scholarly journals Ovariectomy-Induced Dysbiosis May Have a Minor Effect on Bone in Mice

2021 ◽  
Vol 9 (12) ◽  
pp. 2563
Author(s):  
Satoshi Kosaka ◽  
Yuji Nadatani ◽  
Akira Higashimori ◽  
Koji Otani ◽  
Kosuke Fujimoto ◽  
...  

We determined the bone mineral density (BMD) and the expression of serum bone formation marker (procollagen type I N-terminal propeptide: PINP) and bone resorption marker (C-terminal telopeptide of collagen: CTX) by ELISA to evaluate ovariectomy-induced osteoporosis in ovariectomized (OVX) mice. The intestinal microbiota of the mice was assessed using 16S rRNA gene sequencing. OVX mice exhibited a lower BMD of 87% with higher serum levels of CTX and PINP compared to sham-operated (sham) mice. The cecum microbiome of OVX mice showed lower bacterial diversity than that of sham mice. TNFα mRNA levels in the colon were 1.6 times higher, and zonula occludens-1 mRNA and protein expression were lower in OVX mice than in sham mice, suggesting that ovariectomy induced inflammation and increased intestinal permeability. Next, we used antibiotic treatment followed by fecal microbiota transplantation (FMT) to remodel the gut microbiota in the OVX mice. A decrease in PINP was observed in antibiotic-treated mice, while there was no change in BMD or CTX between mice with and without antibiotic treatment. Oral transplantation of the luminal cecal content of OVX or sham mice to antibiotic-treated mice did not affect the BMD or PINP and CTX expression. Additionally, transplantation of the luminal contents of OVX or sham mice to antibiotic-treated OVX mice had similar effects on BMD, PINP, and CTX. In conclusion, although ovariectomy induces dysbiosis in the colon, the changes in the gut microbiota may only have a minor role in ovariectomy-induced osteoporosis.

Cartilage ◽  
2017 ◽  
Vol 9 (3) ◽  
pp. 255-262 ◽  
Author(s):  
Jadwiga Ambroszkiewicz ◽  
Joanna Gajewska ◽  
Grazyna Rowicka ◽  
Witold Klemarczyk ◽  
Magdalena Chelchowska

Objective There is scant research examining the prevalence of thinness in early childhood, despite its potential negative consequences for health and development across the life course. The objective of this study was to assess bone status through measurement of bone mineral density and biochemical bone turnover markers, with special attention paid to carboxylated (c-OC) as well as undercarboxylated (uc-OC) forms of osteocalcin, in the groups of thin and normal-weight children. Design The study included 80 healthy prepubertal children (median age 7.0 years), who were divided (according to Cole’s international cutoffs) into 2 subgroups: thin children ( n = 40, body mass index [BMI] = 13.5 kg/m2) and normal-weight children ( n = 40, BMI = 16.1 kg/m2). Bone mineral density (BMD) and bone mineral content (BMC) were assessed by dual-energy x-ray absorptiometry method. Serum concentrations of C-terminal telopeptide of collagen type I (CTX), total osteocalcin (OC), and c-OC, and uc-OC forms of osteocalcin were determined using enzyme-linked immunosorbent assays. Results In thin children, we observed higher levels of bone resorption marker CTX compared with normal-weight peers. Total osteocalcin concentrations were comparable in both groups of children; however, in thin children we observed higher median values of uc-OC (34.40 vs. 29.30 ng/mL, P < 0.05) and similar c-OC levels (25.65 vs. 28.80 ng/mL). The ratio of c-OC to uc-OC was significantly lower ( P < 0.05) in thin than in normal-weight children. Total BMD and BMC were significantly decreased ( P < 0.0001) in thin children compared with normal-weight peers (0.724 ± 0.092 vs. 0.815 ± 0.060 g/cm2 and 602.7 ± 159.2 vs. 818.2 ± 220.1 g, respectively). Conclusion Increased concentrations of CTX and uc-OC might lead to disturbances in bone turnover and a decrease in bone mineral density in thin children.


