Meta-Analysis Reveals Compositional and Functional Microbial Changes Associated with Osteoporosis

Akinsuyi, Oluwamayowa; Roesch, Luiz Fernando Würdig

doi:10.1128/spectrum.00322-23

Cited by 16 publications

(4 citation statements)

References 87 publications

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“…As such, our results are the first to demonstrate that DP treatment for 8 weeks in female mice reduces the relative abundance of Clostridium sensu stricto 1 present within the fecal microbiome from approximately 10% to zero, and there is a strongly significant negative correlation between the relative abundance of Clostridium sensu stricto 1 and distal femur trabecular BV/TV%. In addition, our results support what has previously been reported in the literature, with reductions in the relative abundance of Clostridium sensu stricto 1 being associated with improvements in bone health ( Akinsuyi and Roesch, 2023 ). Future studies will be necessary to better understand the role of Clostridium sensu stricto 1 and the role that this group of bacteria plays in mediating bone health in not only this model of GIO, but bone health in general.…”

Section: Discussionsupporting

confidence: 91%

“…In the random forest models, Clostridium sensu stricto 1 was the third most important genus in both classifying samples into appropriate groups as well as in the regression model to predict BV/TV%. A recent meta-analysis analyzing gut 16S rRNA amplicon data from patients in China and South Korea revealed that Clostridium sensu stricto 1 was significantly elevated in patients with osteoporosis ( Akinsuyi and Roesch, 2023 ). To our knowledge, there have not been previous reports demonstrating the relation between Clostridium sensu stricto 1 and GIO or DP supplementation.…”

Section: Discussionmentioning

confidence: 99%

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Glucocorticoid-induced osteoporosis is prevented by dietary prune in female mice

Chargo,

Neugebauer,

Guzior

et al. 2024

Front. Cell Dev. Biol.

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Glucocorticoid-induced osteoporosis (GIO) is a significant side effect of prolonged glucocorticoid (GC) treatment. Chronic GC treatment also leads to trabecular bone loss and gut microbiota dysbiosis in mice. The gut dysbiosis is mechanistically linked to GIO, which indicates that the microbiota can be targeted to prevent GIO. Prunes, a dried fruit and prebiotic, have emerged in the literature as an effective treatment for sex-steroid deficiency induced osteoporosis (primary osteoporosis). Prunes also significantly alter the composition of the gut microbiota in both rodent models and human studies. Therefore, we tested if dietary prune (DP) supplementation could prevent GC-induced bone loss and affect microbiota composition in an established model of GIO. Sixteen-week-old, skeletally mature, female C57BL/6J mice were treated with a subcutaneous 5 mg placebo or prednisolone pellet for 8 weeks and fed an AIN-93M control diet or a diet modified to include 5, 15, or 25% (w/w) dried California prune powder. As expected, GC treated mice developed significant trabecular bone loss in the distal femur. More importantly, as little as 5% DP supplementation effectively prevented trabecular bone loss. Further, dose dependent increases in trabecular bone volume fraction were observed in GC + 15% and GC + 25% DP mice. Amazingly, in the placebo (non-GC treated) groups, 25% DP supplementation caused a ∼3-fold increase in distal femur trabecular bone volume fraction; this sizable bone response has not been previously observed in healthy mice with gut targeted natural treatments. Along with the striking effect on bone health, GC treatment and 25% DP supplementation led to drastic shifts in gut microbiota composition and several specific changes are strongly associated with bone health. Taken together, these results are the first to demonstrate that DP supplementation effectively prevents the negative effects of prolonged GC therapy on trabecular bone health and strongly associates with shifts in the composition of the gut microbiota.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Glucocorticoid-induced osteoporosis is prevented by dietary prune in female mice

Chargo,

Neugebauer,

Guzior

et al. 2024

Front. Cell Dev. Biol.

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“…Despite growing evidence of significant differences in gut microbiota composition and metabolic function in patients with urticaria compared to healthy populations ( Lu et al., 2019 ; Wang et al., 2021 ; Zhang et al., 2021 ), our study showed for the first time a significant correlation between increased abundance of the genus Intestinibacter and the risk of urticaria development, which was statistically significant even after FDR correction. There is limited research on this flora constituent, and studies have reported that the abundance of Intestinibacter is associated with type 2 diabetes mellitus ( Neri-Rosario et al., 2023 ), Crohn’s disease ( Forbes et al., 2018 ), prenatal depression ( Fang et al., 2023 ), and osteoporosis ( Akinsuyi and Roesch, 2023 ) and is also influenced by the HLA genotype ( Forbes et al., 2018 ), but its definitive role remains unknown. Functional analysis of Intestinibacter has shown that it is able to degrade fucose, suggesting an indirect involvement in intestinal mucus degradation ( Mueller et al., 2021 ), leading to a compromised intestinal barrier that allows microbes and toxins to infiltrate the body’s circulation and skin, triggering an immune response; however, whether there is a link between this activity and the development of urticaria remains to be investigated.…”

Section: Discussionmentioning

confidence: 99%

Association between gut microbiota and pan-dermatological diseases: a bidirectional Mendelian randomization research

Wang,

Yao,

Lin

et al. 2024

Front. Cell. Infect. Microbiol.

