Intestinal Microbiota: Facts and Fiction

2017 ◽  
Vol 35 (1-2) ◽  
pp. 139-147 ◽  
Author(s):  
Miloslav Kverka ◽  
Helena Tlaskalová-Hogenová
Keyword(s):  
Inflammatory Diseases ◽  
Research Directions ◽  
Vast Number ◽  
Chronic Inflammatory Diseases ◽  
Immune Mediated ◽  
Complex Ecosystem ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
The Impact ◽  
Number Of Bacteria

In humans, the gut microbiota forms a complex ecosystem consisting of a vast number of bacteria, Archaea, fungi and viruses. It represents a major stimulus to the development of the immune system and many other physiological functions, so that it may shape the individual's susceptibility to infectious and immune-mediated diseases. The emergence of new ‘-omics' methods recently revolutionized the way we study the host-microbe interactions, but they also raised new questions and issues. In this review, we discuss the impact of these new data on the current and future therapies for chronic inflammatory diseases. We also outline the major conceptual, technical and interpretational issues that recently led to some misleading conclusions and discuss in brief the current research directions in the field.

scholarly journals ReumaCoV Brasil Registry: Brazilian Study of Patients with Immuno-mediated Chronic Inflammatory Diseases Infected by SARS-CoV-2 

2020 ◽  
Author(s):  
Claudia Diniz Lopes Marques ◽  
Adriana Maria Kakehasi ◽  
Ana Paula Monteiro Gomides ◽  
Danyelly Bruneska Gondim Martins ◽  
Eduardo dos Santos Paiva ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Complex Interaction ◽  
Progression Rate ◽  
Huge Number ◽  
Chronic Inflammatory Diseases ◽  
Immune Mediated ◽  
Increased Risk ◽  
Secondary Outcomes ◽  
In The Beginning ◽  
The Impact

Abstract Patients with immune-mediated rheumatic diseases (IMRD) are at increased risk of infections, including significant morbidity and high mortality. Considering the potential for unfavorable outcomes of SARS-CoV-2 infection in patients with IMRD, a huge number of questions were released regarding the impact of COVID-19 in the beginning of the pandemic. Seeking to better understand this complex interaction, this study was developed to evaluate prospectively patients with IMRD and a suspected or confirmed COVID-19 diagnosis, according to the Ministry of Health of Brazil’s definitions. The primary outcomes will be the IMRD disease activity changes after COVID-19, at four time points: (1) At baseline and prior 6 months; (2) The first rheumatic evaluation after known infection by SARS-CoV-2 (4-6 weeks); (3) 3 months after the inclusion (±15 days); (4) 6 months after inclusion (±15 days). The secondary outcomes will be the progression rate to severe forms of COVID-19, need for intensive care unit admission and mechanical ventilation, death and therapeutic changes related to the IMRD. Two outcomes are of particular interest considering the COVID-19 in IMRD patients, namely pulmonary and the thromboembolic events, and they will be monitored with more attention and details (clinical, lab, function tests and imaging). This protocol was approved by the Brazilian Committee of Ethics in Human Research (CONEP) on April 5th, 2020 (CAAE 30186820.2.1001.8807; Number: 3.933.204) and registered on the Brazilian Registry of Clinical Trials – REBEC (RBR-33YTQC) in June, 1st 2020. We believe this study will provide many clinically relevant data on the general impact of COVID-19 on IMRD patients.

scholarly journals POS1180 TREATMENT COMPLIANCE OF PATIENTS WITH RHEUMATOID ARTHRITIS DURING THE FIRST WAVE OF THE SARS-CoV-2/COVID-19 PANDEMIC IN PORTUGAL: RESULTS FROM THE COVID IN RA (COVIDRA) SURVEY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 871.2-871
Author(s):  
F. Araujo ◽  
N. Gonçalves ◽  
A. F. Mourão
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Diseases ◽  
Immunosuppressive Treatment ◽  
Treatment Compliance ◽  
Web Based ◽  
Symptoms Of Depression ◽  
Immune Mediated ◽  
Attending Physician ◽  
The Impact ◽  
E Mail

