Duodenal Dysbiosis and Relation to the Efficacy of Proton Pump Inhibitors in Functional Dyspepsia
Abstract
:1. Introduction
2. Results
2.1. Study Cohort and Sample Overview
2.2. Duodenal Microbiome Is Altered in FD Patients with PPI Effects
2.3. Specific Effects on Genera and Diversity after Short-Term PPI
2.4. Persisting Microbiota Alterations after Withdrawal of Long-Term PPI
2.5. Duodenal Dysbiosis in Relation to Efficacy of PPI in FD Patients and Controls
3. Discussion
4. Materials and Methods
4.1. Study Population
4.2. Sample Collection
4.3. Sample and Data Processing
4.4. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviation
BABD | Brisbane Aseptic Biopsy Device |
BMI | body mass index |
BS | bile salt |
CLR | centered log-ratio |
dbRDA | distance-based redundancy analysis |
EPS | epigastric pain syndrome |
FD | functional dyspepsia |
FDR | false discovery rate |
GI | gastrointestinal |
IQR | interquartile range |
PAGI-SYM | patient assessment of upper GI symptom severity index |
PDS | postprandial distress syndrome |
PPI | proton pump inhibitor |
SD | standard deviation |
References
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Group | Healthy Controls (n = 30) | FD-Starters (n = 28) | FD-Stoppers (n = 19) | p-Value |
---|---|---|---|---|
Demographic: | ||||
Age (years) | 27 (24–33.5) | 27 (23.5–34.5) | 32 (26.8–49.5) | 0.18 |
Female (%) | 21 (70) | 24 (86) | 14 (74) | 0.35 |
BMI (kg/m2) | 23 (20–25.3) | 22 (19–24) | 21.5 (20.8–24.3) | 0.56 |
FD subtypes: | ||||
PDS subtype (%) | NA | 15 (54) | 10 (53) | 0.95 |
EPS subtype (%) | NA | 3 (11) | 6 (32) | 0.07 |
Overlap (%) | NA | 10 (35) | 3 (15) | 0.13 |
Daily food intake: | ||||
Energy (kcal/day) | 1419 (1308–1627) | 1186 (974.9–1621) | 1284 (937.7–1617) | 0.35 |
Sugars (g/day) | 175.7 (148.2–187.5) | 148.3 (115.1–222.5) | 143.9 (93.42–194.4) | 0.25 |
Fat (g/day) | 46.87 (41.7–57.1) | 40.8 (34.4–52.5) | 45.7 (31.2–61.5) | 0.51 |
Fiber (g/day) | 18.4 (15.2–21.5) | 15.9 (9.3–23) | 12.8 (8.3–17.4) * | 0.02 |
Protein (g/day) | 175.7 (148.2–187.5) | 148.3 (115.1–222.5) * | 143.9 (93.4–194.4) * | <0.01 |
Univariate dbRDA | Mucus-Associated (Brush) | Epithelium-Associated (Biopsy) | ||||||
---|---|---|---|---|---|---|---|---|
F-Value | R2 (%) | p-Value | padj-Value | F-Value | R2 (%) | p-Value | padj-Value | |
subject | 1.47 | 16 | 0.001 | 0.006 | 1.16 | 5.4 | 0.002 | 0.01 |
group | 2.1 | 1.16 | 0.002 | 0.006 | 1.52 | 0.51 | 0.03 | 0.09 |
PPI | 1.64 | 0.34 | <0.05 | 0.09 | 0.92 | 0 | 0.41 | 0.51 |
gender | 1.02 | 0.01 | 0.38 | 0.38 | 1.05 | 0.03 | 0.4 | 0.4 |
age | 1.16 | 0.09 | 0.23 | 0.28 | 1.47 | 0.25 | 0.06 | 0.12 |
BMI | 1.52 | 0.28 | 0.07 | 0.1 | 1.05 | 0.03 | 0.32 | 0.4 |
Group | Controls | FD-Starters | padj Value | ||
---|---|---|---|---|---|
Treatment | Off-PPI (n = 30) | On-PPI (n = 30) | Off-PPI (n = 28) | Off-PPI (n = 30) | |
Brush | |||||
Observed | 42.03 ± 1.36 | 37.79 ± 1.9 * | 36.81 ± 1.6 | 34.79 ± 1.67 | 1 |
Chao1 | 48.98 ± 1.91 | 44.81 ± 2.71 | 43.24 ± 2.28 | 44.89 ± 2.75 | 0.62 |
Shannon | 2.32 ± 0.05 | 2.05 ± 0.08 ** | 2.24 ± 0.07 | 1.92 ± 0.1 ** | 0.66 |
Simpson | 0.79 ± 0.01 | 0.72 ± 0.02 ** | 0.78 ± 0.02 | 0.68 ± 0.03 ** | 0.71 |
Biopsy | |||||
Observed | 43.07 ± 3.33 | 41.43 ± 6.12 | 43.36 ± 7.08 | 42.37 ± 7.32 | 0.97 |
Chao1 | 45.43 ± 3.82 | 43.58 ± 6.95 | 47.74 ± 8.62 | 45.36 ± 8.53 | 0.99 |
Shannon | 2.82 ± 0.07 | 2.8 ± 0.1 | 2.69 ± 0.12 | 2.69 ± 0.12 | 1 |
Simpson | 0.88 ± 0.01 | 0.89 ± 0.01 | 0.86 ± 0.02 | 0.87 ± 0.02 | 1 |
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Wauters, L.; Tito, R.Y.; Ceulemans, M.; Lambaerts, M.; Accarie, A.; Rymenans, L.; Verspecht, C.; Toth, J.; Mols, R.; Augustijns, P.; et al. Duodenal Dysbiosis and Relation to the Efficacy of Proton Pump Inhibitors in Functional Dyspepsia. Int. J. Mol. Sci. 2021, 22, 13609. https://doi.org/10.3390/ijms222413609
Wauters L, Tito RY, Ceulemans M, Lambaerts M, Accarie A, Rymenans L, Verspecht C, Toth J, Mols R, Augustijns P, et al. Duodenal Dysbiosis and Relation to the Efficacy of Proton Pump Inhibitors in Functional Dyspepsia. International Journal of Molecular Sciences. 2021; 22(24):13609. https://doi.org/10.3390/ijms222413609
Chicago/Turabian StyleWauters, Lucas, Raúl Y. Tito, Matthias Ceulemans, Maarten Lambaerts, Alison Accarie, Leen Rymenans, Chloë Verspecht, Joran Toth, Raf Mols, Patrick Augustijns, and et al. 2021. "Duodenal Dysbiosis and Relation to the Efficacy of Proton Pump Inhibitors in Functional Dyspepsia" International Journal of Molecular Sciences 22, no. 24: 13609. https://doi.org/10.3390/ijms222413609