Alteration of gut microbiota in elderly postmenopausal women with osteoporosis

2020 ◽  
Author(s):  
Yingjuan Li ◽  
Guangjian Mu ◽  
Binbin Ma ◽  
Panpan Lu ◽  
Haiquan Huang ◽  
...  

Abstract Osteoporosis is a common bone disorder worldwide and causes bone fragility and fracture. Gut microbiota colonizes the gastrointestinal tract, and is associated with bone metabolism and osteoporosis. In our study, the alteration of gut microbiota in osteoporosis and its effects on bone metabolism were investigated. A total of 36 elderly postmenopausal osteoporotic women and 12 healthy controls were recruited, and their fecal samples were collected for 16S rRNA gene sequencing of gut microbiota on Illumina MiSeq platform. The venous blood and urine samples were also collected to determine the biochemical indexes. There was no obvious difference in Alpha diversity in the experiment group and control group, while differential Beta diversity was observed. The Partial Least Squares Discriminant Analysis (PLS-DA) model and variable importance in projection (VIP) scores showed that the osteoporotic women and healthy controls had different genera of Erysipelotrichaceae , Rothia , and Eubacterium . The metabolic function prediction of gut microbiota indicated that the experiment group had 634 unique functional categories, while the control group had 13 unique functional categories. The biochemical measurement revealed that the osteoclast activity indexes including urine N-terminal telopeptides of type I collagen (NTX), serum NTX, and serum C-terminal telopeptides of type I collagen (CTX) in the experiment group were higher than those in the control group, indicating that the osteoclast activity in osteoporotic women was increased. In addition, the correlation analysis of microbial metabolism with phenotypes showed the pathways in the significant modules of magenta, red, pink, and yellow were positively correlated with urine phosphate, urine creatinine, urine creatinine, serum calcium and other biochemical indexes. Collectively, our study identified the different genera between postmenopausal osteoporotic women and healthy controls, which might be potential targets for the treatment of osteoporosis.

2006 ◽  
Vol 91 (11) ◽  
pp. 4453-4458 ◽  
Author(s):  
Mariateresa Sciannamblo ◽  
Gianni Russo ◽  
Debora Cuccato ◽  
Giuseppe Chiumello ◽  
Stefano Mora

Abstract Context: Patients with congenital adrenal hyperplasia (CAH) receive glucocorticoids as replacement therapy. Glucocorticoid therapy is the most frequent cause of drug-induced osteoporosis. Objective: The objective of the study was to evaluate bone mineral density (BMD) and bone metabolism in CAH patients. Design: This was a cross-sectional observational study. Setting: The study was conducted at a referral center for pediatric endocrinology. Patients and Other Participants: Thirty young patients with the classical form of CAH (aged 16.4–29.7 yr) treated with glucocorticoid from diagnosis (duration of treatment 16.4–29.5 yr) and 138 healthy controls (aged 16.0–30.0 yr) were enrolled. Main Outcome Measures: BMD was measured in the lumbar spine and whole body by dual-energy x-ray absorptiometry. Bone formation and resorption rates were estimated by serum measurements of bone-specific alkaline phosphatase and C-terminal telopeptide of type I collagen, respectively. Results: CAH patients were shorter than controls (women −6.8 and men −13.3 cm). Therefore, several methods were used to account for the effect of this difference on bone measurements. Whole-body BMD measurements were significantly lower, compared with controls (P < 0.03), after controlling for height (on average −2.5% in females and −9.3% in male patients). No differences were found in lumbar spine measurements. Bone-specific alkaline phosphatase and C-terminal telopeptide of type I collagen serum concentrations were higher in CAH patients than control subjects (P < 0.04). BMD measurements and bone metabolism markers did not correlate with the actual glucocorticoid dose or mean dose over the previous 7 yr. Conclusions: Young adult patients with the classical form of CAH have decreased bone density values, compared with healthy controls. This may put them at risk of developing osteoporosis early in life.