Background:The outcomes of the infection by the SARS-CoV-2 in patients with immune-mediated inflammatory diseases were largely unknown during the early days of the COVID-19 pandemic. It was hypothesized that these patients were at higher risk of morbidity and mortality due to their inherent immune dysfunction and immunosuppressive therapy. Several rheumatology societies issued recommendations urging patients not to stop their anti-rheumatic treatments.Objectives:To assess treatment compliance of patients with rheumatoid arthritis (RA) during the first wave of the SARS-CoV-2/COVID-19 pandemic in Portugal.Methods:The web-based survey COVIDRA (COVID in RA) was developed to assess the impact of the first wave mandatory confinement in patients with RA focusing on 5 domains: RA symptoms, attitudes towards medication, employment status, physical exercise and mental health. The questionnaire was sent to RA patients through e-mail and social media of the Portuguese Society of Rheumatology and two patient associations; and it was filled locally at two rheumatology centers in Lisbon. Recruitment took place during June and July 2020. Descriptive statistics were generated by the survey software and were afterwards transported and evaluated using appropriate biostatistics software.Results:We obtained 441 valid questionnaires. Most respondents were female (88.4%), caucasian (93.6%), with a mean age of 58 (+/-13) years. The majority (57.6%) had longstanding disease (>10 years) and were treated with csDMARDs (63.2%) and/or bDMARDs/tsDMARDS (23,7%). Only 14% (N=61) discontinued or reduced the dosage or frequency of their RA treatment. Most of these changes were previously planned by the attending physician (27.9%). Only 11 patients (18%) discontinued their immunosuppressive medication out of fear of becoming infected with SARS-CoV-2 (corresponding to 2.5% of total responders). Another 11 patients did so because they had no prescription, couldn’t go to the community/hospital pharmacy or couldn’t afford the medication. Although these numbers preclude any statistical analysis, when compared to patients who persisted on their treatment, those discontinuing due to fear of contagion were younger (56.4 vs 58.5 years), all female (100 vs 86.8%), with long-lasting disease (≥ 11 years) (90.9% vs 57.5%), more frequently treated with bDMARDs (36.4 vs 23.1%) and presenting more symptoms of depression (54.5 vs 49.7%).Conclusion:Most RA patients complied with their treatment during the first wave of the SARS-CoV-2 pandemic in Portugal. Only a minority changed their immunosuppressive treatment due to fear of SARS-CoV-2 infection. Very similar rates of immunosuppressive discontinuation due to fear of contagion were reported by other authors (such as Schmeiser et al, Pineda-sic et al and Fragoulis et al).Disclosure of Interests:Filipe Araujo Speakers bureau: Pfizer, Biogen, Novartis, Menarini, Consultant of: MSD, Nuno Gonçalves: None declared, Ana Filipa Mourão: None declared.

scholarly journals Blood Immunoproteasome Activity Is Regulated by Sex, Age and in Chronic Inflammatory Diseases: A First Population-Based Study

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3336
Author(s):  
Ilona Elisabeth Kammerl ◽  
Claudia Flexeder ◽  
Stefan Karrasch ◽  
Barbara Thorand ◽  
Margit Heier ◽  
...  
Keyword(s):  
Active Sites ◽  
Mononuclear Cells ◽  
Inflammatory Diseases ◽  
Population Based ◽  
Chronic Inflammatory Disease ◽  
Chronic Obstructive ◽  
Peripheral Blood Mononuclear ◽  
Chronic Inflammatory Diseases ◽  
Study Participants ◽  
The Impact

Dysfunction of the immunoproteasome has been implicated in cardiovascular and pulmonary diseases. Its potential as a biomarker for predicting disease stages, however, has not been investigated so far and population-based analyses on the impact of sex and age are missing. We here analyzed the activity of all six catalytic sites of the proteasome in isolated peripheral blood mononuclear cells obtained from 873 study participants of the KORA FF4 study using activity-based probes. The activity of the immuno- and standard proteasome correlated clearly with elevated leukocyte counts of study participants. Unexpectedly, we observed a strong sex dimorphism for proteasome activity with significantly lower immunoproteasome activity in women. In aging, almost all catalytic activities of the proteasome were activated in aged women while maintained upon aging in men. We also noted distinct sex-related activation patterns of standard and immunoproteasome active sites in chronic inflammatory diseases such as diabetes, cardiovascular diseases, asthma, or chronic obstructive pulmonary disease as determined by multiple linear regression modeling. Our data thus provides a conceptual framework for future analysis of immunoproteasome function as a bio-marker for chronic inflammatory disease development and progression.

scholarly journals Comparative analysis of various metrics of arterial compliance in the study of chronic inflammatory diseases

