scholarly journals Lactobacillus intestinalis YT2 restores the gut microbiota and improves menopausal symptoms in ovariectomized rats

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.

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Yun Tai Kim ◽  
Eun Yeong Lim ◽  
Young-Do Nam ◽  
Hee Soon Shin

Abstract Objectives Menopause is a natural process, where ovaries produce less reproductive hormones, which degrades the quality of life. Hormone replacement therapy was used primarily to reduce menopausal symptoms but new therapies are needed because they have a risk in long-term use. Probiotics are well known for their beneficial effects on bowel health, obesity, and immunity, and they have been reported to have useful effects on menopause in recent years. This study examined the effects of Lactobacillus acidophilus YT1 on menopausal symptoms in ovariectomized (OVX) rats. Methods Twelve weeks-old female SD rats were divided into five groups: (1) sham + DW, (2) OVX + DW, (3) OVX + estradiol, (4) OVX + L. acidophilus YT1, and (5) OVX + Lactobacillus reuteri that were treated once daily for 12 weeks after OVX. Results Pain sensitivity, depression-related behavior, and fat mass were significantly increased at 12 weeks after OVX and the bone mineral density was decreased. These menopause symptoms were significantly recovered by a daily oral treatment of L. acidophilus YT1 for 12 weeks. In addition, L. acidophilus YT1 enhanced intestinal barrier function by up-regulation tight junction expression in Caco-2 cell monolayers. Conclusions The treatment of L. acidophilus YT1 could alleviate menopausal symptoms, such as increased pain sensitivity, depression, body fat, and bone loss in menopausal women, which suggests it could be developed as a functional food and probiotics for elderly women health. Funding Sources This research was supported by the main research Program (E0164502-03) of the Korea Food Research Institute funded by the Minstry of Science and ICT.


2022 ◽  
Vol 8 ◽  
Author(s):  
Yujie Zhu ◽  
Shucheng Liu ◽  
Fengfeng Mei ◽  
Meihui Zhao ◽  
Guanghua Xia ◽  
...  

Osteoporosis is a global health problem, and it is of great significance to replace the drugs with natural functional factors. In this study, we investigated the antiosteoporotic activity of lipids prepared from Tilapia nilotica fish head lipids (THLs) in the ovariectomized osteoporosis rats. THLs are composed of neutral lipids (NL, 77.84%), phospholipids (PL, 11.86%), and glycolipids (GL, 6.47%). There were apparent differences in the fatty acid composition of disparate components, and PL contains the most abundant Ω-3 polyunsaturated fatty acids. The results proved that THLs could improve bone microstructure, increase bone mineral density, and decrease bone resorption. To illustrate the antiosteoporotic mechanism, we analyzed the changes in gut microbial communities, proinflammation factors, serum metabolites, and metabolic pathways. Further study on gut microbiota showed that THLs significantly decreased the content of Alistipes in the gut and dramatically increased the beneficial bacteria such as Oscillospira, Roseburia, and Dubosiella. Meanwhile, proinflammation factors of serum in OVX rats decreased significantly, and metabolites were changed. Therefore, we speculated that THLs improved bone loss through reducing inflammation and changing the metabolites and metabolic pathways such as arachidonic acid metabolism and primary bile acid metabolism, etc., by altering gut microbiota. The results indicated that THLs could be a functional factor with antiosteoporotic activity.


2016 ◽  
Vol 38 (1) ◽  
pp. 283-294 ◽  
Author(s):  
Zhanhai Yin ◽  
Yan Zhang ◽  
Zheyang Wang ◽  
Lin Ding ◽  
Ainiwaerjiang Damaolar ◽  
...  

