scholarly journals Gut Microbiota Plays an Essential Role in the Onset of Membranous Nephropathy: Evidence from Multi-Center Case-Control Study and Animal Model

Author(s):  
Jin Shang ◽  
Yiding Zhang ◽  
Ruixue Guo ◽  
Wenli Liu ◽  
Jun Zhang ◽  
...  

Abstract OBJECTIVE: Membranous nephropathy (MN) is one of the most common causes of nephrotic syndrome in adults. Here we aim to establish a non-invasive diagnostic model using differential gut microbiome and to explore the relationship between gut microbiome and the pathogenesis of MN in animal experiment.DESIGN: A total of 825 fecal samples including MN patients and healthy controls (HC) were collected from Central, East and South China. We obtained crucial operational taxonomic units (OTUs) by 16S rRNA sequencing and then established a diagnostic model using five-fold cross-validation on random forest model. We subsequently validated its efficiency in cross regional cohort. MN rat model was induced by Sheep Anti-Rat Fx1A Serum and was used to explore the relationship between gut microbiome and the pathogenesis of MN.RESULTS: The diversity and richness of gut microbiome was significantly decreased in MN patients. The diagnostic model based on 7 operational OTUs achieved excellent efficiency with an area under curve (AUC) of 98.36% in training group. The different disease states and cross regional cohort validated high diagnostic efficiency. In rat model, urinary protein was significantly relieved by intestine cleaning, while increased again by fecal microbiome transplant (FMT). Interestingly, fecal microbiome from MN patients seems to play a protective role when compared with that from healthy people.CONCLUSION: Gut microbiome can be used as a non-invasive tool for MN diagnosis. The onset of MN depends partially on the existence of naturally colonized microbiome. Adaptive changes of gut microbiome during MN may help relieve urinary protein.

2020 ◽  
Vol 7 (3) ◽  
pp. 92 ◽  
Author(s):  
Michela Cintio ◽  
Elisa Scarsella ◽  
Sandy Sgorlon ◽  
Misa Sandri ◽  
Bruno Stefanon

Several studies have underlined the interplay among host-microbiome and pathophysiological conditions of animals. Research has also focused specifically on whether and how changes in the gut microbiome have provoked the occurrence of pathological phenomena affecting cartilage and joints in humans and in laboratory animals. Here, we tried to evaluate the relationship between the gut microbiome and the hip and elbow arthritis in owned dogs. The study included 14 dogs suffering from chronic arthritis (AD) and 13 healthy dogs (HD). After the first visit and during the period of the study, the dogs, under the supervision of the owner, were fed a semi-moist complete diet supplemented with omega 3 fatty acids. Feces and blood samples were collected in the clinic at the first visit (T0) and after days (T45). The plasma C-reactive protein (CRP) was higher, and the serum vitamin B12 and folate concentrations were lower (p < 0.05) in the AD group in comparison to the HD group. Data of the fecal microbiome showed that the relative abundances of the genus Megamonas were higher in AD (p < 0.001), while the relative abundance of the families Paraprevotellaceae, Porphyromonadaceae, and Mogibacteriaceae was significantly lower in comparison to HD. The results of the study identified several bacterial groups that differed significantly in the fecal microbiome between healthy and diseased dogs. If the observed differences in fecal bacterial composition predispose dogs to hip and elbow arthritis or if these differences reflect a correlation with these conditions deserves further investigation.


Pathogens ◽  
2018 ◽  
Vol 7 (3) ◽  
pp. 57 ◽  
Author(s):  
Ulrich Desselberger

The mammalian gut is colonized by a large variety of microbes, collectively termed ‘the microbiome’. The gut microbiome undergoes rapid changes during the first few years of life and is highly variable in adulthood depending on various factors. With the gut being the largest organ of immune responses, the composition of the microbiome of the gut has been found to be correlated with qualitative and quantitative differences of mucosal and systemic immune responses. Animal models have been very useful to unravel the relationship between gut microbiome and immune responses and for the understanding of variations of immune responses to vaccination in different childhood populations. However, the molecular mechanisms underlying optimal immune responses to infection or vaccination are not fully understood. The gut virome and gut bacteria can interact, with bacteria facilitating viral infectivity by different mechanisms. Some gut bacteria, which have a beneficial effect on increasing immune responses or by overgrowing intestinal pathogens, are considered to act as probiotics and can be used for therapeutic purposes (as in the case of fecal microbiome transplantation).


