Fecal Microbiome Changes and Specific Anti-Bacterial Response in Patients with IBD during Anti-TNF Therapy
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patients and Sample Collection
2.2. DNA Extraction, PCR Amplification, Sequencing, and Data Analysis
2.3. Preparation of Bacterial Lysates
2.4. Indirect Enzyme-Linked Immunosorbent Assays (ELISAs)
2.5. Peripheral Blood Mononuclear Cells (PBMCs)
2.6. Statistical Analysis
3. Results
3.1. Cohort Characteristics
3.2. Individual and Baseline Differences in Gut Bacteriome of Healthy Controls and Patients with IBD
3.3. Factors Influencing Bacterial Diversity
3.4. Changes of the Gut Bacteriome during Anti-TNF Therapy
3.5. Metagenomic Predictions
3.6. Fungal Microbiome
3.7. Serum Antibody Levels against Specific Commensals
3.8. Patients’ PBMCs Produce Increased Levels of IL-17 at the Endpoint of Therapy
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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HC (n = 37) | CD (n = 17) Week 0 | CD (n = 17) Week 38 | ∆ CD (p-Value) | CD vs. HC (p-Value) | UC (n = 10) Week 0 | UC (n = 10) Week 38 | ∆ UC (p-Value) | UC vs. HC (p-Value) | |
---|---|---|---|---|---|---|---|---|---|
Male: female | 15:22 | 5:12 | 0.8042 | 2:8 | - | 0.8684 | |||
Age | 36.5 (28.8, 41.3) | 35.0 (26.5, 44.0) | - | 0.7800 | 31.0 (26.0, 41.3) | - | 0.4228 | ||
BMI | 21.8 (20.5, 26.2) | 22.2 (20.8, 26.9) | - | 0.8274 | 21.3 (19.2, 24.4) | - | 0.1901 | ||
Disease duration in years | - | 4.0 (2.0, 13.5) | - | - | 2.5 (1.0, 7.5) | - | - | ||
Age at diagnosis | - | 26 (22.5, 35) | - | - | 27 (21.5, 31) | - | - | ||
Remitters | - | 11/17 | 13/17 | - | - | 0/10 | 5/10 | - | - |
HBI/pMayo | - | 3 (0, 6) | 1 (0.5, 5) | 0.3931 | - | 7 (3.8, 8.3) | 2.5 (0, 4.3) | 0.0039 | - |
CRP (mg/L) | 0.9 (0.4, 1.9) | 4.2 (1.0, 8.9) | 1.3 (0.5, 5) | 0.0225 | 0.0037 | 4.1 (0.9, 22.3) | 0.95 (0.6, 2.8) | 0.1641 | 0.0124 |
WBC | 5.9 (4.9, 6.9) | 8.0 (6.2, 11.0) | 5.9 (5, 7.8) | 0.0089 | 0.0135 | 10.4 (6.1, 12.3) | 5.9 (4.4, 7.3) | 0.0371 | 0.0071 |
PLT | 247 (218, 272) | 328 (269, 416) | 283 (220, 388) | 0.0697 | 0.0007 | 276 (251, 387) | 278 (222, 310) | 0.4160 | 0.1136 |
Ferritin (µg/L) | NA | 48.1 (19.8, 80.0) | 30.9 (12.3, 56.8) | 0.3778 | NA | 28.0 (11.7, 52.2) | 41.0 (9.5, 78.6) | 0.9219 | NA |
Hb (g/L) | 141 (134, 158) | 130 (123, 150) | 134 (127, 144) | 0.4411 | 0.0495 | 128 (109, 1367) | 134 (121, 146) | 0.0918 | 0.0067 |
FC (μg/g) | NA | 407 (148, 1028) | 162 (38, 284) | 0.0181 | NA | 661 (424, 2838) | 229 (59, 828) | 0.0039 | NA |
Week 0 | Week 38 | HC | Week 0 vs. HC | Week 38 vs. HC | Week 0 vs. Week 38 | ||
