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 P836 Biomarkers response to anti-TNF treatment in Crohn’s disease through the intestinal microbiota

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S648-S649
Author(s):  
L Sanchis ◽  
S Manresa ◽  
J F Martínez ◽  
M Valls ◽  
M Iborra ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Intestinal Microbiota ◽  
Biological Response ◽  
Alpha Diversity ◽  
Short Chain Fatty Acids ◽  
Faecal Calprotectin ◽  
Partial Restoration ◽  
Alpha And Beta Diversity ◽  
E Coli

Abstract Background The alteration of the intestinal microbiota is a necessary requirement for the development of Crohn’s disease (CD). The anti-TNF alfa (TNF) treatment has radically changed the prognosis of the disease, modifying the therapeutic objective which is the induction and subsequent maintenance of mucosal healing. It is unknown, if this cure/improvement correlates with changes in the microbiota. The objectives of the study were: evaluate the changes in the microbiota in CD pre and after six months with TNF, determine the changes in the microbiota based on the clinical-biological response to TNF and calculate the F. prausnitzii/E. coli (F/E) ratio as an indicator of therapeutic response. Methods This was a prospective observational multicentre study that included 27 patients with CD who started treatment with TNF. 16 healthy individuals were included to establish the local healthy microbiota. The existence of disease activity was determined using the Harvey-Bradshaw index (HBI), analytical parameters such as C-reactive protein and faecal calprotectin measured at the beginning of the study, 3 and 6 months; classifying patients as responders (R) and non-responders (NR). The composition of the microbiota (the alpha and beta diversity), as well as the F/E ratio as indicators of dysbiosis, were evaluated by massive genomic sequencing, at the date of inclusion and 6 months after starting TNF through faecal samples. Results Prior to TNF, the loss of Clostridia class genera, producers of short chain fatty acids, as well as the significant increase (p &lt;0.01) of Proteobacteria, highlighting the Escherichia/Shigella genus with respect to healthy controls. The microbiota varied according to response to the TNF: the Proteobacteria phylum affected in NR with respect to healthy and R group (p &lt;0.005). Although, R group (13/27) significantly increase Clostridia class bacteria (such as Faecalibacterium) as well as alpha diversity with respect to NR group (p &lt;0.01), with a tendency towards a microbiota similar to controls. There is a significant association (p &lt;0.001) in the F/E relationship between the R group and NR group The F/E ratio was the most accurate (area under a curve of 0.87), when, we compare this value with HBI and CF as biomarkers of response to TNF. Conclusion The anti-TNF treatment allows partial restoration of the intestinal microbiota in responders with a tendency towards eubiosis, with respect to non-responders. The determination of F. prausnitzii/E. coli ratio can provide a reliable indicator of response to anti-TNF treatment in Crohn’s disease.

Effect of Yoghurt on the Cytokine Profile using a Murine Model of Intestinal Inflammation

2009 ◽  
Vol 7 (2) ◽  
pp. 97-109 ◽  
Author(s):  
A. De Moreno De Leblanc ◽  
S. Chaves ◽  
G. Perdigón
Keyword(s):  
Immune Response ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Intestinal Microbiota ◽  
Intestinal Inflammation ◽  
Industrialized Countries ◽  
Trinitrobenzenesulfonic Acid ◽  
Before And After ◽  
Inflammatory Bowel ◽  
Anti Inflammatory

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, are important problems in industrialized countries. The complete aetiology of both diseases is still unknown but likely involves genetic, environmental and immunological factors. The aim of this work is to study the anti-inflammatory mechanisms reported for yoghurt in a colon cancer model in order to evaluate its usefulness in the treatment of intestinal inflammation such as Crohn's disease. A trinitrobenzenesulfonic acid (TNBS)-induced colitis model was used. The influence of yoghurt feeding was studied before and after TNBS inoculation. The effect on the intestinal microbiota and on the host immune response was evaluated. IgA-producing cells and cells positive for specific cytokines (IL-12, IL-17, IFNγ and IL-10) were analyzed. Yoghurt administration diminished the severity of inflammation in the TNBS-inoculated mice. This effect occurred mainly through IL-10, which was increased in the intestinal tissues throughout the study, and by the decrease observed in IL-17 and IL-12 levels. In addition to this immunomodulatory capacity, another mechanism by which yoghurt could exert the anti-inflammatory activity observed in our model would be through beneficial changes in the intestinal microbiota (increases in the bifidobacteria and lactobacilli populations). These changes in the intestinal microbiota could also be considered one of the causes of the intestinal inflammation reduction. These results show that yoghurt administration modulated the immune response, inducing down regulation of the inflammatory cytokines produced by the immune cells involved in the inflammatory process. The protective effect

