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

Journal of Pineal Research, Год журнала: 2024, Номер 76(3)

Опубликована: Апрель 1, 2024

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

Язык: Английский

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The mechanism of action of indole-3-propionic acid on bone metabolism

Food & Function, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

IPA binds to AhR and PXR receptors, regulating bone metabolic disorders.

Язык: Английский

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Gut-bone axis perturbation: Mechanisms and interventions via gut microbiota as a primary driver of osteoporosis

Journal of Orthopaedic Translation, Год журнала: 2025, Номер 50, С. 373 - 387

Опубликована: Янв. 1, 2025

Язык: Английский

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Gut Microbiota-Bone Axis

Annals of Nutrition and Metabolism, Год журнала: 2025, Номер unknown, С. 1 - 10

Опубликована: Янв. 23, 2025

Knowledge of the complex interplay between gut microbiota and human health is gradually increasing as it has just recently been a field such great interest. Recent studies have reported that communities microorganisms inhabiting influence immune system through cellular responses shape many physiological pathophysiological aspects body, including muscle bone metabolism (formation resorption). Specifically, affects skeletal homeostasis changes in host metabolism, system, hormone secretion, gut-brain axis. The major role on gut-bone axis due to short-chain fatty acids (SCFAs). They ability regulatory T-cell (Tregs) development activate action Wnt10. SCFA production may be mechanism by which microbial community, serum level insulin-like growth factor 1 (IGF-1), leads regulation homeostasis. A specific SCFA, butyrate, diffuses into marrow where expands Tregs. Tregs induce Wnt ligand Wnt10b CD8+ T cells, leading activation signaling stimulation formation. At hormonal level, effect expressed biphasic serotonin. Some microbiota, spore-forming microbes, regulate serotonin gut, serum, feces. Another group bacterial species (Lactococcus, Mucispirillum, Lactobacillus, Bifidobacterium) can increase peripheral/vascular leptin, turn manages brain

Язык: Английский

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Gut–X axis

iMeta, Год журнала: 2025, Номер 4(1)

Опубликована: Фев. 1, 2025

Abstract Recent advances in understanding the modulatory functions of gut and microbiota on human diseases facilitated our focused attention contribution to pathophysiological alterations many extraintestinal organs, including liver, heart, brain, lungs, kidneys, bone, skin, reproductive, endocrine systems. In this review, we applied “gut–X axis” concept describe linkages between other organs discussed latest findings related axis,” underlying mechanisms potential clinical intervention strategies.

Язык: Английский

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Irisin alleviates obesity-induced bone loss by inhibiting interleukin 6 expression via TLR4/MyD88/NF-κB axis in adipocytes

Journal of Advanced Research, Год журнала: 2024, Номер unknown

Опубликована: Апрель 1, 2024

Obesity-induced bone loss affects the life quality of patients all over world. Irisin, one myokines, plays an essential role in and fat metabolism. Investigate effects irisin on metabolism via adipocytes marrow microenvironment. In this study, we fed fibronectin type III domain-containing protein 5 (FNDC5, precursor irisin) knockout mice (FNDC5-/-) with a high-fat diet (HFD) for 10 weeks. The mass was assessed by micro-CT analysis, histological staining, dynamic formation. vitro, lipogenic differentiation mesenchymal stem cells (BMSCs) assayed Oil Red O osteogenic alkaline phosphatase staining. Meanwhile, gene expression BMSC-differentiated RNA sequence involved pathway were determined western blot qRT-PCR performed. FNDC5-/- HFD showed increased body weight, content bone, decreased formation compared those standard (SD). inhibited BMSCs into alleviated inhibition osteogenesis derived from adipocyte supernatant. blocking experiment that reduced production interleukin 6 (IL-6) through downregulating TLR4/MyD88/NF-κB pathway. Immunofluorescence staining further confirmed IL-6 SD, which suffered serious loss. Irisin downregulates activation pathway, thereby reducing to enhance BMSCs. Thus, rescue BMSCs, initially IL-6, is potential therapeutic target mitigate obesity-induced osteoporosis.

Язык: Английский

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

Food Science & Nutrition, Год журнала: 2024, Номер 12(6), С. 4110 - 4121

Опубликована: Март 5, 2024

Among middle-aged and older people, balanced nutritious diets are the foundation for maintaining bone health preventing osteoporosis. This study is aimed at investigating link between dietary folic acid intake risk of osteoporosis among people. A total 20,686 people from National Health Nutritional Examination Survey (NHANES) 2007-2010 screened included, 5312 aged ≥45 years with integral data ultimately enrolled in evaluation. Demographics intake-related gathered analyzed, odds ratio (OR) 95% confidence interval (CI) each tertile category unit increase assessed via multivariate logistic regression models. On this basis, receiver operating characteristic (ROC) curve used to identify optimal cutoff value indicating Of a mean age 62.4 ± 11.0 old, 513 screened, amount group significantly lower than that non-osteoporosis (

Язык: Английский

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

Frontiers in Microbiology, Год журнала: 2024, Номер 15

Опубликована: Май 21, 2024

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

Язык: Английский

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Exercise ameliorates osteopenia in mice via intestinal microbial-mediated bile acid metabolism pathway

Theranostics, Год журнала: 2025, Номер 15(5), С. 1741 - 1759

Опубликована: Янв. 2, 2025

Rationale: Physical exercise is essential for skeletal integrity and bone health. The gut microbiome, as a pivotal modulator of overall physiologic states, closely associated with homeostasis metabolism. However, the potential role intestinal microbiota in exercise-mediated gain remains unclear. Methods: We conducted depletion fecal transplantation (FMT) ovariectomy (OVX) mice aged to investigate whether transfer ecological traits could confer exercise-induced protective effects. study analyzed metabolic profiles via 16S rRNA gene sequencing LC-MS untargeted metabolomics identify key microbial communities metabolites responsible protection. Transcriptome RNA interference were employed explore molecular mechanisms. Results: found that hindered osteogenic benefits exercise, FMT from exercised osteoporotic effectively mitigated osteopenia. Comprehensive profiling microbiome metabolome revealed exercise-matched reshaped microecology landscape. Notably, alterations bile acid metabolism, specifically enrichment taurine ursodeoxycholic acid, mediated effects on mass. Mechanistically, activated apelin signaling pathway restored bone-fat balance recipient MSCs. Conclusion: Our underscored important microbiota-metabolic axis gain, heralding breakthrough treatment osteoporosis.

Язык: Английский

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Clinical correlation between intestinal flora profiles and the incidence of postmenopausal osteoporosis

Gynecological Endocrinology, Год журнала: 2025, Номер 41(1)

Опубликована: Фев. 14, 2025

Purpose This study aimed to explore the characteristics of intestinal microflora polymorphism in postmenopausal women, and determine pathophysiological changes gene flora bone metabolism osteoporosis (PMOP) patients.

Язык: Английский

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