scholarly journals The Microbial Metagenome and Tissue Composition in Mice with Microbiome-Induced Reductions in Bone Strength

2019 ◽  
Author(s):  
Jason D Guss ◽  
Erik Taylor ◽  
Zach Rouse ◽  
Sebastian Roubert ◽  
Catherine H Higgins ◽  
...  
Keyword(s):  
Bone Strength ◽  
Vitamin K ◽  
Gut Microbiome ◽  
Bone Matrix ◽  
Bone Geometry ◽  
The Body ◽  
Metagenomic Analysis ◽  
Limited Information ◽  
Genetic Components ◽  
Microbial Genes

ABSTRACTThe genetic components of microbial species that inhabit the body are known collectively as the microbiome. Modifications to the microbiome have been implicated in disease processes throughout the body and have recently been shown to influence bone. Prior work has associated changes in the microbial taxonomy (phyla, class, species, etc.) in the gut with bone phenotypes but has provided limited information regarding mechanisms. With the goal of achieving a more mechanistic understanding of the effects of the microbiome on bone, we perform a metagenomic analysis of the gut microbiome that provides information on the functional capacity of the microbes (all microbial genes present) rather than only characterizing the microbial taxa. Male C57Bl/6 mice were subjected to disruption of the gut microbiota (ΔMicrobiome) using oral antibiotics (from 4-16 weeks of age) or remained untreated (n=6-7/group). Disruption of the gut microbiome in this manner has been shown to lead to reductions in tissue mechanical properties and whole bone strength in adulthood with only minor changes in bone geometry and density. ΔMicrobiome led to modifications in the abundance of microbial genes responsible for the synthesis of the bacterial cell wall and capsule; bacterially synthesized carbohydrates; and bacterially synthesized vitamins (B and K) (p <0.01). Follow up analysis focused on vitamin K, a factor that has previously been associated with bone health. The vitamin K content of the cecum, liver and kidneys was primarily microbe-derived forms of vitamin K (menaquinones) and was decreased by 32-66% in ΔMicrobiome mice compared to untreated animals (p < 0.01). Bone mineral crystallinity was decreased (p=0.01) was decreased in ΔMicrobiome mice (p < 0.001) and matrix carbonate-phosphoate ratio was increased. This study illustrates the use of metagenomic analysis to link the microbiome to bone phenotypes and implicates microbially synthesized vitamin-K as a regulator of bone matrix quality.

scholarly journals Modifying the Gut Microbiome Through Diet or Antibiotics Alters Bone Phenotypes in Older Mice

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 1184-1184
Author(s):  
Kelsey Smith ◽  
Macy Castaneda ◽  
Chia-Fang Tsai ◽  
Sarah Francisco ◽  
Jacob Nixon ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Bone Tissue ◽  
Bone Strength ◽  
Antibiotic Treatment ◽  
Gut Microbiome ◽  
Bone Geometry ◽  
The Other ◽  
Oral Antibiotic ◽  
Tissue Quality ◽  
Section Modulus

Abstract Objectives Gut microbiota have been shown to influence bone quality and quantity, both risk determinants for osteoporosis. Previous research in young mice showed oral antibiotic treatment during rapid bone gain impaired bone tissue quality. We sought to determine if modifying the gut microbiome of aged mice through diet or antibiotic treatment affects bone geometry and/or strength. Methods A high (HG) or low glycemic (LG) diet was fed in equal amounts to 12-mo. male mice. The diets differed only by starch composition, which was 100% rapidly digested amylopectin in the HG diet or 30% amylopectin/70% amylose in the LG diet. A third group received the LG diet containing antibiotics (ampicillin and neomycin; LGAbx). Feces were collected at baseline and after 10 months of treatment and 16s rRNA sequencing was performed followed by ecological diversity and differential abundance analysis. Femora were harvested after 12 months of treatment for analysis of bone geometry and strength via mechanical testing and imaging. Results Antibiotic treatment reduced alpha diversity, including an average 92% reduction in observed OTUs from baseline compared with 30% reduction in the other groups. Both diet and antibiotic treatment significantly altered taxonomic composition, including an expansion of Proteobacteria in response to antibiotics. Whole bone strength is determined by a combination of the section modulus (the measure of geometry most closely related to bending strength) and the mechanical properties of the bone tissue itself. In HG-fed mice the section modulus was greater than that of the other groups and the bone showed a correspondingly greater strength. However, in LGAbx-fed mice the whole bone strength was 22% lower than bones with similar section modulus in the LG and HG-fed groups, indicating impaired bone tissue material properties. Conclusions Altering diet resulted in significant changes to bone geometry and strength, while changes in the gut microbiota associated with antibiotic treatment resulted in a reduction to bone strength which could not be explained by bone geometry. Our study indicates that dietary or antibiotics treatments applied to mice later in life can alter bone properties, which suggests that interventions to improve bone strength may be effective in older adults. Funding Sources NIH/NIAMS, BrightFocus Foundation, Stanley N. Gershoff Scholarship.

