ProbioticL. reuteriTreatment Prevents Bone Loss in a Menopausal Ovariectomized Mouse Model

Abstract

Estrogen deficiency is a major risk factor for osteoporosis that is associated with bone inflammation and resorption. Half of women over the age of 50 will experience an osteoporosis related fracture in their lifetime, thus novel therapies are needed to combat post-menopausal bone loss. Recent studies suggest an important role for gut-bone signaling pathways and the microbiota in regulating bone health. Given that the bacterium Lactobacillus reuteri ATCC PTA 6475 (L. reuteri) secretes beneficial immunomodulatory factors, we examined if this candidate probiotic could reduce bone loss associated with estrogen deficiency in an ovariectomized (Ovx) mouse menopausal model. Strikingly, L. reuteri treatment significantly protected Ovx mice from bone loss. Osteoclast bone resorption markers and activators (Trap5 and RANKL) as well as osteoclastogenesis are significantly decreased in L. reuteri treated mice. Consistent with this, L. reuteri suppressed Ovx-induced increases in bone marrow CD4+ T-lymphocytes (which promote osteoclastogenesis) and directly suppressed osteoclastogenesis in vitro. We also identif ied that L. reuteri treatment modifies microbial communities in the Ovx mouse gut. Together, our studies demonstrate that L. reuteri treatment suppresses bone resorption and loss associated with estrogen deficiency. Thus, L. reuteri treatment may be a straightforward and cost-effective approach to reduce post-menopausal bone loss.

Sex steroid deficiency–associated bone loss is microbiota dependent and prevented by probiotics

“…Intriguingly, treatment of ovx mice with the LGGM partially protected ovx mice from bone loss. The SpaC protein was shown by our research group to be necessary for LGG to 15, and Jam3 in the SI of Conv.R, and GF mice, and in Col.GF mice, following either leuprolide (375 μg/ month) or vehicle control treatment for 10 weeks. (E) Measurement of serum endotoxin levels in mice from experimental groups described in A.…”

“…This probiotic prevented the increase in CD4 + T cells induced by ovx, secreted anti-TNF factors, and modified microbial communities in the ovx mouse gut (15).…”

“…Indeed, GF mice have increased bone mass, fewer CD4 + T cells and osteoclast precursors in the BM, and lower levels of osteoclastogenic cytokines (10). In addition, antibiotic administration increases bone density in young mice (11,12), while select probiotics blunt the bone loss that normally ensues following ovariectomy (ovx) (13)(14)(15). However, the molecular mechanisms that mediate and function in probiotic-induced host responses have not yet been fully characterized.…”

Probiotics protect mice from CoCrMo particles-induced osteolysis

“…L. reuteri suppressed Ovx-induced increases in bone marrow CD4 + T-lymphocytes, which promote osteoclastogenesis, and directly suppressed osteoclastogenesis in vitro. 33 In another study, the addition of L. reuteri prevented TNF-α-mediated suppression of Wnt10b and osteoblast maturation markers in type 1 diabetes (T1D)-induced osteoporosis. 34 In this study, we showed that probiotic treatment protected mice from wear debris-induced osteolysis.…”

From the gut to the strut: where inflammation reigns, bone abstains

“…They also inhibit Tnfa and Il6 expression and upregulate Il10 in a collagen-induced arthritis model (22) -effects that are likely exerted via NFκB dephosphorylation (23). Importantly, media from the probiotic Lactobacillus is able to decrease both macrophage Tnfa expression and osteoclastogenesis (24,25). Consistent with these findings, Li et al note that probiotic-fed hypogonadal mice display significant decrements in Tnfa and Rankl in both the intestine and BM (7).…”