scholarly journals Association Between Gut Microbiota and Bone Health: Potential Mechanisms and Prospective

2017 ◽  
Vol 102 (10) ◽  
pp. 3635-3646 ◽  
Author(s):  
Yuan-Cheng Chen ◽  
Jonathan Greenbaum ◽  
Hui Shen ◽  
Hong-Wen Deng
Keyword(s):  
Gut Microbiota ◽  
Bone Metabolism ◽  
Bone Health ◽  
Association Studies ◽  
Evidence Synthesis ◽  
Critical Role ◽  
Mucosal Barrier ◽  
Biological Processes ◽  
The Relationship

Abstract Context It has been well established that the human gut microbiome plays a critical role in the regulation of important biological processes and the mechanisms underlying numerous complex diseases. Although researchers have only recently begun to study the relationship between the gut microbiota and bone metabolism, early efforts have provided increased evidence to suggest an important association. Evidence Acquisition In this study, we attempt to comprehensively summarize the relationship between the gut microbiota and bone metabolism by detailing the regulatory effects of the microbiome on various biological processes, including nutrient absorption and the intestinal mucosal barrier, immune system functionality, the gut–brain axis, and excretion of functional byproducts. In this review, we incorporate evidence from various types of studies, including observational, in vitro and in vivo animal experiments, as well as small efficacy clinic trails. Evidence Synthesis We review the various potential mechanisms of influence for the gut microbiota on the regulation of bone metabolism and discuss the importance of further examining the potential effects of the gut microbiota on the risk of osteoporosis in humans. Furthermore, we outline some useful tools/approaches for metagenomics research and present some prominent examples of metagenomics association studies in humans. Conclusion Current research efforts, although limited, clearly indicate that the gut microbiota may be implicated in bone metabolism, and therefore, further exploration of this relationship is a promising area of focus in bone health and osteoporosis research. Although most existing studies investigate this relationship using animal models, human studies are both needed and on the horizon.

scholarly journals Can Hypoxic Conditioning Improve Bone Metabolism? A Systematic Review

2019 ◽  
Vol 16 (10) ◽  
pp. 1799 ◽  
Author(s):  
Marta Camacho-Cardenosa ◽  
Alba Camacho-Cardenosa ◽  
Rafael Timón ◽  
Guillermo Olcina ◽  
Pablo Tomas-Carus ◽  
...  
Keyword(s):  
Bone Metabolism ◽  
Critical Role ◽  
Hypoxia Inducible Factor ◽  
Experimental Studies ◽  
Hormonal Responses ◽  
Hypoxia Exposure ◽  
Ambient Oxygen ◽  
The Impact

Among other functions, hypoxia-inducible factor plays a critical role in bone–vascular coupling and bone formation. Studies have suggested that hypoxic conditioning could be a potential nonpharmacological strategy for treating skeletal diseases. However, there is no clear consensus regarding the bone metabolism response to hypoxia. Therefore, this review aims to examine the impact of different modes of hypoxia conditioning on bone metabolism. The PubMed and Web of Science databases were searched for experimental studies written in English that investigated the effects of modification of ambient oxygen on bone remodelling parameters of healthy organisms. Thirty-nine studies analysed the effect of sustained or cyclic hypoxia exposure on genetic and protein expression and mineralisation capacity of different cell models; three studies carried out in animal models implemented sustained or cyclic hypoxia; ten studies examined the effect of sustained, intermittent or cyclic hypoxia on bone health and hormonal responses in humans. Different modes of hypoxic conditioning may have different impacts on bone metabolism both in vivo and in vitro. Additional research is necessary to establish the optimal cyclical dose of oxygen concentration and exposure time.

scholarly journals The role of probiotics on the roadmap to a healthy microbiota: a symposium report

2020 ◽  
Vol 1 ◽  
Author(s):  
Stacey Lockyer ◽  
Marisol Aguirre ◽  
Louise Durrant ◽  
Bruno Pot ◽  
Kaori Suzuki
Keyword(s):  
Gut Microbiota ◽  
Endocrine System ◽  
Immune Functions ◽  
Epigenetic Programming ◽  
Microbiome Research ◽  
Probiotic Mechanisms ◽  
The Relationship ◽  
Host Genes

