Fecal microbiota in untreated children with Juvenile Idiopathic Arthritis – a comparison with healthy children and healthy siblings

2020 ◽  
pp. jrheum.200551
Author(s):  
Anders Öman ◽  
Johan Dicksved ◽  
Lars Engstrand ◽  
Lillemor Berntson

Objective Changes in the composition of gut microbiota has been suggested to be associated with Juvenile idiopathic arthritis (JIA). The objective in this study was to investigate if the diversity and composition of the fecal microbiota differed between children with JIA and healthy controls, and if the microbiota differed between children with JIA and their healthy siblings. Methods In this multicenter, case-control study, fecal samples were collected from 75 children with JIA and 32 healthy controls. Eight of the healthy controls were siblings to eight children with JIA and they were compared only pairwise with their siblings. The microbiota was determined using sequencing amplicons from the V3 and V4 regions of the 16S rRNA gene. Alpha diversity, community composition of microbiota and relative abundances of taxa were compared between children with JIA and healthy unrelated controls as well as between children with JIA and healthy siblings. Results Our data revealed no significant differences in α-diversity or community composition of microbiota between children with JIA, healthy unrelated controls or healthy siblings. Analyses of relative abundances of phyla, families and genera identified trends of differing abundances of some taxa in children with JIA, in comparison with both healthy controls and healthy siblings, but none of these findings were significant after adjustment for multiple comparisons. Conclusion There were no significant differences in the composition of fecal microbiota in children with JIA compared with healthy controls. The composition of microbiota in children with JIA did not differ significantly from that in their healthy siblings.

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Anders Öman ◽  
Johan Dicksved ◽  
Lars Engstrand ◽  
Lillemor Berntson

Abstract Background Alterations in the composition of the fecal microbiota in children with juvenile idiopathic arthritis (JIA) have been observed in several studies, but it has not been determined whether the standard treatment for JIA changes the composition or function of the microbiota. The first-line disease-modifying anti-rheumatic drug for treatment of JIA is usually methotrexate, followed or supplemented by anti-tumor necrosis factor alpha drugs, such as etanercept. The aim of this study was to investigate the effects of methotrexate and etanercept treatments on the fecal microbiota and the fecal short-chain fatty acids (SCFAs) in children with JIA. Methods In this multicenter study, the composition of fecal microbiota from 45 treatment-naïve children with JIA was compared with that from 29 children treated with methotrexate and 12 children treated with etanercept. We also made pairwise comparisons of 15 children sampled before and during methotrexate treatment and 7 children sampled before and during etanercept treatment. The microbiota was determined using sequencing amplicons from the V3 and V4 regions of the 16S rRNA gene. Alpha-diversity, community composition, and relative abundances of bacterial taxa were analyzed in all comparisons. Analyses of fecal SCFAs, using a high-performance liquid chromatograph, were performed for the pairwise comparisons. Results We did not find any significant differences in α-diversity or community composition of microbiota. However, principal coordinate analysis indicated a change in community composition in 7 of the 15 paired samples before and during methotrexate and 2 of the 7 paired samples before and during etanercept. Comparisons of the relative abundance of taxa revealed minor differences before and during treatment with methotrexate or etanercept, but they were not significant after correction for multiple analyses, and the unpaired and paired analyses did not show similar changes. There were no significant differences in levels of fecal SCFAs before and during treatment with methotrexate or etanercept. Conclusions Treatment with methotrexate or etanercept had minor, but no significant or consistent changes either on composition of microbiota or on levels of SCFAs, suggesting that these changes are not related to the therapeutic effects of methotrexate or etanercept.


Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1682
Author(s):  
Ewa Łoś-Rycharska ◽  
Marcin Gołębiewski ◽  
Marcin Sikora ◽  
Tomasz Grzybowski ◽  
Marta Gorzkiewicz ◽  
...  

