scholarly journals Alterations of the Fecal Microbiota in Chinese Patients With Multiple Sclerosis

2020 ◽  
Vol 11 ◽  
Author(s):  
Zongxin Ling ◽  
Yiwen Cheng ◽  
Xiumei Yan ◽  
Li Shao ◽  
Xia Liu ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Intestinal Microbiota ◽  
Area Under The Curve ◽  
Fecal Microbiota ◽  
Host Immunity ◽  
Chinese Patients ◽  
Healthy Controls ◽  
Cytokines And Chemokines ◽  
Functional Bacteria ◽  
Functional Profiles

Mounting evidence indicates that alterations in the intestinal microbiota may be associated with neurological disorders such as multiple sclerosis (MS). MS is a putative autoimmune disease of the central nervous system. However, it has not been determined whether the intestinal microbiota and host immune status are altered in Chinese patients with stable MS. In our study, 22 Chinese patients with stable MS and 33 healthy controls were enrolled for fecal microbiota analysis and host immunity evaluation. The microbial diversity and composition, bacterial co-occurrence correlations, predictive functional profiles, and microbiota-cytokine correlations between the two groups were compared. We observed that while the overall structure of the fecal microbiota did not change significantly, the abundances of several key functional bacteria, primarily Faecalibacterium, decreased remarkably. Faecalibacterium and Granulicatella could be used to distinguish between patients with MS and healthy controls with an area under the curve of 0.832. PiCRUSt analysis revealed that genes associated with fructose, mannose, and fatty acid metabolism were significantly enriched in the MS microbiota. In addition, we also observed that the levels of several pro- and anti-inflammatory cytokines and chemokines, such as IL-1ra, IL-8, IL-17, and TNF-α changed observably, and the abundances of key functional bacteria like butyrate producers correlated with the changes in the cytokine levels. Our present study indicated that altered composition of the fecal microbiota might play vital roles in the etiopathogenesis of MS by regulating host immunity, which suggests that microbiota-targeting patient-tailored early intervention techniques might serve as novel therapeutic approaches for MS.

scholarly journals Evaluation of changes in intestinal microbiota in Crohn’s disease patients after anti-TNF alpha treatment

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Laura Sanchis-Artero ◽  
Juan Francisco Martínez-Blanch ◽  
Sergio Manresa-Vera ◽  
Ernesto Cortés-Castell ◽  
Marina Valls-Gandia ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Intestinal Microbiota ◽  
Area Under The Curve ◽  
Alpha Diversity ◽  
Amplicon Sequencing ◽  
Fecal Microbiota ◽  
Multicenter Observational Study ◽  
Partial Restoration ◽  
Before And After

AbstractIntestinal dysbiosis is key in the onset and development of Crohn’s disease (CD). We evaluated the microbiota changes in CD patients before and after a six-month anti-TNF treatment, comparing these changes with the microbiota of healthy subjects. This prospective multicenter observational study involved 27 CD patients initiating anti-TNF treatment and 16 healthy individuals. Inflammatory activity was determined at baseline, 3 and 6 months, classifying patients into responders and non-responders. Fecal microbiota was analyzed by massive genomic sequencing thought 16S rRNA amplicon sequencing before and after six months of anti-TNF treatment. The CD cohort showed a decrease in genera of the class Clostridia, short-chain fatty acid producers, and an increase in the phylum Proteobacteria (p < 0.01) versus the healthy cohort. After anti-TNF treatment, the phylum Proteobacteria also increased in non-responders versus responders (13/27) (p < 0.005), with the class Clostridia increasing. In addition, alpha diversity increased in responders versus non-responders (p < 0.01), tending towards eubiosis. An association was found (p < 0.001) in the F.prausnitzii/E.coli ratio between responders and non-responders. The F/E ratio was the most accurate biomarker of anti-TNF response (area under the curve 0.87). Thus, anti-TNF treatment allows partial restoration of intestinal microbiota in responders and the F.prausnitzii/E.coli ratio can provide a reliable indicator of response to anti-TNF in CD.

scholarly journals Inflammation-related plasma and CSF biomarkers for multiple sclerosis

