Gut Microbiota–Medication Interaction in Rheumatic Diseases

Besides its contribution to the development of rheumatic diseases, the gut microbiota interact with anti-rheumatic drugs. The intestinal microbiota can directly metabolize many drugs and indirectly change drug metabolism through a complex multi-dimensional interaction with the host, thus affecting individual response to drug therapy and adverse effects. The focus of the current review is to address recent advances and important progress in our understanding of how the gut microbiota interact with anti-rheumatic drugs and provide perspectives on promoting precision treatment, drug discovery, and better therapy for rheumatic diseases.

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Modulation of Gut Microbiota for the Prevention and Treatment of COVID-19

Journal of Clinical Medicine ◽

10.3390/jcm10132903 ◽

2021 ◽

Vol 10 (13) ◽

pp. 2903

Author(s):

Jiezhong Chen ◽

Luis Vitetta

Keyword(s):

Clinical Trials ◽

Trace Elements ◽

Gut Microbiota ◽

Human Health ◽

Intestinal Microbiota ◽

Narrative Review ◽

Bacterial Metabolites ◽

Gut Dysbiosis ◽

Prevention And Treatment

The gut microbiota is well known to exert multiple benefits on human health including protection from disease causing pathobiont microbes. It has been recognized that healthy intestinal microbiota is of great importance in the pathogenesis of COVID-19. Gut dysbiosis caused by various reasons is associated with severe COVID-19. Therefore, the modulation of gut microbiota and supplementation of commensal bacterial metabolites could reduce the severity of COVID-19. Many approaches have been studied to improve gut microbiota in COVID-19 including probiotics, bacterial metabolites, and prebiotics, as well as nutraceuticals and trace elements. So far, 19 clinical trials for testing the efficacy of probiotics and synbiotics in COVID-19 prevention and treatment are ongoing. In this narrative review, we summarize the effects of various approaches on the prevention and treatment of COVID-19 and discuss associated mechanisms.

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Gut microbiota composition and arterial stiffness measured by pulse wave velocity: case–control study protocol (MIVAS study)

BMJ Open ◽

10.1136/bmjopen-2020-038933 ◽

2021 ◽

Vol 11 (2) ◽

pp. e038933

Author(s):

Rita Salvado ◽

Sandra Santos-Minguez ◽

Cristina Agudo-Conde ◽

Cristina Lugones-Sanchez ◽

Angela Cabo-Laso ◽

...

Keyword(s):

Arterial Stiffness ◽

Gut Microbiota ◽

Pulse Wave Velocity ◽

Wave Velocity ◽

Intestinal Microbiota ◽

Pulse Wave ◽

Case Control Study ◽

Case Control ◽

Microbiota Composition ◽

Control Study

IntroductionIntestinal microbiota is arising as a new element in the physiopathology of cardiovascular diseases. A healthy microbiota includes a balanced representation of bacteria with health promotion functions (symbiotes). The aim of this study is to analyse the relationship between intestinal microbiota composition and arterial stiffness.Methods and analysisAn observational case—control study will be developed. Cases will be defined by the presence of at least one of the following: carotid-femoral pulse wave velocity (cf-PWV), Cardio-Ankle Vascular Index (CAVI), brachial ankle pulse wave velocity (ba or ba-PWV) above the 90th percentile, for age and sex, of the reference population. Controls will be selected from the same population as cases. The study will be developed in Primary Healthcare Centres. We will select 500 subjects (250 cases and 250 controls), between 45 and 74 years of age. Cases will be selected from a database that combines data from EVA study (Spain) and Guimarães/Vizela study (Portugal). Measurements: cf-PWV will be measured using the SphygmoCor system, CAVI, ba-PWV and Ankle-Brachial Index will be determined using VaSera device. Gut microbiome composition in faecal samples will be determined by 16S ribosomal RNA sequencing. Lifestyle will be assessed by food frequency questionnaire, adherence to the Mediterranean diet and IPAQ (International Physical Activity Questionnaire). Body composition will be evaluated by bioimpedance.Ethics and disseminationThe study has been approved by ‘Committee of ethics of research with medicines of the health area of Salamanca’ on 14 December 2018 (cod. 2018-11-136) and the ’Ethics committee for health of Guimaraes’ (Portugal) on 15 October 2019 (ref: 67/2019). All study participants will sign an informed consent form agreeing to participate in the study, in compliance with the Declaration of Helsinki and the WHO standards for observational studies. The results of this study will allow a better description of gut microbiota in patients with arterial stiffness.Trial registration detailsClinicalTrials.gov, identifier NCT03900338

