Loss of Bone and Wnt10b Expression in Male Type 1 Diabetic Mice Is Blocked by the Probiotic Lactobacillus reuteri

Abstract

Type 1 diabetes (T1D)-induced osteoporosis is characterized by a predominant suppression of osteoblast number and activity, as well as increased bone marrow adiposity but no change in osteoclast activity. The fundamental mechanisms and alternative anabolic treatments (with few side effects) for T1D bone loss remain undetermined. Recent studies by our laboratory and others indicate that probiotics can benefit bone health. Here, we demonstrate that Lactobacillus reuteri, a probiotic with anti-inflammatory and bone health properties, prevents T1D-induced bone loss and marrow adiposity in mice. We further found that L. reuteri treatment prevented the suppression of Wnt10b in T1D bone. Consistent with a role for attenuated bone Wnt10b expression in T1D osteoporosis, we observed that bone-specific Wnt10b transgenic mice are protected from T1D bone loss. To examine the mechanisms of this protection, we focused on TNF-α, a cytokine up-regulated in T1D that causes suppression of osteoblast Wnt10b expression in vitro. Addition of L. reuteri prevented TNF-α-mediated suppression of Wnt10b and osteoblast maturation markers. Taken together, our findings reveal a mechanism by which T1D causes bone loss and open new avenues for use of probiotics to benefit the bone.

Probiotics protect mice from CoCrMo particles-induced osteolysis

“…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. Treatment with L. casei ameliorated CoPs-induced bone loss and osteoclast formation.…”

Gut microbiota induce IGF-1 and promote bone formation and growth

“…Consistent with this, Sjogren et al found that bacterial colonization of young adult GF animals resulted in loss of trabecular bone mass and an increase in bone-resorbing osteoclasts (13). However, other studies have suggested that treatment with beneficial microbes modestly increases bone mineral density (21)(22)(23)(24)(25)(26) and protects against bone loss after sex steroid deficiency (27). Discrepant results in studies examining the effect of microbiota on bone may reflect differences in the composition of the resident microbiota, age of the animal at colonization and necropsy, mouse strain, and sex.…”

Epithelial Barrier Function in Gut-Bone Signaling

“…The probiotic Lactobacillus reuteri has anti-TNFα properties, reduces gut inflammation, and strengthens gut barrier function in vitro [104][134][147]. When given to mice, L. reuteri treatment was found to increase bone density in healthy male mice in addition to preventing bone loss in both female ovariectomized mice and type 1 diabetic male mice[134][104, 148][149]. Taken together, these data demonstrate the role of the microbiome and intestine in maintaining bone density.…”

“…Intestinal health has been shown to play a key role in the development of T1D [163–165]. Additionally, T1D induced changes in intestinal health and function have been suggested to contribute to further T1D complications, such as osteoporosis [166]. Intestinal changes that have been reported to precede or be caused by T1D which can influence bone health include intestinal barrier function or permeability and the intestinal microbiota [167–174].…”

“…Our lab demonstrated that treatment with the probiotic Lactobacillus reuteri 6475 prevents T1D-induced bone loss in mice; suggesting a role of the gut microbiota in T1D-induce bone loss. Interestingly, the probiotic treatment prevented several of the bone pathologies of T1D including marrow adiposity, suprpressed Wnt10b expression and suppressed osteoblast activity [149]. The prevention of bone loss occurred despite metabolic dysregulation as indicated by high blood glucose levels.…”