2020 ◽  
Vol 117 (23) ◽  
pp. 12952-12960 ◽  
Author(s):  
Jesse Huang ◽  
Mohsen Khademi ◽  
Lars Fugger ◽  
Örjan Lindhe ◽  
Lenka Novakova ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Neurological Diseases ◽  
Area Under The Curve ◽  
Csf Biomarkers ◽  
Healthy Controls ◽  
Protein Biomarkers ◽  
Neurofilament Light Chain ◽  
Diagnostic Efficacy ◽  
Neurofilament Light

Effective biomarkers for multiple sclerosis diagnosis, assessment of prognosis, and treatment responses, in particular those measurable in blood, are largely lacking. We have investigated a broad set of protein biomarkers in cerebrospinal fluid (CSF) and plasma using a highly sensitive proteomic immunoassay. Cases from two independent cohorts were compared with healthy controls and patients with other neurological diseases. We identified and replicated 10 cerebrospinal fluid proteins including IL-12B, CD5, MIP-1a, and CXCL9 which had a combined diagnostic efficacy similar to immunoglobulin G (IgG) index and neurofilament light chain (area under the curve [AUC] = 0.95). Two plasma proteins, OSM and HGF, were also associated with multiple sclerosis in comparison to healthy controls. Sensitivity and specificity of combined CSF and plasma markers for multiple sclerosis were 85.7% and 73.5%, respectively. In the discovery cohort, eotaxin-1 (CCL11) was associated with disease duration particularly in patients who had secondary progressive disease (PCSF< 4 × 10−5,Pplasma< 4 × 10−5), and plasma CCL20 was associated with disease severity (P= 4 × 10−5), although both require further validation. Treatment with natalizumab and fingolimod showed different compartmental changes in protein levels of CSF and peripheral blood, respectively, including many disease-associated markers (e.g., IL12B, CD5) showing potential application for both diagnosing disease and monitoring treatment efficacy. We report a number of multiple sclerosis biomarkers in CSF and plasma for early disease detection and potential indicators for disease activity. Of particular importance is the set of markers discovered in blood, where validated biomarkers are lacking.

scholarly journals Intestinal dysbiosis featuring abundance of Streptococcus associates with Henoch-Schönlein purpura nephritis (IgA vasculitis with nephritis) in adult

2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Jiaxing Tan ◽  
Zhengxia Zhong ◽  
Yi Tang ◽  
Wei Qin
Keyword(s):  
Gut Microbiota ◽  
Intestinal Microbiota ◽  
Fecal Microbiota ◽  
Healthy Controls ◽  
Henoch Schonlein Purpura ◽  
Intestinal Dysbiosis ◽  
Clinical Indices ◽  
Schonlein Purpura ◽  
Henoch Schönlein Purpura ◽  
Purpura Nephritis

Abstract Background The pathogenesis of Henoch-Schönlein purpura nephritis (HSPN) is closely associated with mucosal infection. But whether intestinal microbiota dysbiosis plays a role in it is not clear. Methods A total of 52 participants including 26 HSPN patients and 26 healthy controls were included. By using 16S ribosomal RNA gene sequencing, the intestinal microbiota composition between HSPN and healthy controls was compared. The diagnostic potency was evaluated by Receiver operating characteristic (ROC) with area under curves (AUC). Meanwhile, correlation analysis was also performed. Results The lower community richness and diversity of fecal microbiota was displayed in HSPN patients and the structure of gut microbiota was remarkedly different. A genus-level comparison indicated a significant increase in the proportions of g-Bacteroides, g-Escherichia–Shigella and g-Streptococcus, and a marked reduction of g-Prevotella_9 in HSPN patients, suggesting that the overrepresentation of potential pathogens and reduction of profitable strains were the main feature of the dysbiosis. The differential taxonomic abundance might make sense for distinguishing HSPN from healthy controls, with AUC of 0.86. The relative abundance of the differential bacteria was also concerned with clinical indices. Among them, Streptococcus spp. was positively associated with the severity of HSPN (P < 0.050). It was found that HSPN patients with higher level of Streptococcus spp. were more likely to suffering from hematuria and hypoalbuminemia (P < 0.050). Conclusions The dysbiosis of gut microbiota was obvious in HSPN patients, and the intestinal mucosal streptococcal infection was distinctive, which was closely related to its severity.

