scholarly journals Shotgun metagenomics reveals an enrichment of potentially cross-reactive bacterial epitopes in ankylosing spondylitis patients, as well as the effects of TNFi therapy and the host’s genotype upon microbiome composition

2019 ◽  
Author(s):  
Jian Yin ◽  
Peter R. Sternes ◽  
Mingbang Wang ◽  
Mark Morrison ◽  
Jing Song ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
Gut Microbiome ◽  
Bacterial Species ◽  
Tnf Inhibitor ◽  
Hla B27 ◽  
Clinical Genetic ◽  
Host Genotype ◽  
Shotgun Metagenomics ◽  
Microbiome Composition ◽  
Immune Mediated

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.

scholarly journals Shotgun metagenomics reveals an enrichment of potentially cross-reactive bacterial epitopes in ankylosing spondylitis patients, as well as the effects of TNFi therapy upon microbiome composition

2019 ◽  
Vol 79 (1) ◽  
pp. 132-140 ◽  
Author(s):  
Jian Yin ◽  
Peter Richard Sternes ◽  
Mingbang Wang ◽  
Jing Song ◽  
Mark Morrison ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
Gut Microbiome ◽  
Bacterial Species ◽  
Metagenomic Sequencing ◽  
Healthy Controls ◽  
Hla B27 ◽  
Clinical Genetic ◽  
Shotgun Metagenomics ◽  
Microbiome Composition ◽  
Shotgun Metagenomic Sequencing

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.

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 ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Ankylosing Spondylitis ◽  
Gut Microbiome ◽  
Marker Gene ◽  
Intestinal Microbiome ◽  
Hla B27 ◽  
Microbial Composition ◽  
Hla Alleles ◽  
Microbiome Composition ◽  
Stool Samples

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.

Integration of culture-dependent and independent methods provides a more coherent picture of the pig gut microbiome

2020 ◽  
Vol 96 (3) ◽  
Author(s):  
Gavin J Fenske ◽  
Sudeep Ghimire ◽  
Linto Antony ◽  
Jane Christopher-Hennings ◽  
Joy Scaria
Keyword(s):  
Bacterial Communities ◽  
Bacterial Species ◽  
Shotgun Metagenomics ◽  
Culture Techniques ◽  
Microbiome Composition ◽  
Culture Independent ◽  
Health And Disease ◽  
The Media ◽  
And Function ◽  
Culture Dependent

ABSTRACT Bacterial communities resident in the hindgut of pigs, have profound impacts on health and disease. Investigations into the pig microbiome have utilized either culture-dependent, or far more commonly, culture-independent techniques using next generation sequencing. We contend that a combination of both approaches generates a more coherent view of microbiome composition. In this study, we surveyed the microbiome of Tamworth breed and feral pigs through the integration high throughput culturing and shotgun metagenomics. A single culture medium was used for culturing. Selective screens were added to the media to increase culture diversity. In total, 46 distinct bacterial species were isolated from the Tamworth and feral samples. Selective screens successfully shifted the diversity of bacteria on agar plates. Tamworth pigs are highly dominated by Bacteroidetes primarily composed of the genus Prevotella whereas feral samples were more diverse with almost equal proportions of Firmicutes and Bacteroidetes. The combination of metagenomics and culture techniques facilitated a greater retrieval of annotated genes than either method alone. The single medium based pig microbiota library we report is a resource to better understand pig gut microbial ecology and function. It allows for assemblage of defined bacterial communities for studies in bioreactors or germfree animal models.

scholarly journals Microsporidian Infection in Mosquitoes (Culicidae) Is Associated with Gut Microbiome Composition and Predicted Gut Microbiome Functional Content

2021 ◽  
Author(s):  
Artur Trzebny ◽  
Anna Slodkowicz-Kowalska ◽  
Johanna Björkroth ◽  
Miroslawa Dabert
Keyword(s):  
16S Rrna ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Bacterial Communities ◽  
Bacterial Species ◽  
Rrna Gene ◽  
Microbial Composition ◽  
Microbiome Composition ◽  
Microsporidian Infection ◽  
Functional Content

