Thyroid-Gut-Axis: How Does the Microbiota Influence Thyroid Function?
Knezevic Jovana,Starchl Christina,Tmava Berisha Adelina,Amrein Karin
A healthy gut microbiota not only has beneficial effects on the activity of the immune system, but also on thyroid function. Thyroid and intestinal diseases prevalently coexist-Hashimoto's thyroiditis (HT) and Graves' disease (GD) are the most common autoimmune thyroid diseases (AITD) and often co-occur with Celiac Disease (CD) and Non-celiac wheat sensitivity (NCWS). This can be explained by the damaged intestinal barrier and the following increase of intestinal permeability, allowing antigens to pass more easily and activate the immune system or cross-react with extraintestinal tissues, respectively. Dysbiosis has not only been found in AITDs, but has also been reported in thyroid carcinoma, in which an increased number of carcinogenic and inflammatory bacterial strains were observed. Additionally, the composition of the gut microbiota has an influence on the availability of essential micronutrients for the thyroid gland. Iodine, iron, and copper are crucial for thyroid hormone synthesis, selenium and zinc are needed for converting T4 to T3, and vitamin D assists in regulating the immune response. Those micronutrients are often found to be deficient in AITDs, resulting in malfunctioning of the thyroid. Bariatric surgery can lead to an inadequate absorption of these nutrients and further implicates changes in thyroid stimulating hormone (TSH) and T3 levels. Supplementation of probiotics showed beneficial effects on thyroid hormones and thyroid function in general. A literature research was performed to examine the interplay between gut microbiota and thyroid disorders that should be considered when treating patients suffering from thyroid diseases. Multifactorial therapeutic and preventive management strategies could be established and more specifically adjusted to patients, depending on their gut bacteria composition. Future well-powered human studies are warranted to evaluate the impact of alterations in gut microbiota on thyroid function and diseases.
Sex-specific association between gut microbiome and fat distribution.
Min Yan,Ma Xiaoguang,Sankaran Kris,Ru Yuan,Chen Lijin,Baiocchi Mike,Zhu Shankuan
The gut microbiome has been linked to host obesity; however, sex-specific associations between microbiome and fat distribution are not well understood. Here we show sex-specific microbiome signatures contributing to obesity despite both sexes having similar gut microbiome characteristics, including overall abundance and diversity. Our comparisons of the taxa associated with the android fat ratio in men and women found that there is no widespread species-level overlap. We did observe overlap between the sexes at the genus and family levels in the gut microbiome, such as Holdemanella and Gemmiger; however, they had opposite correlations with fat distribution in men and women. Our findings support a role for fat distribution in sex-specific relationships with the composition of the microbiome. Our results suggest that studies of the gut microbiome and abdominal obesity-related disease outcomes should account for sex-specific differences.
[Diagnostic and therapeutical significance of macro-TSH in patients with Hashimoto's thyroiditis].
Balázs Csaba,Rácz Károly
INTRODUCTION:Structure, importance and incidence and clinical role of macro-TSH not clarified in thyroid diseases. AIM:This study was undertaken to determine the incidence and biological role of macro-TSH in patients with Hashimoto's thyroiditis. METHOD:Blood samples taken from patients with Hashimoto's thyroiditis were screened for the presence of macro-TSH with the polyethylene glycol method and confirmed with protein G agarose absorption test and gel filtration chromatography. Stimulatory capacity of macro-TSH was measured by CHO cells bio-assay. Patients were treated with L-thyroxine (mean 66.5 µg/day) and half of them with selenium (mean 60 µg/day), respectively. RESULTS:880 patients (728 female, aged 44.8 yr) with Hashimoto's thyroiditis was involved in the study. Macro-TSH was found in the serum of 41 patients (4.6%), the mean TSH 185.4 ± 35 IU/l was before PEG precipitations and after 5.55 ± 1.8 IU/l. Titre of anti-TPO proved to be 445 ± 51 IU/l and gradulally decreased to 212 ± 51 IU/l after one year therapy. Both the precipitation, protein G absorption and gel chromatography supported the presence of anti-TSH antibody in the macro-TSH complex. Stimulatory capacity of macro-TSH on CHO bio-assay was not proved. The macro-TSH was detected in the selenium not treated group for 18 ± 3.2 months, selenium-treated for 12 ± 1.9 months. CONCLUSION:It is concluded that anti-human TSH autoantibodies are a major components of macro-TSH and may cause diagnostic and therapeutical difficulties. The PEG precipitation is a suitable screening method for detection of macro-TSH. Selenium is able to decrease of anti-TPO antibodies and macro-TSH, respectively. When the TSH level is greater than 40.0 IU/l, without the signs of hypothyroidism, the presence of macro-TSH is to be considered. Orv Hetil. 2017; 158(34): 1346-1350.
Hashimoto's Thyroiditis is an Important Risk Factor of Papillary Thyroid Microcarcinoma in Younger Adults.
Liu Yujuan,Li Chengqian,Zhao Wenjuan,Wang Yangang
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme
The association between autoimmune thyroid disease and thyroid cancer remains unclear. We performed a matched case-control study to assess the association between Hashimoto's thyroiditis and papillary thyroid microcarcinoma (PTMC). A total of 927 PTMC cases and 927 age- and gender- matched controls selected from the same population were recruited. Odds ratio (OR) with 95% confidence interval (95% CI) was used to assess the strength of the association between Hashimoto's thyroiditis and PTMC. Conditional logistic regression analysis was carried out, and stratified analyses by age, gender and types of thyroid antibodies were also performed. Hashimoto's thyroiditis was significantly associated with increased risk of PTMC (OR=1.87, 95% CI 1.49-2.34, p<0.001). Stratified analysis by thyroid antibodies also found obvious associations of PTMC risk with TPOAb positivity (OR=1.58, p=0.001) and TGAb positivity (OR=2.35, p<0.001). Stratified analyses by age showed that the association between Hashimoto's thyroiditis and PTMC risk was more significant in younger adults aged between 18 and 30 years (OR=11.48, p<0.001). Further stratified analyses by thyroid antibodies also found that the associations of PTMC risk with TPOAb positivity or TGAb positivity were more significant in younger adults aged between 18 and 30, and the ORs were 8.27 (p<0.001) and 12.71 (p<0.001), respectively. This study suggests an obvious relationship between Hashimoto's thyroiditis and PTMC risk, and Hashimoto's thyroiditis is an important risk of PTMC in younger adults.
Hashimoto's thyroiditis, microcalcification and raised thyrotropin levels within normal range are associated with thyroid cancer.
Ye Zhi-qiang,Gu Dian-na,Hu Hong-ye,Zhou Yi-li,Hu Xiao-qu,Zhang Xiao-hua
World journal of surgical oncology
BACKGROUND:To confirm whether clinical and biochemical parameters or Hashimoto's thyroiditis (HT) could predict the risks of malignancy among subjects who underwent thyroidectomy, as well as to determine the influence of HT on the biological behavior of papillary thyroid cancer (PTC). METHODS:A total of 2,052 patients who underwent initial thyroidectomy were enrolled between June 2006 and August 2008. Serum free T4, free T3, thyrotropin (TSH), thyroglobulin, thyroglobulin antibody, antimicrosomal antibody, tumor-associated status, and thyroid disorders were documented. RESULTS:Binary logistic regression analysis was performed to define the risk predictors for thyroid cancer. Finally, calcification, HT, TSH, and age, were entered into the multivariate model. Multivariate logistic regression analysis revealed the risk of thyroid cancer increases in parallel with TSH concentration within normal range, and the risk for malignancy significantly increased with serum TSH 1.97-4.94 mIU/L, compared with TSH less than 0.35 mIU/L (OR = 1.951, 95% CI = 1.201-3.171, P = 0.007). Increased risks of thyroid cancer were also detected among the patients with HT (OR = 3.732, 95% CI = 2.563-5.435), and microcalcification (OR = 14.486, 95% CI = 11.374-18.449). The effects of HT on the aggressiveness of PTC were not observed in extrathyroidal invasion (P = 0.347), capsular infiltration (P = 0.345), angioinvasion (P = 0.512), and lymph node metastases (P = 0.634). CONCLUSIONS:The risk of malignancy increases in patients with higher level TSH within normal range, as well as the presence of HT and microcalcification. No evidence suggests that coexistent HT alleviates the aggressiveness of PTC.
The clinical features of papillary thyroid cancer in Hashimoto's thyroiditis patients from an area with a high prevalence of Hashimoto's disease.