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A Crosstalk between Diet, Microbiome and microRNA in Epigenetic Regulation of Colorectal Cancer

Nutrients ◽

10.3390/nu13072428 ◽

2021 ◽

Vol 13 (7) ◽

pp. 2428

Author(s):

Małgorzata Guz ◽

Witold Jeleniewicz ◽

Anna Malm ◽

Izabela Korona-Glowniak

Keyword(s):

Colorectal Cancer ◽

Gastrointestinal Tract ◽

Gut Microbiota ◽

Intestinal Microbiota ◽

Current Knowledge ◽

Vital Role ◽

Disease States ◽

Health And Disease ◽

Dietary Components ◽

Non Coding Rnas

A still growing interest between human nutrition in relation to health and disease states can be observed. Dietary components shape the composition of microbiota colonizing our gastrointestinal tract which play a vital role in maintaining human health. There is a strong evidence that diet, gut microbiota and their metabolites significantly influence our epigenome, particularly through the modulation of microRNAs. These group of small non-coding RNAs maintain cellular homeostasis, however any changes leading to impaired expression of miRNAs contribute to the development of different pathologies, including neoplastic diseases. Imbalance of intestinal microbiota due to diet is primary associated with the development of colorectal cancer as well as other types of cancers. In the present work we summarize current knowledge with particular emphasis on diet-microbiota-miRNAs axis and its relation to the development of colorectal cancer.

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Perioperative Multimodal Anesthesia Using Regional Techniques in the Aging Surgical Patient

Pain Research and Treatment ◽

10.1155/2014/902174 ◽

2014 ◽

Vol 2014 ◽

pp. 1-13 ◽

Cited By ~ 5

Author(s):

Diana Nordquist ◽

Thomas M. Halaszynski

Keyword(s):

Drug Therapy ◽

Adverse Effects ◽

Elderly Patients ◽

Regional Anesthesia ◽

Pain Control ◽

The Elderly ◽

Surgical Patient ◽

Cochrane Central Register ◽

Promising Alternative ◽

Age Related

Background. Elderly patients have unique age-related comorbidities that may lead to an increase in postoperative complications involving neurological, pulmonary, cardiac, and endocrine systems. There has been an increase in the number of elderly patients undergoing surgery as this portion of the population is increasing in numbers. Despite advances in perioperative anesthesia and analgesia along with improved delivery systems, monotherapy with opioids continues to be the mainstay for treatment of postop pain. Reliance on only opioids can oftentimes lead to inadequate pain control or increase in the incidence of adverse events. Multimodal analgesia incorporating regional anesthesia is a promising alternative that may reduce needs for high doses and dependence on opioids along with any potential associated adverse effects. Methods. The following databases were searched for relevant published trials: Cochrane Central Register of Controlled Trials and PubMed. Textbooks and meeting supplements were also utilized. The authors assessed trial quality and extracted data. Conclusions. Multimodal drug therapy and perioperative regional techniques can be very effective to perioperative pain management in the elderly. Regional anesthesia as part of multimodal perioperative treatment can often reduce postoperative neurological, pulmonary, cardiac, and endocrine complications. Regional anesthesia/analgesia has not been proven to improve long-term morbidity but does benefit immediate postoperative pain control. In addition, multimodal drug therapy utilizes a variety of nonopioid analgesic medications in order to minimize dosages and adverse effects from opioids while maximizing analgesic effect and benefit.

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Association of Particulate Matter with Autoimmune Rheumatic Diseases among Adults in South Korea

Rheumatology ◽

10.1093/rheumatology/keab127 ◽

2021 ◽

Author(s):

Jun Seok Park ◽

Seulggie Choi ◽

Kyuwoong Kim ◽

Jooyoung Chang ◽

Sung Min Kim ◽

...