Author(s):  
Kusworini Handono ◽  
BP Putra Suryana ◽  
Sulistyorini Sulistyorini

Rheumatoid Arthritis (RA) is a systemic autoimmune disease accompanied by decreasing bone mass density and ultimately leads toosteoporosis. The cause of decreased bone mass density is still unknown, but the inflammation has been suspected as an important factor.The correlation between the severity of inflammation with the decrease in bone mass density in Indonesian RA patients has not been muchstudied. The purpose of this study was to know the assessment in the correlation between levels of C-reactive protein (CRP), Tumour NecrosisFactor-α (TNFα) and bone mineral density (BMD) with bone resorption marker CTx-1 β-Cross Laps in premenopausal RA patients.Thisobservational study using cross sectional design, was carried out in the Rheumatology Clinic and Central Laboratory of RSSA, Malang fromAugust 2009 until October 2010. All 47 RA patients were diagnosed according to revised of the 1997 American College of Rheumatology(ACR). Measurement of CRP levels uses turbidimetry method, TNF-α and CTX-1 β-Cross Laps levels using ELISA methods and the measurementof BMD using DEXA. The results of this study showed mean levels of CRP were 4.288±1.775 g/L, TNF-α were 322.077±275.248 pg/mLand CTX-1 β-Cross Laps were 0.588±0.139 ng mL. The correlation of CRP and TNF-α levels with CTX-1 β-Cross Laps level were r=0.5832,p=0.453 and r=0.615, p=0.041. Correlation of CTX-1 β-Cross Laps level and Femoral Neck BMD was r=–0.469, p=0.143 and r=0.248,p=0.799 for L average BMD. There was no correlation between CRP level and BMD results with bone resorption marker CTX-1 β-Cross Laps,but there is a significant correlation between high levels of TNFα with CTX-1 β-Cross Laps. It seems that TNF-α appears to be contributed tothe decrease of bone mass density in RA patients.


2020 ◽  
Author(s):  
Dana Binyamin ◽  
Orna Nitzan ◽  
Maya Azrad ◽  
Zohar Hamo ◽  
Omry Koren ◽  
...  

Abstract Background: Clostridium difficile (C. difficile) is a major nosocomial pathogen that infects the human gut and can cause diarrheal disease. A dominant risk factor is antibiotic treatment that disrupts the normal gut microbiota. The aim of the study was to examine the correlation between antibiotic treatment received prior to C. difficile infection (CDI) onset and patient gut microbiota.Methods: Stool samples were collected from patients with CDI, presenting at the Baruch Padeh Medical Center Poriya, Israel. Demographic and clinical information, including previous antibiotic treatments, was collected from patient charts, and CDI severity score was calculated. Bacteria were isolated from stool samples, and gut microbiome was analyzed by sequencing the 16S rRNA gene using the Illumina MiSeq platform and QIIME2.Results: In total, 84 patients with C. difficile infection were enrolled in the study; all had received antibiotics prior to disease onset. Due to comorbidities, 46 patients (55%) had received more than one class of antibiotics. The most common class of antibiotics used was cephalosporins (n=44 cases). The intestinal microbiota of the patients was not uniform. Differences in intestinal microbiome were influenced by the different combinations of antibiotics that the patients had received (p = 0.022)Conclusions: The number of different antibiotics administered has a major impact on the CDI patients gut microbiome, mainly on bacterial richness.


2020 ◽  
Author(s):  
Dana Binyamin ◽  
Orna Nitzan ◽  
Maya Azrad ◽  
Zohar Hamo ◽  
Omry Koren ◽  
...  

Abstract Background: Clostridium difficile (C. difficile) is a major nosocomial pathogen that infects the human gut and can cause C. difficile infection (CDI), a diarrheal disease. A dominant risk factor is antibiotic treatment, which disrupts the normal gut microbiota. The aim of the study was to examine the correlation between antibiotic treatment received prior to CDI onset and patient gut microbiota during the infection.Methods: Stool samples were collected from patients with CDI, presenting at the Baruch Padeh Medical Center Poriya, Israel. Demographic and clinical information, including previous antibiotic treatments, was collected from patient charts, and CDI severity score was calculated. Bacteria were isolated from stool samples, and gut microbiome was analyzed by sequencing the 16S rRNA gene, using the Illumina MiSeq platform and QIIME2.Results: In total, 84 patients with CDI were enrolled in the study; all had received antibiotics prior to disease onset. Due to comorbidities, 46 patients (55%) received more than one class of antibiotics. The most common class of antibiotics used was cephalosporins (n=44 cases). The intestinal microbiota of the patients was not uniform. Differences in intestinal microbiome were influenced by the different numbers of antibiotics families that the patients received (p = 0.022)Conclusions: The number of different antibiotics amount has a major impact on the gut microbiome of CDI patients, particularly on its bacterial richness.