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
P.L Kerkhof ◽  
R.B Djorai ◽  
A Maslyanskiy ◽  
E Kolesova ◽  
A.O Konradi ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Ankylosing Spondylitis ◽  
Arterial Stiffness ◽  
Arterial Pressure ◽  
Inflammatory Diseases ◽  
Arterial Compliance ◽  
Poor Correlation ◽  
Funding Source ◽  
Chronic Inflammatory Diseases ◽  
The Impact

Abstract Introduction Arterial compliance (AC), known to depend on age and sex, may be severely compromised in chronic inflammatory diseases. Apart from the various definitions for arterial stiffness that are in vogue, their constituent components are often not unique. Purpose This study compares vascular stiffness measures in various inflammatory diseases and explores a more comprehensive description of vessel wall properties by also considering inherent associated companion metrics. Methods We retrospectively analyzed arterial pressure, ventricular volume by echocardiography (Vivid-7 ultrasound system), along with carotid–femoral pulse wave velocity (PWV, by SphygmoCor, Atcor). Pulse pressure (PP) equals systolic arterial pressure (SAP) minus diastolic arterial pressure (DAP). Effective arterial elastance (Ea) = 0.9 × SAP/SV where SV is stroke volume. AC=SV/PP (Figure 1A). The intrinsic companion (C) to any established difference-based metric is calculated on the basis of the squared mean, e.g., PPC2 = (SAP2 + DAP2). Clearly, AC depends on two differences, each having a companion. Results A total of 177 patients (age range 18 to 80 years, 49 males), characterized by inflammatory disease (51 scleroderma, 62 atherosclerosis, 35 ankylosing spondylitis, and 29 rheumatoid arthritis), yielded reduced levels of vacular compliance irrespective of the method selected. Regression analysis showed weak correlations between the various approaches (i.e., Ea, AC, PWV). Average values for AC are comparable for all 4 diagnostic groups. Ea (P<0.03) and PWV (P<0.014) are lower for ankylosing spondylitis compared to all other groups, likely due to younger age and the higher prevalence of men. Ea is highest in atherosclerosis (P<0.026) versus all other groups. SV is significantly higher in atherosclerosis (P<0.03) compared to scleroderma and rheumatoid arthritis. However, the companions may differ (Figure 1B): PPC is significantly (P=0.017) higher in atherosclerosis (156.3±16.1 mmHg) vs scleroderma (147.2±23.0 mmHg), while SVC in ankylosing spondylitis is higher (P<0.013) than in all other groups. Conclusions Arterial stiffness measures show poor correlation, suggesting limitations to their utility when studying the diagnostic groups described here. Consideration of the companion associated with each difference-based metric is warranted in order to perform a comprehensive analysis of clinical data when evaluating the impact on risk factors and prognosis. Figure 1. A: Compliance components. B: Companions Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Russian Science Foundation

scholarly journals A Brazilian Cohort of Patients With Immuno-Mediated Chronic Inflammatory Diseases Infected by SARS-CoV-2 (ReumaCoV-Brasil Registry): Protocol for a Prospective, Observational Study

10.2196/24357 ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. e24357
Author(s):  
Claudia Marques ◽  
Adriana Maria Kakehasi ◽  
Ana Paula Monteiro Gomides ◽  
Eduardo Dos Santos Paiva ◽  
Edgard Torres dos Reis Neto ◽  
...  
Keyword(s):  
Clinical Laboratory ◽  
Inflammatory Diseases ◽  
Progression Rate ◽  
Immune Mediated ◽  
Increased Risk ◽  
Observational Cohort ◽  
And Function ◽  
The Impact ◽  
Brazilian Cohort