Keyword(s):

Particulate Matter ◽

Adverse Effects ◽

South Korea ◽

Rheumatic Diseases ◽

Lupus Erythematosus ◽

Cox Regression ◽

Statistical Significance ◽

Cox Regression Analysis ◽

Autoimmune Rheumatic Diseases ◽

Quartile Group

Abstract Objective The primary objective is to investigate adverse effects of ambient particulate matter (PM) in various size on the incidence of prevalent autoimmune rheumatic diseases (AIRDs): Rheumatoid Arthritis (RA), Ankylosing Spondylitis (AS), and Systemic Lupus Erythematosus (SLE). Methods We investigated 230,034 participants in three metropolitan cities of South Korea from the National Health Insurance Service-National Sample Cohort (NHIS-NSC). Starting from January 2010, subjects were followed up until the first event of prevalent AIRDs, death, or December 2013. 2008-2009 respective averages of PM2.5 (< 2.5μm) and PMcoarse (2.5μm to 10μm) were linked with participants’ administrative district codes. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were estimated using Cox regression analysis in one- and two-pollutant model. Results Adjusted for age, sex, region, and household income in two-pollutant model, RA incidence was positively associated with 10μg/m³ increment of PM2.5 (aHR = 1.74, 95% CI: 1.06-2.86), but not with PMcoarse (aHR = 1.27, 95% CI: 0.87-1.85). In one-pollutant model, an elevated incidence rate of RA was slightly attenuated (PM2.5 aHR = 1.61, 95% CI: 0.99-2.61; PMcoarse aHR = 1.13, 95% CI: 0.80-1.61), with marginal statistical significance of PM2.5. RA incidence was also higher in 4th quartile group of PM2.5 compared to 1st quartile group (aHR = 1.83, 95% CI: 1.07-3.11). No adverse effects of PM were found on AS or SLE in one- and two-pollutant models. Conclusion Important components of PM10 associated with RA incidence were fine fractions (PM2.5), while no positive association was found between PM and AS or SLE.

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Clostridial Butyrate Biosynthesis Enzymes Are Significantly Depleted in the Gut Microbiota of Nonobese Diabetic Mice

mSphere ◽

10.1128/msphere.00492-18 ◽

2018 ◽

Vol 3 (5) ◽

Cited By ~ 9

Author(s):

Alessandro Tanca ◽

Antonio Palomba ◽

Cristina Fraumene ◽

Valeria Manghina ◽

Michael Silverman ◽

...

Keyword(s):

Gut Microbiota ◽

Intestinal Microbiota ◽

Time Window ◽

High Resolution Mass Spectrometry ◽

Nod Mice ◽

16S Rrna Gene Sequencing ◽

Rrna Gene ◽

Diabetic Mice ◽

Nonobese Diabetic ◽

Nonobese Diabetic Mice

ABSTRACT Increasing evidence suggests that the intestinal microbiota is involved in the pathogenesis of type 1 diabetes (T1D). Here we sought to determine which gut microbial taxa and functions vary between nonobese diabetic (NOD) mice and genetically modified NOD mice protected from T1D (Eα16/NOD) at 10 weeks of age in the time window between insulitis development and T1D onset. The gut microbiota of NOD mice were investigated by analyzing stool samples with a metaproteogenomic approach, comprising both 16S rRNA gene sequencing and microbial proteome profiling through high-resolution mass spectrometry. A depletion of Firmicutes (particularly, several members of Lachnospiraceae) in the NOD gut microbiota was observed compared to the level in the Eα16/NOD mice microbiota. Moreover, the analysis of proteins actively produced by the gut microbiota revealed different profiles between NOD and Eα16/NOD mice, with the production of butyrate biosynthesis enzymes being significantly reduced in diabetic mice. Our results support a model for gut microbiota influence on T1D development involving bacterium-produced metabolites as butyrate. IMPORTANCE Alterations of the gut microbiota early in age have been hypothesized to impact T1D autoimmune pathogenesis. In the NOD mouse model, protection from T1D has been found to operate via modulation of the composition of the intestinal microbiota during a critical early window of ontogeny, although little is known about microbiota functions related to T1D development. Here, we show which gut microbial functions are specifically associated with protection from T1D in the time window between insulitis development and T1D onset. In particular, we describe that production of butyrate biosynthesis enzymes is significantly reduced in NOD mice, supporting the hypothesis that modulating the gut microbiota butyrate production may influence T1D development.