ABSTRACT The ninth International Yakult Symposium was held in Ghent, Belgium in April 2018. Keynote lectures were from Professor Wijmenga on using biobanks to understand the relationship between the gut microbiota and health; and Professor Hill on phage–probiotic interactions. Session one included talks from Professor Plӧsch on epigenetic programming by nutritional and environmental factors; Professor Wilmes on the use of “omics” methodologies in microbiome research and Professor Rescigno on the gut vascular barrier. Session two explored the evidence behind Lactobacillus casei Shirota with Dr Nanno explaining the plasticity in immunomodulation that enables the strain to balance immune functions; Dr Macnaughtan outlining its potential therapeutic use in cirrhosis and Professor Nishida detailing effects in subjects under stress. The third session saw Professor Marchesi describing that both the host genes and the gut microbiota can play a role in cancer; Professor Bergheim highlighting crosstalk between the gut and the liver and Professor Cani describing the relationship between the gut microbiota and the endocrine system. The final session explored probiotic mechanisms, with Professor Lebeer dissecting the challenges in conducting mechanistic studies; Professor Wehkamp describing the mucosal defence system and Professor Van de Wiele detailing methods for modelling the gut microbiota in vitro.

Effects of flavonoids on intestinal inflammation, barrier integrity and changes in gut microbiota during diet-induced obesity

2016 ◽  
Vol 29 (2) ◽  
pp. 234-248 ◽  
Author(s):  
Katherine Gil-Cardoso ◽  
Iris Ginés ◽  
Montserrat Pinent ◽  
Anna Ardévol ◽  
Mayte Blay ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Gut Microbiota ◽  
Intestinal Inflammation ◽  
Mucosal Barrier ◽  
Low Grade ◽  
Protective Effects ◽  
Barrier Integrity ◽  
Diet Induced Obesity

AbstractDiet-induced obesity is associated with low-grade inflammation, which, in most cases, leads to the development of metabolic disorders, primarily insulin resistance and type 2 diabetes. Although prior studies have implicated the adipose tissue as being primarily responsible for obesity-associated inflammation, the latest discoveries have correlated impairments in intestinal immune homeostasis and the mucosal barrier with increased activation of the inflammatory pathways and the development of insulin resistance. Therefore, it is essential to define the mechanisms underlying the obesity-associated gut alterations to develop therapies to prevent and treat obesity and its associated diseases. Flavonoids appear to be promising candidates among the natural preventive treatments that have been identified to date. They have been shown to protect against several diseases, including CVD and various cancers. Furthermore, they have clear anti-inflammatory properties, which have primarily been evaluated in non-intestinal models. At present, a growing body of evidence suggests that flavonoids could exert a protective role against obesity-associated pathologies by modulating inflammatory-related cellular events in the intestine and/or the composition of the microbiota populations. The present paper will review the literature to date that has described the protective effects of flavonoids on intestinal inflammation, barrier integrity and gut microbiota in studies conducted using in vivo and in vitro models.

scholarly journals Personalized Bioconversion of Panax Notoginseng Saponins Mediated by Gut Microbiota Between Chinese-diet and Western-diet Healthy Subjects

2021 ◽  
Author(s):  
Li Wang ◽  
Man-Yun Chen ◽  
Li Shao ◽  
Wei Zhang ◽  
Xiang-Ping Li ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Lactobacillus Rhamnosus ◽  
16S Rrna Gene Sequencing ◽  
Panax Notoginseng ◽  
Rrna Gene ◽  
Bifidobacterium Adolescentis ◽  
Correlative Analysis ◽  
Rrna Gene Sequencing ◽  
The Relationship