Background: Osteoporosis is characterized by impairment of bone mass, strength, and microarchitecture, leading to the susceptibility to fragility fractures, especially in femoral neck region. Transcriptional coactivator with PDZ-binding motif (TAZ) facilitates osteogenesis while suppressing adipogenesis via regulation of transcriptional activities of runt-related transcription factor 2 and peroxisome proliferator-activated receptor γ. Here, we validated the role of TAZ in vivo using an ovariectomized (OVX) rat model of osteoporosis. Methods: Serum alkaline phosphatase, triglyceride, cholesterol and urinary hydroxyproline were measured on an automatic analyzer using diagnostic reagent kits. Serum OCN and C-terminal cross-linked telopeptides of type I collagen were measured using ELISA. Bone mineral density was measured using dual-energy X-ray scanner. Mechanical parameters were detected by three-point bending assays. Bone volume per tissue volume (BV/TV), trabecular thickness (Tb. Th), trabecular number (Tb. No), and trabecular separation (Tb. Sp) were measured by MicroCT. The mRNA and protein levels were quantified by Realtime PCR and Western Blotting respectively. Results: After injections of lentivirus overexpressing TAZ into the femoral neck region, bone mineral density, ultimate force, stiffness, BV/TV, Tb. Th, and Tb. No were significantly increased, whereas Tb. Sp was dramatically decreased. In the TAZ-overexpression region in the femoral neck of OVX rats, the mRNA levels of Runx2 and osteocalcin were obviously elevated, whereas that of PPARγ and adipocyte protein 2 were downregulated. Conclusion: Lentivirus-mediated TAZ gene therapy alleviated the osteoporotic phenotypes in the femoral neck of OVX rats, providing an alternative strategy for the treatment of postmenopausal osteoporosis and prevention of osteoporotic fracture.


2011 ◽  
Vol 212 (2) ◽  
pp. 179-186 ◽  
Author(s):  
Rana Samadfam ◽  
Malaika Awori ◽  
Agnes Bénardeau ◽  
Frieder Bauss ◽  
Elena Sebokova ◽  
...  

Peroxisome proliferator-activated receptor (PPAR) γ agonists, such as pioglitazone (Pio), improve glycemia and lipid profile but are associated with bone loss and fracture risk. Data regarding bone effects of PPARα agonists (including fenofibrate (Feno)) are limited, although animal studies suggest that Feno may increase bone mass. This study investigated the effects of a 13-week oral combination treatment with Pio (10 mg/kg per day)+Feno (25 mg/kg per day) on body composition and bone mass parameters compared with Pio or Feno alone in adult ovariectomized (OVX) rats, with a 4-week bone depletion period, followed by a 6-week treatment-free period. Treatment of OVX rats with Pio+Feno resulted in ∼50% lower fat mass gain compared with Pio treatment alone. Combination treatment with Pio+Feno partially prevented Pio-induced loss of bone mineral content (∼45%) and bone mineral density (BMD; ∼60%) at the lumbar spine. Similar effects of treatments were observed at the femur, most notably at sites rich in trabecular bone. At the proximal tibial metaphysis, concomitant treatment with Pio+Feno prevented Pio exacerbation of ovariectomy-induced loss of trabecular bone, resulting in BMD values in the Pio+Feno group comparable to OVX controls. Discontinuation of Pio or Feno treatment of OVX rats was associated with partial reversal of effects on bone loss or bone mass gain, respectively, while values in the Pio+Feno group remained comparable to OVX controls. These data suggest that concurrent/dual agonism of PPARγ and PPARα may reduce the negative effects of PPARγ agonism on bone mass.


2022 ◽  
Vol 8 ◽  
Author(s):  
Shuangyue Li ◽  
Georgios Kararigas

There has been a recent, unprecedented interest in the role of gut microbiota in host health and disease. Technological advances have dramatically expanded our knowledge of the gut microbiome. Increasing evidence has indicated a strong link between gut microbiota and the development of cardiovascular diseases (CVD). In the present article, we discuss the contribution of gut microbiota in the development and progression of CVD. We further discuss how the gut microbiome may differ between the sexes and how it may be influenced by sex hormones. We put forward that regulation of microbial composition and function by sex might lead to sex-biased disease susceptibility, thereby offering a mechanistic insight into sex differences in CVD. A better understanding of this could identify novel targets, ultimately contributing to the development of innovative preventive, diagnostic and therapeutic strategies for men and women.


2019 ◽  
Vol 244 (3) ◽  
pp. 193-206 ◽  
Author(s):  
Byoung-Seob Ko ◽  
Jin Ah Ryuk ◽  
Joo Tae Hwang ◽  
Ting Zhang ◽  
Xuangao Wu ◽  
...  