scholarly journals Efficacy of targeting bone-specific GIP receptor in ovariectomy-induced bone loss

2018 ◽  
Vol 239 (2) ◽  
pp. 215-227 ◽  
Author(s):  
Guillaume Mabilleau ◽  
Benoit Gobron ◽  
Aleksandra Mieczkowska ◽  
Rodolphe Perrot ◽  
Daniel Chappard
Keyword(s):  
Bone Loss ◽  
Bone Strength ◽  
Bone Remodelling ◽  
Bone Matrix ◽  
The Body ◽  
Whole Body ◽  
Matrix Composition ◽  
Carbonate Substitution ◽  
Alendronate Treatment ◽  
Gip Receptor

Glucose-dependent insulinotropic polypeptide (GIP) has been recognized in the last decade as an important contributor of bone remodelling and is necessary for optimal bone quality. However, GIP receptors are expressed in several tissues in the body and little is known about the direct vs indirect effects of GIP on bone remodelling and quality. The aims of the present study were to validate two new GIP analogues, called [d-Ala2]-GIP-Tag and [d-Ala2]-GIP1–30, which specifically target either bone or whole-body GIP receptors, respectively; and to ascertain the beneficial effects of GIP therapy on bone in a mouse model of ovariectomy-induced bone loss. Both GIP analogues exhibited similar binding capacities at the GIP receptor and intracellular responses as full-length GIP1–42. Furthermore, only [d-Ala2]-GIP-Tag, but not [d-Ala2]-GIP1–30, was undoubtedly found exclusively in the bone matrix and released at acidic pH. In ovariectomized animals, [d-Ala2]-GIP1–30 but not [d-Ala2]-GIP-Tag ameliorated bone stiffness at the same magnitude than alendronate treatment. Only [d-Ala2]-GIP1–30 treatment led to significant ameliorations in cortical microarchitecture. Although alendronate treatment increased the hardness of the bone matrix and the type B carbonate substitution in the hydroxyapatite crystals, none of the GIP analogues modified bone matrix composition. Interestingly, in ovariectomy-induced bone loss, [d-Ala2]-GIP-Tag failed to alter bone strength, microarchitecture and bone matrix composition. Overall, this study shows that the use of a GIP analogue that target whole-body GIP receptors might be useful to improve bone strength in ovariectomized animals.

scholarly journals Evaluating Metagenomic Analysis for Pathogen Transmission in Healthcare Settings

2020 ◽  
Vol 41 (S1) ◽  
pp. s224-s224
Author(s):  
Curt Hewitt ◽  
Katharina Weber ◽  
Danielle LeSassier ◽  
Anthony Kappell ◽  
Kathleen Schulte ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Dna Analysis ◽  
Pathogen Transmission ◽  
Species Level ◽  
Metagenomic Analysis ◽  
Skin Microbiome ◽  
Limited Information ◽  
Culture Methods ◽  
Data Set ◽  
Skin Contact