Author(s):  
Tian Tian ◽  
Markus Heine ◽  
Ioannis Evangelakos ◽  
Michelle Y. Jaeckstein ◽  
Nicola Schaltenberg ◽  
...  

Abstract Several studies suggest a role of extracellular adenine nucleotides in regulating adipose tissue functions via the purinergic signaling network. Metabolic studies in mice with global deletion of the purinergic receptor P2X7 on the C57BL/6 background indicate that this receptor has only a minor role in adipose tissue for diet-induced inflammation or cold-triggered thermogenesis. However, recent data show that a polymorphism (P451L) present in C57BL/6 mice attenuates P2X7 receptor function, whereas BALB/c mice express the fully functional P451 allele. To determine the potential role of P2rx7 under metabolic and thermogenic stress conditions, we performed comparative studies using male P2rx7 knockout (KO) and respective wild-type controls on both BALB/c and C57BL/6 backgrounds. Our data show that adipose P2rx7 mRNA levels are increased in obese mice. Moreover, P2rx7 deficiency results in reduced levels of circulating CCL2 and IL6 with a moderate effect on gene expression of pro-inflammatory markers in white adipose tissue and liver of BALB/c and C57BL/6 mice. However, P2X7 expression does not alter body weight, insulin resistance, and hyperglycemia associated with high-fat diet feeding on both genetic backgrounds. Furthermore, deficiency of P2rx7 is dispensable for energy expenditure at thermoneutral and acute cold exposure conditions. In summary, these data show that—apart from a moderate effect on inflammatory cytokines—P2X7 plays only a minor role in inflammatory and thermogenic effects of white and brown adipose tissue even on the BALB/c background.


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.


2005 ◽  
Vol 51 (12) ◽  
pp. 2312-2317 ◽  
Author(s):  
Yoshifumi Maeno ◽  
Masaaki Inaba ◽  
Senji Okuno ◽  
Tomoyuki Yamakawa ◽  
Eiji Ishimura ◽  
...  

Abstract Background: Urinary cross-linked N-telopeptide of type I collagen (NTX) is a reliable bone resorption marker in patients with metabolic bone disease. We assessed a clinically available serum NTX assay suitable for anuric patients on hemodialysis (HD). Methods: Serum concentrations of NTX, C-terminal telopeptide of type I collagen (β-CTX), pyridinoline (PYD), and deoxypyridinoline (DPD) were determined as bone resorption markers, and those of bone alkaline phosphatase (BAP) and intact osteocalcin (OC) as bone formation markers, in 113 male HD patients (mean age, 59.3 years; mean HD duration, 67.7 months). Each patient’s bone mineral density (BMD) in the distal third of the radius was measured twice, with a 2-year interval between measurements, by dual-energy x-ray absorptiometry. Results: Serum NTX correlated significantly with β-CTX, PYD, DPD, BAP, and intact OC. NTX, as well as β-CTX, PYD, DPD, BAP, and intact OC, correlated significantly with BMD at the time of measurement. NTX, β-CTX, and DPD correlated significantly with the annual change in BMD during the 2-year period thereafter, in contrast to PYD, BAP, and intact OC. Patients in the highest quartile of serum NTX concentrations showed the fastest rate of bone loss. The sensitivity and specificity for detecting rapid bone loss were 48% and 83%, respectively, for serum NTX. Conclusion: Serum NTX may provide a clinically relevant serum assay to estimate bone turnover in HD patients.


Neurology ◽  
2001 ◽  
Vol 57 (3) ◽  
pp. 445-449 ◽  
Author(s):  
Y. Sato ◽  
I. Kondo ◽  
S. Ishida ◽  
H. Motooka ◽  
K. Takayama ◽  
...  