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Analysis of the use and adverse effects of non-steroidal anti-inflammatory drugs: A pilot study

Vojnosanitetski pregled ◽

10.2298/vsp0603271p ◽

2006 ◽

Vol 63 (3) ◽

pp. 271-277 ◽

Cited By ~ 1

Author(s):

Aneta Peric ◽

Marija Toskic-Radojicic

Keyword(s):

Pilot Study ◽

Adverse Effects ◽

Rheumatic Diseases ◽

Test Results ◽

Stomach Pain ◽

Antiulcer Drugs ◽

Inflammatory Drugs ◽

The Mean ◽

Anti Inflammatory ◽

Number Of Males

Background/Aim. The use and adverse effects of nonsteroidal anti-inflammatory drugs (NSAIDs) in outpatients with rheumatic diseases has not yet been studied enough. The aim of this study was to evaluate the data about the efficacy and safety of NSAIDs obtained from the questionnaires submitted to the outpatients receiving these drugs. Methods. The patients who had been prescribed any of NSAIDs within the period from June to September, 2004 were included in the study. The answers obtained from the questionnaires were statistically analyzed by means of ?2-test. Results. At the time of the study, 150 patients had been prescribed ibuprofen or some other NSAID. Out of the total number of dispensed questionnaires (n = 150), only 45 (30%) were shown to be correctly filled-in. Their analysis showed that 64.4% of the patients had suffered from rheumatic diseases for more than five years, and had regularly used NSAIDs. The average age of these patients was about 70 years, and the number of females was double as high as that of the males. The most frequently used NSAIDs were diclofenac and ibuprofen (46.14%, and 23.24%, respectively). According to the answers given by the patients, the most often adverse reactions were gastric complaints such as nausea (11.1%), and stomach pain (8.9%). Due to this, the majority of the patients (64.4%) used some of the antiulcer drugs, most often ranitidine (31.1%). Conclusion. The results of this pilot study revealed that among the outpatients suffering from rheumatic diseases, the number of females was double as high as the number of males, that these patients were of the mean age of 70 years, and that their diseases lasted longer than five years. Gastric complains such as nausea and gastric pain of mild intensity were the most often adverse effects of NSAIDs reported by our patients. It could be the consequence of the predominant use of diclofenac and ibuprofen, NSAIDs with mild to moderate ulcerogenic potential, as well as the concomitant use of H2-receptor antagonists.

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Gut microbiome dysbiosis in anorexia nervosa

Postępy Higieny i Medycyny Doświadczalnej ◽

10.5604/01.3001.0014.8601 ◽

2021 ◽

Vol 75 ◽

pp. 283-291

Author(s):

Agata Janczy ◽

Magdalena Landowska ◽

Zdzisław Kochan

Keyword(s):

Anorexia Nervosa ◽

Gut Microbiota ◽

Body Mass ◽

Intestinal Microbiota ◽

Gut Microbiome ◽

Dietary Habits ◽

Eating Habits ◽

Current Knowledge ◽

Functional Gastrointestinal Disorders

Anorexia nervosa (AN) is described as an eating disorder, which is characterized by malnutrition, a fear of gaining body mass, and a disturbed self-body image. This disease is dependent on biological, psychological and socio-cultural factors. Among the various biological factors, the importance of intestinal microbiota has recently attracted much attention. Identification of the gut microbiota dysbiosis in patients with AN has opened new and promising research directions. Recent observations focus in particular on the association between intestinal microorganisms and the occurrence of functional gastrointestinal disorders associated with anorexia, anxiety and depression, as well as the regulation of eating habits. The composition of the gut microbiota differs between patients with AN and individuals with normal body mass. This is due to the incorrect diet of patients; on the other hand, there is growing interest in the role of intestinal microbiota in the pathogenesis of AN, its changes through re-nutrition practices, and in particular the modulation of intestinal microbiological composition by means of nutritional interventions or the use of preand probiotics as standard supplements therapy of eating disorders. There is a need for further research about the microbiome - intestine - brain axis. Furthermore, consequences of changes in dietary habits as part of AN treatment are also unknown. However, better knowledge about the relationship between the gut microbiome and the brain can help improve the treatment of this disorder. This review aims to present the current knowledge about the potential role of intestinal microbiota in the pathogenesis, course and treatment of AN.