Zhang Ling,Li Hui,Ji Qing-hai,Zhu Yong-xue,Wang Zhuo-ying,Wang Yu,Huang Cai-ping,Shen Qiang,Li Duan-shu,Wu Yi
BACKGROUND:The goal of this study was to identify the clinicopathological factors of co-existing papillary thyroid cancer (PTC) in patients with Hashimoto's thyroiditis (HT) and provide information to aid in the diagnosis of such patients. METHODS:This study included 6109 patients treated in a university-based tertiary care cancer hospital over a 3-year period. All of the patients were categorised based on their final diagnosis. Several clinicopathological factors, such as age, gender, nodular size, invasive status, central compartment lymph node metastasis (CLNM) and serum thyroid-stimulating hormone (TSH) level, were compared between the various groups of patients. RESULTS:There were 653 patients with a final diagnosis of HT. More PTC was found in those with HT (58.3%; 381 of 653) than those without HT (2416 of 5456; 44.3%; p < 0.05). The HT patients with co-occurring PTC were more likely to be younger, be female, have smaller nodules and have higher TSH levels than those without PTC. A multivariate analysis indicated that the presence of HT and higher TSH levels were risk factors for a diagnosis of PTC. In the PTC patients, the presence of HT or another benign nodule was a protective factor for CLNM, whereas no significant association was found for TSH levels. CONCLUSION:PTC and HT have a close relationship in this region of highly prevalent HT disease. Based on the results of our study, we hypothesise that long-term HT leads to elevated serum TSH, which is the real risk factor for thyroid cancer.
Discordance of serological and sonographic markers for Hashimoto's thyroiditis with gold standard histopathology.
Guan Haixia,de Morais Nathalie Silva,Stuart Jessica,Ahmadi Sara,Marqusee Ellen,Kim Mathew I,Alexander Erik K
European journal of endocrinology
Objective:To investigate the concordance of serologic and sonographic evidence of Hashimoto's thyroiditis with its gold standard histopathologic identification. Design:We performed a retrospective analysis on a cohort of 825 consecutive patients in whom TPOAb and thyroid ultrasound were performed, and in whom thyroid nodule evaluation led to surgical and histopathologic analysis. The presence or absence of Hashimoto's thyroiditis on histopathology was correlated with serologic and sonographic markers. We further assessed the impact of low versus high titers of TPOAb upon this concordance. Results:Of 825 patients, 277 (33.5%) had histologic confirmation of Hashimoto's thyroiditis, 235 patients (28.4%) had elevated serum levels of TPOAb, and 197 (23.8%) had sonographic evidence of diffuse heterogeneity. Of those with histopathologic evidence, only 64% had elevated TPOAb (sensitivity: 63.9%; specificity: 89.4%), while only 49% were sonographically diffusely heterogeneous (sensitivity: 49.1%; specificity: 88.9%). A subset of only 102 of 277 (37%) with histologically proven Hashimoto's thyroiditis was positive for both TPOAb and diffusely heterogeneous. Concordance analysis demonstrated that TPOAb and histopathology had higher agreement (κ = 0.55) than did ultrasound and histopathology (κ = 0.40) for the diagnosis of Hashimoto's thyroiditis. Higher titers of TPOAb correlated with a higher likelihood of Hashimoto's thyroiditis, with a best cutoff of 2.11-fold the upper normal level of TPOAb. Conclusion:Only moderate concordance exists between serological evidence of Hashimoto's thyroiditis and histopathologic findings, though it increases with higher TPOAb concentration. Diffuse heterogeneity on ultrasound is a less-sensitive diagnostic tool than elevated TPOAb.
Changes of intestinal microflora of breast cancer in premenopausal women.
He Chuan,Liu Yue,Ye Shandong,Yin Shiwu,Gu Junfei
European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology
Breast cancer is one of the most common malignant tumors in women. More than half of breast cancer patients are not menopausal at the time of diagnosis. The occurrence and development of premenopausal breast cancer are affected by many factors. Intestinal flora, especially SCFA-producing bacteria, participates in the development of various tumors, and there is a lack of in-depth research in premenopausal breast cancer patients. We used 16S rRNA gene sequencing, targeted metabolomics, and cell culture methods to analyze the changes in the intestinal flora and metabolites of premenopausal breast cancer patients. In addition, we treated breast cancer cells with significantly altered propionate and butyrate in vitro to examine their effects on cell activity. This study followed STROBE guidelines. We found that compared with healthy premenopausal women, the composition and symbiosis of intestinal flora in patients with premenopausal breast cancer changed significantly. The abundance of short-chain fatty acid (SCFA)-producing bacteria was significantly reduced, and the key SCFA-producing enzymes were also significantly reduced. Pediococcus and Desulfovibrio could distinguish premenopausal breast cancer patients from normal premenopausal women. The related propionate and butyrate had a certain ability to inhibit breast cancer cell viability in vitro. As SCFA-producing bacteria, Pediococcus and Desulfovibrio showed potential reference value for the diagnosis of premenopausal breast cancer. The ability of propionate and butyrate to inhibit breast cancer cell lines in vitro suggests that the relevant SCFA receptor may be a new target for the treatment of premenopausal breast cancer.
Gut dysbiosis is associated with primary hypothyroidism with interaction on gut-thyroid axis.
Su Xinhuan,Zhao Ying,Li Yang,Ma Shizhan,Wang Zhe
Clinical science (London, England : 1979)
Background Previous studies have shown that the gut microbiome is associated with thyroid diseases, including Graves' disease, Hashimoto's disease, thyroid nodules, and thyroid cancer. However, the association between intestinal flora and primary hypothyroidism remains elusive. We aimed to characterize gut microbiome in primary hypothyroidism patients. Methods Fifty-two primary hypothyroidism patients and 40 healthy controls were recruited. The differences in gut microbiota between the two groups were analyzed by 16S rRNA sequencing technology. Fecal microbiota transplantation (FMT) was performed in mice using flora from both groups; changes in thyroid function were then assessed in the mice. Results There were significant differences in α and β diversities of gut microbiota between primary hypothyroidism patients and healthy individuals. The random forest analysis indicated that four intestinal bacteria (Veillonella, Paraprevotella, Neisseria, and Rheinheimera) could distinguish untreated primary hypothyroidism patients from healthy individuals with the highest accuracy; this was confirmed by receiver operator characteristic curve analysis. The short chain fatty acid producing ability of the primary hypothyroidism patients' gut was significantly decreased, which resulted in the increased serum lipopolysaccharide (LPS) levels. The FMT showed that mice receiving the transplant from primary hypothyroidism patients displayed decreased total thyroxine levels. Conclusions Our study suggests that primary hypothyroidism causes changes in gut microbiome. In turn, an altered flora can affect thyroid function in mice. These findings could help understand the development of primary hypothyroidism and might be further used to develop potential probiotics to facilitate the adjuvant treatment of this disease.
Prevention of colon cancer: role of short chain fatty acids produced by intestinal flora.
Young G P
Asia Pacific journal of clinical nutrition
Any polysaccharide, whether starch or fibre (ie non-starch polysaccharides) may be fermented in the large bowel by resident microflora (anaerobic bacteria). Amongst other substances, the short chain fatty acid butyrate is produced during fermentation. Butyrate is important in the maintenance of normal epithelial biology; it is probably the means by which dietary fibre prevents colonic epithelial atrophy. Starch which escapes digestion in the small intestine (resistant starch) also prevents colonic epithelial atrophy. Dietary fibres differ greatly in their physicochemistry and also in their biological effects. As a general rule, resistant starch (especially of type 2) tend to behave more like soluble then insoluble nonstarch polysaccharides. In humans, resistant starch results in substantial production of butyrate in the colon. Butyrate can be shown to have "antitumour" effects at various levels (cell and molecular), and this could explain the important inverse association between starch intake and colon cancer incidence (on a country by country basis). The nature of the variables affecting butyrate production from dietary polysaccharides by resident microflora need to be explored with a view to better understanding the practical application of this to cancer prevention.
"With a little help from my friends" - The role of microbiota in thyroid hormone metabolism and enterohepatic recycling.
Virili Camilla,Centanni Marco
Molecular and cellular endocrinology
The gut microbiota is composed of over 1200 species of anaerobes and aerobes bacteria along with bacteriophages, viruses and fungal species. Increasing evidence indicates that the intestinal microbiota, beside digestive equilibrium, is also crucial for immunologic, hormonal and metabolic homeostasis. The intestinal microbiota interacts with distant organs by signals which may be part of the bacteria themselves or their metabolites. Dysbiosis has been observed in inflammatory or autoimmune disorders such as multiple sclerosis or type 1 diabetes as well as in obesity and type 2 diabetes. Functional thyroid disorders were associated with bacterial overgrowth and a different microbial composition. Although thyroid metabolism was apparently disregarded, the interference of microbiota on peripheral iodothyronine homeostasis is an intriguing issue. In this review we focused on the interactions of intestinal microbiota with thyroid-related micronutrients and with the metabolic steps of endogenous and exogenous iodothyronines.
Intestinal microbiota changes in Graves' disease: a prospective clinical study.
