Probiotics in Gut-Bone Signaling

Schepper, Jonathan D.; Irwin, Regina; Kang, Jun‐Koo; Dagenais, Kevin; Lemon, Tristan; Shinouskis, Ally; Parameswaran, Narayanan; McCabe, Laura R.

doi:10.1007/978-3-319-66653-2_11

Cited by 51 publications

(39 citation statements)

References 103 publications

(191 reference statements)

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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%

“…The Lactobacilli strains LGG and LR are both used as probiotics to benefit the health of mice and humans. (126) Both LR (L. reuteri 6475) and LGG are human-derived strains that do not (in the case of L. reuteri) or are not expected to (in the case of LGG) colonize the mouse gut. Because we did not disrupt the microbiome prior to addition of the probiotics, it is unlikely that the probiotics colonized the gut.…”

Section: Discussionmentioning

confidence: 99%

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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

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134

137

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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%

Section: Discussionmentioning

confidence: 99%

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

Self Cite

134

137

View full text Add to dashboard Cite

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“…antibiotic overuse, exposure to pollution and poor nutritional intake), has led to a ‘dysbiotic drift’ (Logan, 2015). Indeed, dysbiosis or ‘life in distress’ is considered by some researchers to manifest as an imbalance in the microbial assemblages in the human body to a state that is detrimental to health (Logan, Jacka, & Prescott, 2016; Schepper et al, 2017; Sokol et al, 2019). However, it is important to note that the complexities of characterizing ‘dysbiotic’ patterns are considerable and the concept remains controversial.…”

Section: Introductionmentioning

confidence: 99%

Rekindling old friendships in new landscapes: The environment–microbiome–health axis in the realms of landscape research

Robinson

Jørgensen

2020

People and Nature

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1. Humans are spending less time in biodiverse environments, and according to the Old Friends and Biodiversity hypotheses, this has led to fewer interactions with diverse immunoregulatory micro-organisms or 'old friends'.2. Non-communicable diseases such as asthma and inflammatory bowel disease are on the rise, and the development and progression of these 'modern' diseases may be attributed in part, to the breakdown of this evolutionary relationship between humans and environmental microbiota.3. There is a growing interest in the environment-microbiome-health axis as a mechanism to explain some of the health benefits linked to spending time in nature.4. This may provide a platform for proposing a new, holistic and transdisciplinary approach to public and environmental health.5. The field of landscape research-which combines social and natural sciencesresponds to emerging socioecological issues and can make a significant contribution towards this approach.6. This paper explores innovative, landscape research-based approaches to understanding the complex relationships between the environment, the microbiome and human health. 7. Transdisciplinarity will play an important role moving forward. This forms a major discussion point in this paper, along with future research directions, key research questions and novel concepts supported by recent technological advancements.8. The development of a new field of study-Microbioscape Research as a crossover between microbiome science and landscape research-is also discussed.

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“…Since valeric acid is produced by probiotic bacteria 15 , we calculated the Spearman correlation between B.vulgatus and common probiotic bacteria 16,17 Table 6). MR-Egger (intercept) result (p-value = 0.517) showed no horizontal pleiotropy for B.vulgatus to influence valeric acid levels.…”

Section: Scfas Significantly Associated With Bmdmentioning

confidence: 99%

“…https://doi.org/10.1101/2020.03. 16 is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint…”

Section: Gene Expression In Osteoclast-like Cells and Osteoblastsmentioning

confidence: 99%

Gut microbiota impacts bone via B.vulgatus-valeric acid-related pathways

Lin

Xiao

Liu

et al. 2020

Preprint

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Although gut microbiota influences osteoporosis risk, the individual species involved, and underlying mechanisms, are unknown. We performed integrative analyses in a Chinese cohort with metagenomics/targeted metabolomics/whole-genome sequencing. Bacteroides vulgatus was found negatively associated with bone mineral density (BMD), this association was validated in US Caucasians. Serum valeric acid was positively associated with BMD, and B.vulgatus causally downregulated it. Ovariectomized mice fed B.vulgatus had decreased bone formation and increased bone resorption, lower BMD and poorer bone micro-structure. Valeric acid suppressed NF-κB p65 protein production (pro-inflammatory), and enhanced IL-10 mRNA expression (anti-inflammatory), leading to suppressed maturation of osteoclast-like cells, and enhanced maturation of osteoblasts in vitro. B.vulgatus and valeric acid represent promising targets for osteoporosis prevention/treatment.

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Probiotics in Gut-Bone Signaling

Cited by 51 publications

References 103 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

Rekindling old friendships in new landscapes: The environment–microbiome–health axis in the realms of landscape research

Gut microbiota impacts bone via B.vulgatus-valeric acid-related pathways

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