The gut microbiota in patients with food allergy, and the skin microbiota in atopic dermatitis patients differ from those of healthy people. We hypothesize that relationships may exist between gut and skin microbiota in patients with allergies. The aim of this study was to determine the possible relationship between gut and skin microbiota in patients with allergies, hence simultaneous analysis of the two compartments of microbiota was performed in infants with and without allergic symptoms. Fifty-nine infants with food allergy and/or atopic dermatitis and 28 healthy children were enrolled in the study. The skin and gut microbiota were evaluated using 16S rRNA gene amplicon sequencing. No significant differences in the α-diversity of dermal or fecal microbiota were observed between allergic and non-allergic infants; however, a significant relationship was found between bacterial community structure and allergy phenotypes, especially in the fecal samples. Certain clinical conditions were associated with characteristic bacterial taxa in the skin and gut microbiota. Positive correlations were found between skin and fecal samples in the abundance of Gemella among allergic infants, and Lactobacillus and Bacteroides among healthy infants. Although infants with allergies and healthy infants demonstrate microbiota with similar α-diversity, some differences in β-diversity and bacterial species abundance can be seen, which may depend on the phenotype of the allergy. For some organisms, their abundance in skin and feces samples may be correlated, and these correlations might serve as indicators of the host’s allergic state.


Author(s):  
Albert Shieh ◽  
S Melanie Lee ◽  
Venu Lagishetty ◽  
Carter Gottleib ◽  
Jonathan P Jacobs ◽  
...  

Abstract Purpose To determine whether correcting vitamin D deficiency with cholecalciferol (vitamin D3, D3) or calcifediol (25-hydroxyvitamin D3, 25(OH)D3) changes gut microbiome composition. Methods 18 adults with vitamin D deficiency (25-hydroxyvitamin D [25(OH)D] <20 ng/ml) received 60 mcg/day of D3 or 20 mcg/day of 25(OH)D3 for 8 weeks. Changes in serum 25(OH)D, 1,25-diydroxyvitamin D (1,25(OH)2D), and 24,25-dihydroxyvitamin D (24,25(OH)2D) were assessed. We characterized composition of the fecal microbiota using 16S rRNA gene sequencing, and examined changes in α-diversity (Chao 1, Faith’s Phylogenetic Diversity, Shannon Index), β-diversity (DEICODE), and genus-level abundances (DESeq2). Results Vitamin D3 and 25(OH)D3 groups were similar. After 8 weeks of vitamin D3, mean 25(OH)D and 24,25(OH)2D increased significantly, but 1,25(OH)2D did not (25(OH)D: 17.8 to 30.1 ng/ml [p=0.002]; 24,25(OH)2D: 1.1 to 2.7 ng/ml [p=0.003]; 1,25(OH)2D: 49.5 to 53.0 pg/ml [p=0.9]). After 8 weeks of 25(OH)D3, mean 25(OH)D, 24,25(OH)2D, and 1,25(OH)2D increased significantly (25(OH)D: 16.7 to 50.6 ng/ml [p<0.0001]; 24,25(OH)2D: 1.3 to 6.2 ng/ml [p=0.0001]; 1,25(OH)2D: 56.5 to 74.2 pg/ml [p=0.05]). Fecal microbial α-diversity and β-diversity did not change with D3 or 25D3 supplementation. Mean relative abundance of Firmicutes increased and mean relative abundance of Bacterioidetes decreased from baseline to four weeks, but returned to baseline by study completion. DESeq2 analysis did not confirm any statistically significant taxonomic changes. Main conclusions In a small sample of healthy adults with vitamin D deficiency, restoration of vitamin D sufficiency with vitamin D3 or 25(OH)D3 did not lead to lasting changes in the fecal microbiota.


Gut ◽  
2019 ◽  
Vol 69 (3) ◽  
pp. 569-577 ◽  
Author(s):  
Yiran Wei ◽  
Yanmei Li ◽  
Li Yan ◽  
Chunyan Sun ◽  
Qi Miao ◽  
...  

