Targeting the gut microbiota-related metabolites for osteoporosis: The inextricable connection of gut-bone axis

Zhang, Yuan-Wei; Wu, Yan; Liu, Xiang-Fei; Chen, Xiao; Su, Jia-Can

doi:10.1016/j.arr.2024.102196

Cited by 25 publications

(8 citation statements)

References 218 publications

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“…Its mechanism of action can directly participate in the control of bone metabolism by regulating the hormone level in vivo and the host immune system. It can also indirectly participate in the regulation of bone metabolism by mediating various endogenous metabolites (such as short chain fatty acids, gut derived serotonin, bioactive peptides) or affecting the intestinal mucosal barrier, and the integrity of the intestinal mucosal barrier is an important bridge mediating the microbe gut bone axis ( Cooney et al, 2020 ; Tu et al, 2023 ; Zhang et al, 2024 ). The gut barrier is crucial to maintain the equilibrium between the gut bacteria and the host, serving as a protective mechanism against harmful microorganisms ( Allaire et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Genus_Ruminococcus and order_Burkholderiales affect osteoporosis by regulating the microbiota-gut-bone axis

Li,

Wang,

Pei

et al. 2024

Front. Microbiol.

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BackgroundThis study aimed to clarify the relationship between the gut microbiota and osteoporosis combining Mendelian randomization (MR) analysis with animal experiments.MethodsWe conducted an analysis on the relationship between differential bacteria and osteoporosis using open-access genome-wide association study (GWAS) data on gut microbe and osteoporosis obtained from public databases. The analysis was performed using two-sample MR analysis, and the causal relationship was examined through inverse variance weighting (IVW), MR Egger, weighted median, and weighted mode methods. Bilateral oophorectomy was employed to replicate the mouse osteoporosis model, which was assessed by micro computed tomography (CT), pathological tests, and bone transformation indexes. Additionally, 16S rDNA sequencing was conducted on fecal samples, while SIgA and indexes of IL-6, IL-1β, and TNF-α inflammatory factors were examined in colon samples. Through immunofluorescence and histopathology, expression levels of tight junction proteins, such as claudin-1, ZO-1, and occludin, were assessed, and conduct correlation analysis on differential bacteria and related environmental factors were performed.ResultsA positive correlation was observed between g_Ruminococcus1 and the risk of osteoporosis, while O_Burkholderiales showed a negative correlation with the risk of osteoporosis. Furthermore, there was no evidence of heterogeneity or pleiotropy. The successful replication of the mouse osteoporosis model was assessed, and it was found that the abundance of the O_Burkholderiales was significantly reduced, while the abundance of g_Ruminococcus was significantly increased in the ovariectomized (OVX)-mice. The intestinal SIgA level of OVX mice decreased, the expression level of inflammatory factors increased, barrier damage occurred, and the content of LPS in the colon and serum significantly increased. The abundance level of O_Burkholderiales is strongly positively correlated with bone formation factors, gut barrier indicators, bone density, bone volume fraction, and trabecular bone quantity, whereas it was strongly negatively correlated with bone resorption factors and intestinal inflammatory factors, The abundance level of g_Ruminococcus shows a strong negative correlation with bone formation factors, gut barrier indicators, and bone volume fraction, and a strong positive correlation with bone resorption factors and intestinal inflammatory factors.ConclusionO_Burkholderiales and g_Ruminococcus may regulate the development of osteoporosis through the microbiota-gut-bone axis.

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Section: Discussionmentioning

confidence: 99%

Genus_Ruminococcus and order_Burkholderiales affect osteoporosis by regulating the microbiota-gut-bone axis

Li,

Wang,

Pei

et al. 2024

Front. Microbiol.

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“…(2) enhancing the investment and construction of nutritional departments in hospitals or health care units and further emphasizing the significance of nutritional support for maintaining resident health; and (3) strengthening the formulation and updating of clinical guidelines related to dietary nutrients, thereby guiding clinical practice more effectively (Saunders et al, 2023;Zhang, Wu, et al, 2024).…”

Section: Discussionmentioning

confidence: 99%

“…Hence, it is of great clinical significance to investigate the link between the risk of osteoporosis and dietary folic acid intake in the middle‐aged and elderly population and further explore relevant intervention measures to promote dietary folic acid intake based on this. Specifically, the following measures could more intuitively integrate dietary recommendations into current medical practices, including (1) Integrating nutritional interventions for dietary folic acid intake with healthcare systems to provide more sources of nutrient intake; (2) enhancing the investment and construction of nutritional departments in hospitals or health care units and further emphasizing the significance of nutritional support for maintaining resident health; and (3) strengthening the formulation and updating of clinical guidelines related to dietary nutrients, thereby guiding clinical practice more effectively (Saunders et al., 2023 ; Zhang, Wu, et al., 2024 ).…”