Abstract Background: Panax notoginseng saponins (PNS) as the main effective substances from P. notoginseng with low bioavailability could be bio-converted by human gut microbiota. In our previous study, PNS metabolic variations mediated by gut microbiota have been observed between high fat, high protein (HF-HP)-diet and low fat, plant fiber-rich (LF-PF)-diet subjects. In this study, we aimed to correspondingly characterize the relationship between distinct gut microbiota profiles and PNS metabolites. Methods: Gut microbiota were collected from HF-HP and LF-PF healthy adults, respectively and profiled by 16S rRNA gene sequencing. PNS were incubated with gut microbiota in vitro. A LC-MS/MS method was developed to quantify the five main metabolites yields including ginsenoside F1 (GF1), ginsenoside Rh2 (GRh2), ginsenoside compound K (GC-K), protopanaxatriol (PPT) and protopanaxadiol (PPD). The selected microbial species, Bifidobacterium adolescentis and Lactobacillus rhamnosus, were employed to metabolize PNS for the corresponding metabolites.Results: The five main metabolites were significantly different between the two diet groups. Compared with HF-HP group, the microbial genus Blautia, Bifidobacterium, Clostridium, Corynebacterium, Dorea, Enhydrobacter, Lactobacillus, Roseburia, Ruminococcus, SMB53, Streptococcus, Treponema and Weissella were enriched in LF-PF group, while Phascolarctobacterium and Oscillospira were relatively decreased. Furthermore, Spearman’s correlative analysis revealed gut microbiota enriched in LF-PF and HF-HP groups were positively and negatively associated with PNS metabolites yields, respectively. Conclusions: Our data showed gut microbiota diversity led to the personalized bioconversion of PNS.

scholarly journals Gut microbiota, probiotics, prebiotics and bone health: a review

2018 ◽  
Vol 3 ◽  
pp. 101-110
Author(s):  
Nan Shang ◽  
Jianping Wu
Keyword(s):  
Gut Microbiota ◽  
Bone Metabolism ◽  
Bone Health ◽  
Health Management ◽  
Endocrine System ◽  
Pathogen Resistance ◽  
Bone Diseases ◽  
Future Research ◽  
Host Immune System ◽  
Metabolic Bone Diseases

Gut microbiota is widely accepted to play a crucial role to host health via the regulation of many physiological functions, including metabolism, nutrition, pathogen resistance, and immune function. Over the last decades, accumulating evidence has also pinpointed a role for gut microbiota on bone metabolism and the development of metabolic bone diseases, such as osteoporosis. Emerging evidence suggests the potential of gut microbiota as a promising target for bone health management. In this contribution, we have examined the available literature to understand the role of gut microbiota on bone metabolism as well as the underlying mechanisms. Furthermore, the application and effectiveness of using probiotics/prebiotics as means to modify gut microbiota and bone health are discussed. In this relation, animal studies and human trails suggest that alternation of gut microbiota composition can exert the activity of bone metabolism and therefore lead to the change of bone quality. It is believed that gut microbiota regulates bone metabolism via host immune system, endocrine system and mineral absorption. Supplementation with probiotics and prebiotics to both animals and humans has demonstrated promising, but sometimes conflicting results, on bone health. Thus, future research is expected to reveal the influence of the variations in age, gender, dose, delivery method, and treatment duration, among others on the probiotics/prebiotics-targeted bone diseases treatment.

scholarly journals Remodeling of hepatic stellate cells orchestrated the stroma-derived oxaliplatin-resistance through CCN3 paracrine in hepatocellular carcinoma

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Xia Liao ◽  
Yang Bu ◽  
Fan Chang ◽  
Fengan Jia ◽  
Ge Song ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatic Stellate Cells ◽  
Critical Role ◽  
Stellate Cells ◽  
Clinical Samples ◽  
Pathway Activation ◽  
The Relationship