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Role of Microbiome in Rheumatic Diseases

Hong Kong Bulletin on Rheumatic Diseases ◽

10.1515/hkbrd-2017-0010 ◽

2017 ◽

Vol 17 (2) ◽

pp. 58-63 ◽

Cited By ~ 1

Author(s):

Chi Kit Au ◽

Tin Lok Lai ◽

Cheuk Wan Yim

Keyword(s):

Rheumatoid Arthritis ◽

Gut Microbiota ◽

Immune Responses ◽

Rheumatic Diseases ◽

Pivotal Role ◽

Human Gut ◽

Future Role ◽

Human Gut Microbiota ◽

Rheumatic Manifestations

AbstractMajority of rheumatic diseases are complex and multifactorial in etiology. Emerging studies has suggested that the change of human microbiota, especially in the gut, play a pivotal role in its pathogenesis. Dysequilibrium of the gut microbiota triggers the imbalance between pro- and anti- inflammatory immune responses and results in different rheumatic manifestations, such as rheumatoid arthritis (RA) and spondyloarthritis (SpA). In this article, current and future role of the human gut microbiota in rheumatic diseases are discussed.

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Integrated Fecal Microbiome and Serum Metabolomics Analysis Reveals Abnormal Changes in Rats with Immunoglobulin A Nephropathy and the Intervention Effect of Zhen Wu Tang

Frontiers in Pharmacology ◽

10.3389/fphar.2020.606689 ◽

2021 ◽

Vol 11 ◽

Author(s):

Jicheng Li ◽

Yiwen Cao ◽

Ruirui Lu ◽

Honglian Li ◽

Yu Pang ◽

...

Keyword(s):

Gut Microbiota ◽

Renal Disease ◽

Intestinal Microbiota ◽

Renal Damage ◽

Immunoglobulin A ◽

Metabolic Phenotype ◽

Immunoglobulin A Nephropathy ◽

Metabolic Phenotypes ◽

Potential Relationship ◽

Rdna Sequencing

Immunoglobulin A nephropathy (IgAN), an autoimmune renal disease with complicated pathogenesis, is one of the principal reasons for end-stage renal disease in the clinic. Evidence has linked apparent alterations in the components of the microbiome and metabolome to renal disease in rats. However, thus far, there is insufficient evidence that supports the potential relationship between gut microbiome, circulating metabolites, and IgAN. This study was designed to probe the effects of IgAN on intestinal microecology and metabolic phenotypes and to understand the possible underlying mechanisms. Fecal and serum samples were collected from IgAN rats. Composition of the gut microbiota and biochemical changes in the metabolites was analyzed using 16S rDNA sequencing and untargeted metabolomics. The IgAN rats exhibited renal insufficiency and increased concentration of 24-h urine protein, in addition to deposition of IgA and IgG immune complexes in the kidney tissues. There was a disturbance in the balance of gut microbiota in IgAN rats, which was remarkably associated with renal damage. Marked changes in microbial structure and function were accompanied by apparent alterations in 1,403 serum metabolites, associated with the disorder of energy, carbohydrate, and nucleotide metabolisms. Administration of Zhen Wu Tang ameliorated microbial dysbiosis and attenuated the renal damage. Besides, treatment with Zhen Wu Tang modulated the metabolic phenotype perturbation in case of gut microbiota dysbiosis in IgAN rats. In conclusion, these findings provided a comprehensive understanding of the potential relationship between the intestinal microbiota and metabolic phenotypes in rats with IgAN. Elucidation of the intestinal microbiota composition and metabolic signature alterations could identify predictive biomarkers for disease diagnosis and progression, which might contribute to providing therapeutic strategies for IgAN.

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