The different ojayeonjonghwan remedies all contain five fruit and seed water extracts, and they have been used for reproductive health in men and women. We hypothesized that the two OJa remedies would differently improve the early menopause-related vasomotor and neurological symptoms in estrogen-deficient animals. Ovariectomized (OVX) rats had either 0.5% dextrin (OVX-control), conjugated equine estrogen (150 μg/kg body weight; positive-control), 0.5% ojayeonjonghwan remedy-1 (OJa1), or 0.5% ojayeonjonghwan remedy-2(OJa2) in high-fat diet for 12 weeks. Normal-control rats (sham operation) were fed the same high-fat diet as OVX-control rats. Tail skin temperature, depressiveness, memory function, and body composition were determined. The mRNA expressions of hippocampal serotonin receptor (5HT)1A and 5HT2A and brain-derived neurotrophic factor(BDNF) were measured. OJa1 and OJa2 groups had lower tail skin temperatures than OVX-control. Bone mineral density (BMD) and lean body mass (LBM) measured by DEXA increased only in OJa2, and were similar to the positive- and normal-controls ( P < 0.05). In the forced swim test immobile time, an index of depressiveness was much lower in OJa1 and OJa2 than the control group. Memory as measured by passive avoidance, water maze, and Y maze tests was impaired in the OVX-control group, compared to the normal-control ( P < 0.05), but normalized in OJa1 comparable to the positive- and normal-control groups. The neurological impairments were associated with serum serotonin levels and 5HT2A mRNA expression in the midbrain, and decreased hippocampal BDNF mRNA and protein expressions in the OVX-control group compared to normal-controls ( P < 0.05). OJa1 increased serum serotonin levels and 5HT2A expression in the midbrain, and hippocampal BDNF expression to similar levels as normal-controls ( P < 0.05). In conclusion, OJa1 and OJa2 improved hot flashes and depression and maintained BMD and LBM. OJa2 prevented the impairment of memory function in OVX rats. OJa1 and OJa2 have the potential to be effective therapies for postmenopausal vasomotor and neurological symptoms. Impact statement Menopausal symptoms impair the quality of life of many women, and although conventional treatments are often effective, their use is limited by adverse effects. Ojayeonjonghwan, OJa, is a traditional Oriental medicine that is used for both male and female reproductive health and has a long history of safe use. We evaluated the effectiveness of two variations of OJa (OJa1 and OJa2) for treating menopausal symptoms in ovariectomized (OVX) rats. Both OJa preparations were effective for relieving indicators of hot flashes and depression, and for preventing loss of bone mineral density and lean body mass. Only OJa 2 prevented memory dysfunction. These results show that the traditional Oriental medicine, Ojayeonjonghwan, has the potential to relieve menopausal symptoms in women and should be further evaluated in human clinical trials as an alternative to convention therapies in women for whom conventional therapies are not indicated or found to be ineffective.


Endocrinology ◽  
2014 ◽  
Vol 155 (6) ◽  
pp. 2178-2189 ◽  
Author(s):  
M. P. Mosti ◽  
A. K. Stunes ◽  
M. Ericsson ◽  
H. Pullisaar ◽  
J. E. Reseland ◽  
...  

Estrogen deficiency promotes bone loss and skeletal muscle dysfunction. Peroxisome proliferator-activated receptors (PPARs) have 3 subtypes (α, δ, and γ). PPARγ agonists induce bone loss, whereas PPARα agonists increase bone mass. Although PPARδ agonists are known to influence skeletal muscle metabolism, the skeletal effects are unsettled. This study investigated the musculoskeletal effects of the PPARδ agonist GW501516 in ovariectomized (OVX) rats. Female Sprague Dawley rats, 12 weeks of age, were allocated to a sham-operated group and 3 OVX groups; high-dose GW501516 (OVX-GW5), low-dose GW501516 (OVX-GW1), and a control group (OVX-CTR), respectively (n = 12 per group). Animals received GW501516 or vehicle (methylcellulose) daily for 4 months by gavage. Bone mineral density (BMD) was assessed by dual x-ray absorptiometry at the femur, spine, and whole body. Bone microarchitecture at the proximal tibia was assessed by microcomputed tomography, and dynamic histomorphometry was performed. Quadriceps muscle morphology and the relative expression of mitochondrial proteins were analyzed. Bone metabolism markers and metabolic markers were measured in plasma. After 4 months, the OVX-GW5 group displayed lower femoral BMD than OVX-CTR. Trabecular separation was higher in the GW-treated groups, compared with OVX-CTR. The OVX-GW5 group also exhibited lower cortical area fraction and a higher structure model index than OVX-CTR. These effects coincided with impaired bone formation in both GW groups. The OVX-GW5 group displayed elevated triglyceride levels and reduced adiponectin levels, whereas no effects on muscle morphology or mitochondrial gene expression appeared. In summary, the PPARδ agonist GW501516 negatively affected bone properties in OVX rats, whereas no effects were detected in skeletal muscle.