ObjectiveThe significance of the liver-microbiome axis has been increasingly recognised as a major modulator of autoimmunity. The aim of this study was to take advantage of a large well-defined corticosteroids treatment-naïve group of patients with autoimmune hepatitis (AIH) to rigorously characterise gut dysbiosis compared with healthy controls.DesignWe performed a cross-sectional study of individuals with AIH (n=91) and matched healthy controls (n=98) by 16S rRNA gene sequencing. An independent cohort of 28 patients and 34 controls was analysed to validate the results. All the patients were collected before corticosteroids therapy.ResultsThe gut microbiome of steroid treatment-naïve AIH was characterised with lower alpha-diversity (Shannon and observed operational taxonomic units, both p<0.01) and distinct overall microbial composition compared with healthy controls (p=0.002). Depletion of obligate anaerobes and expansion of potential pathobionts including Veillonella were associated with disease status. Of note, Veillonella dispar, the most strongly disease-associated taxa (p=8.85E–8), positively correlated with serum level of aspartate aminotransferase and liver inflammation. Furthermore, the combination of four patients with AIH-associated genera distinguished AIH from controls with an area under curves of approximately 0.8 in both exploration and validation cohorts. In addition, multiple predicted functional modules were altered in the AIH gut microbiome, including lipopolysaccharide biosynthesis as well as metabolism of amino acids that can be processed by bacteria to produce immunomodulatory metabolites.ConclusionOur study establishes compositional and functional alterations of gut microbiome in AIH and suggests the potential for using gut microbiota as non-invasive biomarkers to assess disease activity.


Gut ◽  
2016 ◽  
Vol 67 (1) ◽  
pp. 108-119 ◽  
Author(s):  
Floris Imhann ◽  
Arnau Vich Vila ◽  
Marc Jan Bonder ◽  
Jingyuan Fu ◽  
Dirk Gevers ◽  
...  

ObjectivePatients with IBD display substantial heterogeneity in clinical characteristics. We hypothesise that individual differences in the complex interaction of the host genome and the gut microbiota can explain the onset and the heterogeneous presentation of IBD. Therefore, we performed a case–control analysis of the gut microbiota, the host genome and the clinical phenotypes of IBD.DesignStool samples, peripheral blood and extensive phenotype data were collected from 313 patients with IBD and 582 truly healthy controls, selected from a population cohort. The gut microbiota composition was assessed by tag-sequencing the 16S rRNA gene. All participants were genotyped. We composed genetic risk scores from 11 functional genetic variants proven to be associated with IBD in genes that are directly involved in the bacterial handling in the gut: NOD2, CARD9, ATG16L1, IRGM and FUT2.ResultsStrikingly, we observed significant alterations of the gut microbiota of healthy individuals with a high genetic risk for IBD: the IBD genetic risk score was significantly associated with a decrease in the genus Roseburia in healthy controls (false discovery rate 0.017). Moreover, disease location was a major determinant of the gut microbiota: the gut microbiota of patients with colonic Crohn's disease (CD) is different from that of patients with ileal CD, with a decrease in alpha diversity associated to ileal disease (p=3.28×10−13).ConclusionsWe show for the first time that genetic risk variants associated with IBD influence the gut microbiota in healthy individuals. Roseburia spp are acetate-to-butyrate converters, and a decrease has already been observed in patients with IBD.


2021 ◽  
Author(s):  
Xinyi Cao ◽  
Dayong Zhao ◽  
Lisa Röttjers ◽  
Karoline Faust ◽  
Hongjie Zhang

Abstract At certain nutrient concentrations, shallow freshwater lakes are generally characterized by two contrasting ecological regimes with disparate patterns of biodiversity and biogeochemical cycles: a macrophyte-dominated regime (MDR) and a phytoplankton-dominated regime (PDR).To reveal ecological mechanisms that affect bacterioplankton along the regime shift, Illumina MiSeq sequencing of the 16S rRNA gene combined with a novel network clustering tool (Manta) were used to identify patterns of bacterioplankton community composition across the regime shift in Taihu Lake, China. Marked divergence in the composition and ecological assembly processes of bacterioplankton community were observed under the regime shift. The alpha diversity of bacterioplankton community was observed to consistently and continuously decrease with the regime shift from MDR to PDR, while the beta diversity presents the opposite. Moreover, as the regime shifted from MDR to PDR, the contribution of deterministic processes first decreased and then increased again closer to the PDR, most likely as a consequence of differences in nutrient concentration. The topological properties of bacterioplankton co-occurrence networks along the regime shift differed, and the co-occurrences among species changed in structure and were significantly shaped by the environmental variables along the regime transition from MDR to PDR. The divergent environmental state of the regimes with diverse nutritional status may be the most important factor that contributes to the dissimilarity of bacterioplankton community composition along the regime shift and could be represented by phosphorus concentrations as well as several indicator species.