scholarly journals Expression and clinical significance of IL7R, NFATc2, and RNF213 in familial and sporadic multiple sclerosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Seyedeh Zahra Hosseini Imani ◽  
Zohreh Hojati ◽  
Sheyda Khalilian ◽  
Fariba Dehghanian ◽  
Majid Kheirollahi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Family History ◽  
Area Under The Curve ◽  
Group Versus ◽  
Expression Level ◽  
Inflammatory Factors ◽  
Control Group ◽  
Healthy Controls ◽  
Roc Curve Analysis ◽  
Axonal Dysfunction

AbstractMultiple sclerosis (MS) is a chronic inflammatory and autoimmune disorder of the central nervous system characterized by myelin loss and axonal dysfunction. Increased production of inflammatory factors such as cytokines has been implicated in axon destruction. In the present study, we compared the expression level of IL7R, NFATc2, and RNF213 genes in the peripheral blood of 72 MS patients (37 familial MS, 35 sporadic MS) and 74 healthy controls (34 individuals with a family history of the disease, 40 healthy controls without a family history) via Real-time PCR. Our results showed that the expression level of IL7R was decreased in the sporadic patients in comparison with other groups. Additionally, there was an increased NFATc2 expression level in MS patients versus healthy controls. Increased expression of NFATc2 in sporadic and familial groups compared to the controls, and familial group versus FDR was also seen. Our results also represented an increased expression level of RNF213 in familial patients as compared to the control group. The similar RNF213 expression between sporadic and control group, as well as FDR and familial group was also seen. Diagnostic evaluation was performed by receiver operating characteristic (ROC) curve analysis and area under the curve (AUC) calculation. The correlation of clinical parameters including onset age and Expanded Disability Status Scale (EDSS) with our gene expression levels were also assessed. Overall, decreased expression level of IL7R in the sporadic cases and increased expression level of NFATc2 may be associated with the pathogenesis of MS disease. Confirmation of the effects of differential expression of RNF213 gene requires further studies in the wider statistical populations.

scholarly journals Expression and clinical significance of IL7R, NFATc2, and RNF213 in familial and sporadic multiple sclerosis

2021 ◽  
Author(s):  
Seyedeh Zahra Hosseini Imani ◽  
Zohreh Hojati ◽  
Fariba Dehghanian ◽  
Sheyda Khalilian ◽  
Majid Kheirollahi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Family History ◽  
Area Under The Curve ◽  
Expression Level ◽  
Inflammatory Factors ◽  
Control Group ◽  
Healthy Controls ◽  
Roc Curve Analysis ◽  
Sporadic Group ◽  
Axonal Dysfunction

Abstract Background Multiple sclerosis (MS) is a chronic inflammatory and autoimmune disorder of the central nervous system characterized by myelin loss and axonal dysfunction. Increased production of inflammatory factors such as cytokines has been implicated in axon destruction in myelin-less areas. In the present study, we compared the expression level of IL7R, NFATc2, and RNF213 genes in the peripheral blood of 72 MS patients (37 familial MS, 35 sporadic MS) and 74 healthy controls (34 individuals with a family history of the disease, 40 healthy controls without a family history) via Real-time PCR. Results Our results showed that the expression level of IL7R was decreased in MS patients versus healthy controls. Also IL7R expression was significantly down-regulated in the sporadic group as compared to other groups. Additionally, there was an increased NFATc2 expression level in MS patients versus healthy controls. Increased expression of NFATc2 in sporadic and familial groups compared to the controls was also seen. Our results represented an increased expression level of RNF213 in the familial patients as compared to the control group. Diagnostic evaluation was performed by ROC curve analysis and area under the curve (AUC) calculation. The correlation of clinical parameters including onset age and EDSS with our gene expression levels were also assessed. Conclusions Overall, decreased expression level of IL7R and increased expression level of NFATc2 may be associated with the pathogenesis of MS disease. The RNF213 should be evaluated further for its potential as a candidate biomarker of inflammatory activity in MS in a larger cohort.

scholarly journals Introduction of Colonic and Fecal Microbiota From an Adult Pig Differently Affects the Growth, Gut Health, Intestinal Microbiota and Blood Metabolome of Newborn Piglets

2021 ◽  
Vol 12 ◽  
Author(s):  
Renli Qi ◽  
Zhuo Zhang ◽  
Jing Wang ◽  
Xiaoyu Qiu ◽  
Qi Wang ◽  
...  
Keyword(s):  
Intestinal Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Body Weight Gain ◽  
Intestinal Barrier ◽  
Fecal Microbiota ◽  
Inflammatory Factors ◽  
Gut Health ◽  
Metabolome Analysis ◽  
16S Rdna Sequence Analysis ◽  
Functional Bacteria

