<i>Lactobacillus reuteri</i> reduces bone loss in older women with low bone mineral density: a randomized, placebo‐controlled, double‐blind, clinical trial

Nilsson, Anders; Sundh, Daniel; Bäckhed, Fredrik; Lorentzon, Mattias

doi:10.1111/joim.12805

Cited by 209 publications

(214 citation statements)

References 30 publications

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“…(121) In addition to altering the gut microbiome and reducing intestinal inflammation, probiotics are known to promote intestinal barrier function and benefit bone health. (50,(53)(54)(55)(56)(57)63,67,68,71,73,75,76,(122)(123)(124)(125)(126)(127)(128)(129)(130)(131)(132) Consistent with these studies, we found that treatment with LR as well as LGG uniquely altered the microbiota composition, which was significantly different from mice treated with GC alone. We hypothesize that each of these compositions have a different balance of healthy versus disease-promoting bacteria, which could be playing a role in its differential effects on the intestinal barrier and furthermore bone health.…”

Section: Discussionsupporting

confidence: 85%

Involvement of the Gut Microbiota and Barrier Function in Glucocorticoid-Induced Osteoporosis

Schepper

Collins

Rios‐Arce

et al. 2019

Journal of Bone and Mineral Research

125

119

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Glucocorticoids (GCs) are potent immune‐modulating drugs with significant side effects, including glucocorticoid‐induced osteoporosis (GIO). GCs directly induce osteoblast and osteocyte apoptosis but also alter intestinal microbiota composition. Although the gut microbiota is known to contribute to the regulation of bone density, its role in GIO has never been examined. To test this, male C57/Bl6J mice were treated for 8 weeks with GC (prednisolone, GC‐Tx) in the presence or absence of broad‐spectrum antibiotic treatment (ABX) to deplete the microbiota. Long‐term ABX prevented GC‐Tx‐induced trabecular bone loss, showing the requirement of gut microbiota for GIO. Treatment of GC‐Tx mice with a probiotic (Lactobacillus reuteri [LR]) prevented trabecular bone loss. Microbiota analyses indicated that GC‐Tx changed the abundance of Verrucomicobiales and Bacteriodales phyla and random forest analyses indicated significant differences in abundance of Porphyromonadaceae and Clostridiales operational taxonomic units (OTUs) between groups. Furthermore, transplantation of GC‐Tx mouse fecal material into recipient naïve, untreated WT mice caused bone loss, supporting a functional role for microbiota in GIO. We also report that GC caused intestinal barrier breaks, as evidenced by increased serum endotoxin level (2.4‐fold), that were prevented by LR and ABX treatments. Enhancement of barrier function with a mucus supplement prevented both GC‐Tx–induced barrier leakage and trabecular GIO. In bone, treatment with ABX, LR or a mucus supplement reduced GC‐Tx–induced osteoblast and osteocyte apoptosis. GC‐Tx suppression of Wnt10b in bone was restored by the LR and high‐molecular‐weight polymer (MDY) treatments as well as microbiota depletion. Finally, we identified that bone‐specific Wnt10b overexpression prevented GIO. Taken together, our data highlight the previously unappreciated involvement of the gut microbiota and intestinal barrier function in trabecular GIO pathogenesis (including Wnt10b suppression and osteoblast and osteocyte apoptosis) and identify the gut as a novel therapeutic target for preventing GIO. © 2019 American Society for Bone and Mineral Research.

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Section: Discussionsupporting

confidence: 85%

Involvement of the Gut Microbiota and Barrier Function in Glucocorticoid-Induced Osteoporosis

Schepper

Collins

Rios‐Arce

et al. 2019

Journal of Bone and Mineral Research

125

119

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“…Bifidobacterium adolescentis , a human gut commensal bacterium, promoted T H 17 cell induction when colonized in mice . Prior studies have shown probiotics to have potential in limiting sex‐steroid deprivation‐associated bone loss in the aging skeleton . Considering that probiotics can eradicate SFB colonization, our research suggests that this approach could be applied by pediatricians to optimize bone modeling and the attainment of peak bone mass in the growing skeleton.…”

Section: Discussionmentioning

confidence: 89%

“…(144) Prior studies have shown probiotics to have potential in limiting sex-steroid deprivationassociated bone loss in the aging skeleton. (145)(146)(147)(148) Considering that probiotics can eradicate SFB colonization, (140) our research suggests that this approach could be applied by pediatricians to optimize bone modeling and the attainment of peak bone mass in the growing skeleton. Appreciating that the late pubertal/adolescence phase accounts for roughly 40% of peak bone mass accrual, (39)(40)(41)(42) therapeutic interventions supporting normal skeletal growth and maturation have lifelong implications for skeletal health and disease.…”