AbstractThe animal gut microbiota consist of many different microorganisms, mainly bacteria, but archaea, fungi, protozoans, and viruses may also be present. This complex and dynamic community of microorganisms may change during parasitic infection. In the present study, we investigated the effect of the presence of microsporidians on the composition of the mosquito gut microbiota and linked some microbiome taxa and functionalities to infections caused by these parasites. We characterised bacterial communities of 188 mosquito females, of which 108 were positive for microsporidian DNA. To assess how bacterial communities change during microsporidian infection, microbiome structures were identified using 16S rRNA microbial profiling. In total, we identified 46 families and four higher taxa, of which Comamonadaceae, Enterobacteriaceae, Flavobacteriaceae and Pseudomonadaceae were the most abundant mosquito-associated bacterial families. Our data suggest that the mosquito gut microbial composition varies among host species. In addition, we found a correlation between the microbiome composition and the presence of microsporidians. The prediction of metagenome functional content from the 16S rRNA gene sequencing suggests that microsporidian infection is characterised by some bacterial species capable of specific metabolic functions, especially the biosynthesis of ansamycins and vancomycin antibiotics and the pentose phosphate pathway. Moreover, we detected a positive correlation between the presence of microsporidian DNA and bacteria belonging to Spiroplasmataceae and Leuconostocaceae, each represented by a single species, Spiroplasma sp. PL03 and Weissella cf. viridescens, respectively. Additionally, W. cf. viridescens was observed only in microsporidian-infected mosquitoes. More extensive research, including intensive and varied host sampling, as well as determination of metabolic activities based on quantitative methods, should be carried out to confirm our results.

scholarly journals Pharmacologically induced weight loss is associated with distinct gut microbiome changes in obese rats

2021 ◽  
Author(s):  
Silvia Raineri ◽  
Julia A Sherriff ◽  
Kevin S.J Thompson ◽  
Huw Jones ◽  
Paul T Pfluger ◽  
...  
Keyword(s):  
Weight Loss ◽  
Food Intake ◽  
Detailed Analysis ◽  
Relative Abundance ◽  
Gut Microbiome ◽  
Bacterial Species ◽  
Shotgun Metagenomics ◽  
Fecal Microbiome ◽  
Obese Rats ◽  
The Impact

Background: Obesity, metabolic disease and some psychiatric conditions are associated with changes to relative abundance of bacterial species and specific genes in the fecal microbiome. Little is known about the impact of pharmacologically induced weight loss on distinct gut microbiome species and their respective gene programs in obese individuals. Results: Using shotgun metagenomics, the composition of the microbiome was obtained for two cohorts of obese female Wistar rats (n=10-12, total of 82) maintained on a high fat diet before and after a 42-day treatment with a panel of four anti-obesity drugs (tacrolimus/FK506, bupropion, naltrexone and sibutramine), alone or in combination. We found that sibutramine treatment induced consistent weight loss through reducing food intake. Decreased weight loss in sibutramine-treated rats was associated with changes to the gut microbiome that included increased beta-diversity, increased Bacteroides/Firmicutes ratio and increased relative abundance of multiple Bacteroides species. In addition, the relative abundance of multiple genes was found to be differentially abundant, including significant reductions in components of flagellum and genes involved in flagellum assembly. Conclusions: This study provides a large resource comprising complete shotgun metagenomics datasets of the fecal microbiome coupled with weight change and food intake at day 3, day 15 and day 42 from 82 obese rats treated with a range of compounds used for weight loss, which are available to the community for detailed analysis. Furthermore, by conducting a detailed analysis of the microbiome associated with sibutramine-induced weight loss, we have identified multiple weight-loss associated microbial taxa and pathways. These include a reduction in components of flagellum and the flagellum assembly pathway that points to a potential role of sibutramine-induced weight-loss on regulating bacterially driven anti-inflammatory responses.

scholarly journals Metabolic and gut microbiome changes following GLP-1 or dual GLP-1/GLP-2 receptor agonist treatment in diet-induced obese mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Mette Simone Aae Madsen ◽  
Jacob Bak Holm ◽  
Albert Pallejà ◽  
Pernille Wismann ◽  
Katrine Fabricius ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Receptor Agonist ◽  
Plasma Cholesterol ◽  
Caloric Intake ◽  
Abundant Species ◽  
Shotgun Metagenomics ◽  
Microbiome Composition ◽  
Obesity And Diabetes ◽  
Rdna Sequencing ◽  
Glucagon Like Peptide

