scholarly journals HLA alleles associated with risk of ankylosing spondylitis and rheumatoid arthritis influence the gut microbiome

2019 ◽  
Author(s):  
Mark Asquith ◽  
Peter R. Sternes ◽  
Mary-Ellen Costello ◽  
Lisa Karstens ◽  
Sarah Diamond ◽  
...  

ABSTRACTObjectivesHLA alleles affect susceptibility to more than 100 diseases, but the mechanisms to account for these genotype-disease associations are largely unknown. HLA-alleles strongly influence predisposition to ankylosing spondylitis (AS) and rheumatoid arthritis (RA). Both AS and RA patients have discrete intestinal and faecal microbiome signatures. Whether these changes are cause or consequence of the diseases themselves is unclear. To distinguish these possibilities, we examine the effect ofHLA-B27andHLA-DRB1RA-risk alleles on the composition of the intestinal microbiome in healthy individuals.Methods568 samples from 6 intestinal sites were collected from 107 otherwise healthy unrelated subjects and stool samples from 696 twin pairs from the TwinsUK cohort. Microbiome profiling was performed using sequencing of the 16S rRNA bacterial marker gene. All patients were genotyped using the Illumina CoreExome SNP microarray, and HLA genotypes were imputed from these data.ResultsAssociation was observed betweenHLA-B27genotype, and RA-riskHLA-DRB1alleles, and overall microbial composition (P=0.0002 and P=0.00001 respectively). These associations were replicated in the TwinsUK cohort stool samples (P=0.023 and P=0.033 respectively).ConclusionsThis study shows that the changes in intestinal microbiome composition seen in AS and RA are at least partially due to effects ofHLA-B27and –DRB1on the gut microbiome. These findings support the hypothesis that HLA alleles operate to cause or increase the risk of these diseases through interaction with the intestinal microbiome, and suggest that therapies targeting the microbiome may be effective in their prevention and/or treatment.

Kidney360 ◽  
2021 ◽  
pp. 10.34067/KID.0006132020
Author(s):  
Dominic S. Raj ◽  
Michael B. Sohn ◽  
David M. Charytan ◽  
Jonathan Himmelfarb ◽  
T. Alp Ikizler ◽  
...  

Background: The intestinal microbiome is an appealing target for interventions in end-stage kidney disease (ESKD) because of its likely contribution to uremic toxicity. Before conducting clinical trials of microbiome-altering treatments, it is necessary to understand the within-person and between-person variability in the composition and function of the gut microbiome in patients with ESKD. Methods: Multi-center, non-randomized, crossover feasibility study of maintenance hemodialysis patients consisting of 3 phases: pre-treatment (8 weeks), treatment during which the prebiotic, p-inulin (Prebiotin®), was administered at a dose of 8 gm twice daily (12 weeks), and post-treatment (8 weeks). Stool samples were collected 1-2 times/week and blood was collected weekly for 28 weeks. The gut microbiome was characterized using 16S ribosomal RNA sequencing and metabolomic profiling. Results: Eleven of the 13 participants completed the 28-week study. Inter-participant variability was greater than intra-participant variability for microbiome composition (p<0.001 by UniFrac distances), and metabolomic composition (p<0.001 by Euclidean distances). p-Inulin was well-tolerated by 12 of 13 participants. Adherence to the frequent sample collection and self-aliquoting of stool samples were both 96%. A change in the microbiome composition from pre-treatment to post-treatment was evident by the overall shifts in weighted UniFrac distances (p=0.004) and a progressive decrease in prevalence of high intra-class correlations indicating an increase in intra-participant microbiome diversity during and after p-inulin treatment. An effect of p-inulin on the metabolomic profile was not evident. Conclusions: The intra-participant stability of the gut microbiome under no-treatment conditions, the tolerability of p-inulin, the signals of increased diversity of the microbiome with p-inulin treatment, and the willingness of participants to provide stool samples all support the feasibility of a larger trial to investigate interventions targeting the gut microbiome in patients with ESKD. Whether p-inulin has sufficient efficacy as an intervention requires evaluation in larger studies.


