Fecal Microbiota Underlying the Coexistence of Schizophrenia and Multiple Sclerosis in Chinese Patients.

Both schizophrenia (SZ) and multiple sclerosis (MS) affect millions of people worldwide and impose a great burden on society. Recent studies indicated that MS elevated the risk of SZ and vice versa, whereas the underlying pathological mechanisms are still obscure. Considering that fecal microbiota played a vital role in regulating brain functions, the fecal microbiota and serum cytokines from 90 SZ patients and 71 age-, gender-, and BMI-matched cognitively normal subjects (referred as SZC), 22 MS patients and 33 age-, gender-, and BMI-matched healthy subjects (referred as MSC) were analyzed. We found that both diseases demonstrated similar microbial diversity and shared three differential genera, including the down-regulated Faecalibacterium, Roseburia, and the up-regulated Streptococcus. Functional analysis indicated that the three genera were involved in pathways such as "carbohydrate metabolism" and "amino acid metabolism." Moreover, the variation patterns of serum cytokines associated with MS and SZ patients were a bit different. Among the six cytokines perturbed in both diseases, TNF-α increased, while IL-8 and MIP-1α decreased in both diseases. IL-1ra, PDGF-bb, and RANTES were downregulated in MS patients but upregulated in SZ patients. Association analyses showed that Faecalibacterium demonstrated extensive correlations with cytokines in both diseases. Most notably, Faecalibacterium correlated negatively with TNF-α. In other words, fecal microbiota such as Faecalibacterium may contribute to the coexistence of MS and SZ by regulating serum cytokines. Our study revealed the potential roles of fecal microbiota in linking MS and SZ, which paves the way for developing gut microbiota-targeted therapies that can manage two diseases with a single treat.

Akkermansia muciniphila in neuropsychiatric disorders: friend or foe?

An accumulating body of evidence suggests that the bacterium Akkermansia muciniphila exhibits positive systemic effects on host health, mainly by improving immunological and metabolic functions, and it is therefore regarded as a promising potential probiotic. Recent clinical and preclinical studies have shown that A. muciniphila plays a vital role in a variety of neuropsychiatric disorders by influencing the host brain through the microbiota-gut-brain axis (MGBA). Numerous studies observed that A. muciniphila and its metabolic substances can effectively improve the symptoms of neuropsychiatric disorders by restoring the gut microbiota, reestablishing the integrity of the gut mucosal barrier, regulating host immunity, and modulating gut and neuroinflammation. However, A. muciniphila was also reported to participate in the development of neuropsychiatric disorders by aggravating inflammation and influencing mucus production. Therefore, the exact mechanism of action of A. muciniphila remains much controversial. This review summarizes the proposed roles and mechanisms of A. muciniphila in various neurological and psychiatric disorders such as depression, anxiety, Parkinson's disease, Alzheimer's disease, multiple sclerosis, strokes, and autism spectrum disorders, and provides insights into the potential therapeutic application of A. muciniphila for the treatment of these conditions.

Probiotics for the treatment of depression and its comorbidities: A systemic review.

Depression is one of the most common psychiatric conditions, characterized by significant and persistent depressed mood and diminished interest, and often coexists with various comorbidities. The underlying mechanism of depression remain elusive, evidenced by the lack of an appreciate therapy. Recent abundant clinical trials and animal studies support the new notion that the gut microbiota has emerged as a novel actor in the pathophysiology of depression, which partakes in bidirectional communication between the gut and the brain through the neuroendocrine, nervous, and immune signaling pathways, collectively known as the microbiota-gut-brain (MGB) axis. Alterations in the gut microbiota can trigger the changes in neurotransmitters, neuroinflammation, and behaviors. With the transition of human microbiome research from studying associations to investigating mechanistic causality, the MGB axis has emerged as a novel therapeutic target in depression and its comorbidities. These novel insights have fueled idea that targeting on the gut microbiota may open new windows for efficient treatment of depression and its comorbidities. Probiotics, live beneficial microorganisms, can be used to modulate gut dysbiosis into a new eubiosis and modify the occurrence and development of depression and its comorbidities. In present review, we summarize recent findings regarding the MGB axis in depression and discuss the potential therapeutic effects of probiotics on depression and its comorbidities.

Association between transforming growth factor-beta 1 polymorphisms and risk of pre-eclampsia: a meta-analysis.