Yan Hui-Xian,An Wen-Cheng,Chen Fang,An Bo,Pan Yue,Jin Jing,Xia Xue-Pei,Cui Zhi-Jun,Jiang Lin,Zhou Shu-Jing,Jin Hong-Xin,Ou Xiao-Hong,Huang Wei,Hong Tian-Pei,Lyu Zhao-Hui
Graves' disease (GD) occurs due to an autoimmune dysfunction of thyroid gland cells, leading to manifestations consistent with hyperthyroidism. Various studies have confirmed the link between autoimmune conditions and changes in the composition of intestinal microbial organisms. However, few studies have assessed the relationship between the GD and the changes in intestinal microbiota. Therefore, the present study aimed to investigate changes in intestinal flora that may occur in the setting of GD. Thirty-nine patients with GD and 17 healthy controls were enrolled for fecal sample collection. 16S rRNA sequencing was used to analyze the diversity and composition of the intestinal microbiota. High-throughput sequencing of 16S rRNA genes of intestinal flora was performed on Illumina Hiseq2500 platform. Comparing to healthy individuals, the number of Bacilli, Lactobacillales, Prevotella, Megamonas and Veillonella strains were increased, whereas the number of Ruminococcus, Rikenellaceae and Alistipes strains were decreased among patients with GD. Furthermore, patients with GD showed a decrease in intestinal microbial diversity. Therefore, it indicates that the diversity of microbial strains is significantly reduced in GD patients, and patients with GD will undergo significant changes in intestinal microbiota, by comparing the intestinal flora of GD and healthy controls. These conclusions are expected to provide a preliminary reference for further researches on the interaction mechanism between intestinal flora and GD.
Alteration of the intestinal flora may participate in the development of Graves' disease: a study conducted among the Han population in southwest China.
Yang Mengxue,Sun Bowen,Li Jianhui,Yang Bo,Xu Jie,Zhou Xue,Yu Jie,Zhang Xuan,Zhang Qun,Zhou Shan,Sun Xiaohua
Objectives:The pathogenesis of Graves' disease (GD) remains unclear. In terms of environmental factors, GD development may be associated with chronic inflammation caused by alteration of the intestinal flora. This study explored the association of intestinal flora alteration with the development of GD among the Han population in southwest China. Design and methods:Fifteen GD patients at the Affiliated Hospital of Zunyi Medical College between March 2016 and March 2017 were randomly enrolled. Additionally, 15 sex- and age-matched healthy volunteers were selected as the control group during the same period. Fresh stool samples were collected, and bacterial 16S RNA was extracted and amplified for gene sequencing with the Illumina MiSeq platform. The sequencing results were subjected to operational taxonomic unit-based classification, classification verification, alpha diversity analysis, taxonomic composition analysis and partial least squares-discriminant analysis (PLS-DA). Results:The diversity indices for the GD group were lower than those for the control group. The GD group showed significantly higher abundances of Firmicutes, Proteobacteria and Actinobacillus and a higher Firmicutes/Bacteroidetes ratio than the control group. PLS-DA suggested the satisfactory classification of the flora between the GD group and the control group. The abundances of the genera Oribacterium, Mogibacterium, Lactobacillus, Aggregatibacter and Mogibacterium were significantly higher in the GD group than in the control group (P < 0.05). Conclusions:The intestinal flora of GD patients was significantly different from that of the healthy population. Thus, alteration of intestinal flora may be associated with the development of GD.
Dysbiosis of the gut microbiome is associated with thyroid cancer and thyroid nodules and correlated with clinical index of thyroid function.
Zhang Jiaming,Zhang Fanghua,Zhao Changying,Xu Qian,Liang Cheng,Yang Ying,Wang Huiling,Shang Yongfang,Wang Ye,Mu Xiaofeng,Zhu Dequan,Zhang Chunling,Yang Junjie,Yao Minxiu,Zhang Lei
PURPOSE:Thyroid cancer and thyroid nodules are the most prevalent form of thyroid endocrine disorder. The balance of gut microbiome is highly crucial for a healthy human body, especially for the immune and endocrine system. However, the relationship between gut microbiome and the thyroid endocrine disorders such as thyroid cancer and thyroid nodules has not been reported yet. METHODS:A cohort of 74 patients was recruited for this study. Among them, 20 patients had thyroid cancer, 18 patients had thyroid nodules, and 36 were matched healthy controls. Gut microbiome composition was analyzed by 16S rRNA (16S ribosomal RNA) gene-based sequencing protocol. RESULTS:We compared the gut microbiome results of 74 subjects and established the correlation between gut microbiome and thyroid endocrine function for both thyroid cancer and thyroid nodules. The results inferred that alpha and beta diversity were different for patients with thyroid tumor than the healthy controls (p < 0.01). In comparison to healthy controls, the relative abundance of Neisseria (p < 0.001) and Streptococcus (p < 0.001) was significantly higher for thyroid cancer and thyroid nodules. Butyricimonas (p < 0.001) and Lactobacillus (p < 0.001) displayed notably lower relative abundance for thyroid cancer and thyroid nodules, respectively. It was also found that the clinical indexes were correlated with gut microbiome. CONCLUSION:Our results indicate that both thyroid cancer and thyroid nodules are associated with the composition of gut microbiome. These results may support further clinical diagnosis to a great extent and help in developing potential probiotics to facilitate the treatment of thyroid cancer and thyroid nodules.
Bifidobacterium in the gut microbiota confer resilience to chronic social defeat stress in mice.
Yang Chun,Fujita Yuko,Ren Qian,Ma Min,Dong Chao,Hashimoto Kenji
Accumulating evidence suggests that abnormalities in the composition of the gut microbiota may play a role in the pathogenesis of depression. Although approximately 30% mice are resilient to chronic social defeat stress (CSDS), the role of gut microbiota in this stress resilience is unknown. In this study, male C57BL/6 mice were exposed to a different CD1 aggressor mouse for 10 min on 10 consecutive days. A social interaction test was applied to distinguish between resilient and susceptible mice. Using 16S rRNA analysis, we examined the composition of gut microbiota in feces from control, resilient, and susceptible mice. The marked appearance of Bifidobacterium was detected in the resilient mice, whereas in the control and susceptible mice, Bifidobacterium were below the detection limit. Oral intake of Bifidobacterium significantly increased the number of resilient mice after CSDS compared with vehicle-treated mice. These findings suggest that Bifidobacterium may confer resilience to CSDS. Therefore, supplementation of Bifidobacterium may prevent the onset of depression from stress in humans. In addition, supplementation of Bifidobacterium may prevent or minimize relapse from remission induced by inflammation and/or stress in depressed patients.
Potential Influences of Gut Microbiota on the Formation of Intracranial Aneurysm.
Shikata Fumiaki,Shimada Kenji,Sato Hiroki,Ikedo Taichi,Kuwabara Atsushi,Furukawa Hajime,Korai Masaaki,Kotoda Masakazu,Yokosuka Kimihiko,Makino Hiroshi,Ziegler Emma A,Kudo Daisuke,Lawton Michael T,Hashimoto Tomoki
Hypertension (Dallas, Tex. : 1979)
Gut microbiota modulates metabolic and immunoregulatory axes and contributes to the pathophysiology of diseases with inflammatory components, such as atherosclerosis, diabetes mellitus, and ischemic stroke. Inflammation is emerging as a critical player in the pathophysiology of an intracranial aneurysm. Therefore, we hypothesized that the gut microbiota affects aneurysm formation by modulating inflammation. We induced intracranial aneurysms in mice by combining systemic hypertension and a single injection of elastase into the cerebrospinal fluid. Depletion of the gut microbiota was achieved via an oral antibiotic cocktail of vancomycin, metronidazole, ampicillin, and neomycin. Antibiotics were given 3 weeks before aneurysm induction and either continued until the end of the experiment or stopped 1 day before aneurysm induction. We also assessed the effects of the gut microbiota depletion on macrophage infiltration and mRNA levels of inflammatory cytokines. Gut microbiota depletion by antibiotics reduced the incidence when antibiotics were started 3 weeks before aneurysm induction and continued until the end of the experiment (83% versus 6%, P<0.001). Even when antibiotics were stopped 1 day before aneurysm induction, the gut microbiota depletion significantly reduced the incidence of aneurysms (86% versus 28%, P<0.05). Both macrophage infiltration and mRNA levels of inflammatory cytokines were reduced with gut microbiota depletion. These findings suggest that the gut microbiota contributes to the pathophysiology of aneurysms by modulating inflammation. Human studies are needed to determine the exact contribution of the gut microbiota to the pathophysiology of aneurysm formation and disease course in humans.
Molecular estimation of alteration in intestinal microbial composition in Hashimoto's thyroiditis patients.