Background: The prevalence of healthcare-acquired infections (HAIs) and rising levels of antimicrobial resistance place a significant burden on modern healthcare systems. Cultures are typically used to track HAIs; however, culture methods provide limited information and are not applicable to all pathogens. Next-generation sequencing (NGS) can detect and characterize pathogens present within a sample, but few research studies have explored how NGS could be used to detect pathogen transmission events under HAI-relevant scenarios. The objective of this CDC-funded project was to evaluate and correlate sequencing approaches for pathogen transmission with standard culture-based analysis. Methods: We modeled pathogen transfer via hand contact using synthetic skin. These skin coupons were seeded with a community of commensal organisms to mimic the human skin microbiome. Pathogens were added at physiologically relevant high or low levels prior to skin-to-skin contact. The ESKAPE pathogens: E. faecium, S. aureus, K. pneumoniae, A. baumannii, P. aeruginosa, and Enterobacter spp plus C. difficile were employed because they are the most common antibiotic resistant HAIs. Pathogen transfer between skin coupons was measured following direct skin contact and fomite surface transmission. The effects of handwashing or fomite decontamination were also evaluated. Transferred pathogens were enumerated via culture to establish a robust data set against which DNA and RNA sequence analyses of the same samples could be compared. These data also provide a quantitative assessment of individual ESKAPE+C pathogen transfer rates in skin contact scenarios. Results: Metagenomic and metatranscriptomic analysis using custom analysis pipelines and reference databases successfully identified the commensal and pathogenic organisms present in each sample at the species level. This analysis also identified antibiotic resistance genes and plasmids. Metatranscriptomic analysis permitted not only gene identification but also confirmation of gene expression, a critical factor in the evaluation of antibiotic resistance. DNA analysis does not require cell viability, a key differentiator between sequencing and culturing reflected in simulated handwashing data. Sensitivity remains a key limitation of metagenomic analysis, as shown by the poor species identification and gene content characterization of pathogens present at low abundance within the simulated microbial community. Species level identification typically failed as ratios fell below 1:1,000 pathogen CFU:total community CFU. Conclusions: These findings demonstrate the strengths and weaknesses of NGS for molecular epidemiology. The data sets produced for this study are publicly available so they can be employed for future metagenomic benchmarking studies.Funding: NoneDisclosures: None

Vitamin D and sleep duration: Is there a bidirectional relationship?

2020 ◽  
Vol 41 (4) ◽  
Author(s):  
Maryam Mosavat ◽  
Aisling Smyth ◽  
Diana Arabiat ◽  
Lisa Whitehead
Keyword(s):  
Vitamin D ◽  
Sleep Duration ◽  
Vitamin D Supplementation ◽  
The Body ◽  
Bone Homeostasis ◽  
Limited Information ◽  
Physiological Processes ◽  
Vitamin D Levels ◽  
Bidirectional Relationship ◽  
Sleep Length

AbstractVitamin D contributes to numerous physiological processes within the body but primarily calcium and bone homeostasis. Emerging evidence highlights a novel role for vitamin D in maintaining and regulating optimal sleep. Sleep is a known regulator of bone health, highlighting the interconnectedness between vitamin D concentrations, sleep duration and bone metabolism. It is possible that the relationship between sleep length and vitamin D is bidirectional, with vitamin D playing a role in sleep health and conversely, sleep affecting vitamin D levels. Nevertheless, limited information on the direction of the interaction is available, and much remains to be learned concerning the complex relationship between insufficient sleep duration and vitamin D deficiency. Given the potential to implement interventions to improve sleep and vitamin D supplementation, understanding this relationship further could represent a novel way to support and improve health.

scholarly journals Adopting seasonal regimen (Ritucharya) to modulate the seasonal variation in gut microbiome

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Deepthi. R ◽  
Vandana Rani M ◽  
Delvin T. Robin ◽  
Anusree Dileep
Keyword(s):  
Public Health ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Health Management ◽  
Disease Process ◽  
The Body ◽  
Leaky Gut ◽  
Human Gut ◽  
Extrinsic Factors ◽  
Application Prospects

AbstractThe science of Ayurveda with its strong and unique fundamentals holds its domain forever amidst all scientific and medical advancements. The concept of Shadkriyakala (the different phases of disease formation) holds relevance in preventive medicine and public health management as it provides ample chance to halt the disease process at each stage by timely intervention. In this review, we would like to bring to the limelight the relevance of Ritucharya (seasonal regimen) in primary prevention by modulating the gut microbiota. The modern gut microbiome researches now help us to better explore the Ayurveda theories of Agni (digestive fire) and Ama (metabolic toxins) preached centuries back. Ayurveda firmly proclaims that no disease ever arises without the derangement of Agni (digestive fire). The whole preventive and treatment methodology in Ayurveda focuses upon the modulation and management of “Agni” (digestive fire). When the functioning of Agni is deranged, Ama (metabolic toxin) is produced and it vitiates the doshas which spread throughout the body and manifest as varied diseases. A biomedical perspective of our reviews suggests that dysbiosis of microbial flora can cause a leaky gut by which the toxins of deranged digestive metabolism enter the bloodstream. Consequently, an inflammatory response occurs within the body which expresses out as diseases opportunistically. We meticulously reviewed the influence of extrinsic factors namely diet and climate on human gut microbiota, and our analysis emphasises the application prospects of Ritucharya (seasonal regimen), in regulating the dynamic host-microbe interaction.