Background Patients with immune-mediated rheumatic diseases (IMRD) are at increased risk of infections, including significant morbidity and high mortality. Considering the potential for unfavorable outcomes of SARS-CoV-2 infection in patients with IMRD, several questions were raised regarding the impact of COVID-19 at the start of the pandemic. Objective This paper presents the protocol of a study that aims to prospectively evaluate patients with IMRD and a confirmed COVID-19 diagnosis (using criteria provided by the Brazilian Ministry of Health). Methods The study comprised a prospective, observational cohort (patients with IMRD and COVID-19) and a comparison group (patients with only IMRD), with a follow-up time of 6 months to evaluate differences in health outcomes. The primary outcomes will be changes in IMRD disease activity after SARS-CoV-2 infection at 4 time points: (1) at baseline, (2) within 4-6 weeks after infection, (3) at 3 months after the second assessment (±15 days), and (4) at 6 months (±15 days). The secondary outcomes will be the progression rate to moderate or severe forms of COVID-19, need for intensive care unit admission and mechanical ventilation, death, and therapeutic changes related to IMRD. Two outcomes—pulmonary and thromboembolic events in patients with both IMRD and SARS-CoV-2 infection—are of particular interest and will be monitored with close attention (clinical, laboratory, and function tests as well as imaging). Results Recruitment opened in May 2020, with 1300 participants recruited from 43 sites as of November 2020. Patient recruitment will conclude by the end of December 2020, with follow-up occurring until April 2021. Data analysis is scheduled to start after all inclusion data have been collected, with an aim to publish a peer-reviewed paper in December 2020. Conclusions We believe this study will provide clinically relevant data on the general impact of COVID-19 on patients with IMRD. Trial Registration Brazilian Registry of Clinical Trials RBR-33YTQC; http://www.ensaiosclinicos.gov.br/rg/RBR-33ytqc/ International Registered Report Identifier (IRRID) DERR1-10.2196/24357

scholarly journals Antivirulence Activity of the Human Gut Metabolome

mBio ◽  
2014 ◽  
Vol 5 (4) ◽  
Author(s):  
L. Caetano M. Antunes ◽  
Julie A. K. McDonald ◽  
Kathleen Schroeter ◽  
Christian Carlucci ◽  
Rosana B. R. Ferreira ◽  
...  
Keyword(s):  
Small Molecules ◽  
Chemical Cues ◽  
Therapeutic Potential ◽  
Host Cells ◽  
Human Gut ◽  
Complex Ecosystem ◽  
Microbe Interactions ◽  
Health And Disease ◽  
Host Microbe Interactions

ABSTRACTThe mammalian gut contains a complex assembly of commensal microbes termed microbiota. Although much has been learned about the role of these microbes in health, the mechanisms underlying these functions are ill defined. We have recently shown that the mammalian gut contains thousands of small molecules, most of which are currently unidentified. Therefore, we hypothesized that these molecules function as chemical cues used by hosts and microbes during their interactions in health and disease. Thus, a search was initiated to identify molecules produced by the microbiota that are sensed by pathogens. We found that a secreted molecule produced by clostridia acts as a strong repressor ofSalmonellavirulence, obliterating expression of theSalmonellapathogenicity island 1 as well as host cell invasion. It has been known for decades that the microbiota protects its hosts from invading pathogens, and these data suggest that chemical sensing may be involved in this phenomenon. Further investigations should reveal the exact biological role of this molecule as well as its therapeutic potential.IMPORTANCEMicrobes can communicate through the production and sensing of small molecules. Within the complex ecosystem formed by commensal microbes living in and on the human body, it is likely that these molecular messages are used extensively during the interactions between different microbial species as well as with host cells. Deciphering such a molecular dialect will be fundamental to our understanding of host-microbe interactions in health and disease and may prove useful for the design of new therapeutic strategies that target these mechanisms of communication.

scholarly journals Gut Microbiota and Iron: The Crucial Actors in Health and Disease

2018 ◽  
Vol 11 (4) ◽  
pp. 98 ◽  
Author(s):  
Bahtiyar Yilmaz ◽  
Hai Li
Keyword(s):  
Gut Microbiota ◽  
Inflammatory Diseases ◽  
Life Forms ◽  
Iron Availability ◽  
Human Beings ◽  
Human Gastrointestinal Tract ◽  
Dynamic Modulation ◽  
Microbe Interactions ◽  
Health And Disease ◽  
Host Microbe Interactions

Iron (Fe) is a highly ample metal on planet earth (~35% of the Earth’s mass) and is particularly essential for most life forms, including from bacteria to mammals. Nonetheless, iron deficiency is highly prevalent in developing countries, and oral administration of this metal is so far the most effective treatment for human beings. Notably, the excessive amount of unabsorbed iron leave unappreciated side effects at the highly interactive host–microbe interface of the human gastrointestinal tract. Recent advances in elucidating the molecular basis of interactions between iron and gut microbiota shed new light(s) on the health and pathogenesis of intestinal inflammatory diseases. We here aim to present the dynamic modulation of intestinal microbiota by iron availability, and conversely, the influence on dietary iron absorption in the gut. The central part of this review is intended to summarize our current understanding about the effects of luminal iron on host–microbe interactions in the context of human health and disease.

