Article Figures & Data
Figures
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FIG 1Dynamics of the gut microbiota in NZB/W F1 mice. Fecal pellets were collected at 10, 14, and 18 weeks of age (predisease time points; n = 5 per time point) and 23, 28, and 33 weeks of age (post-disease-onset time points; n = 3 or 4 per time point) and were subjected to 16S rRNA sequencing analysis. The disease onset in NZB/W F1 mice is ∼20 weeks of age. (A) PCoA plot, showing alterations of overall community structures (P < 0.01). (B) Bacterial diversity, as indicated by the number of OTUs. The increase of OTUs from the pre-disease-onset stage to the post-disease-onset stages was significant (P < 0.01). (C) Time-dependent changes in the relative abundance of different bacterial species. Smoothing was performed with the ggplot2 package, using locally weighted regression. In all figures, P values were corrected for multiple comparisons by controlling the FDRs.
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FIG 2Changes in the gut microbiota in NZB/W F1 mice in response to immunosuppressant (Dex) treatment. NZB/W F1 mice were treated with 2 mg/kg body weight Dex (intraperitoneal injections five times per week) from 20 to 34 weeks of age. Fecal pellets were collected at 34 weeks of age and subjected to 16S rRNA sequencing analysis. (A) PCoA plot, showing the separation of overall bacterial structures (P < 0.01). (B) Bacterial diversity, as indicated by the Shannon index (P < 0.001). (C) Identification of a bacterial species for which there was a significant change from the pre-disease-onset stage (pre) to the post-disease-onset stage (post) and Dex treatment significantly reversed the change (P < 0.01 in both cases). Ctr, control. (D) Spearman correlation analysis between the abundance (shown as a proportion, where, e.g., 0.2 represents 20%) of the bacterial species (Lacto [Lactobacillaceae, Lactobacillus, other]) identified in panel C and two measurements of the SLE disease state, i.e., renal function (RenalFunc) and systemic autoimmunity (SysAuto). See Materials and Methods for calculation of these two measurements.
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FIG 3Gut microbiota dysbiosis in SLE patients with active disease, compared to non-SLE controls. The inclusion and exclusion criteria are listed in Materials and Methods. A fecal sample was collected from each patient or control subject at the time of the first visit, and the samples were subjected to 16S rRNA sequencing analysis. (A) PCoA plot, showing no separation of overall bacterial structures (P > 0.05). (B) Significant difference in bacterial diversity levels, as indicated by the Shannon index (P < 0.05). (C) No significant difference in Firmicutes/Bacteroidetes (FB) ratios (P > 0.05). (D) Significant difference in the relative abundance of the phylum Proteobacteria, a representation of facultative anaerobic Gram-negative bacteria (P < 0.05). (E) Significant changes in several bacterial species, with the P values indicated (nonparametric Mann-Whitney test). DESeq2 analysis was also performed, and the DESeq2 P values were 0.037, 0.007, and 0.007, respectively. P values were corrected for multiple comparisons by controlling the FDRs.