2021 ◽  
Vol 12 ◽  
Author(s):  
Vladimir Tesar ◽  
Zdenka Hruskova

The discovery of anti-podocyte antibodies in primary membranous nephropathy (MN) has revolutionized our approach toward the diagnosis and treatment of this disease. Evaluation of serum levels of anti-podocyte antibodies paved the way for non-invasive diagnosis and helped distinguish between primary and secondary MN although the relationship between anti-podocyte antibodies and cancer remains to be elucidated. Serum levels of anti-PLA2R antibodies directed against the major podocyte autoantigen are related to MN activity and the decrease in serum levels of anti-PLA2R antibodies in response to treatment (immunologic remission) also serves as an early indicator of the later putative proteinuric remission, enabling personalization of the treatment. The serum levels of anti-podocyte antibodies also enable the prediction of renal outcomes in terms of both remission and the risk of progression to end-stage renal disease. The positivity of anti-PLA2R antibodies before renal transplantation is associated with the risk of recurrence of MN. It remains to be established if all these relations observed in patients with anti-PLA2R antibodies are also valid for expanding spectrum of antibodies directed against recently discovered minor antigens (e.g., THSD7A, NELL-1, semaphorin 3B).


2020 ◽  
Author(s):  
Jin Shang ◽  
Zhigang Ren ◽  
Ang Li ◽  
Ruixue Guo ◽  
Yiding Zhang ◽  
...  

Abstract Background Diabetic nephropathy is characterized by increased incidence, deficient diagnostic methods and poor prognosis. New idea about altered gut microbiome associated with diagnosis and development of diabetic nephropathy remains to be verified. The major aim of our study is to relate fecal microbiome to clinically diagnosed diabetic kidney disease (DKD) or pathologically identified diabetic nephropathy (defined as DN) and further evaluate diagnosis potential of microbial markers for DKD/DN. We carried out 16S rRNA sequencing on a discovery cohort consisting of 352 patients (DKD = 120, DM = diabetes mellitus = 92, Con = healthy controls = 140) to identify microbial taxa and construct DKD classifier. Functional relevance and clinic correlation of microbiome changes were performed using PICRUSt and Spearman analysis, respectively. Independent 60 DKDs and 116 non-DKDs (DM = 46, Con = 70) were used to validate the results. The same analysis was performed on DKD pathologic subtypes (DN = 22, MN = membranous nephropathy = 22). Results DKD/DM samples had a distinct microbiome signature with lower alpha-diversity and significantly different microbial composition compared with Con (P < 0.001). Expansion of opportunistic pathogens (Peptostreptococcaceae_incertae_sedis, Clostridium_sensu_stricto_1, Streptococcus, Enterococcus, Erysipelotrichaceae_incertae_sedis), sulphate-reducing bacteria (Desulfovibrio) and depletion of bacteria producing short-chain fatty acids (SCFA) (Bacteroides, Faecalibacterium, Blautia and Roseburia) were major contributors to above differences. Interestingly, mucosa-associated bacteria including Akkermansia and Ruminococcus were also increased in DKD. The combination of 11 microbial markers could separate 120 DKDs from 232 non-DKDs with an area under curve (AUC) of 88.12%. Correspondingly, diagnostic power of microbial biomarkers was evaluated in a validation cohort of 60 patients and 116 non-DKDs (AUC = 79.75%). Besides DKD-related lipid and arginine metabolism, we also observed an increase of metabolism of aromatic amino acid in DM. Additionally, microbial comparison was carried out between pathologic subtypes of DKD, which could be used to distinguish DN from MN with 77.69% AUC. Conclusion Gut microbiome-related changes were associated with pathogenesis of DKD/DN; Microbiota-targeted markers could be an alternative test for DKD diagnosis and a non-invasive choice to differentiate DKD pathologic subtypes.


