scholarly journals Gut dysbiosis induces the development of pre-eclampsia through bacterial translocation

Gut ◽  
2020 ◽  
Vol 69 (3) ◽  
pp. 513-522 ◽  
Author(s):  
Xia Chen ◽  
Pan Li ◽  
Mian Liu ◽  
Huimin Zheng ◽  
Yan He ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Metabolic Diseases ◽  
In Situ Hybridisation ◽  
Gut Dysbiosis ◽  
Causative Relationship ◽  
Cytokine Levels ◽  
Rrna Sequencing ◽  
Faecal Microbiome

ObjectivePre-eclampsia (PE) is one of the malignant metabolic diseases that complicate pregnancy. Gut dysbiosis has been identified for causing metabolic diseases, but the role of gut microbiome in the pathogenesis of PE remains unknown.DesignWe performed a case–control study to compare the faecal microbiome of PE and normotensive pregnant women by 16S ribosomal RNA (rRNA) sequencing. To address the causative relationship between gut dysbiosis and PE, we used faecal microbiota transplantation (FMT) in an antibiotic-treated mouse model. Finally, we determined the microbiome translocation and immune responses in human and mouse placental samples by 16S rRNA sequencing, quantitative PCR and in situ hybridisation.ResultsPatients with PE showed reduced bacterial diversity with obvious dysbiosis. Opportunistic pathogens, particularly Fusobacterium and Veillonella, were enriched, whereas beneficial bacteria, including Faecalibacterium and Akkermansia, were markedly depleted in the PE group. The abundances of these discriminative bacteria were correlated with blood pressure (BP), proteinuria, aminotransferase and creatinine levels. On successful colonisation, the gut microbiome from patients with PE triggered a dramatic, increased pregestational BP of recipient mice, which further increased after gestation. In addition, the PE-transplanted group showed increased proteinuria, embryonic resorption and lower fetal and placental weights. Their T regulatory/helper-17 balance in the small intestine and spleen was disturbed with more severe intestinal leakage. In the placenta of both patients with PE and PE-FMT mice, the total bacteria, Fusobacterium, and inflammatory cytokine levels were significantly increased.ConclusionsThis study suggests that the gut microbiome of patients with PE is dysbiotic and contributes to disease pathogenesis.

scholarly journals Gut Microbiome of a Multiethnic Community Possessed No Predominant Microbiota

2021 ◽  
Vol 9 (4) ◽  
pp. 702
Author(s):  
Wei Wei Thwe Khine ◽  
Anna Hui Ting Teo ◽  
Lucas Wee Wei Loong ◽  
Jarett Jun Hao Tan ◽  
Clarabelle Geok Hui Ang ◽  
...  
Keyword(s):  
Young Adults ◽  
Gut Microbiome ◽  
Dietary Habits ◽  
Race And Gender ◽  
Cytokine Levels ◽  
Health Promoting ◽  
And Gender ◽  
Sugary Beverages ◽  
Faecal Microbiome ◽  
Scale Types

With increasing globalisation, various diets from around the world are readily available in global cities. This study aimed to verify if multiethnic dietary habits destabilised the gut microbiome in response to frequent changes, leading to readily colonisation of exogenous microbes. This may have health implications. We profiled Singapore young adults of different ethnicities for dietary habits, faecal type, gut microbiome and cytokine levels. Subjects were challenged with Lactobacillus casei, and corresponding changes in microbiome and cytokines were evaluated. Here, we found that the majority of young adults had normal stool types (73% Bristol Scale Types 3 and 4) and faecal microbiome categorised into three clusters, irrespective of race and gender. Cluster 1 was dominated by Bacteroides, Cluster 2 by Prevotella, while Cluster 3 showed a marginal increase in Blautia, Ruminococaceae and Ruminococcus, without a predominant microbiota. These youngsters in the three faecal microbiome clusters preferred Western high sugary beverages, Southeast Asian plant-rich diet and Asian/Western diets in rotation, respectively. Multiethnic dietary habits (Cluster 3) led to a gut microbiome without predominant microbiota yet demonstrated colonisation resistance to Lactobacillus. Although Bacteroides and Prevotella are reported to be health-promoting but also risk factors for some illnesses, Singapore-style dietary rotation habits may alleviate Bacteroides and Prevotella associated ill effects. Different immunological outcome was observed during consumption of the lactobacilli among the three microbiome clusters.