Tables
- TABLE 1
Differentially represented bacterial species between SLE and non-SLE individuals
Bacterial species Strain name OTU no. Sequence identity (%) SLE vs non-SLE Blautia wexlerae AUH-JLD17 7 100 Increased Blautia wexlerae AUH-JLD56 7 100 Increased Blautia sp. strain Marseille P3602 7 100 Increased Blautia sp. strain GD8 23 100 Increased Blautia faecis M25 25 100 Increased Blautia caecimuris SJ18 492 99 Increased Blautia sp. strain AUH-JLD3 585 98 Increased Blautia sp. strain Marseille P3387 585 98 Increased Odoribacter laneus JCM 63 100 Decreased Odoribacter laneus YIT 63 100 Decreased Odoribacter laneus JCM 63 100 Decreased Odoribacter splanchnicus 67 100 Decreased Alistipes onderdonkii 13 100 Decreased Alistipes sp. LS-J 13 100 Decreased Alistipes sp. LS-M 13 100 Decreased Alistipes shahii WAL 8301 164 100 Decreased Alistipes obesi ph8 164 100 Decreased Alistipes ihumii AP11 188 100 Decreased Alistipes sp. strain cv1 188/210 100 Decreased Alistipes indistinctus JCM 188/252 100 Decreased Alistipes indistinctus YIT 188/252 100 Decreased Alistipes sp. strain S216 252 100 Decreased Alistipes finegoldii DSM 17242 398 99 Decreased Alistipes finegoldii JCM 16770 398 99 Decreased Alistipes finegoldii CIP 107999 398 99 Decreased Alistipes finegoldii AHN 2437 398 99 Decreased - TABLE 2
Demographic, immunological, and clinical features of SLE patients
Subject no. Age (yr) Sexa Raceb Immunological featuresc Clinical symptomsd SLEDAI score BMI (kg/m2)e Medication(s)f 01 39 F AA ANA, dsDNA, C3, C4, hem CL, PS 0 36.6 HCQ, belimumab 02 21 F Caucasian ANA, dsDNA, sm, C3, C4, hem Alopecia, LN, PS, Neuro 8 36.4 HCQ, MMF, belimumab 03 40 F Caucasian ANA, C3, C4, hem Alopecia, SE 3 21.5 HCQ, MMF, belimumab 04 64 F AA ANA, C3, C4 Alopecia, MR, PS 6 31.4 HCQ, MMF, belimumab 05 65 F Caucasian ANA, dsDNA, C3, C4 LN 13 26.2 HCQ, MMF 06 41 M Caucasian ANA, dsDNA, C3 LN, PS, IA 2 43.5 MTX 07 27 M AA ANA, dsDNA, sm, ACL, C3, C4 MR, LN 6 31.6 HCQ, MMF 09 56 F Caucasian ANA, dsDNA, hem PS 1 36.5 HCQ, MMF, belimumab 10 25 F Caucasian ANA, dsDNA, ACL, B2G, C3, C4 MR, LN, PS 8 39.1 HCQ, MMF, rituximab 11 73 F Caucasian ANA, sm SE 0 18.4 HCQ, MMF 17 23 M Caucasian ANA, dsDNA, hem LN 2 21.0 HCQ, AZA 19 36 M Caucasian ANA, dsDNA, sm, C4, hem MR, SE 0 37.2 HCQ, MMF 20 29 F AA ANA, dsDNA, sm, C3, C4 MR, IA 2 33.9 HCQ 23 66 F Caucasian ANA, dsDNA, hem None 0 33.2 HCQ, AZA, tacrolimus ↵a F, female; M, male.
↵b Race categories were African American (not Caribbean) (AA) and Caucasian, non-Hispanic.
↵c Immunological features included antinuclear antibodies (ANA), anti-dsDNA antibodies (dsDNA), anti-Smith antibodies (sm), anticardiolipin antibodies (ACL), β2-glycoprotein (B2G), lupus anticoagulant (LAC), complement C3 (C3), complement C4 (C4), and hematological manifestation (hem).
↵d Clinical symptoms included alopecia, cutaneous lupus (CL), malar rash (MR), lupus nephritis (LN), photosensitivity (PS), inflammatory arthritis (IA), serositis (SE), and neurolupus (Neuro).
↵e BMI, body mass index.
↵f Medications included hydroxychloroquine (HCQ), mycophenolate mofetil (MMF), methotrexate (MTX), azathioprine (AZA), belimumab, rituximab, and tacrolimus.
Supplemental material
- Supplemental file 1 -
PCA plot with age and cage as separating factors (Fig. S1); species richness (Fig. S2).
PDF, 56K
- Supplemental file 2 -
OTU table (NZB/W F1 mice over time).
XLSX, 108K
- Supplemental file 3 -
OTU table (Dex vs. control).
XLSX, 102K
- Supplemental file 4 -
OTU table (SLE vs. non-SLE).
XLSX, 104K
- Supplemental file 5 -
Complete list of all taxa tested for differential abundance (P values; predisease vs. postdisease).
XLSX, 58K
- Supplemental file 6 -
Complete list of all taxa tested for differential abundance (P values; Dex vs. control).
XLSX, 59K
- Supplemental file 7 -
Complete list of all taxa tested for differential abundance (P values; SLE vs. non-SLE).
XLSX, 60K
- Supplemental file 1 -