2022 ◽  
Vol 12 ◽  
Author(s):  
Guangying Cui ◽  
Shanshuo Liu ◽  
Zhenguo Liu ◽  
Yuan Chen ◽  
Tianwen Wu ◽  
...  

Objective: The gut microecosystem is the largest microecosystem in the human body and has been proven to be linked to neurological diseases. The main objective of this study was to characterize the fecal microbiome, investigate the differences between epilepsy patients and healthy controls, and evaluate the potential efficacy of the fecal microbiome as a diagnostic tool for epilepsy.Design: We collected 74 fecal samples from epilepsy patients (Eps, n = 24) and healthy controls (HCs, n = 50) in the First Affiliated Hospital of Zhengzhou University and subjected the samples to 16S rRNA MiSeq sequencing and analysis. We set up a train set and a test set, identified the optimal microbial markers for epilepsy after characterizing the gut microbiome in the former and built a diagnostic model, then validated it in the validation group.Results: There were significant differences in microbial communities between the two groups. The α-diversity of the HCs was higher than that of the epilepsy group, but the Venn diagram showed that there were more unique operational taxonomic unit (OTU) in the epilepsy group. At the phylum level, Proteobacteria and Actinobacteriota increased significantly in Eps, while the relative abundance of Bacteroidota increased in HCs. Compared with HCs, Eps were enriched in 23 genera, including Faecalibacterium, Escherichia-Shigella, Subdoligranulum and Enterobacteriaceae-unclassified. In contrast, 59 genera including Bacteroides, Megamonas, Prevotella, Lachnospiraceae-unclassified and Blautia increased in the HCs. In Spearman correlation analysis, age, WBC, RBC, PLT, ALB, CREA, TBIL, Hb and Urea were positively correlated with most of the different OTUs. Seizure-type, course and frequency are negatively correlated with most of the different OTUs. In addition, twenty-two optimal microbial markers were identified by a fivefold cross-validation of the random forest model. In the established train set and test set, the area under the curve was 0.9771 and 0.993, respectively.Conclusion: Our study was the first to characterize the gut microbiome of Eps and HCs in central China and demonstrate the potential efficacy of microbial markers as a noninvasive biological diagnostic tool for epilepsy.


2020 ◽  
Vol 19 (3) ◽  
pp. 243-249 ◽  
Author(s):  
Sevket Balta

: Vascular diseases are the main reason for morbidity and mortality worldwide. As we know, the earlier phase of vascular diseases is endothelial dysfunction in humans, the endothelial tissues play an important role in inflammation, coagulation, and angiogenesis, via organizing ligand-receptor associations and the various mediators’ secretion. We can use many inflammatory non-invasive tests (flowmediated dilatation, epicedial fat thickness, carotid-intima media thickness, arterial stiffness and anklebrachial index) for assessing the endothelial function. In addition, many biomarkers (ischemia modified albumin, pentraxin-3, E-selectin, angiopoietin, endothelial cell specific molecule 1, asymmetrical dimethylarginine, von Willebrand factor, endothelial microparticles and endothelial progenitor cells) can be used to evaluate endothelial dysfunction. We have focused on the relationship between endothelial dysfunction and inflammatory markers of vascular disease in this review.


2019 ◽  
Vol 1 (7) ◽  
pp. 10-13
Author(s):  
D. Yu. Ershov ◽  
I. N. Lukyanenko ◽  
E. E. Aman

The article shows the need to develop diagnostic methods for monitoring the quality of lubrication systems, which makes it possible to study the dynamic processes of contacting elements of the friction systems of instrument mechanisms, taking into account roughness parameters, the presence of local surface defects of elements and the bearing capacity of a lubricant. In the present article, a modern diagnostic model has been developed to control the quality of the processes of production and operation of friction systems of instrument assemblies. With the help of the developed model, it becomes possible to establish the relationship of diagnostic and design parameters of the mechanical system, as well as the appearance of possible local defects and lubricant state, which characterize the quality of friction systems used in many mechanical assemblies of the mechanisms of devices. The research results are shown in the form of nomograms to assess the defects of the elements of friction mechanisms of the mechanisms of the devices.