---|---|---|---|---|---|---|---|
IgM | CD | 2.1 (1.3; 3.4) | 2.4 (1.4; 7.6) | 1.1 (0.8; 1.8) | 0.020 | <0.001 | <0.001 |
UC | 2.6 (0.9; 4.0) | 1.3 (1.0; 3.2) | ns | ns | ns | ||
IgA | CD | 1.9 (0.5; 5.0) | 2.2 (0.6; 6.6) | 0.7 (0.5; 1.4) | 0.009 | 0.010 | ns |
UC | 2.5 (1.3; 4.4) | 3.2 (1.3; 5.7) | 0.039 | 0.024 | ns | ||
IgG | CD | 15.9 (8.1; 35.1) | 11.2 (5.3; 20.4) | 1.1 (0.8; 1.8) | <0.001 | 0.002 | ns |
UC | 10.5 (6.5; 18.1) | 10.6 (5.7; 59.8) | 0.019 | <0.001 | ns |
CD w0 vs. HC | CD w38 vs. HC | CD w0 vs. w38 | UC w0 vs. HC | UC w38 vs. HC | UC w0 vs. w38 | |
---|---|---|---|---|---|---|
Lactobacillus | ns | ns | ↗ p = 0.005 | ns | ns | ns |
Bifidobacterium | ns | ns | ↗ p = 0.010 | ns | ns | ns |
Blautia | ns | ns | ↗ p = 0.005 | ns | ns | ns |
Roseburia | ns | ns | ↗ p < 0.001 | ns | ns | ns |
Faecalibacterium | ns | ns | ns | ns | ns | ns |
Bacteroides | ns | ns | ↗ p = 0.005 | ns | ns | ns |
Escherichia | ns | ns | ↗ p = 0.003 | ns | ns | ns |
Prevotella | ns | ns | ↗ p = 0.005 | ns | ns | ns |
Ruminococcus | ns | ns | ↗ p = 0.001 | ns | ns | ns |
Eubacterium | ns | ns | ↗ p < 0.001 | ns | ns | ns |
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Schierova, D.; Roubalova, R.; Kolar, M.; Stehlikova, Z.; Rob, F.; Jackova, Z.; Coufal, S.; Thon, T.; Mihula, M.; Modrak, M.; et al. Fecal Microbiome Changes and Specific Anti-Bacterial Response in Patients with IBD during Anti-TNF Therapy. Cells 2021, 10, 3188. https://doi.org/10.3390/cells10113188
Schierova D, Roubalova R, Kolar M, Stehlikova Z, Rob F, Jackova Z, Coufal S, Thon T, Mihula M, Modrak M, et al. Fecal Microbiome Changes and Specific Anti-Bacterial Response in Patients with IBD during Anti-TNF Therapy. Cells. 2021; 10(11):3188. https://doi.org/10.3390/cells10113188
Chicago/Turabian StyleSchierova, Dagmar, Radka Roubalova, Martin Kolar, Zuzana Stehlikova, Filip Rob, Zuzana Jackova, Stepan Coufal, Tomas Thon, Martin Mihula, Martin Modrak, and et al. 2021. "Fecal Microbiome Changes and Specific Anti-Bacterial Response in Patients with IBD during Anti-TNF Therapy" Cells 10, no. 11: 3188. https://doi.org/10.3390/cells10113188
APA StyleSchierova, D., Roubalova, R., Kolar, M., Stehlikova, Z., Rob, F., Jackova, Z., Coufal, S., Thon, T., Mihula, M., Modrak, M., Kverka, M., Bajer, L., Kostovcikova, K., Drastich, P., Hercogova, J., Novakova, M., Vasatko, M., Lukas, M., Tlaskalova-Hogenova, H., & Jiraskova Zakostelska, Z. (2021). Fecal Microbiome Changes and Specific Anti-Bacterial Response in Patients with IBD during Anti-TNF Therapy. Cells, 10(11), 3188. https://doi.org/10.3390/cells10113188