PURPOSE: Pre-eclampsia (PE) is a common pregnancy-specific disorder characterized by hypertension and proteinuria. Previous studies have generated conflicting results regarding the association of transforming growth factor-beta 1 (TGF-ß1) gene polymorphisms (+869 T/C, -509 C/T, +915 G/C, and -800 G/A) with PE risk. Therefore, we conducted this meta-analysis to more precisely assess the role of TGF-ß1 gene polymorphisms in PE. METHODS: Eligible studies were retrieved from PubMed, Embase, Web of Science, Elsevier Science Direct, and several Chinese databases. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to calculate the associations. RESULTS: A total of 11 eligible studies (1463 cases/1754 controls) were included in this meta-analysis. A statistically significant association was found between the TGF-ß1 + 869 T/C polymorphism and PE risk in the Asian population and in subgroup analyses of the Hardy-Weinberg equilibrium (HWE) in controls and healthy pregnant controls. There was a statistically significant association between TGF-ß1 - 509 C/T polymorphism and PE risk among Asian women, and in the subgroup analysis of healthy pregnant controls. No obvious association was observed under any genetic model for the TGF-ß1 + 915 G/C and -800 G/A polymorphisms and PE risk, or between the TGF-ß1 + 869 T/C and -509 C/T polymorphisms and severity of PE. CONCLUSIONS: The present study suggested that the TGF-ß1 + 869 T/C and -509 C/T polymorphisms are associated with an increased risk of PE in the Asian population. Further case-controlled studies with larger sample sizes are needed to confirm our results.

Contribution of Lactobacillus iners to Vaginal Health and Diseases: A Systematic Review.

Lactobacillus iners, first described in 1999, is a prevalent bacterial species of the vaginal microbiome. As L. iners does not easily grow on de Man-Rogosa-Sharpe agar, but can grow anaerobically on blood agar, it has been initially overlooked by traditional culture methods. It was not until the wide application of molecular biology techniques that the function of L. iners in the vaginal microbiome was carefully explored. L. iners has the smallest genome among known Lactobacilli and it has many probiotic characteristics, but is partly different from other major vaginal Lactobacillus species, such as L. crispatus, in contributing to the maintenance of a healthy vaginal microbiome. It is not only commonly present in the healthy vagina but quite often recovered in high numbers in bacterial vaginosis (BV). Increasing evidence suggests that L. iners is a transitional species that colonizes after the vaginal environment is disturbed and offers overall less protection against vaginal dysbiosis and, subsequently, leads to BV, sexually transmitted infections, and adverse pregnancy outcomes. Accordingly, under certain conditions, L. iners is a genuine vaginal symbiont, but it also seems to be an opportunistic pathogen. Further studies are necessary to identify the exact role of this intriguing species in vaginal health and diseases.

Lactobacillus iners Is Associated with Vaginal Dysbiosis in Healthy Pregnant Women: A Preliminary Study.

Vaginal dysbiosis has been identified to be associated with adverse pregnancy outcomes, such as preterm delivery and premature rupture of membranes. However, the overall structure and composition of vaginal microbiota in different trimesters of the pregnant women has not been fully elucidated. In this study, the physiological changes of the vaginal microbiota in healthy pregnant women were investigated. A total of 83 healthy pregnant participants were enrolled, who are in the first, second, or third pregnancy trimester. Quantitative real-time PCR was used to explore the abundant bacteria in the vaginal microbiota. No significant difference in the abundance of Gardnerella, Atopobium, Megasphaera, Eggerthella, Leptotrichia/Sneathia, or Prevotella was found among different trimesters, except Lactobacillus. Compared with the first pregnancy trimester, the abundance of L. iners decreased in the second and third trimester while the abundance of L. crispatus was increased in the second trimester. Moreover, we also found that vaginal cleanliness is correlated with the present of Lactobacillus, Atopobium, and Prevotella and leukocyte esterase is associated with Lactobacillus, Atopobium, Gardnerella, Eggerthella, Leptotrichia/Sneathia, and Prevotella. For those whose vaginal cleanliness raised or leukocyte esterase became positive, the richness of L. iners increased, while that of L. crispatus decreased significantly. Our present data indicated that the altered vaginal microbiota, mainly Lactobacillus, could be observed among different trimesters of pregnancy and L. iners could be considered as a potential bacterial marker for evaluating vaginal cleanliness and leukocyte esterase.

Association Between Serum Free Fatty Acids Levels and Gestational Diabetes Mellitus: a Cross-Sectional Study.