2011 ◽  
Vol 80 (4) ◽  
pp. 391-396 ◽  
Author(s):  
Iveta Gradošová ◽  
Helena Živná ◽  
Klára Švejkovská ◽  
Vladimír Palička ◽  
Aleš Tichý ◽  
...  

Amlodipine (dihydropyridine-type calcium channel blocker) is a widely used agent for the treatment of hypertension in human and veterinary medicine but detailed information about its effects on bone metabolism are missing. Therefore, the aim of our study was to investigate the effect of amlodipine on bone metabolism in male albino Wistar rats. Amlodipine (0.3 mg/100 g body weight; gavage) was administered to 8 rats for 8 weeks. Control group (n = 8) received aqua pro inj. (0.2 ml/100 g body weight; gavage). Bone marker concentrations of carboxy-terminal cross-linking telopeptide of type I collagen (CTX-I) and aminoterminal propeptide of procollagen type I in serum, and of bone alkaline phosphatase (BALP) in both serum and bone homogenate were measured by enzyme immunoassay. We investigated the expression of bone morphogenetic protein 2 (BMP-2) in proximal tibia using Western blotting, and bone mineral density was measured by Dual-energy X-ray Absorptiometry in lumbar and caudal vertebrae and in femoral areas. Mechanical properties of the femurs were measured by three-point bending of the shaft and compression testing of the femoral neck. After 8 weeks of amlodipine administration there was a significant decrease in serum concentrations of BALP (p = 0.0009) and CTX-I (p = 0.003), and the content of BALP in bone homogenate (p = 0.026) compared to the control. In addition, Western blot analysis indicated increased BMP-2 protein concentration after amlodipine administration. Our findings suggest that amlodipine has a retarding influence on bone metabolism in rats by decreasing bone turnover, which probably in consequence increases expression of BMP-2.


Metabolites ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 482
Author(s):  
Jae-Kwon Jo ◽  
Seung-Ho Seo ◽  
Seong-Eun Park ◽  
Hyun-Woo Kim ◽  
Eun-Ju Kim ◽  
...  

Obesity can be caused by microbes producing metabolites; it is thus important to determine the correlation between gut microbes and metabolites. This study aimed to identify gut microbiota-metabolomic signatures that change with a high-fat diet and understand the underlying mechanisms. To investigate the profiles of the gut microbiota and metabolites that changed after a 60% fat diet for 8 weeks, 16S rRNA gene amplicon sequencing and gas chromatography-mass spectrometry (GC-MS)-based metabolomic analyses were performed. Mice belonging to the HFD group showed a significant decrease in the relative abundance of Bacteroidetes but an increase in the relative abundance of Firmicutes compared to the control group. The relative abundance of Firmicutes, such as Lactococcus, Blautia, Lachnoclostridium, Oscillibacter, Ruminiclostridium, Harryflintia, Lactobacillus, Oscillospira, and Erysipelatoclostridium, was significantly higher in the HFD group than in the control group. The increased relative abundance of Firmicutes in the HFD group was positively correlated with fecal ribose, hypoxanthine, fructose, glycolic acid, ornithine, serum inositol, tyrosine, and glycine. Metabolic pathways affected by a high fat diet on serum were involved in aminoacyl-tRNA biosynthesis, glycine, serine and threonine metabolism, cysteine and methionine metabolism, glyoxylate and dicarboxylate metabolism, and phenylalanine, tyrosine, and trypto-phan biosynthesis. This study provides insight into the dysbiosis of gut microbiota and metabolites altered by HFD and may help to understand the mechanisms underlying obesity mediated by gut microbiota.


2016 ◽  
Vol 101 (8) ◽  
pp. 3222-3230 ◽  
Author(s):  
Jean Redmond ◽  
Anthony J. Fulford ◽  
Landing Jarjou ◽  
Bo Zhou ◽  
Ann Prentice ◽  
...  