Ishaq Hafiz Muhammad,Mohammad Imran Shair,Guo Hui,Shahzad Muhammad,Hou Yin Jian,Ma Chaofeng,Naseem Zahid,Wu Xiaokang,Shi Peijie,Xu Jiru
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
The gut microbiota has a crucial effect on human health and physiology. Hypothyroid Hashimoto's thyroiditis (HT) is an autoimmune disorder manifested with environmental and genetic factors. However, it is hypothesized that intestinal microbes might play a vital role in the pathogenesis of HT. The aim of current was to investigate and characterize the gut microbial composition of HT patients both quantitatively and qualitatively. The fecal samples from 29 HT patients and 12 healthy individuals were collected. The PCR-DGGE targeted V3 site of 16S rRNA gene and real time PCR for Bifidobacterium Lactobacillus, Bacteroides vulgatus and Clostridium leptum were performed. Pyrosequencing of 16S rRNA gene with V4 location was performed on 20 randomly selected samples. The comparative analysis of diversity and richness indices revealed diversification of gut microbiota in HT as compared to control. The statistical data elucidate the alterations in phyla of HT patients which was also affirmed at the family level. We observed the declined abundance of Prevotella_9 and Dialister, while elevated genera of the diseased group included Escherichia-Shigella and Parasutterella. The alteration in gut microbial configuration was also monitored at the species level, which showed an increased abundance of E. coli in HT. Therefore, the current study is in agreement with the hypothesis that HT patients have intestinal microbial dysbiosis. The taxa statistics at species-level along with each gut microbial community were modified in HT. Thus, the current study may offer the new insights into the treatment of HT patients, disease pathway, and mechanism.
Comparison of parathyroid hormone kinetics in endoscopic thyroidectomy via bilateral areola with open thyroidectomy.
Zhang Daqi,Wang Tie,Dionigi Gianlorenzo,Zhang Jiao,Zhao Yishen,Xue Gaofeng,Liang Nan,Sun Hui
BACKGROUND:In this study, we aimed to compare the kinetics of intact parathyroid hormone (iPTH) during the perioperative period of endoscopic thyroidectomy via bilateral areola approach (ETBAA) in the same period, following a traditional open thyroidectomy approach (OTA). METHODS:We conducted a prospective observational study of patients who were undergoing thyroidectomy and level VI clearance. Patients who had been affected by papillary thyroid cancer (PTC) were stratified into three groups: those eligible for endoscopic treatment (ETBAA); patients who were eligible for ETBAA but had opted for OTA (OTA-L); and patients who were not suitable for endoscopic intervention (OTA-H). A process for locating parathyroid glands was utilized to stratify gland dissection laboriousness. In Type A, the gland is firmly fixed to thyroid gland. This type can be sub-classified into three subtypes. A1: the parathyroid gland is attached to the inherent thyroid capsule. A2: the gland is partially embedded in the thyroid gland. A3: the gland is located in the thyroid tissue. Type B is defined as a gland which is separated from the thyroid gland. The iPTH was sampled at wound closure. RESULTS:There were 100 patients in each group. We found a significant difference between the ETBAA and OTA-H groups for type A2, as well as a loss of parathyroid glands and a number of parathyroid transplantation procedures. The endoscopic group was treated during an earlier stage of thyroid cancer. The iPTH profile of each group decreased, although this was the most consistent in the OTA-H group. A comparison of ETBAA with OTA-L demonstrates that the iPTH level change is similar. CONCLUSION:There is no advantage of endoscopic treatment for preserving parathyroid function.
Adjuvant chemotherapy-associated lipid changes in breast cancer patients: A real-word retrospective analysis.
He Tao,Wang Chengshi,Tan Qiuwen,Wang Zhu,Li Jiayuan,Chen Tao,Cui Kaijun,Wu Yunhao,Sun Jiani,Zheng Danxi,Lv Qing,Chen Jie
Adjuvant chemotherapy may cause alterations in serum lipids in postoperative breast cancer (BC) patients, but the specific alterations caused by different chemotherapy regimens remain unclear. The aim of this study was to investigate the status of serum lipids pre- and post-chemotherapy and to compare the side effects of different chemotherapy regimens on serum lipid.We retrospectively analysed the lipid profiles of 1934 consecutive postoperative BC patients who received one of the following chemotherapy regimens:The levels of triglycerides (TG), total cholesterols (TC), and low-density lipoprotein (LDL-C) were significantly elevated in patients who received chemotherapy regimens above (P < .001). With respect to different chemotherapy regimens, FEC had less side effects on lipid profiles (TG (P = .006), high-density lipoprotein (HDL-C) (P < .001), and LDL-C (P < .001)) than TC regimen and AC-T and EC-T regimen. Also, the incidence of newly diagnosed dyslipidemia after chemotherapy was lower in FEC group than TC group and AC-T and EC-T group (P < .001). Additionally, the magnitude of the alterations in lipid profiles (TG, TC, HDL-C, and LDL-C) was greater in premenopausal patients than that of the postmenopausal patients (P = .004; P < .001; P = .002; P = .003, respectively). Moreover, after adjusting for multiple baseline covariates, anthracycline-plus-taxane-based regimens (AC-T and EC-T) were still statistically associated with a high level of TG (P = .004) and a low level of HDL-C (P = .033) after chemotherapy compared with FEC regimen. Also, body mass index (BMI) > 24 was associated with abnormal lipid profiles (TG, TC, HDL-C, LDL-C) post-chemotherapy compared with BMI ≤ 24 (P < .001; P = .036; P = .012; P = .048, respectively).BC patients receiving chemotherapy may have elevated lipid profiles, and anthracycline-based regimen had less side effects on lipid profiles compared with regimens containing taxane. Therefore, it is necessary to take lipid metabolism into consideration when making chemotherapy decisions and dyslipidemia prevention and corresponding interventions are indispensable during the whole chemotherapy period.
Status of lipid and lipoprotein in female breast cancer patients at initial diagnosis and during chemotherapy.
Li Xin,Liu Zi-Li,Wu Yu-Tuan,Wu He,Dai Wei,Arshad Bilal,Xu Zhou,Li Hao,Wu Kai-Nan,Kong Ling-Quan
Lipids in health and disease
BACKGROUND:The lipid profile status among breast cancer patients at initial diagnosis and during chemotherapy remain controversial. The aim of this study is to study the status of lipid and lipoprotein in female breast cancer patients at initial diagnosis and during chemotherapy. METHODS:We conducted a retrospective cohort study of the status of the lipid and lipoprotein in 1054 primarily diagnosed breast cancer patients and 2483 normal controls with age stratification, from July 2015 to October 2016. At the same time, the status of lipid and lipoprotein were also analyzed among 394 breast cancer patients before and after adjuvant chemotherapy. RESULTS:The incidence of dyslipidemia was significantly lower in breast cancer group(42.98%) compared to normal group(58.28%)(P < 0.001). The levels of total cholesterol (TC), triglycerides (TG), HDL cholesterol (HDL-C), LDL cholesterol (LDL-C) among breast cancer group were significantly lower compared to normal control group (P < 0.05). With age stratification, the levels of TC and LDL-C in breast cancer group were still significantly lower than those in control group (P < 0.001). And the levels of TC, TG, LDL-C, apolipoprotein B were significantly higher among post chemotherapeutic patients compared to prechemotherapeutic patients, however HDL-C and Apo-A1 levels were contrary. CONCLUSIONS:Breast cancer patients have lower incidence of dyslipidemia compared to normal populations. However, the situation of dyslipidemia may become worsened after chemotherapy. Therefore, lipid monitoring and dyslipidemia prevention and treatment should be conducted for breast cancer patients at initial diagnosis and during chemotherapy.
The effect of preoperative serum triglycerides and high-density lipoprotein-cholesterol levels on the prognosis of breast cancer.
Li Xing,Tang Hailin,Wang Jin,Xie Xinhua,Liu Peng,Kong Yanan,Ye Feng,Shuang Zeyu,Xie Zeming,Xie Xiaoming
Breast (Edinburgh, Scotland)
OBJECTIVES:Although dyslipidemia has been documented to be associated with several types of cancer including breast cancer, it remains uncertainty the prognostic value of serum lipid in breast cancer. The purpose of this study is to evaluate the association between the preoperative plasma lipid profile and the prognostic of breast cancer patients. METHODS:The levels of preoperative serum lipid profile (including cholesterol [CHO], Triglycerides [TG], high-density lipoprotein-cholesterol [HDL-C], low-density lipoprotein-cholesterol [LDL-C], apolipoprotein A-I [ApoAI], and apolipoprotein B [ApoB]) and the clinical data were retrospectively collected and reviewed in 1044 breast cancer patients undergoing operation. Kaplan-Meier method and the Cox proportional hazards regression model were used in analyzing the overall survival [OS] and disease-free survival [DFS]. RESULTS:Combining the receiver-operating characteristic and Kaplan-Meier analysis, we found that preoperative lower TG and HDL-C level were risk factors of breast cancer patients. In multivariate analyses, a decreased HDL-C level showed significant association with worse OS (HR: 0.528; 95% CI: 0.302-0.923; P = 0.025), whereas a decreased TG level showed significant association with worse DFS (HR: 0.569; 95% CI: 0.370-0.873; P = 0.010). CONCLUSIONS:Preoperative serum levels of TG and HDL-C may be independent factor to predict outcome in breast cancer patient.