Proteinase-activated receptors in ovine cervical function

2005 ◽  
Vol 17 (7) ◽  
pp. 693 ◽  
Author(s):  
Sharon E. Mitchell ◽  
John J. Robinson ◽  
Margaret E. King ◽  
Lynda M. Williams
Keyword(s):  
Gene Expression ◽  
In Situ Hybridisation ◽  
Prostaglandin F2α ◽  
Cervical Dilation ◽  
Proteinase Activated Receptors ◽  
Pregnant Ewe ◽  
High Level ◽  
And Function

In sheep, inflammation not only functions in cervical dilation at parturition, but also plays an important part in the non-pregnant ewe cervix, as demonstrated by the high level of expression of interleukin (IL)-8 at oestrus. Ewes artificially induced to ovulate have significantly lower levels of IL-8 gene expression at oestrus compared with natural oestrus, indicating an inhibition of inflammation and function, offering an explanation for the low rates of conception in vaginally inseminated synchronised ewes. To identify potential pro-inflammatory agents to combat the anti-inflammatory effects of hormonal synchronisation of oestrus, we have investigated the role of proteinase-activated receptor (PAR)-1 and PAR-2. To localise and measure the level of expression of these receptors, ovine-specific probes were derived for PAR-1 and PAR-2 and used for quantitative in situ hybridisation in the ovine cervix. Both PAR-1 and PAR-2 were expressed in the luminal epithelium of the cervix throughout the oestrous cycle, with expression being highest at oestrus. The gene expression of PAR-2 at oestrus was approximately 30% higher than that of PAR-1. Artificial synchronisation of oestrus by either an intravaginal progesterone sponge or prostaglandin F2α injections did not inhibit PAR-1 or PAR-2 expression at oestrus; rather, in the case of PAR-2, progesterone synchronisation increased it. Both synchronising procedures increased the expression of PAR-1 and PAR-2 during the luteal phase of the cycle. Therefore, agonists of PAR-1 and PAR-2 may be potentially useful pro-inflammatory agents countering the inhibition of inflammation by hormonal synchronisation.

scholarly journals Analyzing the Role of Gut Microbiota on the Onset of Autoimmune Diseases Using TNFΔARE Murine Model

2021 ◽  
Vol 10 (1) ◽  
pp. 73
Author(s):  
Vivienne Edwards ◽  
Dylan L. Smith ◽  
Francoise Meylan ◽  
Linda Tiffany ◽  
Sarah Poncet ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Disease Transmission ◽  
Bioinformatics Analysis ◽  
Inflammatory Diseases ◽  
Anaerobic Conditions ◽  
Fecal Matter ◽  
Rrna Sequencing ◽  
Inflammatory Bowel ◽  
Transmission Status

Very little is known about disease transmission via the gut microbiome. We hypothesized that certain inflammatory features could be transmitted via the gut microbiome and tested this hypothesis using an animal model of inflammatory diseases. Twelve-week-old healthy C57 Bl/6 and Germ-Free (GF) female and male mice were fecal matter transplanted (FMT) under anaerobic conditions with TNFΔARE−/+ donors exhibiting spontaneous Rheumatoid Arthritis (RA) and Inflammatory Bowel Disease (IBD) or with conventional healthy mice control donors. The gut microbiome analysis was performed using 16S rRNA sequencing amplification and bioinformatics analysis with the HIVE bioinformatics platform. Histology, immunohistochemistry, ELISA Multiplex analysis, and flow cytometry were conducted to confirm the inflammatory transmission status. We observed RA and IBD features transmitted in the GF mice cohort, with gut tissue disruption, cartilage alteration, elevated inflammatory mediators in the tissues, activation of CD4/CD8+ T cells, and colonization and transmission of the gut microbiome similar to the donors’ profile. We did not observe a change or transmission when conventional healthy mice were FMT with TNFΔARE−/+ donors, suggesting that a healthy microbiome might withstand an unhealthy transplant. These findings show the potential involvement of the gut microbiome in inflammatory diseases. We identified a cluster of bacteria playing a role in this mechanism.