Microbiota transplantation is a rapid and effective method for changing and reshaping the intestinal microbiota and metabolic profile in humans and animals. This study compared the different influences of the introduction of fecal microbes and colonic microbes from a fat, adult pig in newborn pigs. Both colonic microbiota transplantation (CMT) and fecal microbiota transplantation (FMT) promoted growth and improved gut functions in suckling pigs up to weaning. FMT was more beneficial for body weight gain and body fat deposition in piglets, while CMT was more beneficial for intestinal health and mucosal immunity. 16S rDNA sequence analysis indicated that both CMT and FMT significantly increased the abundances of beneficial or functional bacteria, such as Lactobacillus and Prevotella_2 genera, in the piglets, and reduced the abundances of harmful bacteria, such as Escherichia–Shigella. Blood metabolome analysis showed that transplantation, especially FMT, enhanced lipid metabolism in piglets. In addition, while CMT also changed amino acid metabolism and increased anti-inflammatory metabolites such as 3-indoleacetic acid and 3-indolepropionic acid in piglets, FMT did not. Of note, FMT damaged the intestinal barrier of piglets to a certain extent and increased the levels of inflammatory factors in the blood that are potentially harmful to the health of pigs. Taken together, these results suggested that intestinal and fecal microbiota transplantations elicited similar but different physiological effects on young animals, so the application of microbiota transplantation in animal production requires the careful selection and evaluation of source bacteria.

scholarly journals Multiple Sclerosis Patients have an Altered Gut Mycobiome and Increased Fungal to Bacterial Richness

2021 ◽  
Author(s):  
Meeta Yadav ◽  
Soham Ali ◽  
Rachel L. Shrode ◽  
Shailesh K. Shahi ◽  
Samantha N. Jensen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Intestinal Microbiome ◽  
Healthy Controls ◽  
Healthy Human ◽  
Relapsing Remitting ◽  
Bacterial Microbiome ◽  
Fungal Microbiome ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Functional Profiles

AbstractTrillions of microbes such as bacteria, fungi, and viruses exist in the healthy human gut microbiome. Although gut bacterial dysbiosis has been extensively studied in multiple sclerosis (MS), the significance of the fungal microbiome (mycobiome) is an understudied and neglected part of the intestinal microbiome in MS. The aim of this study was to characterize the gut mycobiome of patients with relapsing-remitting multiple sclerosis (RRMS), compare it to healthy controls, and examine its association with changes in the bacterial microbiome. We characterized and compared the mycobiome of 20 RRMS patients and 33 healthy controls (HC) using Internal Transcribed Spacer 2 (ITS2) and compared mycobiome interactions with the bacterial microbiome using 16S rRNA sequencing. Our results demonstrate an altered mycobiome in RRMS patients compared with HC. RRMS patients showed an increased abundance of Basidiomycota and decreased Ascomycota at the phylum level with an increased abundance of Candida and Epicoccum genera along with a decreased abundance of Saccharomyces compared to HC. We also observed an increased ITS2/16S ratio, altered fungal and bacterial associations, and altered fungal functional profiles in MS patients compared to HC.This study demonstrates that RRMS patients had a distinct mycobiome with associated changes in the bacterial microbiome compared to HC. There is an increased fungal to bacterial ratio as well as more diverse fungal-bacterial interactions in RRMS patients compared to HC. Our study is the first step towards future studies in delineating the mechanisms through which the fungal microbiome can influence MS disease.

scholarly journals Altered Plasma Metabolic Profiles in Chinese Patients With Multiple Sclerosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Fan Yang ◽  
Shao-chang Wu ◽  
Zong-xin Ling ◽  
Shan Chao ◽  
Li-juan Zhang ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Amino Acids ◽  
Inflammatory Cytokines ◽  
Healthy Subjects ◽  
Chinese Patients ◽  
Metabolic Profiles ◽  
Cytokines And Chemokines ◽  
Tnf Α ◽  
Sphingosine 1 Phosphate ◽  
Anti Inflammatory