Impact of pre-diagnostic triglycerides and HDL-cholesterol on breast cancer recurrence and survival by breast cancer subtypes.
Lofterød Trygve,Mortensen Elin S,Nalwoga Hawa,Wilsgaard Tom,Frydenberg Hanne,Risberg Terje,Eggen Anne Elise,McTiernan Anne,Aziz Sura,Wist Erik A,Stensvold Andreas,Reitan Jon B,Akslen Lars A,Thune Inger
BACKGROUND:High triglycerides and low levels of high density lipoprotein (HDL)-cholesterol are observed to promote tumor growth. However, whether breast cancer heterogeneity may explain the contradictory influence of triglycerides and cholesterol observed on breast cancer prognosis remains unclear. METHODS:A population-based survival study among 464 breast cancer cases identified within the Tromsø study was conducted. Pre-diagnostic triglycerides, total-cholesterol and HDL-cholesterol were measured, and detailed clinical and histopathological data were obtained. Using tissue microarray, all breast cancer cases were reclassified into the following subtypes: Luminal A, Luminal B, HER2-enriched, and triple negative breast cancer (TNBC). Multivariable Cox proportional hazards regression models were used to study the associations between pre-diagnostic lipids and breast cancer recurrence, mortality, and survival. RESULTS:A total of 464 breast cancer patients, with mean age at diagnosis of 57.9 years, were followed for a mean 8.4 years. TNBC patients in the highest tertile of triglycerides (≥ 1.23 mmol/l) had 3 times higher overall mortality compared to TNBC patients in the lowest tertile (≤ 0.82 mmol/l) (HR 2.99, 95% CI 1.17-7.63), and the 5-year overall survival was 19% lower for TNBC patients in the highest vs. lowest tertile of triglycerides (65% vs. 84%). TNBC patients in the highest tertile of the HDL-cholesterol/total-cholesterol ratio (≥0.35), compared to those in the lowest tertile (≤0.27), had a 67% reduced overall mortality risk (HR 0.33, 95% CI 0.12-0.89). No associations were observed between lipids and prognostic outcome among breast cancer patients overall, or among patients with luminal A and luminal B subtypes. Among HER2-enriched patients, pre-diagnostic triglyceride level was inversely associated with overall mortality. CONCLUSION:Our study suggests that pre-diagnostic triglycerides and the HDL-cholesterol/total-cholesterol ratio may independently provide unique information regarding prognostic outcome among triple negative breast cancer patients. However, a small sample size underlines the need for additional studies.
Profiles of lipids, blood pressure and weight changes among premenopausal Chinese breast cancer patients after adjuvant chemotherapy.
Yeo Winnie,Mo Frankie K F,Pang Elizabeth,Suen Joyce J S,Koh Jane,Loong Herbert H F,Yip Christopher C H,Ng Rita Y W,Yip Claudia H W,Tang Nelson L S,Liem Giok S
BMC women's health
BACKGROUND:Adjuvant chemotherapy improves outcome of patients with early breast cancer. However, chemotherapy may be associated with long term toxicities. In this retrospective cohort study, the objectives were to determine body weight, body mass index (BMI), blood pressure and fasting lipids levels of young premenopausal Chinese breast cancer patients after adjuvant chemotherapy. Potential factors associated with these parameters were identified. METHODS:Eligibility criteria include premenopausal Chinese patients who were diagnosed to have stage I-III breast cancer within 3-10 years, age < 45 and having received adjuvant chemotherapy at the time of breast cancer diagnosis. Information at initial breast cancer diagnosis were retrieved from patients' medical records and include age at diagnosis, tumor characteristics, anti-cancer treatments, blood pressure and body weight and height. At study entry, all patients had additional background demographics collected, as well as blood pressure, body weight and fasting serum lipid profiles measured. Incidence of chemotherapy-related amenorrhoea (CRA) and menopause were determined. Factors associated with weight gain, hypertension and dyslipidaemias were analyzed. RESULTS:Two hundred and eighty patients were studied. The median age at breast cancer diagnosis was 41 years (range: 24-45). The median time from breast cancer diagnosis to study entry was 5.0 years. The median age at study entry was 46.5 years (range: 28-54). 91.1% developed CRA; 48.9% had become menopausal and 10% were peri-menopausal. Between initial breast cancer diagnosis and the time of study entry, the median weight gain was 1.8 kg; 63.2% gained weight by >2%; 52.1% were overweight/obese; 30.7% had hypertension. Abnormal total-cholesterol and LDL-cholesterol occurred in 34.3% and 56.1% respectively. On multivariate analyses, older age was associated with reduced risk while occurrence of CRA and having received taxane-containing regimens were associated with increased risk of weight gain. Oestrogen-receptor positivity was associated with reduced risk while overweight/obese statuses were associated with increased risk of hypertension. Use of tamoxifen was associated with reduced risk of abnormal LDL-cholesterol. Weight gain, overweight/obese, older age, progression to post/peri-menopausal status at study entry, having received corticosteroid premedication before adjuvant chemotherapy and having received taxane-containing adjuvant chemotherapy were associated with increased risk of dyslipidaemias. CONCLUSION:Among young premenopausal Chinese breast cancer patients who had received adjuvant chemotherapy, the current study has revealed that although there was only a median weight gain of 1.8 kg, there was a nearly 60% increase in abnormal BMI. Further, a significant proportion of patients were detected to have hypertension and dyslipidaemias. Interventional studies with lifestyle modifications are warranted.
Homocysteine, folate, and cobalamin levels in hyperthyroid women before and after treatment.
Orzechowska-Pawilojc Anna,Siekierska-Hellmann Małgorzata,Syrenicz Anhelli,Sworczak Krzysztof
INTRODUCTION:Hyperhomocysteinaemia is an independent risk factor for premature atherosclerotic vascular disease and venous thrombosis. Hypothyroidism is associated with mild hyperhomocysteinaemia. The aim of the present study was to assess plasma total homocysteine (tHcy) and its determinants (folate, cobalamin) in hyperthyroid patients before and after treatment. MATERIAL AND METHODS:Thirty hyperthyroid and thirty healthy premenopausal women were studied. The hyperthyroid patients were investigated in the untreated state and again after restoration of euthyroidism. The levels of homocysteine, folate, cobalamin, and thyroid stimulating hormone (TSH), free thyroxine (fT(4)), free triiodothyronine (fT(3)), and renal function were measured before and after treatment. RESULTS:In hyperthyroidism, tHcy was lower than in the control group. The serum level of folate was higher and serum cobalamin was lower in the hyperthyroid state. Following antithyroid drug therapy, tHcy significantly increased and folate decreased. The level of cobalamin remained unchanged. Univariate analysis in the hyperthyroid group indicated that tHcy significantly negatively correlated only with fT(3). CONCLUSIONS:Lower homocysteine levels in hyperthyroid state can be explained by the influence of thyroid hormone. High level of folate is only partially responsible for these changes.
The Association Between Hyperhomocysteinemia and Thyroid Nodule Prevalence in an Adult Population.
Pan Qingrong,Wang Ying,Wang Guang
Metabolic syndrome and related disorders
Thyroid nodule is the most common disorder of thyroid. Metabolic syndrome was regarded as an important factor for the prevalence of thyroid nodule. Homocysteine has been shown to be related to metabolic syndrome, inflammation, and several common cancers. In this study, we aimed to investigate the relationship between serum homocysteine and the prevalence of thyroid nodule. This was a cross-sectional study that included 2040 adults in a health checkup population in Beijing Chao-yang hospital. Thyroid ultrasound data, together with anthropometric characteristics, metabolic parameters, and serum homocysteine, were recorded respectively. Hyperhomocysteinemia (defined as serum homocysteine ≥15 μmol/L) was detected in 452 participants (21.91%). Thyroid nodule prevalence was significantly higher in hyperhomocysteinemia participants than in normal homocysteine participants (52.57% vs. 45.16%, = 0.006). Logistic regression analysis revealed that age [odds ratio (OR) 1.054; < 0.001], female gender (OR 2.242; < 0.001), body mass index (OR 1.050; < 0.001), and serum homocysteine level (OR 1.022; = 0.001) were the independent risk factors for thyroid nodule. Subjects with hyperhomocysteinemia have significantly higher thyroid nodule prevalence. Homocysteine is an independent risk factor for thyroid nodule. It implies that individuals with hyperhomocysteinemia have higher susceptibility to thyroid nodule.
Homocysteine pre-treatment increases redox capacity in both endothelial and tumor cells.