scholarly journals Longitudinal analysis of serum cytokine levels and gut microbial abundance links IL-17/IL-22 with Clostridia and insulin sensitivity in humans

2020 ◽  
Author(s):  
Ada Admin ◽  
Xin Zhou ◽  
Jethro S. Johnson ◽  
Daniel Spakowicz ◽  
Wenyu Zhou ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Gut Microbiome ◽  
Metabolic Diseases ◽  
Human Microbiome ◽  
Human Microbiome Project ◽  
Serum Levels ◽  
Discrete Groups ◽  
Cytokine Levels ◽  
Using Data ◽  
Study Participants

Recent studies using mouse models suggest that interaction between the gut microbiome and IL-17/IL-22 producing cells plays a role in the development of metabolic diseases. We investigated this relationship in humans using data from the prediabetes study of the Integrated Human Microbiome Project (iHMP). Specifically, we addressed the hypothesis that early in the onset of metabolic diseases there is a decline in serum levels of IL-17/IL-22, with concomitant changes in the gut microbiome. Clustering iHMP study participants on the basis of longitudinal IL-17/IL-22 profiles identified discrete groups. Individuals distinguished by low levels of IL-17/IL-22 were linked to established markers of metabolic disease, including insulin sensitivity. These individuals also displayed gut microbiome dysbiosis, characterized by decreased diversity, and IL-17/IL-22-related declines in the phylum <i>Firmicutes,</i> class <i>Clostridia</i>, and<i> </i>order <i>Clostridiales.</i> This ancillary analysis of the iHMP data therefore supports a link between the gut microbiome, IL-17/IL-22 and the onset of metabolic diseases. This raises the possibility for novel, microbiome-related therapeutic targets that may effectively alleviate metabolic diseases in humans as they do in animal models.

scholarly journals Synergistic Inhibitory Effect of the Gut Microbiome and Lithocholic Acid on Liver Fibrosis

2021 ◽  
Author(s):  
Junwei Shao ◽  
Tiantian Ge ◽  
Senzhong Chen ◽  
Zhi Chen
Keyword(s):  
Liver Fibrosis ◽  
Liver Function ◽  
Gut Microbiome ◽  
Lithocholic Acid ◽  
Inhibitory Effect ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Serum Biochemical ◽  
The Relationship

Abstract Background: Lithocholic acid are essential signaling molecules that mediate the relationship between the gut microbiome and liver function by regulating inflammation. The purpose of this study is to investigate the role of lithocholic acid in liver fibrosis. Methods: A liver fibrosis mouse model was induced by carbon tetrachloride followed by gavage of lithocholic acid, and the effects of lithocholic acid were evaluated by serum biochemical analysis and liver histology. Plasma cytokine levels and the number of immune cells were determined by cytometric bead array and flow cytometry, respectively. Results: Lithocholic acid treatment increased the recruitment of NK cells and reduced the activation of NKT cells, and reduced M1 macrophages differentiation and increased M2 macrophages differentiation. Furthermore, the lithocholic acid prevented inflammatory liver disease by reducing TNF-α and IL-22 secretion. However, the effect of lithocholic acid disappeared when the host gut microbiome was treated with antibiotics. Conclusions: It showed that the activation of lithocholic acid-mediated signaling was linked to the inhibition of inflammation and improvement of liver fibrosis. The role of lithocholic acid in liver fibrosis is mediated by the gut microbiome. The association between the gut microbiome, lithocholic acid, and liver function can serve as a therapeutic target for liver fibrosis.