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BackgroundGut microbiota has been associated with dermatological problems in earlier observational studies. However, it is unclear whether gut microbiota has a causal function in dermatological diseases.MethodsThirteen dermatological diseases were the subject of bidirectional Mendelian randomization (MR) research aimed at identifying potential causal links between gut microbiota and these diseases. Summary statistics for the Genome-Wide Association Study (GWAS) of gut microbiota and dermatological diseases were obtained from public datasets. With the goal of evaluating the causal estimates, five acknowledged MR approaches were utilized along with multiple testing corrections, with inverse variance weighted (IVW) regression serving as the main methodology. Regarding the taxa that were causally linked with dermatological diseases in the forward MR analysis, reverse MR was performed. A series of sensitivity analyses were conducted to test the robustness of the causal estimates.ResultsThe combined results of the five MR methods and sensitivity analysis showed 94 suggestive and five significant causal relationships. In particular, the genus Eubacterium_fissicatena_group increased the risk of developing psoriasis vulgaris (odds ratio [OR] = 1.32, pFDR = 4.36 × 10−3), family Bacteroidaceae (OR = 2.25, pFDR = 4.39 × 10−3), genus Allisonella (OR = 1.42, pFDR = 1.29 × 10−2), and genus Bacteroides (OR = 2.25, pFDR = 1.29 × 10−2) increased the risk of developing acne; and the genus Intestinibacter increased the risk of urticaria (OR = 1.30, pFDR = 9.13 × 10−3). A reverse MR study revealed insufficient evidence for a significant causal relationship. In addition, there was no discernible horizontal pleiotropy or heterogeneity.ConclusionThis study provides novel insights into the causality of gut microbiota in dermatological diseases and therapeutic or preventive paradigms for cutaneous conditions.

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“…Probiotics are also reported to attenuate age-related bone loss by increasing the relative abundance of SCFA producing bacteria in the gut, which was reflected by the significantly increased concentration of SCFA measured in the stool of aged mice that consumed probiotics [ 42 ]. The mechanism by which SCFAs reduced bone resorption is closely associated with increased intestinal calcium absorption, osteoblast differentiation, and decreasing osteoclast activity [ 43 , 44 ]. Similarly, Yuan et al [ 45 ] observed that Bacteroidetes vulgatus probiotic treatment restored gut microbial composition and subsequently downregulates the Lipopolysaccharide/TLR-4/p-NF-κB pathway.…”

Section: Factors That Alter the Gut Microbiotamentioning

confidence: 99%

Association between Dysbiosis in the Gut Microbiota of Primary Osteoporosis Patients and Bone Loss

Waldbaum,

Xhumari,

Akinsuyi

et al. 2023

Aging and disease

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In recent decades, gut microbiome research has experienced significant growth, driven by technological advances that enable quantifying bacterial taxa with greater precision. Age, diet, and living environment have emerged as three key factors influencing gut microbes. Dysbiosis, resulting from alterations in these factors, may lead to changes in bacterial metabolites that regulate pro- and anti-inflammatory processes and consequently impact bone health. Restoration of a healthy microbiome signature could mitigate inflammation and potentially reduce bone loss associated with osteoporosis or experienced by astronauts during spaceflight. However, current research is hindered by contradictory findings, insufficient sample sizes, and inconsistency in experimental conditions and controls. Despite progress in sequencing technology, defining a healthy gut microbiome across global populations remains elusive. Challenges persist in identifying accurate gut bacterial metabolics, specific taxa, and their effects on host physiology. We suggest greater attention be directed towards this issue in Western countries as the cost of treating osteoporosis in the United States reaches billions of dollars annually, with expenses projected to continue rising.

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Meta-Analysis Reveals Compositional and Functional Microbial Changes Associated with Osteoporosis

Abstract: Osteoporosis is the most common metabolic bone disease associated with aging. Mounting evidence has linked changes in the gut microbiota to the pathophysiology of osteoporosis.

Cited by 16 publications

References 87 publications

Glucocorticoid-induced osteoporosis is prevented by dietary prune in female mice

Glucocorticoid-induced osteoporosis is prevented by dietary prune in female mice

Association between gut microbiota and pan-dermatological diseases: a bidirectional Mendelian randomization research

Association between Dysbiosis in the Gut Microbiota of Primary Osteoporosis Patients and Bone Loss

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