Díaz-Santiago Elena,Rodríguez-Caso Luis,Cárdenas Casimiro,Serrano José J,Quesada Ana R,Medina Miguel Ángel
Redox report : communications in free radical research
OBJECTIVE:We studied the modulatory effects of homocysteine pre-treatment on the disulfide reduction capacity of tumor and endothelial cells. METHODS:Human MDA-MB-231 breast carcinoma and bovine aorta endothelial cells were pre-treated for 1-24 hours with 0.5-5 mM homocysteine or homocysteine thiolactone. After washing to eliminate any rest of homocysteine or homocysteine thiolactone, cell redox capacity was determined by using a method for measuring disulfide reduction. RESULTS:Homocysteine pre-treatments for 1-4 hours at a concentration of 0.5-5 mM increase the disulfide reduction capacity of both tumor and endothelial cells. This effect cannot be fully mimicked by either cysteine or homocysteine thiolactone pre-treatments of tumor cells. DISCUSSION:Taken together, our data suggest that homocysteine can behave as an anti-oxidant agent by increasing the anti-oxidant capacity of tumor and endothelial cells.
Hyperhomocysteinemia in women with advanced breast cancer.
Gatt A,Makris A,Cladd H,Burcombe R J,Smith J M,Cooper P,Thompson D,Makris M
International journal of laboratory hematology
Patients with malignancy have an increased risk of venous thromboembolic disease but the pathophysiology of this association has not been precisely defined. Hyperhomocysteinemia has become established as one of the commonest conditions associated with venous and arterial thrombosis. We examined the prevalence of hyperhomocysteinemia in women with early (group A, n = 31), metastatic breast cancer (group B, n = 41) and in a group of healthy females (group C, n = 29). Blood samples were collected at diagnosis or prior to treatment. We measured both total plasma homocysteine (tHcy) and red cell folate (RCF). The Mean (SD) tHcy were group A - 9.43 micromol/l (5.6), group B - 11.34 micromol/l (5.1) and group C - 7.9 micromol/l (1.5). A total of 39% of patients with metastatic and 22.6% with early breast cancer had tHcy concentrations above the upper limit of normal. Women with metastatic disease had significantly higher tHcy compared with controls (P < 0.01) but not when compared with women with early breast cancer. Also, no difference was observed when women with early disease were compared with controls. We found no correlation between age and tHcy. Lower RCF levels were identified in group B compared with group A, but this does not fully explain the increased tHcy levels seen within the same group. We conclude that hyperhomocysteinemia is common in women with advanced breast cancer. This observation could explain the high rate of venous thrombosis in women with metastatic breast malignancy.
Is Increase of Homocysteine, Anti-Cardiolipin, Anti-Phospholipid Antibodies associated with Breast Tumors?
Abdollahi Alireza,Omranipour Ramesh
Acta medica Iranica
Patients with malignancy are at higher risk of thrombotic complications due to the hypercoagulability state. Our objective in this study was to assess the serum concentrations of Homocysteine, anti phospholipid antibodies, and anti cardiolipin in patients with benign and malignant breast tumors and study the effect of chemotherapy on the serum levels of these markers. A case control study was carried out on 100 women with malignant breast tumor and 100 age matched control with benign breast tumors.Serum concentrations of heomocystein, anti cardiolipin antibody (IgG and IgMaCL) and anti-phospholipid antibody (IgG and IgMaPL) were measured in all cases. The malignant group was followed for six months, and serum levels of above-mentioned markers were measured again after surgical removal of breast tumor and chemotherapy. Current results showed a significantly higher serum concentration of Homocysteine, IgG and IgMaPL, IgG and IgM aCL in patients with malignant tumor before chemotherapy compared with benign tumor patients. We found a significant decrease in these markers after chemotherapy (P Value<0.05).We propose performing these tests (Homocysteine, IgG and IgM aPL, aCL) in patients with breast malignancy and starting prophylactic anti-thrombotic treatment in those with high serum levels of the markers. In addition, since the serum levels of the markers in patients with malignancy reduce after adjuvant therapies, we strongly recommend using adjuvant chemotherapy in these patients.
Changes in lipid profiles during and after (neo)adjuvant chemotherapy in women with early-stage breast cancer: A retrospective study.
Tian Wei,Yao Yihan,Fan Guocai,Zhou Yunxiang,Wu Miaowei,Xu Dong,Deng Yongchuan
Many different treatments may affect the serum lipid profiles of breast cancer patients. This study analyzed serum lipid levels at different periods during treatment to observe the changes in lipid profiles during and after chemotherapy and to compare the different effects of different chemotherapy regimens on serum lipid profiles. A total of 805 patients were included in this study. We measured the lipid profiles of patients who received surgery without chemotherapy prior to the operation and at 3, 6 and 12 months after operation. In addition, in patients who underwent chemotherapy, the lipid profiles were measured prior to chemotherapy, prior to the last cycle of chemotherapy and 6 months after chemotherapy. Lipid profile measurements included total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), homocysteine (HCY), and uric acid (UA). (Neo)Adjuvant chemotherapy exerted an adverse temporary effect on lipid levels (manifested as increased TG and LDL-C levels, and decreased HDL-C levels, particularly in the adjuvant chemotherapy group) during the chemotherapy periods. However, this influence was not sustained, as the lipid profiles levels were generally restored to baseline levels 6 months after chemotherapy completion. Different age groups showed different changes in lipid levels that were influenced by chemotherapy. The younger group (20-40 years old) showed a greater increase in TC and LDL-C levels during chemotherapy than the 41-65-year-old group. Chemotherapy exerts an adverse temporary effect, and the effects of different regimens on lipid levels are similar. Furthermore, lipid profiles in younger women may be more sensitive to chemotherapy.
Systemic chemotherapy interferes in homocysteine metabolism in breast cancer patients.
Yamashita Eliana K,Teixeira Bianca M,Yoshihara Renata N,Kuniyoshi Renata K,Alves Beatriz C A,Gehrke Flávia S,Vilas-Bôas Viviane A,Correia João A,Azzalis Ligia A,Junqueira Virginia B C,Pereira Edimar Cristiano,Fonseca Fernando L A
Journal of clinical laboratory analysis
BACKGROUND:Hyperhomocysteinemia in breast cancer (BC) patients can be a risk factor for thromboembolic events. This study aimed to evaluate homocysteine and its cofators (folic acid and vitamin B12) concentrations and platelet count at diagnosis of BC, 3 and 6 months after the beginning of chemotherapy treatment and to correlate them with clinical data. METHODS:Thirty-five BC patients were included; blood samples were obtained by venipuncture. Plasmatic Hcy and cofactors concentrations were measured by competitive chemiluminescent enzyme immunoassay method. Platelet count was done using an automated analyzer. Statistical analysis was performed using the software SPSS. RESULTS:During chemotherapy, homocysteine (P = 0.032) and vitamin B12 (P < 0.001) concentrations increased, while folate and platelets decreased (P < 0.001). Among the clinical data, the menopausal status showed significant positive correlation (P = 0.022) with homocysteine concentration increase. CONCLUSIONS:Evaluation of homocysteine concentrations during chemotherapy is extremely important because their levels increase during chemotherapy treatment, thus increasing the risk of thromboembolism development.
Impact of hyperhomocysteinemia on breast cancer initiation and progression: epigenetic perspective.
Naushad Shaik Mohammad,Reddy Cheruku Apoorva,Kumaraswami Konda,Divyya Shree,Kotamraju Srigiridhar,Gottumukkala Suryanarayana Raju,Digumarti Raghunadha Rao,Kutala Vijay Kumar
Cell biochemistry and biophysics
Our recent study showing association of hyperhomocysteinemia and hypomethioninemia in breast cancer and other studies indicating association of hyperhomocysteinemia with metastasis and development of drug resistance in breast cancer cells treated with homocysteine lead us to hypothesize that homocysteine might modulate the expression of certain tumor suppressors, i.e., RASSF1, RARβ1, CNND1, BRCA1, and p21, and might influence prognostic markers such as BNIP3 by inducing epigenetic alteration. To demonstrate this hypothesis, we have treated MCF-7 and MDA-MB-231 cells with different doses of homocysteine and observed dose-dependent inhibition of BRCA1 and RASSF1, respectively. In breast cancer tissues, we observed the following expression pattern: BNIP3 > BRCA1 > RARβ1 > CCND1 > p21 > RASSF1. Hyperhomocysteinemia was positively associated with BRAC1 hypermethylation both in breast cancer tissue and corresponding peripheral blood. Peripheral blood CpG island methylation of BRCA1 in all types of breast cancer and methylation of RASSF1 in ER/PR-negative breast cancers showed positive correlation with total plasma homocysteine. The methylation of RASSF1 and BRCA1 was associated with breast cancer initiation as well as progression, while BRCA1 methylation was associated with DNA damage. Vitamin B12 showed inverse association with the methylation at both the loci. RFC1 G80A and cSHMT C1420T variants showed positive association with methylation at both the loci. Genetic variants influencing remethylation step were associated positively with BRCA1 methylation and inversely with RASSF1 methylation. GCPII C1561T variant showed inverse association with BRCA1 methylation. We found good correlation of BRAC1 (r = 0.90) and RASSF1 (0.92) methylation pattern between the breast cancer tissue and the corresponding peripheral blood. To conclude, elevated homocysteine influences methionine dependency phenotype of breast cancer cells and is associated with breast cancer progression by epigenetic modulation of RASSF1 and BRCA1.
