compared to vehicle treatment. Cortical thickness and cortical area of the mid-diaphyseal part of tibia were decreased in the vehicle-treated ovx mice but not in L. Mix-treated ovx mice compared to sham mice. The bone protective effects of L. Mix in ovx mice were associated with a protection against ovx-induced reduction of the frequency of regulatory T-cells and of the expression of Tgfβ in the bone marrow. In conclusion, the probiotic L. Mix exerted a moderate stimulatory effect on trabecular and cortical bone width when treatment is initiated 1.5 weeks after ovariectomy in mice. This effect was associated with effects on bone protecting regulatory T-cells. The results suggest that L. Mix may exert beneficial effects on bone mass when treatment is started after ovariectomy.

A probiotic mix partially protects against castration-induced bone loss in male mice

“…Mix, we saw a protective effect on bone but no effect on body weight with L . Mix ( Ohlsson et al 2014 , 2021 ). However, the effect of castration on body composition is completely different for male and female mice.…”

“…Teklad diet 2016 does not contain alfalfa or soybean meal, thus minimizing the occurrence of natural phytoestrogens that can interfere in studies of castration-induced bone loss. We made the decision to use the C57BL/6J mouse strain since we used this strain in earlier studies of the effect of probiotic bacteria on castration-induced bone loss and wanted to be able to compare the results ( Ohlsson et al 2014 , 2021 , Lawenius et al 2020 , 2022 ). At 12 weeks of age, the mice were randomized into four groups ( n = 13–15) and subjected to orx or sham surgery under inhalation anesthesia with isoflurane (Baxter Medical AB, Kista, Sweden).…”

“…At 12 weeks of age, the mice were randomized into four groups ( n = 13–15) and subjected to orx or sham surgery under inhalation anesthesia with isoflurane (Baxter Medical AB, Kista, Sweden). The number of mice in each group was decided based on experience from earlier studies with similar treatments and parameters studied ( Ohlsson et al 2014 , 2021 , Lawenius et al 2020 , 2022 ). In these studies, we found small but consistent effects on the bone with the number of observations ranging from 8 to 15 per group.…”

“…We have previously demonstrated that a probiotic mixture of three lactobacilli ( L . Mix) can prevent bone loss in ovariectomized (ovx) female mice and postmenopausal women ( Ohlsson et al 2014 , 2021 , Jansson et al 2019 ). Normal aging in males will cause a decrease in sex hormone levels and bone mass, and hypogonadism is an important risk factor for osteoporosis in men ( Vanderschueren et al 2014 ).…”

New Advances in Improving Bone Health Based on Specific Gut Microbiota

“…The therapeutic use of gut microbes as a target for skeletal diseases has become a current hot topic. Gut microbial dysbiosis is one of the important pathogenic mechanisms underlying primary osteoporosis, and several therapies based on gut microbes are used to alleviate primary osteoporosis ( Ohlsson and Sjögren, 2015 ), such as antibiotics ( Cox et al., 2014 ), probiotics ( Ohlsson et al., 2021 ), prebiotics (oligosaccharides and polysaccharides) ( Porwal et al., 2020 ; Zhang et al., 2021 ), and faecal bacteria transplants ( Ding et al., 2020 ). From the perspective of the gut microbes, which are beneficial to bone health, some studies have found that external factors, as a novel approach, could intervene in the composition of the gut microbes to increase beneficial bacteria and reduce the abundance of bacteria that are detrimental to bone health, and subsequently influence bone metabolism and bone mass changes.…”