2021 ◽  
Vol 11 ◽  
Author(s):  
Gang Du ◽  
Wei Dong ◽  
Qing Yang ◽  
Xueying Yu ◽  
Jinghong Ma ◽  
...  

Emerging evidence indicates that gut dysbiosis may play a regulatory role in the onset and progression of Huntington’s disease (HD). However, any alterations in the fecal microbiome of HD patients and its relation to the host cytokine response remain unknown. The present study investigated alterations and host cytokine responses in patients with HD. We enrolled 33 HD patients and 33 sex- and age- matched healthy controls. Fecal microbiota communities were determined through 16S ribosomal DNA gene sequencing, from which we analyzed fecal microbial richness, evenness, structure, and differential abundance of individual taxa between HD patients and healthy controls. HD patients were evaluated for their clinical characteristics, and the relationships of fecal microbiota with these clinical characteristics were analyzed. Plasma concentrations of interferon gamma (IFN-γ), interleukin 1 beta (IL-1β), IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, and tumor necrosis factor alpha were measured by Meso Scale Discovery (MSD) assays, and relationships between microbiota and cytokine levels were analyzed in the HD group. HD patients showed increased α-diversity (richness), β-diversity (structure), and altered relative abundances of several taxa compared to those in healthy controls. HD-associated clinical characteristics correlated with the abundances of components of fecal microbiota at the genus level. Genus Intestinimonas was correlated with total functional capacity scores and IL-4 levels. Our present study also revealed that genus Bilophila were negatively correlated with proinflammatory IL-6 levels. Taken together, our present study represents the first to demonstrate alterations in fecal microbiota and inflammatory cytokine responses in HD patients. Further elucidation of interactions between microbial and host immune responses may help to better understand the pathogenesis of HD.


2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S599-S599
Author(s):  
Christopher J Lehmann ◽  
Robert Keskey ◽  
Matthew Odenwald ◽  
Ravi Nayak ◽  
Maryam Khalid ◽  
...  

Abstract Background Liver transplant (LT) recipients have abnormal microbiota before and after transplantation. (1,2) Associations between fecal microbiota, microbial metabolites, and clinical outcomes in liver transplantation are not well established. We correlated fecal microbiota composition and metabolite concentrations with early LT outcomes, including infection. Methods In a prospective observational study, we collected peri-transplant fecal samples and determined microbiota composition by 16S ribosomal RNA gene sequencing in LT recipients. Fecal short chain fatty acid (SCFA) and bile acid concentrations were measured by targeted GC- and LC-MS analyses, respectively. Inverse Simpson index was used to determine microbiota alpha-diversity in subjects and healthy controls. Clinical outcomes including length of stay, ICU admission, liver function, antibiotic use, immunosuppressive requirement and post-operative infection were correlated with microbiota composition. Results 69 patients were enrolled, 70 liver transplants were performed and 307 peri-transplant fecal samples were collected and analyzed. Compared to healthy controls, the fecal microbiota of LT recipients had reduced alpha-diversity (p&lt; 0.001). [Fig1] Bacteroidetes, Ruminococcaceae, and Lachnospiraceae, three taxa associated with a health-promoting microbiota, and their metabolites, SCFA and secondary bile acids, were markedly diminished 55% of LT patients.(3) Intestinal domination ( &gt;30% frequency) by Enterococcus or Proteobacteria species was common and occurred in 36% of LT recipients. 76 post-operative infections occurred in 40 LT recipients, with Enterococci causing 52% and Proteobacteria 41% of bacterial infections. In subjects with fecal samples collected within 5 days of infection, 9/17 infections were caused by the organism dominating the microbiota. [Fig2] Microbiota Composition and Metabolite Production 16s gene sequencing color coded by taxonomy. Each bar represents one stool sample nearest to LT compared to healthy controls. Alpha diversity measured by inverse simpson index. Absolute values of microbial metabolites and ratio of primary to secondary bile acids. Comparison of Microbiota Composition and Post Operative Infection All bacterial infections captured with a microbiota sample within 5 days of infection. Conclusion Microbiota diversity and microbially derived metabolites are markedly reduced in &gt;50% of LT recipients. Intestinal domination and post-operative infections caused by antibiotic-resistant Enterococcus and Proteobacteria correlate with loss of Bacteroidetes, Ruminococcaceae, and Lachnospiraceae species, suggesting a potential role for microbiota reconstitution therapy in LT patients. Disclosures Eric G. Pamer, MD;FIDSA, Nothing to disclose


2020 ◽  
Author(s):  
Dandan Jiang ◽  
Xin He ◽  
Marc Valitutto ◽  
Li Chen ◽  
Qin Xu ◽  
...  