Context: Ethnic groups differ in fragility fracture risk and bone metabolism. Differences in diurnal rhythms (DRs) of bone turnover and PTH may play a role. Objective: We investigated the DRs of plasma bone turnover markers (BTMs), PTH, and 1,25(OH)2D in three groups with pronounced differences in bone metabolism and plasma PTH. Participants: Healthy Gambian, Chinese, and white British adults (ages 60–75 years; 30 per country). Interventions: Observational study with sample collection every 4 hours for 24 hours. Main Outcomes: Levels of plasma C-terminal telopeptide of type I collagen, procollagen type-1 N-propeptide, N-mid osteocalcin, bone alkaline phosphatase, PTH, and 1,25-dihydroxyvitamin D were measured. DRs were analyzed with random-effects Fourier regression and cross-correlation and regression analyses to assess associations between DRs and fasting and 24-hour means of BTMs and PTH. Results: Concentrations of BTMs, PTH, and 1,25-dihydroxyvitamin D were higher in Gambians compared to other groups (P < .05). The DRs were significant for all variables and groups (P < .03) and were unimodal, with a nocturnal peak and a daytime nadir for BTMs, whereas PTH had two peaks. The DRs of BTMs and PTH were significantly cross-correlated for all groups (P < .05). There was a significant positive association between C-terminal telopeptide of type I collagen and PTH in the British and Gambian groups (P = .03), but not the Chinese group. Conclusions: Despite ethnic differences in plasma BTMs and PTH, DRs were similar. This indicates that alteration of rhythmicity and loss of coupling of bone resorption and formation associated with an elevated PTH in other studies may not uniformly occur across different populations and needs to be considered in the interpretation of PTH as a risk factor of increased bone loss.


Author(s):  
MV Osikov ◽  
EV Davydova ◽  
KS Abramov

Efferent physical therapy holds promise as an adjunct to the combination treatment of femoral fractures in young, working-age individuals. The aim of the study was to investigate the dynamics of bone turnover markers at different stages of femoral fracture consolidation in patients undergoing ozone therapy. The study enrolled 20 men (group 2, 47.8 ± 3.5 years) with a femoral shaft fracture (AO/ASIF 32А, 32В). The control group (group 1, 46.8 ± 3.7 years) comprised 10 healthy males. Subgroup 2a (n = 10) was assigned to receive standard therapy; subgroup 2b (n = 10) was assigned to receive standard therapy complemented by minor autohemotherapy (MAHT) at 20 mg/L ozone concentrations. On days 7, 30 and 90, fracture consolidation was assessed on the RUST scale and blood levels of С-terminal telopeptides of type I collagen (bCTx, pg/ml) and procollagen type I carboxy-terminal propeptide (PICP, ng/ml) were measured. On day 7, the total RUST score in subgroups 2a and 2b was 4 points; on day 30, it was 6.5 and 8.7 points, respectively, and on day 90, it reached 10 and 11.5 points, respectively. Bone mineral density was as high as 90% in the MAHT subgroup vs. 78% in subgroup 2а, indicating faster bone healing. On day 30, bCTx levels in subgroup 2b were higher than in subgroup 2a (2289.4 [2145.3; 2365.4] vs. 1894.6 [1745.3; 2098.2], respectively. On day 7, PICP was significantly elevated in subgroup 2b in comparison with subgroup 2a; its levels peaked on days 30 and 90 (day 30: 268.3 [231.2; 286.3] vs. 183.2 [174.6; 195.6]; day 90: 584.6 [512.3; 589.3] vs. 351.2 [312.3; 369.4]. Thus, MAHT produces a positive effect on the quality and intensity of bone healing in men with isolated closed femoral shaft fractures.


Author(s):  
Harold J. Boutte ◽  
Jacqueline Chen ◽  
Todd N. Wylie ◽  
Kristine M. Wylie ◽  
Yan Xie ◽  
...  