2019 ◽  
Author(s):  
Jian Yin ◽  
Peter R. Sternes ◽  
Mingbang Wang ◽  
Mark Morrison ◽  
Jing Song ◽  
...  

ABSTRACTDiverse evidence including clinical, genetic and microbiome studies support a major role of the gut microbiome in the common immune-mediated arthropathy, ankylosing spondylitis (AS). To further investigate this we performed metagenomic analysis of a case-control cohort of 250 Han-Chinese subjects. Previous reports of gut dysbiosis in AS were re-confirmed and several notable bacterial species and functional categories were differentially abundant. TNF-inhibitor (TNFi) therapy at least partially restored the perturbed microbiome observed in untreated AS cases to that of healthy controls, including several important bacterial species that have been previously associated with AS and other related diseases. Enrichment of bacterial peptides homologous to HLA-B27-presented epitopes was observed in the stools of AS patients, suggesting that either HLA-B27 fails to clear these or that they are involved in driving HLA-B27-associated immune reactions. TNFi therapy of AS patients was also associated with a reduction of potentially arthritogenic bacterial peptides, relative to untreated patients. An AS-associated SNP in RUNX3 significantly influenced the microbiome in two independent cohorts, highlighting a host genotype (other than HLA-B27) potentially influencing AS via the microbiome. These findings emphasise the key role that the gut microbiome plays in driving the pathogenesis of AS.


2019 ◽  
Vol 71 (10) ◽  
pp. 1642-1650 ◽  
Author(s):  
Mark Asquith ◽  
Peter R. Sternes ◽  
Mary‐Ellen Costello ◽  
Lisa Karstens ◽  
Sarah Diamond ◽  
...  

2019 ◽  
Vol 79 (1) ◽  
pp. 132-140 ◽  
Author(s):  
Jian Yin ◽  
Peter Richard Sternes ◽  
Mingbang Wang ◽  
Jing Song ◽  
Mark Morrison ◽  
...  

ObjectivesDiverse evidence including clinical, genetic and microbiome studies support a major role of the gut microbiome in the common immune-mediated arthropathy, ankylosing spondylitis (AS). We set out to (1) further define the key microbial characteristics driving disease, and (2) examine the effects of tumour necrosis factor-inhibitor (TNFi) therapy upon the microbiome.MethodsThe stools from a case–control cohort of 250 Han-Chinese subjects underwent shotgun metagenomic sequencing. All subjects were genotyped using the Illumina CoreExome SNP microarray.ResultsPrevious reports of gut dysbiosis in AS were reconfirmed and several notable bacterial species and functional categories were differentially abundant. TNFi therapy was correlated with a restoration the perturbed microbiome observed in untreated AS cases to that of healthy controls, including several important bacterial species that have been previously associated with AS and other related diseases. Enrichment of bacterial peptides homologous to HLA-B27-presented epitopes was observed in the stools of patients with AS, suggesting that either HLA-B27 fails to clear these or that they are involved in driving HLA-B27-associated immune reactions. TNFi therapy largely restored the perturbed microbiome observed in untreated AS cases to that of healthy controls, including several important bacterial species that have been previously associated with AS and other related diseases. TNFi therapy of patients with AS was also associated with a reduction of potentially arthritogenic bacterial peptides, relative to untreated patients.ConclusionThese findings emphasise the key role that the gut microbiome plays in driving the pathogenesis of AS and highlight potential therapeutic and/or preventative targets.


Life ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 246
Author(s):  
Felix C.F. Schmitt ◽  
Martin Schneider ◽  
William Mathejczyk ◽  
Markus A. Weigand ◽  
Jane C. Figueiredo ◽  
...  