Molecular Biology and the Major Psychoses

1997 ◽  
Vol 31 (1) ◽  
pp. 12-16 ◽  
Author(s):  
Andrew Lloyd ◽  
Gavin Dixon ◽  
Xu Feng Huang ◽  
Phillip Ward ◽  
Stan Catts ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Messenger Rna ◽  
Potential Role ◽  
In Situ Hybridisation ◽  
Northern Analysis ◽  
Expression Of Genes ◽  
Expression Studies ◽  
Biological Studies

Objective:To highlight the potential role of molecular biological studies in examining the expression of genes of interest in brain tissue to elucidate the pathophysiological basis of the major psychoses. Method:To review the principles underlying the available techniques for expression studies. Results:Detection of messenger RNA by in situ hybridisation and quantitation by Northern analysis are powerful tools to detect abnormalities in gene expression in brain tissue. Conclusion:The availability of simple techniques to examine the expression of RNA and protein products of individual genes, including examination at the level of individual cells, offers a clear opportunity to define the molecular basis of the major psychoses.

Lipopolysaccharide reduces gonadotrophin-releasing hormone (GnRH) gene expression: role of RFamide-related peptide-3 and kisspeptin

2019 ◽  
Vol 31 (6) ◽  
pp. 1134 ◽  
Author(s):  
Chooi Yeng Lee ◽  
ShengYun Li ◽  
Xiao Feng Li ◽  
Daniel A. E. Stalker ◽  
Claire Cooke ◽  
...  
Keyword(s):  
Gene Expression ◽  
In Situ Hybridisation ◽  
Releasing Hormone ◽  
Related Peptide ◽  
Concomitant Reduction ◽  
Intracerebroventricular Injections ◽  
Gonadotrophin Releasing Hormone ◽  
Lh Secretion

RFamide-related peptide (RFRP)-3 reduces luteinising hormone (LH) secretion in rodents. Stress has been shown to upregulate the expression of the RFRP gene (Rfrp) with a concomitant reduction in LH secretion, but an effect on expression of the gonadotrophin-releasing hormone (GnRH) gene (Gnrh1) has not been shown. We hypothesised that lipopolysaccharide (LPS)-induced stress affects expression of Rfrp, the gene for kisspeptin (Kiss1) and/or Gnrh1, leading to suppression of LH levels in rats. Intracerebroventricular injections of RFRP-3 (0.1, 1, 5 nmol) or i.v. LPS (15μgkg−1) reduced LH levels. Doses of 1 and 5 nmol RFRP-3 were then administered to analyse gene expression by in situ hybridisation. RFRP-3 (5 nmol) had no effect on Gnrh1 or Kiss1 expression. LPS stress reduced GnRH and Kiss1 expression, without affecting Rfrp1 expression. These data indicate that LPS stress directly or indirectly reduces Gnrh1 expression, but this is unlikely to be due to a change in Rfrp1 expression.

scholarly journals Distinct signatures of gut microbiome and metabolites associated with significant fibrosis in non-obese NAFLD

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Giljae Lee ◽  
Hyun Ju You ◽  
Jasmohan S. Bajaj ◽  
Sae Kyung Joo ◽  
Junsun Yu ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
External Validation ◽  
Nonalcoholic Fatty Liver ◽  
Significant Fibrosis ◽  
Representative Species ◽  
Microbiome Diversity ◽  
Rrna Sequencing ◽  
Obese Subjects ◽  
Metagenome Sequencing