Background & Aims: Loss of functional small bowel surface area causes short bowel syndrome (SBS), intestinal failure, and parenteral nutrition (PN) dependence. The gut adaptive response following resection may be difficult to predict, and it may take up to two years to determine which patients will wean from PN. Here we examined features of gut microbiota and bile acid (BA) metabolism in determining adaptation and ability to wean from PN. Methods: Stool and sera were collected from healthy controls and from SBS patients (n=52) with ileostomy, jejunostomy, ileocolonic and jejunocolonic anastomoses fed with PN plus enteral nutrition or who were exclusively enterally fed. We undertook 16S rRNA gene sequencing, BA profiling and 7α-hydroxy-4-cholesten-3-one (C4) quantitation with LC-MS/MS, and serum amino acid analyses. Results: SBS patients exhibited altered gut microbiota with reduced gut microbial diversity compared to healthy controls. We observed differences in the microbiomes of SBS patients with ileostomy vs. jejunostomy, jejunocolonic vs. ileocolonic anastomoses, and PN-dependence compared to those who weaned from PN. Stool and serum BA composition and C4 concentrations were also altered in SBS patients, reflecting adaptive changes in enterohepatic BA cycling. Stools from patients who weaned from PN were enriched in secondary BAs including deoxycholic acid and lithocholic acid. Conclusions: Shifts in gut microbiota and BA metabolites may generate a favorable luminal environment in select SBS patients, promoting the ability to wean from PN. Pro-adaptive microbial species and select BA may provide novel targets for patient-specific therapies for SBS.


2018 ◽  
Vol 36 (1) ◽  
pp. 37-43 ◽  
Author(s):  
Jun Zhou ◽  
Peirui Zhong ◽  
Ying Liao ◽  
Jing Liu ◽  
Yuan Liao ◽  
...  

Objectives To investigate the effects of electroacupuncture (EA) on subchondral bone mass and cartilage degeneration in an experimental animal model of osteoarthritis (OA) induced by ovariectomy (OVX). Methods Ninety 3-month-old female Sprague-Dawley rats were randomly divided into the following three groups (n = 30 each): sham operation without treatment (control group); OVX without treatment (OVX group);, and ovariectomy with EA treatment (EA group). Rats in the EA group received EA treatment from the day of OVX. Ten rats in each group were randomly killed at 4, 8 and 12 weeks after operation. Results EA reduced urine C-terminal cross-linking telopeptide of type I collagen from 4 weeks after OVX, reduced C-terminal cross-linking telopeptide of type II collagen and body weight from 8 weeks after OVX, and increased serum 17β-oestradiol from 4 weeks after OVX compared with the OVX group (all p<0.01). In the EA group, trabecular bone volume ratio, trabecular thickness and trabecular number increased, and trabecular separation were reduced at each time point compared with the OVX group (p<0.05, p<0.01, respectively). In the EA group, osteoprotegerin (OPG) expression was increased and receptor activator of nuclear factor kappa-B ligand (RANKL) expression was reduced at each time point compared with the OVX group (p<0.05, p<0.01, respectively). Mankin scores and mRNA expression of matrix metalloproteinase-13 (MMP-13) were lower in EA versus OVX groups at 12 weeks after OVX (both p<0.01). Conclusion The results suggest that EA inhibits subchondral bone loss by regulating RANK/RANKL/OPG signalling and protects articular cartilage by inhibiting MMP-13 in OVX rats.


2012 ◽  
Vol 56 (4) ◽  
pp. 259-264 ◽  
Author(s):  
Claudia Cardoso Netto ◽  
Vivian Cristine Correia Vieira ◽  
Lizanka Paola Figueiredo Marinheiro ◽  
Sherry Agellon ◽  
Hope Weiler ◽  
...  