BACKGROUND: This study aimed to assess the relationship between serum free fatty acid (FFA) levels and gestational diabetes mellitus (GDM) in Chinese pregnant women. METHODS: A cross-sectional study was performed among 779 eligible pregnant women who underwent detailed prenatal visits in Hangzhou, China. RESULTS: Patients with GDM had significantly higher serum FFA levels than those without GDM. Spearman's correlation analysis showed that FFA levels were positively correlated with fasting plasma glucose, 1hPG, 2hPG, HOMA-IR, triglyceride, and sialic acid (p < 0.05) and negatively correlated with serum amylase level (all with p < 0.05). Stepwise logistic regression analysis further showed that elevated FFA levels significantly contributed to the risk for GDM. CONCLUSIONS: Our findings suggested that serum FFA levels were significantly associated with GDM.

Slow reduction of IP-10 Levels predicts HBeAg seroconversion in chronic hepatitis B patients with 5 years of entecavir treatment.

The aim of this study was to determine the correlation between dynamic changes in serum cytokine/chemokine expression levels in response to entecavir (ETV) treatment and HBV e antigen (HBeAg) seroconversion in patients with chronic hepatitis B (CHB). Four cytokines (interleukin [IL]-4, IL-6, IL-8, and interferon-γ) and five chemokines (macro-phage inflammatory protein [MIP]-1α, MIP-1ß, platelet derived growth factor-BB, and interferon-inducible protein 10 [IP-10]) before ETV therapy and at 3, 6, 12, 24, 36 and 60 months during therapy in 105 CHB patients were analyzed. The results showed that the low decrease rate of IP-10 levels after 1 year of ETV treatment was an independent predictor of HBeAg seroconversion at year 5 (Hazard ratio = 0.972). The area under the receiver operating characteristic curves for the decrease rate of IP-10 levels after 1 year of treatment to discriminate a year-5 HBeAg seroconversion was 0.752 (p = 0.005). The results indicate that higher IP-10 level at year one of ETV treatment is associated with an increased probability of HBeAg seroconversion. Quantification of IP-10 during ETV treatment may help to predict long-term HBeAg seroconversion in patients with CHB.

Low Serum Amylase is Associated with Gestational Diabetes Mellitus in Chinese Pregnant Women.

BACKGROUND: The association between low serum amylase levels and type 2 diabetes mellitus and metabolic syndrome has been clearly disclosed. However, the relationship between serum amylase levels and gestational diabetes mellitus (GDM) has not been extensively studied. This study aimed to assess the association of serum amylase with GDM. METHODS: A cross-sectional study was performed among 878 Chinese pregnant women who underwent detailed prenatal visits in Hangzhou, China. RESULTS: A total of 108 (12.30%) subjects fulfilled the diagnostic criteria of GDM. Patients with GDM had significantly lower levels of serum amylase than those without GDM. The prevalence rate of GDM decreased across serum amylase increasing tertiles (p for trend < 0.001). Correlation analysis showed that serum amylase level was negatively correlated with fasting plasma glucose, 1hPG, 2hPG, HOMA-IR, triglyceride, free fatty acid, and thyroid stimulating hormone (all with p < 0.05). Multiple logistic regression showed that low serum amylase level predicted increased risk of GDM. CONCLUSIONS: Our findings suggest that low serum amylase level is significantly associated with increased risk of GDM.

Associations Between Inflammatory Markers, Hemostatic Markers, and Microvascular Complications in 182 Chinese Patients With Type 2 Diabetes Mellitus.

OBJECTIVE: To examine the associations between inflammatory markers, coagulation and fibrinolysis parameters, and microvascular complications in 182 Chinese patients with type 2 diabetes mellitus (T2DM) who sought treatment at a large hospital in Zhejiang province, China. METHODS: We investigated the relationships of blood inflammatory markers with hemostatic markers in 87 patients with T2DM who did not have complications and 95 patients with T2DM who had microvascular complications. RESULTS: C-reactive protein (CRP) and interleukin-6 (IL-6) were significantly correlated with fibrinogen, thrombin-antithrombin III complex (TAT III), plasminogen activator inhibitor-1 (PAI-1), von Willebrand factor (vWF), and coagulation factors (F) VII in patients with T2DM who had microvascular complications (P <.05). Based on logistic regression analysis, the highest-tertile groups of fibrinogen, FVII, and FVIII, corresponded to a greater risk of high CRP, whereas risk of high IL-6 was significantly greater in the groups with highest-tertile values for fibrinogen, FVII, TAT III, PAI-1, and activated protein C (APC). CONCLUSIONS: Elevated levels of CRP and IL-6 might be associated with increased coagulability and a tendency towards thrombus formation in patients with T2DM who have microvascular complications.