Section: Discussionmentioning

confidence: 98%

Specific Commensal Bacterium Critically Regulates Gut Microbiota Osteoimmunomodulatory Actions During Normal Postpubertal Skeletal Growth and Maturation

et al. 2020

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The commensal gut microbiota critically regulates immunomodulatory processes that influence normal skeletal growth and maturation. However, the influence of specific microbes on commensal gut microbiota osteoimmunoregulatory actions is unknown. We have shown previously that the commensal gut microbiota enhances TH17/IL17A immune response effects in marrow and liver that have procatabolic/antianabolic actions in the skeleton. Segmented filamentous bacteria (SFB), a specific commensal gut bacterium within phylum Firmicutes, potently induces TH17/IL17A‐mediated immunity. The study purpose was to delineate the influence of SFB on commensal gut microbiota immunomodulatory actions regulating normal postpubertal skeletal development. Two murine models were utilized: SFB‐monoassociated mice versus germ‐free (GF) mice and specific‐pathogen‐free (SPF) mice +/− SFB. SFB colonization was validated by 16S rDNA analysis, and SFB‐induced TH17/IL17A immunity was confirmed by upregulation of Il17a in ileum and IL17A in serum. SFB‐colonized mice had an osteopenic trabecular bone phenotype, which was attributed to SFB actions suppressing osteoblastogenesis and enhancing osteoclastogenesis. Intriguingly, SFB‐colonized mice had increased expression of proinflammatory chemokines and acute‐phase reactants in the liver. Lipocalin‐2 (LCN2), an acute‐phase reactant and antimicrobial peptide, was substantially elevated in the liver and serum of SFB‐colonized mice, which supports the notion that SFB regulation of commensal gut microbiota osteoimmunomodulatory actions are mediated in part through a gut–liver–bone axis. Proinflammatory TH17 and TH1 cells were increased in liver‐draining lymph nodes of SFB‐colonized mice, which further substantiates that SFB osteoimmune‐response effects may be mediated through the liver. SFB‐induction of Il17a in the gut and Lcn2 in the liver resulted in increased circulating levels of IL17A and LCN2. Recognizing that IL17A and LCN2 support osteoclastogenesis/suppress osteoblastogenesis, SFB actions impairing postpubertal skeletal development appear to be mediated through immunomodulatory effects in both the gut and liver. This research reveals that specific microbes critically impact commensal gut microbiota immunomodulatory actions regulating normal postpubertal skeletal growth and maturation. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

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“…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, ).…”

Section: Resultsmentioning

confidence: 99%

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

Liu

Zhao

Yang

et al. 2019

Worldviews Ev Based Nurs

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Background: Calcium homeostasis and bone health are an increasing concern for middleaged and older adults. Many studies have explored the positive effects of probiotics, prebiotics, or synbiotics on serum calcium and bone mineral density (BMD) or other parameters related to bone health. However, the participants, the species, doses and duration of interventions, outcomes, and measurements varied among these studies.Aims: To systematically evaluate the effect of probiotics, prebiotics, or synbiotics on maintaining calcium homeostasis and improving bone health in middle-aged and older adults. . Randomized controlled trials (RCTs) involving probiotics, prebiotics, or synbiotics for middle-aged or older adults were employed for meta-analysis by using RevMan 5.3, and heterogeneity and risk of bias assessment were performed.Results: A total of eight studies, involving 564 participants, were included. Probiotics, prebiotics, or synbiotics supplementation was able to significantly elevate serum calcium levels (0.52 mg/dl, 95% CI [0.38, 0.66]), heterogeneity: p = .13, I 2 = 44%), while the results of metaanalysis failed to support the effects of this supplementation on the parameters related to bone health in middle-aged and older adults, including BMD, parathyroid hormone, osteocalcin, and alkaline phosphatase.Linking Evidence to Action: Probiotics, prebiotics, or synbiotics supplementation exerts a facilitating influence on the level of serum calcium, while the present study has not yet supported the beneficial effects of such interventions on bone health. Therefore, further studies with high-quality RCTs are required to determine the effects of probiotics, prebiotics, or synbiotics supplementation on middle-aged and older adults.

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Lactobacillus reuteri reduces bone loss in older women with low bone mineral density: a randomized, placebo‐controlled, double‐blind, clinical trial

Abstract: Supplementation with L. reuteri 6475 should be further explored as a novel approach to prevent age-associated bone loss and osteoporosis.

Cited by 209 publications

References 30 publications

Involvement of the Gut Microbiota and Barrier Function in Glucocorticoid-Induced Osteoporosis

Involvement of the Gut Microbiota and Barrier Function in Glucocorticoid-Induced Osteoporosis

Specific Commensal Bacterium Critically Regulates Gut Microbiota Osteoimmunomodulatory Actions During Normal Postpubertal Skeletal Growth and Maturation

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

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