Changes in the gut microbiome have already been associated with postoperative complications in major abdominal surgery. However, it is still unclear whether these changes are transient or a long-lasting effect. Therefore, the aim of this prospective clinical pilot study was to examine long-term changes in the gut microbiota and to correlate these changes with the clinical course of the patient. Methods: In total, stool samples of 62 newly diagnosed colorectal cancer patients undergoing primary tumor resection were analyzed by 16S-rDNA next-generation sequencing. Stool samples were collected preoperatively in order to determine the gut microbiome at baseline as well as at 6, 12, and 24 months thereafter to observe longitudinal changes. Postoperatively, the study patients were separated into two groups—patients who suffered from postoperative complications (n = 30) and those without complication (n = 32). Patients with postoperative complications showed a significantly stronger reduction in the alpha diversity starting 6 months after operation, which does not resolve, even after 24 months. The structure of the microbiome was also significantly altered from baseline at six-month follow-up in patients with complications (p = 0.006). This was associated with a long-lasting decrease of a large number of species in the gut microbiota indicating an impact in the commensal microbiota and a long-lasting increase of Fusobacterium ulcerans. The microbial composition of the gut microbiome shows significant changes in patients with postoperative complications up to 24 months after surgery.


Pathogens ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 463
Author(s):  
Mariusz Sikora ◽  
Albert Stec ◽  
Magdalena Chrabaszcz ◽  
Aleksandra Knot ◽  
Anna Waskiel-Burnat ◽  
...  

(1) Background: A growing body of evidence highlights that intestinal dysbiosis is associated with the development of psoriasis. The gut–skin axis is the novel concept of the interaction between skin diseases and microbiome through inflammatory mediators, metabolites and the intestinal barrier. The objective of this study was to synthesize current data on the gut microbial composition in psoriasis. (2) Methods: We conducted a systematic review of studies investigating intestinal microbiome in psoriasis, using the PRISMA checklist. We searched MEDLINE, EMBASE, and Web of Science databases for relevant published articles (2000–2020). (3) Results: All of the 10 retrieved studies reported alterations in the gut microbiome in patients with psoriasis. Eight studies assessed alpha- and beta-diversity. Four of them reported a lack of change in alpha-diversity, but all confirmed significant changes in beta-diversity. At the phylum-level, at least two or more studies reported a lower relative abundance of Bacteroidetes, and higher Firmicutes in psoriasis patients versus healthy controls. (4) Conclusions: There is a significant association between alterations in gut microbial composition and psoriasis; however, there is high heterogeneity between studies. More unified methodological standards in large-scale studies are needed to understand microbiota’s contribution to psoriasis pathogenesis and its modulation as a potential therapeutic strategy.


2021 ◽  
Author(s):  
Yishay Pinto ◽  
Sigal Frishman ◽  
Sondra Turjeman ◽  
Adi Eshel ◽  
Meital Nuriel-Ohayon ◽  
...  

AbstractGestational diabetes mellitus (GDM) is a condition in which non-diabetic women are diagnosed with glucose intolerance during pregnancy, typically in the second trimester. GDM can lead to a wide range of obstetrical and metabolic complications for both mother and neonate1. Early identification of GDM risk, along with a better understanding of its pathophysiology during the first trimester of pregnancy, may be effective in reducing GDM incidence, as well as its associated short and long term morbidities2. Here, we comprehensively profiled the gut microbiome, metabolome, inflammatory cytokines, nutrition and clinical records of 394 women during the first trimester of pregnancy. We found elevated levels of proinflammatory serum cytokines in those who later developed GDM. The women’s stool samples were also characterized by decreased levels of several fecal short-chain fatty acids and altered microbiome. We next tested the hypothesis that differences in GDM-associated microbial composition during the first trimester drove inflammation and insulin-resistance. Stool samples collected early in pregnancy from women from three populations who did and did not later develop GDM were transplanted to germ-free mice and confirmed that both inflammation and insulin-resistance are induced by the microbiome of pregnant women more than 10 weeks prior to GDM diagnosis. Following these observations, we used a machine-learning approach to predict GDM based on first trimester clinical, microbial and inflammatory markers. Our model showed high predictive accuracy. Overall, our results suggest that the gut microbiome of women in the first trimester plays a remarkable role in inflammation-induced GDM pathogenesis and point to dozens of GDM markers during the first trimester of pregnancy, some of which may be targets for therapeutic intervention.