Relationship between Serum Sialic Acid and Hemostatic Markers in Patients with Type 2 Diabetes Mellitus.

BACKGROUND: Serum sialic acid (SA) is an acute phase response marker. Additionally, it is an independent risk factor for atherosclerotic disease and is higher in patients with type 2 diabetes mellitus (T2DM). The objective of this study was to determine the association of SA with blood coagulation and fibrinolysis in T2DM patients. METHODS: The levels of serum SA and blood coagulation and fibrinolysis markers were measured in patients with T2DM. The associations of SA with hemostatic markers and other variables were assessed. RESULTS: There were significant correlations between SA and fibrinogen, D-dimer, factor (F) IX, and platelet (PLT) that were independent of smoking, body mass index (BMI), waist-to-hip ratio, hemoglobin A(1c) (HbA1c), fasting plasma glucose (FPG), triglycerides (TG), total cholesterol (TC) to high-density lipoprotein cholesterol (HDL-C) ratio, and antithrombotic therapy history. Based on logistic regression analyses, the highest tertile groups of fibrinogen, D-dimer, F VIII, F IX, and PLT showed a significantly increased risk of high SA compared with the lowest tertiles after adjusting for age, gender, and antithrombotic therapy history. SA also significantly correlated with duration of diabetes, BMI, FPG, TG, low-density lipoprotein cholesterol (LDL-c), TC-to-HDL-C ratio, and albumin-to-creatinine ratio (ACR). CONCLUSIONS: Elevated serum SA levels are associated with increased coagulability and higher risk of thrombus formation in T2DM patients.

Meta-analysis of the association of AhR Arg554Lys, AhRR Pro185Ala, and ARNT Val189Val polymorphisms and endometriosis risk in Asians.

PURPOSE: Several studies have suggested an association between the polymorphisms AhR Arg554Lys, AhRR Pro185Ala, and ARNT Val189Val and endometriosis, but results have been inconclusive. The aim of the present study was to assess these associations by meta-analysis. METHODS: Eligible literatures were retrieved from PubMed, ISI Web of Science, Elsevier Science Direct, and several Chinese databases. The pooled odds ratios (ORs) and the corresponding 95 % confidence intervals (CIs) were calculated with a random or fixed-effect model. RESULTS: A total of six eligible studies were included. Regarding the AhR Arg554Lys and ARNT Val189Val polymorphisms, no obvious associations were found in either overall analysis or subgroup analysis based on the country, source of control, sample size, and genotyping method. For the AhRR Pro185Ala polymorphism, overall results suggested a marginal association with endometriosis susceptibility under the dominant model (OR = 1.65, 95 % CI = 1.00-2.72). Furthermore, a significantly increased risk for endometriosis was found in the subgroups which used the TaqMan method for genotype analysis or had a sample size ≥200. CONCLUSIONS: This meta-analysis suggested that the polymorphisms of AhR Arg554Lys and ARNT Val189Val are not associated with endometriosis, while the AhRR Pro185Ala polymorphism may be associated with endometriosis risk. However, further case-control studies with larger sample sizes are needed to confirm our results.

Association of TNF-alpha, IL-6 and IL-1beta gene polymorphisms with polycystic ovary syndrome: a meta-analysis.

BACKGROUND: Several studies on the association of TNF-alpha (-308 G/A), IL-6 (-174 G/C) and IL-1beta (-511 C/T) polymorphisms with polycystic ovary syndrome (PCOS) risk have reported conflicting results. The aim of the present study was to assess these associations by meta-analysis. RESULTS: A total of 14 eligible articles (1665 cases/1687 controls) were included in this meta-analysis. The results suggested that there was no obvious association between the TNF-alpha (-308 G/A) polymorphism and PCOS in the overall population or subgroup analysis by ethnicity, Hardy-Weinberg equilibrium (HWE) in controls, genotyping method, PCOS diagnosis criteria, and study sample size. Also, no obvious association was found between the TNF-alpha (-308 G/A) polymorphism and obesity in patients with PCOS (body mass index [BMI] ≥ 25 kg/m(2) vs. BMI < 25 kg/m(2)). Regarding the IL-6 (-174 G/C) polymorphism, also no association was found in the overall population in heterozygote comparison, dominant model, and recessive model. Even though an allelic model (odds ratio [OR] = 0.63, 95% confidence interval [CI] = 0.41-0.96) and a homozygote comparison (OR = 0.52, 95% CI = 0.30-0.93) showed that the IL-6 (-174 G/C) polymorphism was marginally associated with PCOS. Further subgroup analysis suggested that the effect size was not significant among HWE in controls (sample size ≤ 200) and genotyping method of pyrosequencing under all genetic models. Similarly, there was no association between the IL-1beta (-511 C/T) polymorphism and PCOS in the overall population or subgroup analysis under all genetic models. Furthermore, no significant association was found between the IL-1beta (-511 C/T) polymorphism and several clinical and biochemical parameters in patients with PCOS. CONCLUSIONS: The results of this meta-analysis suggest that the TNF-alpha (-308 G/A), IL-6 (-174 G/C), and IL-1beta (-511 C/T) polymorphisms may not be associated with PCOS risk. However, further case-control studies with larger sample sizes are needed to confirm our results.