Abstract Enteroendocrine L-cell derived peptide hormones, notably glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2), have become important targets in the treatment of type 2 diabetes, obesity and intestinal diseases. As gut microbial imbalances and maladaptive host responses have been implicated in the pathology of obesity and diabetes, this study aimed to determine the effects of pharmacologically stimulated GLP-1 and GLP-2 receptor function on the gut microbiome composition in diet-induced obese (DIO) mice. DIO mice received treatment with a selective GLP-1 receptor agonist (liraglutide, 0.2 mg/kg, BID) or dual GLP-1/GLP-2 receptor agonist (GUB09–145, 0.04 mg/kg, BID) for 4 weeks. Both compounds suppressed caloric intake, promoted a marked weight loss, improved glucose tolerance and reduced plasma cholesterol levels. 16S rDNA sequencing and deep-sequencing shotgun metagenomics was applied for comprehensive within-subject profiling of changes in gut microbiome signatures. Compared to baseline, DIO mice assumed phylogenetically similar gut bacterial compositional changes following liraglutide and GUB09-145 treatment, characterized by discrete shifts in low-abundant species and related bacterial metabolic pathways. The microbiome alterations may potentially associate to the converging biological actions of GLP-1 and GLP-2 receptor signaling on caloric intake, glucose metabolism and lipid handling.

scholarly journals Impact of air pollution on buff-tailed bumblebees (Bombus terrestris) and their gut microbiome

2020 ◽  
Vol 2 (7A) ◽  
Author(s):  
Hannah Sampson ◽  
Julian Ketley ◽  
Eamonn Mallon ◽  
Julie Morrissey
Keyword(s):  
Air Pollution ◽  
Gut Microbiome ◽  
Bombus Terrestris ◽  
Bacterial Species ◽  
Published Data ◽  
Bacterial Cells ◽  
Microbiome Composition ◽  
Bee Health

Bumblebees play a major role in global pollination. Consequently, their health is of high importance for food security worldwide. Yet, recent population estimates show that their numbers are declining. This decline has been attributed to habitat loss, infection and use of pesticides. An important factor for bee health that contributes to population survival is the gut microbiome composition. The bee gut microbiome provides protection from pathogens, is specific to the host and helps break down food. Without a balanced gut microbiome, the health of the bee is threatened through increased infection and mortality. The bee gut microbiome is relatively simple, being dominated by 8 core bacterial species providing a convenient study system. Previous published data shows that air pollution has an impact on bacterial behaviour. Therefore, our hypothesis is exposure to air pollution causes an imbalance in the bee gut microbiome. To test this, we exposed bees to black carbon (BC), a major component of air pollution particulate matter. We assessed the effects on bee behaviour, microbiome composition and gut bacteria treated in vitro. Bees treated with BC showed a significant increase in viable bacterial cells in their faecal community. Independent culture of gut commensals showed that BC significantly alters the structure of their biofilms, which are important for colonisation in vivo. This supports the hypothesis that air pollution can cause an imbalance in the bee gut microbiome, and may adversely influence bee health and pollinator populations.

scholarly journals Microbial co-occurrence complicates associations of gut microbiome with US immigration, dietary intake and obesity

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Zheng Wang ◽  
Mykhaylo Usyk ◽  
Yoshiki Vázquez-Baeza ◽  
Guo-Chong Chen ◽  
Carmen R. Isasi ◽  
...  
Keyword(s):  
Dietary Intake ◽  
Gut Microbiome ◽  
Bacterial Species ◽  
Population Based ◽  
Shotgun Metagenomics ◽  
Fiber Degradation ◽  
Westernized Diet ◽  
Metagenomics Data ◽  
Health And Disease ◽  
Positive Correlations