Abstract Background Hepatic stellate cells (HSCs) have a key role in fibrogenesis and in the filtrates of the hepatocellular carcinoma (HCC) stroma, in which they are remodeled and play a critical role in HCC progression. However, the precise role of HSCs trending, infiltration and paracrine in orchestrating the stroma-derived oxaliplatin-resistance in HCC is still vague. Methods The chemo-resistant models were established to explore the correlation between HSC cells and the condition of chemoresistance. The HCC clinical samples were collected to confirm this phenomenon. Then, the relationship between secretory CCN3 from oxaliplatin-resistant HCC and the infiltration of HSCs in associated HCC microenvironment was evaluated. Finally, the role and mechanism of HSCs remodeling in the orchestration of oxaliplatin-resistant HCC were explored. Results The increased infiltration of HSCs and collagen accumulation were found in the microenvironment of oxaliplatin-resistant HCC. The cDNA profiles of the oxaliplatin-resistant HCC was reanalyzed, and CCN3 was one of the significantly increased genes. In HCC clinical samples, the levels of CCN3 and α-SMA are positively correlated, and high expression of CCN3 and α-SMA are positively associated with malignant phenotype and poor prognosis. Then the enhanced abilities of migration and proliferation of HSCs, and elevation of the cytokines paracrine from HSCs relating to HCC malignancy were proved in vitro and in vivo, and which were related to CCN3-ERK signaling pathway activation. Conclusions HSCs remodeling are positively related to CCN3 paracrine in hepatocellular carcinoma, which orchestrated the stroma-derived resistance to chemotherapy in HCC.

scholarly journals Bones and Joints: The Effects of Cannabinoids on the Skeleton

2019 ◽  
Vol 104 (10) ◽  
pp. 4683-4694 ◽  
Author(s):  
Joel Ehrenkranz ◽  
Michael A Levine
Keyword(s):  
Bone Metabolism ◽  
English Language ◽  
Bone Growth ◽  
Evidence Synthesis ◽  
Endocannabinoid System ◽  
Bone Biology ◽  
Design Data ◽  
Transmembrane Receptors

Abstract Context The endocannabinoid system uses tissue-specific lipid ligands and G protein‒coupled transmembrane receptors to regulate neurologic, metabolic, and immune responses. Recent studies demonstrate that the endocannabinoid system influences bone metabolism. With the increasing use of endocannabinoid mimetics (e.g., tetrahydrocannabinol and cannabidiol), the involvement of endocannabinoids in bone growth and remodeling has become clinically relevant. Evidence Acquisition This literature review is based on a search of PubMed and Google Scholar databases as of June 2019 for all English-language publications relating to cannabinoids and bone. We evaluated retrieved articles for relevance, experimental design, data acquisition, statistical analysis, and conclusions. Evidence Synthesis Preclinical studies establish a role for endocannabinoids in bone metabolism. These studies yield complex and often contradictory results attributed to differences in the specific experimental model examined. Studies using human cells or subjects are limited. Conclusions In vitro and animal models document that endocannabinoids are involved in bone biology. The relevance of these observations to humans is not clear. The increasing long-term use of medical and recreational cannabis underscores the need to better understand the role of endocannabinoids in human bone metabolism. Moreover, it is important to evaluate the role of endocannabinoids as a therapeutic target to prevent and treat disorders associated with bone loss.

scholarly journals Endothelial Cells as Tools to Model Tissue Microenvironment in Hypoxia-Dependent Pathologies

2021 ◽  
Vol 22 (2) ◽  
pp. 520
Author(s):  
Aleksandra Majewska ◽  
Kinga Wilkus ◽  
Klaudia Brodaczewska ◽  
Claudine Kieda
Keyword(s):  
Endothelial Cells ◽  
Alternative Methods ◽  
Biological Processes ◽  
Animal Testing ◽  
Tissue Microenvironment ◽  
Vessel Permeability ◽  
Biological Phenomena ◽  
The Relationship ◽  
Different Tissues

Endothelial cells (ECs) lining the blood vessels are important players in many biological phenomena but are crucial in hypoxia-dependent diseases where their deregulation contributes to pathology. On the other hand, processes mediated by ECs, such as angiogenesis, vessel permeability, interactions with cells and factors circulating in the blood, maintain homeostasis of the organism. Understanding the diversity and heterogeneity of ECs in different tissues and during various biological processes is crucial in biomedical research to properly develop our knowledge on many diseases, including cancer. Here, we review the most important aspects related to ECs’ heterogeneity and list the available in vitro tools to study different angiogenesis-related pathologies. We focus on the relationship between functions of ECs and their organo-specificity but also point to how the microenvironment, mainly hypoxia, shapes their activity. We believe that taking into account the specific features of ECs that are relevant to the object of the study (organ or disease state), especially in a simplified in vitro setting, is important to truly depict the biology of endothelium and its consequences. This is possible in many instances with the use of proper in vitro tools as alternative methods to animal testing.