Associations between estrogen receptor-beta polymorphisms and endometriosis risk: a meta-analysis.

BACKGROUND: Many epidemiological studies have suggested an association between estrogen receptor-beta (ER-ß) polymorphisms with endometriosis risk. However, the results of these studies have been inconsistent. In the present study, we performed a meta-analysis to clarify the associations between the ER-ß rs4986938 and rs1256049 polymorphisms and endometriosis risk. METHODS: Eligible publications were retrieved from the PubMed, ISI Web of Science, and several Chinese language databases. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random or fixed effect model. RESULTS: A total of eight studies (1100 cases/1485 controls) for the rs4986938 polymorphism and four studies (353 cases/450 controls) for the rs1256049 polymorphism were included in this meta-analysis. Regarding the rs4986938 polymorphism, no obvious associations were found for all genetic models when all studies were pooled into the meta-analysis. In the subgroup analyses by ethnicity, study sample size, endometriosis-associated infertility, and stage of endometriosis, a significantly increased risk was observed among mixed populations (dominant model, OR=2.03, 95% CI=1.56-2.64) and among cases with endometriosis-associated infertility (dominant model, OR=1.83, 95% CI=1.26-2.67). Regarding the rs1256049 polymorphism, no obvious associations were found for all genetic models in the overall population. Subgroup analyses by ethnicity and study sample size revealed that only one study of a mixed population with small sample size showed an increased risk of endometriosis. No publication bias was found in the present study. CONCLUSIONS: The results of this meta-analysis suggest that the ER-ß rs4986938 and rs1256049 polymorphisms may not be associated with endometriosis risk, while the observed increased risk of endometriosis-associated infertility may be due to bias by the inclusion of small-scale studies. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_184.

Increased diversity of fungal flora in the vagina of patients with recurrent vaginal candidiasis and allergic rhinitis.

Recurrent vaginal candidiasis (RVC) is considered to be a hypersensitivity disorder that is associated with allergic rhinitis (AR) in immune deficiencies; however, whether or not the composition of the vaginal fungal flora in patients with AR and RVC is altered and if such alterations in patients with AR are associated with the development of RVC remain unclear. In the present study, a cultivation-independent method with the 18S rRNA gene clone library was used to analyze the diversity and composition of the vaginal fungal flora in patients with AR and RVC and to explore the association. Three fungal phyla (Ascomycotae, 22 out of 28; Basidiomycetes, 5 out of 28; and Oomycetes, 1 out of 28) were identified from groups of healthy volunteers, patients with AR, patients with RVC, and patients with RVC complicated by AR, including 28 phylotypes of fungal flora (10, 15, 17, and 21 phylotypes for each group, respectively). The predominant genera of fungi identified in the vagina included Candida, uncultured fungi, and Dothideomycetes. An increased proportion of Candida albicans accompanied with decreased proportions of Saccharomyces cerevisiae and uncultured fungi was observed in patients with AR or RVC (P < 0.05). Candida glabrata, Eladia saccula, Trichosporon jirovecii, and Phytophthora spp. occurred simultaneously in the three patient groups. The composition of the fungal communities in the four groups was statistically different (P < 0.001). The vaginal fungal diversity in patients with AR or RVC was significantly higher compared with healthy volunteers (P < 0.05). The data revealed an increased diversity and varied composition of the vaginal fungal flora in patients with AR and RVC and indicated that disturbed vaginal fungal flora in patients with AR might be correlated with disease progression in patients with RVC.