Prospective Investigation of Serum Metabolites, Coffee Drinking, Liver Cancer Incidence, and Liver Disease Mortality.
Loftfield Erikka,Rothwell Joseph A,Sinha Rashmi,Keski-Rahkonen Pekka,Robinot Nivonirina,Albanes Demetrius,Weinstein Stephanie J,Derkach Andriy,Sampson Joshua,Scalbert Augustin,Freedman Neal D
Journal of the National Cancer Institute
BACKGROUND:Coffee has been consistently associated with lower risk of liver cancer and chronic liver disease, suggesting that coffee affects mechanisms underlying disease development. METHODS:We measured serum metabolites using untargeted metabolomics in 1:1 matched nested case-control studies of liver cancer (n = 221 cases) and fatal liver disease (n = 242 cases) in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention cohort (n = 29 133). Associations between baseline coffee drinking and metabolites were identified using linear regression; conditional logistic regression models were used to identify associations with subsequent outcomes. RESULTS:Overall, 21 metabolites were associated with coffee drinking and also each subsequent endpoint; nine metabolites and trigonelline, a known coffee biomarker, were identified. Tyrosine and two bile acids, glycochenodeoxycholic acid (GCDCA) and glycocholic acid (GCA), were inversely associated with coffee but positively associated with both outcomes; odds ratios (ORs) comparing the 90th to 10th percentile (modeled on a continuous basis) ranged from 3.93 (95% confidence interval [CI] = 2.00 to 7.74) for tyrosine to 4.95 (95% CI = 2.64 to 9.29) for GCA and from 4.00 (95% CI = 2.42 to 6.62) for GCA to 6.77 (95% CI = 3.62 to 12.65) for GCDCA for liver cancer and fatal liver disease, respectively. The remaining six metabolites and trigonelline were positively associated with coffee drinking but inversely associated with both outcomes; odds ratio ranged from 0.16 to 0.37. Associations persisted following diet adjustment and for outcomes occurring greater than 10 years after blood collection. CONCLUSIONS:A broad range of compounds were associated with coffee drinking, incident liver cancer, and liver disease death over 27 years of follow-up. These associations provide novel insight into chronic liver disease and liver cancer etiology and support a possible hepatoprotective effect of coffee.
Surgery Strategies for Gastric Cancer With Liver Metastasis.
Luo Zai,Rong Zeyin,Huang Chen
Frontiers in oncology
Gastric cancer with liver metastasis is defined as advanced gastric cancer and remains one of the deadliest diseases with poor prognosis. Approximately 4-14% of patients with gastric cancers presented with liver metastases at the initial diagnosis. Owing to its incurability, first-line treatment for gastric cancer with liver metastases is systematic chemotherapy, whereas surgery is usually performed to alleviate severe gastrointestinal symptoms. However, continuously emerging retrospective studies confirmed the role of surgery in gastric cancer with liver metastases and showed significantly improved survival rate in patients assigned to a group of surgery with or without chemotherapy. Therefore, more and more convincing data that resulted from prospective randomized clinical trials is in need to clarify the surgery strategies in patients with gastric cancer with liver metastasis.
Role of gut microbiota in liver disease.
Albhaisi Somaya A M,Bajaj Jasmohan S,Sanyal Arun J
American journal of physiology. Gastrointestinal and liver physiology
The gut microbiome is the natural intestinal inhabitant that has been recognized recently as a major player in the maintenance of human health and the pathophysiology of many diseases. Those commensals produce metabolites that have various effects on host biological functions. Therefore, alterations in the normal composition or diversity of microbiome have been implicated in various diseases, including liver cirrhosis and nonalcoholic fatty liver disease. Moreover, accumulating evidence suggests that progression of dysbiosis can be associated with worsening of liver disease. Here, we review the possible roles for gut microbiota in the development, progression, and complication of liver disease.
A story of liver and gut microbes: how does the intestinal flora affect liver disease? A review of the literature.
Giuffrè Mauro,Campigotto Michele,Campisciano Giuseppina,Comar Manola,Crocè Lory Saveria
American journal of physiology. Gastrointestinal and liver physiology
Each individual is endowed with a unique gut microbiota (GM) footprint that mediates numerous host-related physiological functions, such as nutrient metabolism, maintenance of the structural integrity of the gut mucosal barrier, immunomodulation, and protection against microbial pathogens. Because of increased scientific interest in the GM, its central role in the pathophysiology of many intestinal and extraintestinal conditions has been recognized. Given the close relationship between the gastrointestinal tract and the liver, many pathological processes have been investigated in the light of a microbial-centered hypothesis of hepatic damage. In this review we introduce to neophytes the vast world of gut microbes, including prevalent bacterial distribution in healthy individuals, how the microbiota is commonly analyzed, and the current knowledge of the role of GM in liver disease pathophysiology. Also, we highlight the potentials and downsides of GM-based therapy.
Molecular Alteration Analysis of Human Gut Microbial Composition in Graves' disease Patients.
Ishaq Hafiz Muhammad,Mohammad Imran Shair,Shahzad Muhammad,Ma Chaofeng,Raza Muhammad Asif,Wu Xiaokang,Guo Hui,Shi Peijie,Xu Jiru
International journal of biological sciences
The gut microbial association with host co-existence is critical for body homeostasis and pathogenicity. Graves' disease (GD) is an autoimmune disease manifested with hyperthyroidism and ophthalmopathy. However, we hypothesized that gut bacteria could affect an important role in GD pathogenicity. The current study aim was to characterize and investigate the intestinal bacterial composition of GD qualitatively and quantitatively. 27 GD and 11 healthy controls were enrolled for fecal sample collection. The PCR-DGGE of 16S rRNA gene by targeting V3 region and Real-time PCR for , were performed. High-throughput sequencing of 16S rRNA gene with the V3+V4 site was perormed on Hiseq2500 platform on randomly 20 selected samples. The relative analysis of richness indices and diversity illustrated lesser diversification of intestinal bacteria in GD patients in contrast to controls. The data statistics shows the alteration in phyla of GD as compared to control. At the family taxonomic level, the relative abundance of Prevotellaceae and Pasteurellaceae were significantly higher in patients, while Enterobacteriaceae, Veillonellaceae, and Rikenellaceae were significantly lower in the diseased group as compared to control. At the genus level, a significant raised in genera count of the diseased group were while significantly decreased in the genera of the GD group were and The modulation in intestinal bacterial composition was checked at species level particularly abundance was raised in GD. The outcomes of the current study are aligned with the proposed hypothesis of gut microbial dysbiosis in GD. Statistically, alpha indices and differential abundance analyses of each intestinal bacterial community were significantly changed in GD. Therefore, the current study may provide a new insight into the GD pathogenesis and, in turn, explore its contribution in possible treatments.
Gut microbiota in experimental murine model of Graves' orbitopathy established in different environments may modulate clinical presentation of disease.
Masetti Giulia,Moshkelgosha Sajad,Köhling Hedda-Luise,Covelli Danila,Banga Jasvinder Paul,Berchner-Pfannschmidt Utta,Horstmann Mareike,Diaz-Cano Salvador,Goertz Gina-Eva,Plummer Sue,Eckstein Anja,Ludgate Marian,Biscarini Filippo,Marchesi Julian Roberto,
BACKGROUND:Variation in induced models of autoimmunity has been attributed to the housing environment and its effect on the gut microbiota. In Graves' disease (GD), autoantibodies to the thyrotropin receptor (TSHR) cause autoimmune hyperthyroidism. Many GD patients develop Graves' orbitopathy or ophthalmopathy (GO) characterized by orbital tissue remodeling including adipogenesis. Murine models of GD/GO would help delineate pathogenetic mechanisms, and although several have been reported, most lack reproducibility. A model comprising immunization of female BALBc mice with a TSHR expression plasmid using in vivo electroporation was reproduced in two independent laboratories. Similar orbital disease was induced in both centers, but differences were apparent (e.g., hyperthyroidism in Center 1 but not Center 2). We hypothesized a role for the gut microbiota influencing the outcome and reproducibility of induced GO. RESULTS:We combined metataxonomics (16S rRNA gene sequencing) and traditional microbial culture of the intestinal contents from the GO murine model, to analyze the gut microbiota in the two centers. We observed significant differences in alpha and beta diversity and in the taxonomic profiles, e.g., operational taxonomic units (OTUs) from the genus Lactobacillus were more abundant in Center 2, and Bacteroides and Bifidobacterium counts were more abundant in Center 1 where we also observed a negative correlation between the OTUs of the genus Intestinimonas and TSHR autoantibodies. Traditional microbiology largely confirmed the metataxonomics data and indicated significantly higher yeast counts in Center 1 TSHR-immunized mice. We also compared the gut microbiota between immunization groups within Center 2, comprising the TSHR- or βgal control-immunized mice and naïve untreated mice. We observed a shift of the TSHR-immunized mice bacterial communities described by the beta diversity weighted Unifrac. Furthermore, we observed a significant positive correlation between the presence of Firmicutes and orbital-adipogenesis specifically in TSHR-immunized mice. CONCLUSIONS:The significant differences observed in microbiota composition from BALBc mice undergoing the same immunization protocol in comparable specific-pathogen-free (SPF) units in different centers support a role for the gut microbiota in modulating the induced response. The gut microbiota might also contribute to the heterogeneity of induced response since we report potential disease-associated microbial taxonomies and correlation with ocular disease.