2020 ◽  
Vol 75 (6) ◽  
pp. 577-584
Author(s):  
G. R. Bikbavova ◽  
M. A. Livzan

In recent decades, an increase in the incidence of ulcerative colitis has been observed throughout the world. The purpose of this review is to generalize the available information on the influence of environmental factors and intestinal microbiome on the occurrence and development of ulcerative colitis, the role of bacteria metabolism products in the pathogenesis of the disease. Studied literature, we came to the conclusion that lifestyle in the era of post-industrial society has a significant impact on the microbial composition of the intestine and leads to changes in its diversity in patients suffering from ulcerative colitis. The changes include a decrease in the number of residential flora with anti-inflammatory activity, which synthesize short-chain fatty acids, and an increase in the number of potentially pathogenic and pathogenic microorganisms. Within the phylums Firmicutes and Proteobacteria, the proportional ratio changes. The combination of aggression factors (deterioration of the intestinal microbiome composition, the presence of aggressive intestinal metabolites) leads to intestinal mucosa permeability disfunction, impairing its barrier function. Food and bacterial agents can penetrate deeper layers of the intestinal wall through mucosal defects, which then stimulate the development of inflammatory and immune responses.


Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1874 ◽  
Author(s):  
Angela Horvath ◽  
Marija Durdevic ◽  
Bettina Leber ◽  
Katharina di Vora ◽  
Florian Rainer ◽  
...  

Probiotics have been used in trials to therapeutically modulate the gut microbiome and have shown beneficial effects in cirrhosis. However, their effect on the microbiome of cirrhosis patients is not fully understood yet. Here, we tested the effects of a multispecies probiotic on microbiome composition in compensated cirrhosis. The gut microbiome composition of 58 patients with compensated cirrhosis from a randomized controlled trial who received a daily dose of multispecies probiotics or placebo for six months was analysed by 16S rRNA gene sequencing. Microbiome composition of patients who received probiotics was enriched with probiotic strains and the abundance of Faecalibacterium prausnitzii, Syntrophococcus sucromutans, Bacteroides vulgatus, Alistipes shahii and a Prevotella species was increased in the probiotic group compared to the placebo group. Patients who had microbiome changes in response to probiotic treatment also showed a significant increase in neopterin and a significant decrease in faecal zonulin levels after intervention, which was not observed in placebo-treated patients or patients with unchanged microbiome compositions. In conclusion, multispecies probiotics may enrich the microbiome of compensated cirrhotic patients with probiotic bacteria during a six-month intervention and beneficially change the residential microbiome and gut barrier function.


2009 ◽  
Vol 150 (43) ◽  
pp. 2000-2003
Author(s):  
Eszter Varga ◽  
Ágnes Petró ◽  
Rita Jáger ◽  
László Varga

A szerzők egy 35 éves nőbeteg kórtörténetét ismertetik, akinél 29 éves korában szeronegatív rheumatoid arthritist igazoltak a reumatológiai osztályon. A betegség remisszióját sikeres graviditás követte, majd két évvel később kizárólag axiális tüneteket mutató spondylarthritist diagnosztizáltak. A major hisztokompatibilitási komplex vizsgálata során a hagyományos szerológiai módszerekkel a HLA B27 spondylarthritis ankylopoeticára jellemző, valamint HLA DR1 rheumatoid arthritisre jellemző haplotípust mutattak ki. A HLA DRB-polimorfizmus vizsgálata során a rheumatoid arthritis létrejöttében és kórlefolyásában szerepet játszó HLA DR B1 0101 allél jelenlétét igazolták. A betegben tehát ritka kombinációként a spondylarthritis ankylopoetica és a rheumatoid arthritis létrejöttében is szerepet játszó HLA-formáció egyaránt megtalálható volt.


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