Abstract Nonalcoholic fatty liver disease (NAFLD) is associated with obesity but also found in non-obese individuals. Gut microbiome profiles of 171 Asians with biopsy-proven NAFLD and 31 non-NAFLD controls are analyzed using 16S rRNA sequencing; an independent Western cohort is used for external validation. Subjects are classified into three subgroups according to histological spectra of NAFLD or fibrosis severity. Significant alterations in microbiome diversity are observed according to fibrosis severity in non-obese, but not obese, subjects. Ruminococcaceae and Veillonellaceae are the main microbiota associated with fibrosis severity in non-obese subjects. Furthermore, stool bile acids and propionate are elevated, especially in non-obese subjects with significant fibrosis. Fibrosis-related Ruminococcaceae and Veillonellaceae species undergo metagenome sequencing, and four representative species are administered in three mouse NAFLD models to evaluate their effects on liver damage. This study provides the evidence for the role of the microbiome in the liver fibrosis pathogenesis, especially in non-obese subjects.

scholarly journals Glycodelin mRNA is expressed in the genital tract of male and female rats (Rattus norvegicus)

1999 ◽  
Vol 23 (1) ◽  
pp. 57-66 ◽  
Author(s):  
C Keil ◽  
B Husen ◽  
J Giebel ◽  
G Rune ◽  
R Walther
Keyword(s):  
Epithelial Cells ◽  
Reproductive Tract ◽  
In Situ Hybridisation ◽  
Physiological Role ◽  
Reproductive Organs ◽  
Female Rats ◽  
Male And Female Rats ◽  
First Time

In the present study we demonstrate for the first time the expression of glycodelin mRNA in the female and male genital tracts of rats using non-radioactive in situ hybridisation. Glycodelin fragment 1 (+41 to +141) shares 100% homology with the human gene sequence. In the ovary, glycodelin mRNA was restricted to granulosa cells. In the uterus, glycodelin mRNA was expressed in all epithelial cells of the endometrium. In the male reproductive tract, glycodelin mRNA was distributed in all epithelial cells of the epididymis, the prostate and the seminal vesicle. However, in the testis, glycodelin mRNA was predominantly found in spermatogonia and in spermatocytes of the seminiferous epithelium. The expression in several reproductive organs of rats offers an excellent tool to study further the physiological role of glycodelin, which is so far thought to act as an immunosuppressive factor.

Primary cutaneous Ewing sarcoma/primitive neuroectodermal tumour: a clinicopathological analysis of seven cases highlighting diagnostic pitfalls and the role of FISH testing in diagnosis

2009 ◽  
Vol 62 (10) ◽  
pp. 915-919 ◽  
Author(s):  
M V Shingde ◽  
M Buckland ◽  
K J Busam ◽  
S W McCarthy ◽  
J Wilmott ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
In Situ Hybridisation ◽  
Molecular Testing ◽  
Fish Analysis ◽  
Fluorescence In Situ Hybridisation ◽  
Clinicopathological Analysis ◽  
Blue Cell

Aims:To perform a clinicopathological analysis of a series of primary cutaneous Ewing sarcomas/primitive neuroectodermal tumours (ES/PNET) to highlight the pathological features, discuss the differential diagnosis, emphasise the role of molecular testing (particularly fluorescence in situ hybridisation, FISH) in diagnosis and outline the patients’ clinical course.Methods:Seven cases of primary cutaneous ES/PNET were identified from the authors’ consultation files.Results:The patients were aged 16–61 years (median 25). Five were female and two were male. Five cases involved the limbs and two the trunk. Five were initially misdiagnosed (three as carcinoma and two as melanoma). All cases were characterised histologically by sheet-like growth of small round cells with little cytoplasm and showed strong membranous staining for CD99 and positive but variable staining for FLI-1. Six patients showed an EWS rearrangement (five on FISH analysis and one on RT-PCR). All tumours were completely excised. Three patients received adjuvant chemotherapy, one of whom also received radiotherapy. Follow-up was available in all cases (range 11–57 months; median 41). No recurrences or metastases occurred.Conclusions:Although rare, primary cutaneous ES/PNET should be considered in the differential diagnosis of cutaneous “small blue cell tumours”. Immunostaining for FLI-1 and molecular testing for evidence of an EWS rearrangement are useful ancillary investigations to confirm the diagnosis. The prognosis of primary cutaneous ES/PNET appears to be more favourable than extracutaneous ES/PNET.

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