Abstract Background:The Chinese monal (Lophophorus lhuysii) is an endangered bird species, with a wild population restricted to the mountains of southwest China, and only one known captive population in the world. We investigated the fecal microbiota and metabolome of wild and captive Chinese monals to explore differences and similarities in nutritional status and digestive characteristics. An integrated approach combining 16S ribosomal RNA (16S rRNA) gene sequencing and ultra-high performance liquid chromatography (UHPLC) based metabolomics were used to examine the fecal microbiota composition and the metabolomic profile of Chinese monals. Results: The results showed that the alpha diversity of gut microbes in the wild group were significantly higher than that in the captive group and the core bacterial taxa in the two groups showed remarkable differences at phylum, class, order, and family levels. Metabolomic profiling also revealed differences, mainly related to galactose, starch and sucrose metabolism, fatty acid, bile acid biosynthesis and bile secretion. Furthermore, strong correlations of metabolite types and bacterial genus were detected. Conclusions: There were remarkable differences in the gut microbiota composition and metabolomic profile between wild and captive Chinese monals. This study has established a baseline for a normal gut microbiota and metabolomic profile for wild Chinese monals, thus allowing us to evaluate if differences seen in captive organisms have an impact on their overall health and reproduction.


2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 63-63
Author(s):  
Patrícia M Oba ◽  
Meredith Carroll ◽  
Tammi Epp ◽  
Christine Warzecha ◽  
Jessica L Varney ◽  
...  

Abstract Previously, a Saccharomyces cerevisiae fermentation product (SCFP) was demonstrated to positively alter fecal microbiota, fecal metabolites, and circulating immune cell functionality in adult dogs. The objective of this study was to determine the fecal characteristics, microbiota, and metabolites of trained dogs subjected to an exercise challenge. All procedures were approved by the Four Rivers Kennel IACUC prior to experimentation. Thirty-six adult dogs (mean age: 7.1 y; mean BCS: 4.9) were used. Dogs were randomly assigned to control or SCFP-supplemented (250 mg/d) diets, trained, and fed for a few mo prior to exercise challenge. Fresh fecal samples were collected for the measurement of fecal characteristics, microbiota, and metabolites before and after an exercise challenge (10 mile run). Fecal microbiota data were evaluated using QIIME2. All other data were analyzed using the Mixed Models procedure of SAS, with treatment and exercise as fixed effects, dog as random effect, and P &lt; 0.05 considered significant. For both treatments, fecal scores and butyrate and propionate concentrations were lower and fecal pH and ammonia, isobutyrate, isovalerate, and total BCFA concentrations were higher after exercise challenge. SCFP did not affect fecal scores, pH, dry matter, or fermentative end-product concentrations after exercise challenge. Alpha-diversity or beta-diversity (unweighted PCoA plot) were not affected by SCFP before or after exercise challenge. The weighted PCoA plot, however, showed clustering of dogs before exercise and after exercise, regardless of treatment. Fecal Collinsella, Slackia, Turicibacter, Blautia, Dorea, Ruminococcus, Faecalibacterium, Catenibacterium, Clostridium (Erysipelotrichaceae family), and Eubacterium relative abundances were higher, while fecal Bacteroides, Parabacteroides, Prevotella (Prevotellaceae family), Phascolarctobacterium, Fusobacterium, Suttella and Anaerobiospirillum relative abundances were lower after exercise challenge. SCFP increased fecal Lactobacillus compared to controls. Our data demonstrate that exercise and SCFP alter fecal microbiota in dogs. Higher SCFP dosages may provide greater changes and may be of interest in future studies.


Sign in / Sign up

Export Citation Format

Share Document