scholarly journals Role of the Microbiome in Regulating Bone Metabolism and Susceptibility to Osteoporosis

2021 ◽  
Author(s):  
Owen Cronin ◽  
Susan A. Lanham-New ◽  
Bernard M. Corfe ◽  
Celia L. Gregson ◽  
Andrea L. Darling ◽  
...  
Keyword(s):  
Bone Metabolism ◽  
Bone Health ◽  
Randomized Clinical Trials ◽  
Research Priorities ◽  
Research Field ◽  
Biological Interactions ◽  
Bone Maintenance ◽  
Modifiable Factors ◽  
The Relationship

AbstractThe human microbiota functions at the interface between diet, medication-use, lifestyle, host immune development and health. It is therefore closely aligned with many of the recognised modifiable factors that influence bone mass accrual in the young, and bone maintenance and skeletal decline in older populations. While understanding of the relationship between micro-organisms and bone health is still in its infancy, two decades of broader microbiome research and discovery supports a role of the human gut microbiome in the regulation of bone metabolism and pathogenesis of osteoporosis as well as its prevention and treatment. Pre-clinical research has demonstrated biological interactions between the microbiome and bone metabolism. Furthermore, observational studies and randomized clinical trials have indicated that therapeutic manipulation of the microbiota by oral administration of probiotics may influence bone turnover and prevent bone loss in humans. In this paper, we summarize the content, discussion and conclusions of a workshop held by the Osteoporosis and Bone Research Academy of the Royal Osteoporosis Society in October, 2020. We provide a detailed review of the literature examining the relationship between the microbiota and bone health in animal models and in humans, as well as formulating the agenda for key research priorities required to advance this field. We also underscore the potential pitfalls in this research field that should be avoided and provide methodological recommendations to facilitate bridging the gap from promising concept to a potential cause and intervention target for osteoporosis.

scholarly journals NEDD4L-induced ubiquitination mediating UBE2T degradation inhibits progression of lung adenocarcinoma via PI3K-AKT signaling

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yongbing Chen ◽  
Haihua Hong ◽  
Qingqing Wang ◽  
Junqiang Li ◽  
Wenfeng Zhang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Half Life ◽  
Critical Role ◽  
E3 Ligase ◽  
Akt Signaling ◽  
Cell Counting ◽  
Cell Progression ◽  
The Relationship

Abstract Background A number of studies have indicated that Ubiquitin-conjugating enzyme E2T (UBE2T), as an oncogene, promotes progression and metastasis of lung cancer, including lung adenocarcinoma (LUAD), but it is completely unknown whether and how UBE2T is ubiquitylated and degraded, and by which E3 ligase. NEDD4L plays a critical role in the regulation of cellular processes of various cancers, most of which is attributed to its E3 ubiquitin ligase function. However, the relationship between NEDD4L and UBE2T in LUAD has not been elucidated. Methods The relationship between NEDD4L and UBE2T in LUAD tissues and cells was found by bioinformatic analyses and immunoblotting. Cell counting kit-8, colony formation assay, half-life analysis and the in vivo ubiquitylation assay, generation of xenograft model were performed to determine how NEDD4L regulates UBE2T and its downstream signaling pathway in vitro and in vivo. Results Bioinformatic analyses found that NEDD4L, as a potential correlation E3 ligase of UBE2T, was negatively correlated with UBE2T in LUAD. Consistently, UBE2T protein half-life was shortened or extended by NEDD4L overexpression or depletion, respectively. NEDD4L inhibited LUAD cell progression in vitro and in vivo via inducing the ubiquitination-mediated UBE2T degradation, which repressed PI3K-AKT signaling. Similarly, NEDD4L predicted a better patient survival, whereas UBE2T predicted a worse survival. Conclusions Collectively, our results reveal that NEDD4L is a novel E3 ligase of UBE2T, which can inhibit PI3K-AKT signaling by targeting for UBE2T ubiquitination and degradation, resulting in repression of LUAD cell progression.

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