2021 ◽  
Vol 22 (7) ◽  
pp. 3566
Author(s):  
Chae Bin Lee ◽  
Soon Uk Chae ◽  
Seong Jun Jo ◽  
Ui Min Jerng ◽  
Soo Kyung Bae

Metformin is the first-line pharmacotherapy for treating type 2 diabetes mellitus (T2DM); however, its mechanism of modulating glucose metabolism is elusive. Recent advances have identified the gut as a potential target of metformin. As patients with metabolic disorders exhibit dysbiosis, the gut microbiome has garnered interest as a potential target for metabolic disease. Henceforth, studies have focused on unraveling the relationship of metabolic disorders with the human gut microbiome. According to various metagenome studies, gut dysbiosis is evident in T2DM patients. Besides this, alterations in the gut microbiome were also observed in the metformin-treated T2DM patients compared to the non-treated T2DM patients. Thus, several studies on rodents have suggested potential mechanisms interacting with the gut microbiome, including regulation of glucose metabolism, an increase in short-chain fatty acids, strengthening intestinal permeability against lipopolysaccharides, modulating the immune response, and interaction with bile acids. Furthermore, human studies have demonstrated evidence substantiating the hypotheses based on rodent studies. This review discusses the current knowledge of how metformin modulates T2DM with respect to the gut microbiome and discusses the prospect of harnessing this mechanism in treating T2DM.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Aaro Salosensaari ◽  
Ville Laitinen ◽  
Aki S. Havulinna ◽  
Guillaume Meric ◽  
Susan Cheng ◽  
...  

AbstractThe collection of fecal material and developments in sequencing technologies have enabled standardised and non-invasive gut microbiome profiling. Microbiome composition from several large cohorts have been cross-sectionally linked to various lifestyle factors and diseases. In spite of these advances, prospective associations between microbiome composition and health have remained uncharacterised due to the lack of sufficiently large and representative population cohorts with comprehensive follow-up data. Here, we analyse the long-term association between gut microbiome variation and mortality in a well-phenotyped and representative population cohort from Finland (n = 7211). We report robust taxonomic and functional microbiome signatures related to the Enterobacteriaceae family that are associated with mortality risk during a 15-year follow-up. Our results extend previous cross-sectional studies, and help to establish the basis for examining long-term associations between human gut microbiome composition, incident outcomes, and general health status.


2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Klaske Oberman ◽  
Iris Hovens ◽  
Jacco de Haan ◽  
Joana Falcao-Salles ◽  
Barbara van Leeuwen ◽  
...  

Abstract Background Inflammation is considered a key factor in the development of postoperative cognitive dysfunction (POCD). Therefore, we hypothesized that pre-operative anti-inflammatory treatment with ibuprofen would inhibit POCD in our rat-model. Methods Male Wistar rats of 3 or 23 months old received a single injection of ibuprofen (15 mg/kg i.p.) or were control handled before abdominal surgery. Timed blood and fecal samples were collected for analyses of inflammation markers and gut microbiome changes. Behavioral testing was performed from 9 to 14 days after surgery, in the open field, novel object- and novel location-recognition tests and Morris water maze. Neuroinflammation and neurogenesis were assessed by immune histochemistry after sacrifice on postoperative day 14. Results Ibuprofen improved short-term spatial memory in the novel location recognition test, and increased hippocampal neurogenesis. However, these effects were associated with increased hippocampal microglia activity. Whereas plasma cytokine levels (IL1-β, IL6, IL10, and TNFα) were not significantly affected, VEGF levels increased and IFABP levels decreased after ibuprofen. Long-term memory in the Morris water maze was not significantly improved by ibuprofen. The gut microbiome was neither significantly affected by surgery nor by ibuprofen treatment. In general, effects in aged rats appeared similar to those in young rats, though less pronounced. Conclusion A single injection of ibuprofen before surgery improved hippocampus-associated short-term memory after surgery and increased neurogenesis. However, this favorable outcome seemed not attributable to inhibition of (neuro)inflammation. Potential contributions of intestinal and blood-brain barrier integrity need further investigation. Although less pronounced compared to young rats, effects in aged rats indicate that even elderly individuals could benefit from ibuprofen treatment.


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