Transabdominal bowel sonography modifications in patients with active Crohn's disease before and after infliximab treatment

2001 ◽  
Vol 120 (5) ◽  
pp. A273-A273
Author(s):  
C SERRA ◽  
P GIONCHETTI ◽  
L VOLPE ◽  
C MORELLI ◽  
M CAMPIERI ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Infliximab Treatment ◽  
Before And After ◽  
Bowel Sonography

scholarly journals Metagenomic Profiling of Fecal-Derived Bacterial Membrane Vesicles in Crohn’s Disease Patients

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2795
Author(s):  
Nader Kameli ◽  
Heike E. F. Becker ◽  
Tessa Welbers ◽  
Daisy M. A. E. Jonkers ◽  
John Penders ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Membrane Vesicles ◽  
Amplicon Sequencing ◽  
Size Exclusion ◽  
Bacterial Membrane ◽  
Microbial Composition ◽  
Fecal Samples ◽  
Exclusion Chromatography

Background: In the past, many studies suggested a crucial role for dysbiosis of the gut microbiota in the etiology of Crohn’s disease (CD). However, despite being important players in host–bacteria interaction, the role of bacterial membrane vesicles (MV) has been largely overlooked in the pathogenesis of CD. In this study, we addressed the composition of the bacterial and MV composition in fecal samples of CD patients and compared this to the composition in healthy individuals. Methods: Fecal samples from six healthy subjects (HC) in addition to twelve CD patients (six active, six remission) were analyzed in this study. Fecal bacterial membrane vesicles (fMVs) were isolated by a combination of ultrafiltration and size exclusion chromatography. DNA was obtained from the fMV fraction, the pellet of dissolved feces as bacterial DNA (bDNA), or directly from feces as fecal DNA (fDNA). The fMVs were characterized by nanoparticle tracking analysis and cryo-electron microscopy. Amplicon sequencing of 16s rRNA V4 hypervariable gene regions was conducted to assess microbial composition of all fractions. Results: Beta-diversity analysis showed that the microbial community structure of the fMVs was significantly different from the microbial profiles of the fDNA and bDNA. However, no differences were observed in microbial composition between fDNA and bDNA. The microbial richness of fMVs was significantly decreased in CD patients compared to HC, and even lower in active patients. Profiling of fDNA and bDNA demonstrated that Firmicutes was the most dominant phylum in these fractions, while in fMVs Bacteroidetes was dominant. In fMV, several families and genera belonging to Firmicutes and Proteobacteria were significantly altered in CD patients when compared to HC. Conclusion: The microbial alterations of MVs in CD patients particularly in Firmicutes and Proteobacteria suggest a possible role of MVs in host-microbe symbiosis and induction or progression of inflammation in CD pathogenesis. Yet, the exact role for these fMV in the pathogenesis of the disease needs to be elucidated in future studies.

scholarly journals Fecal microbiota Profiling in Irritable Bowel Syndrome and Inflammatory Bowel Disease Patients with Irritable Bowel Syndrome-Type Symptoms

2021 ◽  
Author(s):  
Xiufang Cui ◽  
Haiyang Wang ◽  
Ziping Ye ◽  
Yi Li ◽  
Xinyun Qiu ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Irritable Bowel Syndrome ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Intestinal Microbiota ◽  
Bowel Disease ◽  
Sectional Study ◽  
Genus Level ◽  
Inflammatory Bowel ◽  
Irritable Bowel