scholarly journals Introduction to the human gut microbiota

2017 ◽  
Vol 474 (11) ◽  
pp. 1823-1836 ◽  
Author(s):  
Elizabeth Thursby ◽  
Nathalie Juge
Keyword(s):  
Gut Microbiota ◽  
Inflammatory Diseases ◽  
Intestinal Bacteria ◽  
Life Time ◽  
Gi Tract ◽  
Human Gut ◽  
Human Gut Microbiota ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
Dynamic Population

The human gastrointestinal (GI) tract harbours a complex and dynamic population of microorganisms, the gut microbiota, which exert a marked influence on the host during homeostasis and disease. Multiple factors contribute to the establishment of the human gut microbiota during infancy. Diet is considered as one of the main drivers in shaping the gut microbiota across the life time. Intestinal bacteria play a crucial role in maintaining immune and metabolic homeostasis and protecting against pathogens. Altered gut bacterial composition (dysbiosis) has been associated with the pathogenesis of many inflammatory diseases and infections. The interpretation of these studies relies on a better understanding of inter-individual variations, heterogeneity of bacterial communities along and across the GI tract, functional redundancy and the need to distinguish cause from effect in states of dysbiosis. This review summarises our current understanding of the development and composition of the human GI microbiota, and its impact on gut integrity and host health, underlying the need for mechanistic studies focusing on host–microbe interactions.

scholarly journals Systematic review and meta-analysis: the impact of co-occurring immune-mediated inflammatory diseases on the disease localization and behavior of Crohn’s disease

2021 ◽  
Vol 14 ◽  
pp. 175628482110048
Author(s):  
Mohamed Attauabi ◽  
Mirabella Zhao ◽  
Flemming Bendtsen ◽  
Johan Burisch
Keyword(s):  
Systematic Review ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Inflammatory Diseases ◽  
Meta Analysis ◽  
Random Effect ◽  
Immune Mediated ◽  
Increased Risk ◽  
The Impact ◽  
Upper Gastrointestinal

Background: Patients with Crohn’s disease (CD) are at increased risk of co-occurring immune-mediated inflammatory diseases (IMIDs). As discrepancy exists regarding the phenotypic presentation of CD among patients with such co-occurring IMIDs, we aimed to conduct a systematic review with meta-analysis characterizing the phenotype of CD among this subgroup of patients. Methods: PubMed, Embase, and Scopus were searched from their earliest records to October 2019 for studies reporting the behavior and localization of CD according to the Vienna or Montreal Classifications and CD-related surgery in patients with co-occurring IMIDs. These studies were the subject of a random effect meta-analysis. Results: After reviewing 24,413 studies, we identified a total of 23 studies comprising 1572 and 35,043 CD patients with and without co-occurring IMIDs, respectively, that fulfilled our inclusion criteria. Overall, patients with co-occurring IMIDs were more likely to have upper gastrointestinal inflammation than were patients without co-occurring IMIDs [relative risk (RR) = 1.49 (95% confidence interval (CI) 1.09–2.04), p = 0.01, I2 = 7%]. In addition, presence of primary sclerosing cholangitis (PSC) was associated with a lower occurrence of ileal affection [RR = 0.44 (95% CI 0.24–0.81), p < 0.01, I2 = 32%], increased occurrence of colonic affection [RR = 1.78 (95% CI 1.33–2.38), p < 0.01, I2 = 32%] and an increased likelihood of non-stricturing and non-penetrating behavior [RR = 1.43 (95% CI 0.97–2.11), p = 0.07, I2 = 86%]. The latter reached significance when cumulating different IMIDs [RR = 1.30 (95% CI 1.09–1.55), p < 0.01, I2 = 88%]. CD patients with PSC also underwent fewer CD-related surgeries [RR = 0.55 (95% CI 0.34–0.88), p = 0.01, I2 = 0%], irrespective of CD location or behavior. Conclusion: This study emphasizes that CD patients with co-existing PSC are likely to have a unique inflammatory distribution primarily confined to the colon, while patients with IMIDs in general have higher likelihood of affection of upper gastrointestinal tract and a non-stricturing and non-penetrating behavior. As such a phenotype of CD is typically associated with a milder disease course; future studies are needed to confirm these results.

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