Section: Discussionmentioning

confidence: 99%

Linking the relationship between dietary folic acid intake and risk of osteoporosis among middle‐aged and older people: A nationwide population‐based study

Zhang,

Hu,

Wang

et al. 2024

Food Science & Nutrition

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Among middle‐aged and older people, balanced and nutritious diets are the foundation for maintaining bone health and preventing osteoporosis. This study is aimed at investigating the link between dietary folic acid intake and the risk of osteoporosis among middle‐aged and older people. A total of 20,686 people from the National Health and Nutritional Examination Survey (NHANES) 2007–2010 are screened and included, and 5312 people aged ≥45 years with integral data are ultimately enrolled in evaluation. Demographics and dietary intake‐related data are gathered and analyzed, and the odds ratio (OR) and 95% confidence interval (CI) of each tertile category of dietary folic acid intake and each unit increase in folic acid are assessed via multivariate logistic regression models. On this basis, the receiver operating characteristic (ROC) curve is used to identify the optimal cutoff value of dietary folic acid intake for indicating the risk of osteoporosis. Of 5312 people with a mean age of 62.4 ± 11.0 years old, a total of 513 people with osteoporosis are screened, and the dietary folic acid intake amount of the osteoporosis group is significantly lower than that of the non‐osteoporosis group (p < .001). The lowest tertile category is then used to act as a reference category, and a higher dietary folic acid intake amount is observed to be positively related to lower odds for risk of osteoporosis. This trend is also not changed in adjustments for combinations of different covariates (p all < .05). Based on this, a dietary folic acid intake of 475.5 μg/day is identified as an optimal cutoff value for revealing osteoporosis. Collectively, this nationwide population‐based study reveals that a higher daily dietary folic acid intake has potential protective effects on osteoporosis in middle‐aged and older people.

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“…14,15 The underlying mechanisms by which gut microbiota regulates OP include modulation of inorganic salt and mineral absorption, levels of growth factors and hormones, as well as restoration and maintenance of the intestinal epithelial barrier. [16][17][18][19][20] Gut microbiotaderived metabolites may be the dominant drivers in the above "brain-gut-bone axis." Several important microbial metabolites including short-chain fatty acids (SCFAs), trimethylamine-N-oxide (TMAO), and secondary bile acids have been proved to affect bone metabolism by regulating oxidative stress and osteoimmunity.…”

Section: Introductionmentioning

confidence: 99%

Gut microbially produced tryptophan metabolite melatonin ameliorates osteoporosis via modulating SCFA and TMAO metabolism

Chen,

Yang,

Deng

et al. 2024

Journal of Pineal Research

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Osteoporosis (OP) is a severe global health issue that has significant implications for productivity and human lifespan. Gut microbiota dysbiosis has been demonstrated to be closely associated with OP progression. Melatonin (MLT) is an important endogenous hormone that modulates bone metabolism, maintains bone homeostasis, and improves OP progression. Multiple studies indicated that MLT participates in the regulation of intestinal microbiota and gut barrier function. However, the promising effects of gut microbiota‐derived MLT in OP remain unclear. Here, we found that OP resulted in intestinal tryptophan disorder and decreased the production of gut microbiota‐derived MLT, while administration with MLT could mitigate OP‐related clinical symptoms and reverse gut microbiota dysbiosis, including the diversity of intestinal microbiota, the relative abundance of many probiotics such as Allobaculum and Parasutterella, and metabolic function of intestinal flora such as amino acid metabolism, nucleotide metabolism, and energy metabolism. Notably, MLT significantly increased the production of short‐chain fatty acids and decreased trimethylamine N‐oxide‐related metabolites. Importantly, MLT could modulate the dynamic balance of M1/M2 macrophages, reduce the serum levels of pro‐inflammatory cytokines, and restore gut‐barrier function. Taken together, our results highlighted the important roles of gut microbially derived MLT in OP progression via the “gut‐bone” axis associated with SCFA metabolism, which may provide novel insight into the development of MLT as a promising drug for treating OP.

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Targeting the gut microbiota-related metabolites for osteoporosis: The inextricable connection of gut-bone axis

Cited by 25 publications

References 218 publications

Genus_Ruminococcus and order_Burkholderiales affect osteoporosis by regulating the microbiota-gut-bone axis

Genus_Ruminococcus and order_Burkholderiales affect osteoporosis by regulating the microbiota-gut-bone axis

Linking the relationship between dietary folic acid intake and risk of osteoporosis among middle‐aged and older people: A nationwide population‐based study

Gut microbially produced tryptophan metabolite melatonin ameliorates osteoporosis via modulating SCFA and TMAO metabolism

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