Abstract BACKGROUND: The intestinal microbiota is thought to be involved in the occurrence of Inflammatory Bowel Disease in remission (IBDR) with Irritable Bowel Syndrome (IBS)-type symptoms, but the specific distinct profile of these bacteria remains unclear. Therefore, the purpose of this research is to investigate this issue by conducting a cross-sectional study.METHODS: IBS patients were diagnosed according to Rome Ⅳ criteria, IBD diagnosed according to the criteria of European Crohn & Colitis Organization (ECCO), IBDR patients with IBS-type symptoms were defined according to related IBS-type symptoms meeting the Rome IV criteria in IBDR patients, and were included Crohn’s disease in remission (CDR) and ulcerative colitis in remission (UCR) based on Crohn’s Disease Activity Index (DAI) and Mayo Scoring System respectively. Healthy controls come from the physical examination center and exclude people with underlying diseases. All enrolled subjects were divided into six groups, as followed: Health Control, IBS, CDR with IBS-type symptoms (CDR-IBS+), CDR without IBS-type symptoms (CDR-IBS-), UCR-IBS+ and UCR-IBS-. We collected fresh fecal samples from all subjects and applied 16S rRNA sequencing analysis to detect the structure and diversity of the microbiota among different groups. RESULTS: A total of 97 subjects were included in this study, of which 18 were health controls, 34 IBS patients, 25 CDR and 20 UCR. The richness of intestinal microbiota in CDR-IBS-was significantly lower than that in the control and IBS groups based on the analysis of observed species and Chao index (P<0.05). The observed species index in CDR-IBS+ was significantly higher than CDR-IBS- group (median index: 254.8 vs 203, P=0.036). No difference was found in Alpha diversity between UCR-IBS+ and UCR-IBS-. At phylum level, there was no significant difference between UC or CD with IBS-type symptoms and those without related symptoms. At genus level, the number of Faecalibacterium in CDR-IBS+ increased significantly while Fusobacterium decreased compared with CDR-IBS-(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 UCR-IBS - group, the number of Faecalibacterium in UCR-IBS+ group decreased, while the number of Streptococcus increased, but there was no statistical difference in the genus structure. Regardless of the phylum or genus level, the abundance and composition of the microbiota of IBS patients were not distinct from those of healthy people.CONCLUSIONS: CD patients in remission with IBS-type symptoms may be related to the increase of Faecalibacterium and decrease of Fusobacterium. UC patients in remission with IBS-type symptoms cannot be explained by changes in the abundance and structure of intestinal microbiota from our across-sectional study.

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 A novel collagen area fraction index to quantitatively assess bowel fibrosis in patients with Crohn’s disease

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Xue-hua Li ◽  
Zhuang-nian Fang ◽  
Tian-ming Guan ◽  
Jin-jiang Lin ◽  
Can-hui Sun ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Operating Characteristic ◽  
Characteristic Curve ◽  
Intraclass Correlation ◽  
Area Under The Curve ◽  
Area Fraction ◽  
Strongly Correlated ◽  
Fibrosis Score ◽  
High Repeatability

Abstract Background A validated histopathological tool to precisely evaluate bowel fibrosis in patients with Crohn’s disease is lacking. We attempted to establish a new index to quantify the severity of bowel fibrosis in patients with Crohn’s disease-associated fibrostenosis. Methods We analyzed the histopathological data of 31 patients with Crohn’s disease strictures undergoing surgical resection. The most representative sections of resected strictured segments were stained with Masson trichrome to manifest bowel fibrosis. The collagen area fraction and histological fibrosis score were simultaneously calculated for the same section to evaluate the severity of bowel fibrosis. Results Collagen area fraction strongly correlated with histological fibrosis scores (r = 0.733, P < 0.001). It showed a stronger correlation (r = 0.561, P < 0.001) with the degree of bowel strictures than the histological fibrosis score did (r = 0.468, P < 0.001). It was also shown to be more accurate for diagnosing Crohn’s disease strictures (area under the receiver operating characteristic curve = 0.815, P < 0.001) compared with the histological fibrosis score (area under the curve = 0.771, P < 0.001). High repeatability was observed for the collagen area fraction, with an intraclass correlation coefficient of 0.915 (P < 0.001). Conclusions Collagen area fraction is a simple and reliable index to quantify the severity of bowel fibrosis in patients with Crohn’s disease-associated fibrostenosis.

scholarly journals Linking Strain Engraftment in Fecal Microbiota Transplantation With Maintenance of Remission in Crohn’s Disease

2020 ◽  
Vol 159 (6) ◽  
pp. 2193-2202.e5
Author(s):  
Lingjia Kong ◽  
Jason Lloyd-Price ◽  
Tommi Vatanen ◽  
Philippe Seksik ◽  
Laurent Beaugerie ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Maintenance Of Remission
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