Background: Bone loss and hypovitaminosis D are reported in patients taking antiepileptic drugs, but little is known about changes in bone and calcium metabolism from valproic acid (VPA).Objective: To assess the relationship of VPA to bone mass and calcium metabolism in 40 adults with epilepsy on long-term VPA monotherapy, 40 age- and sex-matched epileptic patients taking phenytoin (PHT), and 40 healthy control subjects. Bone mineral density (BMD) of the second metacarpal was determined as T- and Z-scores.Results: BMD reduction from control values was 14% (12% in men, 16% in women) with VPA and 13% (12% in men, 15% in women) with PHT. Among patients on VPA, nine (23%) had T-scores below −2.5 SD, suggesting osteoporosis; 15 (37%) had T-scores between −1 and −2.5 SD, suggesting osteopenia. Serum concentrations of calcium were significantly higher with VPA than in PHT or control groups. Serum concentrations of bone Gla protein (a bone formation marker) and pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (ICTP; a bone resorption marker) associated with either drug significantly exceeded control values. Z-scores for BMD in the VPA group correlated negatively with calcium and ICTP. High ICTP correlated positively with ionized calcium, implying that increased bone resorption caused the latter.Conclusion: Long-term VPA monotherapy can increase bone resorption, leading to decreased BMD.


2021 ◽  
pp. 1-14
Author(s):  
E.Y. Lim ◽  
E.-J. Song ◽  
J.G. Kim ◽  
S.Y. Jung ◽  
S.-Y. Lee ◽  
...  

There are many studies focusing on the alleviation of menopausal symptoms; however, little is known about the role of gut microorganisms in menopausal symptoms. Ovariectomized (OVX) rats were administered a novel strain (YT2) of Lactobacillus intestinalis (a species with significantly reduced abundance in OVX rats) and the potential probiotic effect on the improvement of menopausal symptoms was evaluated. Of note, the gut microbial composition completely shifted after ovariectomy in rats. Treatment with L. intestinalis YT2 significantly alleviated menopausal symptoms, such as increased fat mass, decreased bone mineral density, increased pain sensitivity, depression-like behaviour, and cognitive impairment. Additionally, the administration of L. intestinalis YT2 restored the intestinal microbial composition, including an increased Firmicutes/Bacteroides ratio. L. intestinalis YT2 also promoted gut barrier integrity by increasing the mRNA levels of tight junction-related markers. In conclusion, L. intestinalis YT2 treatment alleviated menopausal symptoms via the modulation of the gut microbiota. Importantly, these results suggest that L. intestinalis YT2 should be considered as a therapeutic probiotic agent for menopausal women.


2018 ◽  
Vol 120 (3) ◽  
pp. 283-289 ◽  
Author(s):  
Marloes Dekker Nitert ◽  
Luisa F. Gomez-Arango ◽  
Helen L. Barrett ◽  
H. David McIntyre ◽  
Gregory J. Anderson ◽  
...  

AbstractFe is an essential nutrient for many bacteria, and Fe supplementation has been reported to affect the composition of the gut microbiota in both Fe-deficient and Fe-replete individuals outside pregnancy. This study examined whether the dose of Fe in pregnancy multivitamin supplements affects the overall composition of the gut microbiota in overweight and obese pregnant women in early pregnancy. Women participating in the SPRING study with a faecal sample obtained at 16 weeks’ gestation were included in this substudy. For each subject, the brand of multivitamin used was recorded. Faecal microbiome composition was assessed by 16S rRNA sequencing and analysed with the QIIME software suite. Dietary intake of Fe was assessed using a FFQ at 16 weeks’ gestation. Women were grouped as receiving low (<60 mg/d, n 94) or high (≥60 mg/d; n 65) Fe supplementation. The median supplementary Fe intake in the low group was 10 (interquartile range (IQR) 5–10) v. 60 (IQR 60–60) mg/d in the high group (P<0·001). Dietary Fe intake did not differ between the groups (10·0 (IQR 7·4–13·3) v. 9·8 (IQR 8·2–13·2) mg/d). Fe supplementation did not significantly affect the composition of the faecal microbiome at any taxonomic level. Network analysis showed that the gut microbiota in the low Fe supplementation group had a higher predominance of SCFA producers. Pregnancy multivitamin Fe content has a minor effect on the overall composition of the gut microbiota of overweight and obese pregnant women at 16 weeks’ gestation.


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