1993 ◽  
Vol 139 (2) ◽  
pp. 253-258 ◽  
Author(s):  
A. M. Salicioni ◽  
R. W. Carón ◽  
R. P. Deis

ABSTRACT There is evidence that the adrenals play a role in the regulation of the synthesis and release of gonadotrophins in various vertebrates. The aim of this study was to determine the part played by adrenal steroids, with special reference to progesterone, on the concentration of LH in ovariectomized (OVX) and oestrogen-primed rats. OVX rats received a single s.c. injection of vehicle or oestradiol benzoate (OB, 20 μg/rat). This day was designated as day 0. Three or four days later (day 3–day 4), the rats were treated with mifepristone (10 mg/kg) or with two doses of progesterone antiserum and blood samples were obtained at 13.00 and 18.00 h. OB treatment of OVX rats reduced serum LH at 13.00 h and 18.00 h on day 3 but only at 13.00 h on day 4. The administration of mifepristone at 08.00 h to OVX and oestrogen-treated rats induced a significant increase in serum LH at 18.00 h on days 3 and 4, without modifying the values at 13.00 h. When mifepristone was given at 13.00 h a much larger increase in serum LH was obtained at 18.00 h. In OVX and oestrogen-treated rats, adrenalectomy on day 2 (08.00–09.00 h) induced an increase in serum LH at 18.00 h similar to that observed in the OVX and oestrogen-primed rats after mifepristone treatment. In order to determine the specificity of the effect of mifepristone, a group of OVX and oestrogentreated rats was injected with progesterone antiserum at 08.00 and 13.00 h on day 3. Serum LH concentrations at 13.00 and 18.00 h on day 3 were similar to values obtained in OVX rats treated with oestrogen and mifepristone. Serum progesterone was measured at 08.00 and 13.00 h in OVX and OVX and oestrogenprimed rats. At both times, values were similar in OVX rats but oestrogen treatment significantly increased serum progesterone levels. The important role of adrenal progesterone on the regulation of LH secretion in OVX and oestrogen-primed rats is evident from these results. Blocking progesterone action at the receptor level, we showed that OB significantly increased LH values at 18.00 h. On the basis of these studies it is tempting to speculate on the possibility of an inhibitory or stimulatory effect of oestrogen on serum LH concentration in OVX rats, according to the presence or absence of adrenal progesterone action. Journal of Endocrinology (1993) 139, 253–258


2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Shu-Jem Su ◽  
Yao-Tsung Yeh ◽  
Huey-Wen Shyu

Biochanin A (BCA) is a major isoflavone abundant in red clover (Trifolium pretense). The protective effect of BCA on bone loss in an ovariectomized (OVX) animal model has never been clarified. The objective of this study was to investigate the biological effects of BCA on bone loss in OVX ratsin vivoand on the development of osteoblasts and osteoclastsin vitro. Ovariectomy resulted in a marked increase in body weight and a decrease in femoral bone mineral density and trabecular bone volume that was prevented by BCA or 17β-estradiol (E2) treatment. However, an increase in uterine weight was observed in E2-treated OVX rats, but not in response to BCA treatment. Treatment with BCA increased the mRNA expression of osterix, collagen type I, alkaline phosphatase (ALP), and osteocalcin and decreased the mRNA expression of tartrate-resistant acid phosphatase (TRAP) and the receptor activator of nuclear factor-κB ligand (RANKL)/osteoprotegerin (OPG) ratio in the femur of OVX rats. Treatment with BCA or E2 prevented the OVX-induced increase in urinary deoxypyridinoline (DPD) and serum tumor necrosis factorα(TNF-α) and interleukin-1β(IL-1β).In vitro, BCA induced preosteoblasts to differentiate into osteoblasts and increased osteoblast mineralization. BCA inhibited preosteoclasts and osteoclast proliferation and decreased osteoclast bone resorption. These findings suggest that BCA treatment can effectively prevent the OVX-induced increase in bone loss and bone turnover possibly by increasing osteoblastic activities and decreasing osteoclastic activities.


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