OBJECTIVE: To analyze if female Wistar rats at 56 weeks of age are a suitable model to study osteoporosis. MATERIALS AND METHODS: Female rats with 6 and 36 weeks of age (n = 8 per group) were kept over a 20-week period and fed a diet for mature rodents complete in terms of Ca, phosphorous, and vitamin D. Excised femurs were measured for bone mass using dual-energy x-ray absorptiometry, morphometry, and biomechanical properties. The following serum mar-kers of bone metabolism were analyzed: parathyroid hormone (PTH), osteocalcin (OC), osteoprotegerin (OPG), receptor activator of nuclear factor Κappa B ligand (RANKL), C-terminal peptides of type I collagen (CTX-I), total calcium, and alkaline phosphatase (ALP) activity. RESULTS: Rats at 56 weeks of age showed important bone metabolism differences when compared with the younger group, such as, highest diaphysis energy to failure, lowest levels of OC, CTX-I, and ALP, and elevated PTH, even with adequate dietary Ca. CONCLUSION: Rats at 26-week-old rats may be too young to study age-related bone loss, whereas the 56-week-old rats may be good models to represent the early stages of age-related changes in bone metabolism.


2021 ◽  
Author(s):  
Fei Xie ◽  
Xue Jiang ◽  
Yang Yi ◽  
Zi-Jia Liu ◽  
Chen Ma ◽  
...  

Abstract The potential for preventive and therapeutic applications of H2 have now been confirmed in various disease. However, the effects of H2 on health status have not been fully elucidated. Our previous study reported changes in the body weight and 13 serum biochemical parameters during the six-month hydrogen intervention. To obtain a more comprehensive understanding of the effects of long-term hydrogen consumption, the plasma metabolome and gut microbiota were investigated in this study. Compared with the control group, 14 and 10 differential metabolites (DMs) were identified in hydrogen-rich water (HRW) and hydrogen inhalation (HI) group, respectively. Pathway enrichment analysis showed that HRW intake mainly affected starch and sucrose metabolism, and DMs in HI group were mainly enriched in arginine biosynthesis. 16S rRNA gene sequencing showed that HRW intake induced significant changes in the structure of gut microbiota, while no marked bacterial community differences was observed in HI group. HRW intake mainly induced significant increase in the abundance of Lactobacillus, Ruminococcus, Clostridium XI, and decrease in Bacteroides. HI mainly induced decreased abundances of Blautia and Paraprevotella. The results of this study provide basic data for further research on hydrogen medicine. Determination of the effects of hydrogen intervention on microbiota profiles could also shed light on identification of mechanism underlying the biological effects of molecular hydrogen.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yue Hu ◽  
Fang Chen ◽  
Haiyong Ye ◽  
Bin Lu

AbstractStress is one of the major causes of irritable bowel syndrome (IBS), which is well-known for perturbing the microbiome and exacerbating IBS-associated symptoms. However, changes in the gut microbiome and metabolome in response to colorectal distention (CRD), combined with restraint stress (RS) administration, remains unclear. In this study, CRD and RS stress were used to construct an IBS rat model. The 16S rRNA gene sequencing was used to characterize the microbiota in ileocecal contents. UHPLC-QTOF-MS/MS assay was used to characterize the metabolome of gut microbiota. As a result, significant gut microbial dysbiosis was observed in stress-induced IBS rats, with the obvious enrichment of three and depletion of 11 bacterial taxa in IBS rats, when compared with those in the control group (q < 0.05). Meanwhile, distinct changes in the fecal metabolic phenotype of stress-induced IBS rats were also found, including five increased and 19 decreased metabolites. Furthermore, phenylalanine, tyrosine and tryptophan biosynthesis were the main metabolic pathways induced by IBS stress. Moreover, the altered gut microbiota had a strong correlation with the changes in metabolism of stress-induced IBS rats. Prevotella bacteria are correlated with the metabolism of 1-Naphthol and Arg.Thr. In conclusion, the gut microbiome, metabolome and their interaction were altered. This may be critical for the development of stress-induced IBS.


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