Abstract Background Obesity and related comorbidities are major health concerns among many US immigrant populations. Emerging evidence suggests a potential involvement of the gut microbiome. Here, we evaluated gut microbiome features and their associations with immigration, dietary intake, and obesity in 2640 individuals from a population-based study of US Hispanics/Latinos. Results The fecal shotgun metagenomics data indicate that greater US exposure is associated with reduced ɑ-diversity, reduced functions of fiber degradation, and alterations in individual taxa, potentially related to a westernized diet. However, a majority of gut bacterial genera show paradoxical associations, being reduced with US exposure and increased with fiber intake, but increased with obesity. The observed paradoxical associations are not explained by host characteristics or variation in bacterial species but might be related to potential microbial co-occurrence, as seen by positive correlations among Roseburia, Prevotella, Dorea, and Coprococcus. In the conditional analysis with mutual adjustment, including all genera associated with both obesity and US exposure in the same model, the positive associations of Roseburia and Prevotella with obesity did not persist, suggesting that their positive associations with obesity might be due to their co-occurrence and correlations with obesity-related taxa, such as Dorea and Coprococcus. Conclusions Among US Hispanics/Latinos, US exposure is associated with unfavorable gut microbiome profiles for obesity risk, potentially related to westernized diet during acculturation. Microbial co-occurrence could be an important factor to consider in future studies relating individual gut microbiome taxa to environmental factors and host health and disease.

scholarly journals Predictors of extra-articular manifestations in axial spondyloarthritis and their influence on TNF-inhibitor prescribing patterns: results from the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis

RMD Open ◽  
2020 ◽  
Vol 6 (2) ◽  
pp. e001206 ◽  
Author(s):  
Mohammad H Derakhshan ◽  
Linda Dean ◽  
Gareth T Jones ◽  
Stefan Siebert ◽  
Karl Gaffney
Keyword(s):  
Ankylosing Spondylitis ◽  
Axial Spondyloarthritis ◽  
Human Leukocyte ◽  
Prescribing Patterns ◽  
British Society ◽  
Tnf Inhibitor ◽  
Hla B27 ◽  
Patient Reported ◽  
Bowel Diseases ◽  
Biologics Register

ObjectivesExtra-articular manifestations (EAMs) are important systemic features of axial spondyloarthritis (axSpA), which may influence the choice of tumour necrosis factor-inhibitor (TNFi). We examined the cumulative incidence and predictors of EAMs and the influence of these on first TNFi choice in a ‘real-world’ cohort of patients with axSpA.MethodsClinical and patient-reported outcomes of 2420 patients with axSpA from 83 centres were collected by the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis. Lifestyle factors for EAMs (acute anterior uveitis (AAU), inflammatory bowel diseases (IBD), psoriasis) were compared with those without EAMs. Also, the association between pretreatment EAMs and choice of first TNFi (adalimumab, etanercept, certolizumab) was analysed.ResultsAAU was directly associated with human leukocyte antigen (HLA)-B27 (incidence rate ratio (IRR) 1.95, 95% CI 1.40 to 2.73) and inversely associated with ever-smoking (IRR=0.71, 95% CI 0.55 to 0.92). For both psoriasis and IBD, there was an inverse relationship with HLA-B27 (IRR 0.54, 95% CI 0.36 to 0.79 and IRR 0.63, 95% CI 0.43 to 0.91, respectively). A diagnosis of either AAU (OR 3.79, 95% CI 2.11 to 6.80) or IBD (OR 5.50, 95% CI 2.09 to 14.46) was associated with preference for adalimumab versus others. In contrast, a diagnosis of either AAU (OR 0.14, 95% CI 0.06 to 0.33) or IBD (OR 0.17, 95% CI 0.05 to 0.57) was associated with less preference for etanercept over other TNFi.ConclusionThe higher occurrence of AAU and lower occurrence of psoriasis and IBD in HLA-B27-positive patients with axSpA are consistent with current pathophysiology. Patients with previous AAU and IBD are more likely to be prescribed adalimumab and less likely to receive etanercept, consistent with the superior efficacy of monoclonal TNFi for these indications. Future work will determine whether EAMs influence TNFi survival, or effectiveness, and whether this varies between agents.

scholarly journals Immune-mediated necrotising myopathy after treatment with adalimumab in a patient with HLA-B27 ankylosing spondylitis

2021 ◽  
Author(s):  
A. Chavarría-Miranda ◽  
A. Hernández Lain ◽  
O. Toldos González ◽  
M.I. Pedraza Hueso
Keyword(s):  
Ankylosing Spondylitis ◽  
Hla B27 ◽  
Immune Mediated
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