Multiple sclerosis (MS) is an autoimmune disease that leads to the demyelination of nerve axons. An increasing number of studies suggest that patients with MS exhibit altered metabolic profiles, which might contribute to the course of MS. However, the alteration of metabolic profiles in Chinese patients with MS and their potential roles in regulating the immune system remain elusive. In this study, we performed a global untargeted metabolomics approach in plasma samples from 22 MS-affected Chinese patients and 21 healthy subjects. A total of 42 differentially abundant metabolites (DAMs) belonging to amino acids, lipids, and carbohydrates were identified in the plasma of MS patients and compared with those in healthy controls. We observed an evident reduction in the levels of amino acids, such as L-tyrosine, L-isoleucine, and L-tryptophan, whereas there was a great increase in the levels of L-glutamic acid and L-valine in MS-affected patients. The levels of lipid and carbohydrate metabolites, such as sphingosine 1-phosphate and myo-inositol, were also reduced in patients with MS. In addition, the concentrations of proinflammatory cytokines, such as IL-17 and TNF-α, were significantly increased, whereas those of several anti-inflammatory cytokines and chemokines, such as IL-1ra, IL-7, and MIP-1α, were distinctly reduced in the plasma of MS patients compared with those in healthy subjects. Interestingly, some DAMs, such as L-tryptophan and sphingosine 1-phosphate, showed an evident negative correlation with changes in the level of TNF-α and IL-17, while tightly positively correlating with altered concentrations of anti-inflammatory cytokines and chemokines, such as MIP-1α and RANTES. Our results revealed that altered metabolomic profiles might contribute to the pathogenesis and course of MS disease by modulating immuno-inflammatory responses in the peripheral system, which is essential for eliciting autoimmune responses in the central nervous system, thus resulting in the progression of MS. This study provides potential clues for developing therapeutic strategies for MS in the near future.

scholarly journals Fecal microbiota profiling in irritable bowel syndrome and inflammatory bowel disease patients with irritable bowel syndrome-type symptoms

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiufang Cui ◽  
Haiyang Wang ◽  
Ziping Ye ◽  
Yi Li ◽  
Xinyun Qiu ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Irritable Bowel Syndrome ◽  
Intestinal Microbiota ◽  
Bowel Disease ◽  
Fecal Microbiota ◽  
Healthy Controls ◽  
Rdna Gene ◽  
Significant Difference ◽  
Inflammatory Bowel ◽  
Irritable Bowel

Abstract Background The intestinal microbiota is thought to be involved in the occurrence of inflammatory bowel disease in remission with irritable bowel syndrome (IBS)-type symptoms, but the specific distinct profile of these bacteria remains unclear. This cross-sectional study aims to investigate the fecal microbiota profiling in patients with these diseases. Methods Fecal samples from 97 subjects, including Crohn’s disease patients in remission with IBS-type symptoms (CDR-IBS+) or without IBS-type symptoms (CDR-IBS−), ulcerative colitis patients in remission with IBS-type symptoms (UCR-IBS+) or without IBS-type symptoms (UCR-IBS−), IBS patients and healthy controls, were collected and applied 16S ribosomal DNA (rDNA) gene sequencing. The V4 hypervariable regions of 16S rDNA gene were amplified and sequenced by the Illumina MiSeq platform. The differences in the sample diversity index in groups were analyzed with R software. Results The richness of the intestinal microbiota in the CDR-IBS group was markedly lower than those in the control and IBS groups based on the analysis of observed species and the Chao index (P < 0.05). The observed species index in the CDR-IBS+ group was higher than that in the CDR-IBS− group (median index: 254.8 vs 203, P = 0.036). No difference was found in alpha diversity between UCR patients with IBS-type symptoms and those without related symptoms. At the genus level, the number of Faecalibacterium in CDR patients with IBS-type symptoms increased significantly, while Fusobacterium decreased versus those without such symptoms (mean relative abundance of Faecalibacterium: 20.35% vs 5.18%, P < 0.05; Fusobacterium: 1.51% vs 5.2%, P < 0.05). However, compared with the UCR-IBS− group, the number of Faecalibacterium in the UCR-IBS+ group decreased, while the number of Streptococcus increased, but there was no significant difference in the genus structure. The abundance and composition of the microbiota of IBS patients were not distinct from those of healthy controls. Conclusions The IBS-type symptoms in CD patients in remission may be related to an increase in Faecalibacterium and a decrease in Fusobacterium. The IBS-type symptoms in UC patients in remission cannot be explained by changes in the abundance and structure of the intestinal microbiota.

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