Vibrational Analysis of Human Femur Bone

2018 ◽  
Author(s):  
Reza Sadeghi ◽  
Firooz Bakhtiari-Nejad ◽  
Taha Goudarzi
Keyword(s):  
Natural Frequencies ◽  
Vibrational Analysis ◽  
Bone Geometry ◽  
The Body ◽  
Mode Shapes ◽  
Pelvic Bone ◽  
Cross Sectional ◽  
Femur Bone ◽  
Bone Structures ◽  
Elderly Falls

Femur bone is the longest and largest bone in the human skeleton. This bone connects the pelvic bone to the knee and carries most of the body weight. The static behavior of femur bone has been a center of investigation for many years while little attention has been given to its dynamic and vibrational behavior, which is of great importance in sports activities, car crashes and elderly falls. Investigation of natural frequencies and mode shapes of bone structures are important to understand the dynamic and vibrating behaviors. Vibrational analysis of femoral bones is presented using finite element method. In the analysis, the bone was modeled with isotropic and orthotropic mechanical properties. The effect of surrounding bone muscles has also been accounted for as a viscoelastic medium embedding the femur bone. Natural frequencies extracted considering the effects of age aggravated by weakening the elastic modulus and density loss. The effects of real complex bone geometry on natural frequencies are studied and are compared with a simple circular cross-sectional model.

scholarly journals 414 A randomized phase II study of systemic therapy plus WeiLeShu (WLS) versus systemic therapy alone in patients with metastatic colorectal cancer (mCRC)

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A445-A445
Author(s):  
Ruyi Zhang ◽  
Xiaoxuan Tu ◽  
Zhou Tong ◽  
Hangyu Zhang ◽  
Xudong Zhu ◽  
...  
Keyword(s):  
Random Forest ◽  
Systemic Therapy ◽  
Gut Microbiome ◽  
Clinical Benefit ◽  
Metabolic Pathways ◽  
Random Forest Model ◽  
Metagenomic Analysis ◽  
Dependent Manner ◽  
Inflammatory Microenvironment ◽  
Forest Model

BackgroundIn recent years, the role of inflammatory microenvironment induced by gut microbiome in the occurrence and development of CRC has received increased attention across a number of disciplines. WLS is a probiotics product consisted of with 6 billion live probiotics, mainly Lactobacillus helveticus and Bifidobacterium longum. To further explore the influence of gut microbiome in the anti-tumor efficacy of patients with mCRC, we conducted a randomized controlled trial (NCT04021589).MethodsPatients receiving corresponding systemic therapy were randomly included into the WLS-intervention and the control arms. Fecal samples were collected at baseline and about two months after treatment initiation. Gut microbiota composition was assessed using shotgun metagenomic sequencing. Best clinical response was dichotomized as partial remission (clinical benefit, CB) versus stable disease or disease progression (non-clinical benefit, NCB). Metagenomic analysis across patients with CB and NCB was conducted and random forest model training was employed to predict the efficacy of treatment.Abstract 414 Figure 1Metabolic pathways for differential enrichment. Metabolic pathways for differential enrichment of the gut microbiome genome in microbiota preparation group through KEGG analysisResultsA total of 40 patients with mCRC in two tertiary hospitals were enrolled. Dynamic metagenomic analysis indicated that during systemic treatment, the a diversity of the gut microbiome were all decreased in both arms. It has been reported that higher a diversity is associated with a better prognosis, while the degree of decline in WLS-intervention group was a relatively minor change. GO enrichment analysis of differential genes indicated a strong enrichment for genes related to lipid metabolism after WLS intervention (figure 1; p<0.01). Lipopolysaccharide (LPS) could regulate the accumulation of monocyte-like macrophages and promote the inflammatory microenvironment in a chemokine-dependent manner, while WLS intervention down-regulated genes related to its synthesis pathway, which may slow the development of CRC. Random forest model showed abundance of Desulfovibrio_vulgaris and Parvimonas_sp._oral_taxon_393 predominantly discriminated between CB and NCB. They were then used to construct a classifier, which achieved an AUC of 0.95 for efficacy prediction.ConclusionsThis prospective randomized pilot study provided insights for influence of the gut microbiome with probiotics in mCRC. WLS could maintain intestinal microecological balance of patients with mCRC by decreasing the degree of abundance of gut microbiome fall after chemotherapy and down-regulating lipopolysaccharide metabolism-related pathway. We established a novel classifier that accurately distinguished between patients with CB and NCB on systemic therapy.Trial RegistrationNCT04021589Ethics ApprovalThis study has been approved by Clinical Research Ethics Committee of the First Affiliated Hospital, College of Medicine, Zhejiang University. Acceptance number: IIT20200348A-R1

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