Effect of <i>Bacillus subtilis</i> C-3102 on bone mineral density in healthy postmenopausal Japanese women: a randomized, placebo-controlled, double-blind clinical trial

Abstract

Gut microbiota influence the host immune system and are associated with various diseases. In recent years, postmenopausal bone loss has been suggested to be related to gut microbiota. In the present study, we investigated the treatment effect of the probiotic Bacillus subtilis C-3102 (C-3102) on bone mineral density (BMD) and its influence on gut microbiota in healthy postmenopausal Japanese women. Seventy-six healthy postmenopausal Japanese women were treated with a placebo or C-3102 spore-containing tablets for 24 weeks. When compared with the placebo, C-3102 significantly increased total hip BMD (placebo = 0.83 ± 0.63%, C-3102 = 2.53 ± 0.52%, p=0.043). There was a significant group-by-time interaction effect for urinary type I collagen cross-linked N-telopeptide (uNTx) (p=0.033), a marker of bone resorption. Specifically, the C-3102 group showed significantly lower uNTx when compared with the placebo group at 12 weeks of treatment (p=0.015). In addition, in the C-3102 group, there was a trend towards a decrease in the bone resorption marker tartrate-resistant acid phosphatase isoform 5b (TRACP-5b) when compared with the placebo group at 12 weeks of treatment (p=0.052). The relative abundance of genus Bifidobacterium significantly increased at 12 weeks of treatment compared with the baseline in the C-3102 group. The relative abundance of genus Fusobacterium was significantly decreased in the C-3102 group at 12 and 24 weeks of treatment compared with the baseline. These data suggested that C-3102 improves BMD by inhibiting bone resorption and modulating gut microbiota in healthy postmenopausal women.

The gut-bone axis: how bacterial metabolites bridge the distance

“…Among them is the enhanced production of antimicrobial peptides by intestinal mac-31). Accordingly, individuals following a vegan or vegetarian diet, or those on a Mediterranean diet, have higher levels of SCFAs (32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45), and studies have indicated that these diets are beneficial to bone health (46,47).…”

“…Another trial with a multispecies probiotic showed a significant reduction in bone turnover, but no significant changes in BMD, perhaps because the trial duration was only 6 months (42). A 1-year-long trial in older women revealed evidence of a favorable change in bone mass in response to probiotic supplementation (43), and in a study in Japanese women, the probiotic Bacillus subtilis C-3102 increased total hip bone BMD by decreasing bone resorption (44).…”

Helicobacter pylori Related Diseases and Osteoporotic Fractures (Narrative Review)

“…Restoring a balanced gut microbiota is considered as a therapeutic tool for various diseases, including OP [ 695 , 730 , 731 , 732 , 733 , 734 , 735 , 736 , 737 ]. Recent studies showed that probiotic and prebiotic supplementation increases bone density in healthy individuals, protects against primary and secondary OP [ 687 , 695 , 699 , 734 , 738 , 739 , 740 ] and exerts beneficial effects in many other extra-digestive diseases [ 740 ]. However, despite the established impact of the gut microbiota on host (patho-) physiology, the potential roles of HPI- and medications-induced gut dysbiosis is not mentioned in current guidelines for OP.…”

Effects of Probiotics, Prebiotics, and Synbiotics on Calcium Homeostasis and Bone Health With Aging: A Systematic Review

“…The numbers of participants were similar and were divided randomly into the intervention group and the control group, among which seven studies were designed as double‐blind trials, and three studies were used cross‐control experiments. The studies met the inclusion were performed in six countries, including America (Holloway et al, ), Japan (Takimoto et al, ), Sweden (Nilsson, Sundh, Backhed, & Lorentzon, ), Taiwan (Tu et al, ), India (Gohel et al, ), and Iran (Asemi et al, ; Farhangi et al, ; Jafarnejad et al, ).…”

“…The values of baseline and end point of serum calcium level ( n = 5) and BMD ( n = 4) were reported in the majority of these trials. Two of the four studies reported BMD was included owing to T score report, and the other two studies were excluded from meta‐analysis because of the relative alteration of reported BMD between baseline and end point (Nilsson et al, ; Takimoto et al, ). Finally, six studies were preserved for meta‐analysis (Asemi et al, ; Farhangi et al, ; Gohel et al, ; Holloway et al, ; Jafarnejad et al, ; Tu et al, ).…”