Gut Microbiome in BALB/c and C57BL/6J Mice Undergoing Experimental Thyroid Autoimmunity Associate with Differences in Immunological Responses and Thyroid Function.
Moshkelgosha Sajad,Masetti Giulia,Berchner-Pfannschmidt Utta,Verhasselt Hedda Luise,Horstmann Mareike,Diaz-Cano Salvador,Noble Alistair,Edelman Barbel,Covelli Danila,Plummer Sue,Marchesi Julian R,Ludgate Marian,Biscarini Filippo,Eckstein Anja,Banga J Paul
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme
Experimental models of hyperthyroid Graves' disease (GD) and Graves' orbitopathy (GO) are efficiently developed by genetic immunisation by electroporation with human thyrotropin hormone receptor (hTSHR) A-subunit plasmid in female BALB/c (H-2d) mice. We investigated susceptibility in C57BL/6 J (H-2b) animals to allow studies on disease mechanisms in transgenic and immune response gene knock-out mice. Higher numbers of female C57BL/6 J were positive for pathogenic thyroid stimulating antibodies, but induced hyperthyroidism remained at a low frequency compared to BALB/c animals. Assessment of hTSHR specific T cells showed reduced proliferation in C57BL/6 J animals accompanied with anti-inflammatory IL-10, with less pro-inflammatory IFN-γ compared to BALB/c. Whilst the orbital tissue from immune BALB/c mice showed inflammation and adipogenesis, in contrast C57BL/6 J animals showed normal pathology. We characterised the gut microbiota using 16 S ribosomal RNA gene sequencing to explore its possible pathogenic role in the model. Despite being housed under identical conditions, we observed significantly different organisation of the microbiota (beta-diversity) in the two strains. Taxonomic differences were also noted, with C57BL/6 J showing an enrichment of Operational Taxonomic Units (OTUs) belonging to the and , followed by , and genera. A higher number of genera significantly correlating with clinical features was observed in C57BL/6 J compared to BALB/c; for example, OTUs correlated negatively with thyroid-stimulating antibodies in C57BL/6 J mice. Thus, our data suggest gut microbiota may play a pivotal immunomodulatory role that differentiates the thyroid function and orbital pathology outcome in these two inbred strains undergoing experimental GO.
Gut microbiota and Hashimoto's thyroiditis.
Virili Camilla,Fallahi Poupak,Antonelli Alessandro,Benvenga Salvatore,Centanni Marco
Reviews in endocrine & metabolic disorders
About two third of the human microbial commensal community, namely the gut microbiota, is hosted by the gastrointestinal tract which represents the largest interface of the organism to the external environment. This microbial community co-evolved in a symbiotic relationship with the human beings. Growing evidence support the notion that the microbiota plays a significant role in maintaining nutritional, metabolic and immunologic homeostasis in the host. Microbiota, beside the expected role in maintaining gastrointestinal homeostasis also exerts metabolic functions in nutrients digestion and absorption, detoxification and vitamins' synthesis. Intestinal microbiota is also key in the correct development of the lymphoid system, 70% of which resides at the intestinal level. Available studies, both in murine models and humans, have shown an altered ratio between the different phyla, which characterize a" normal" gut microbiota, in a number of different disorders including obesity, to which a significant part of the studies on intestinal microbiota has been addressed so far. These variations in gut microbiota composition, known as dysbiosis, has been also described in patients bearing intestinal autoimmune diseases as well as type 1 diabetes mellitus, systemic sclerosis and systemic lupus erythematosus. Being Hashimoto's thyroiditis the most frequent autoimmune disorder worldwide, the analysis of the reciprocal influence with intestinal microbiota gained interest. The whole thyroid peripheral homeostasis may be sensitive to microbiota changes but there is also evidence that the genesis and progression of autoimmune thyroid disorders may be significantly affected from a changing intestinal microbial composition or even from overt dysbiosis. In this brief review, we focused on the main features which characterize the reciprocal influence between microbiota and thyroid autoimmunity described in the most recent literature.
Alterations of the Gut Microbiota in Hashimoto's Thyroiditis Patients.
Zhao Fuya,Feng Jing,Li Jun,Zhao Lei,Liu Yang,Chen Huinan,Jin Ye,Zhu Biqiang,Wei Yunwei
Thyroid : official journal of the American Thyroid Association
BACKGROUND:Hashimoto's thyroiditis (HT) is an organ-specific autoimmune disease in which both genetic predisposition and environmental factors serve as disease triggers. Many studies have indicated that alterations in the gut microbiota are important environmental factors in the development of inflammatory and autoimmune diseases. A comparative analysis was systematically performed of the gut microbiota in HT patients and healthy controls. METHODS:First, a cross-sectional study of 28 HT patients and 16 matched healthy controls was conducted. Fecal samples were collected, and microbiota were analyzed using 16S ribosomal RNA gene sequencing. Second, an independent cohort of 22 HT patients and 11 healthy controls was used to evaluate the diagnostic potential of the selected biomarkers. RESULTS:Similar levels of bacterial richness and diversity were found in the gut microbiota of HT patients and healthy controls (p = 0.11). A detailed fecal microbiota Mann-Whitney U-test (Q value <0.05) revealed that the abundance levels of Blautia, Roseburia, Ruminococcus_torques_group, Romboutsia, Dorea, Fusicatenibacter, and Eubacterium_hallii_group genera were increased in HT patients, whereas the abundance levels of Fecalibacterium, Bacteroides, Prevotella_9, and Lachnoclostridium genera were decreased. A correlation matrix based on the Spearman correlation distance confirmed correlations among seven clinical parameters. Additionally, the linear discriminant analysis effect size method showed significant differences in 27 genera between the two groups that were strongly correlated with clinical parameters. The linear discriminant analysis value was used to select the first 10 species from the 27 different genera as biomarkers, achieving area under the curve values of 0.91 and 0.88 for exploration and validation data, respectively. CONCLUSIONS:Characterization of the gut microbiota in HT patients confirmed that HT patients have altered gut microbiota and that gut microbiota are correlated with clinical parameters, suggesting that microbiome composition data could be used for disease diagnosis. Further investigation is required to understand better the role of the gut microbiota in the pathogenesis of HT.
Alterations in the gut microbiota and metabolite profiles of thyroid carcinoma patients.
Feng Jing,Zhao Fuya,Sun Jiayu,Lin Baiqiang,Zhao Lei,Liu Yang,Jin Ye,Li Shengda,Li Aidong,Wei Yunwei
International journal of cancer
The aim of our study was to investigate the relationship among the gut microbiota community, metabolite profiles and thyroid carcinoma (TC). First, 30 TC patients and 35 healthy controls (HCs) fecal samples were applied to characterize the gut microbial community using 16S rRNA gene sequencing. Differential microbiota compositions were observed, with significant enrichment of 19 and depletion of 8 genera in TC samples compared to those in HCs (Q value <0.05), and some genera were correlated with various clinical parameters, such as lipoprotein A and apolipoprotein B. Furthermore, 6 different genera distinguished TC patients from HCs with the AUC of 0.94. The PICRUSt analysis showed 12 remarkably different metabolic pathways (Q value <0.05). Subsequently, we systematically analyzed the gut microbiota and metabolites in the same TC patients (n = 15) and HCs (n = 15). The characteristics of the gut microbiota community were mostly consistent with the above results (30 TC patients and 35 HCs), and liquid chromatography mass spectrometry analysis was performed to characterize the metabolite profiles. In total, 21 different genera (Q value <0.05) and 72 significantly changed metabolites (VIP > 1.0 and p < 0.05) were observed and correlated to each other. Eight metabolites combined with 5 genera were more effective in distinguishing TC patients from HCs (AUC = 0.97). In conclusion, our study presents a comprehensive landscape of the gut microbiota and metabolites in TC patients, and provides a research direction of the mechanism of interaction between gut microbiota alteration and TC pathogenesis.