Idiosyncratic Drug-Induced Liver Injury and Amoxicillin–Clavulanate: Spotlight on Gut Microbiota, Fecal Metabolome and Bile Acid Profile in Patients
Abstract
:1. Introduction
2. Results
2.1. Hematological and Biochemical Alterations Observed in Patients with Idiosyncratic Drug-Induced Liver Injury
2.2. Analysis of Fecal Gut Microbiota Composition Shows a Specific Profile Associated with Idiosyncratic Drug-Induced Liver Injury
2.3. Idiosyncratic Drug-Induced Liver Injury Is Characterized by a Specific Fecal Metabolome and Bile Acid Profile
2.4. Correlations among Biochemical Parameters, Gut Microbiota Composition, Fecal Metabolome and Fecal and Serum Bile Acid Profiles in Patients with Idiosyncratic Drug-Induced Liver Injury
2.5. Idiosyncratic Drug-Induced Liver Injury Caused by Amoxicillin–Clavulanate Administration Is Characterized by a Specific Pattern of Gut Microbiota Composition Linked to a Particular Metabolome and Bile Acid Profile
3. Discussion
4. Materials and Methods
4.1. Participants and Ethical Approval
4.2. Sample Collection
4.3. Fecal Metagenomic Analysis
4.4. Fecal Metabolomic Analysis
4.5. Fecal Short-Chain Fatty Acids (SCFAs) Quantification
4.6. Fecal Bile Acid Quantification
4.7. Serum Bile Acid Quantification
4.8. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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C | iDILI | H | p Value | |
---|---|---|---|---|
Glucose (mg/dL) | 88 ± 4 | 109 ± 6 | 111 ± 9 | 0.184 |
Urea (mg/dL) | 33 ± 3 | 45 ± 7 | 36 ± 8 | 0.275 |
Creatinine (mg/dL) | 0.80 ± 0.03 | 0.89 ± 0.08 | 0.98 ± 0.15 | 0.930 |
ALT (U/L) | 22 ± 3 | 741 ± 200 ***# | 1349 ± 282 *** | <0.001 |
AST (U/L) | 22 ± 2 | 487 ± 142 ***## | 1048 ± 236 *** | <0.001 |
ALP (U/L) | 70 ± 6 | 246 ± 33 ** | 192 ± 24 *** | 0.004 |
GGT (U/L) | 22 ± 4 | 283 ± 48 *** | 473 ± 70 *** | <0.001 |
TBL (mg/dL) | 0.50 ± 0.05 | 5.59 ± 1.22 ** | 8.90 ± 2.27 *** | 0.002 |
Albumin (g/dL) | 4.71 ± 0.04 | 3.58 ± 0.13 *** | 3.66 ± 0.23 * | 0.006 |
Platelets (103/µL) | 230 ± 17 | 242 ± 16 | 220 ± 27 | 0.631 |
Leukocytes (103/µL) | 5.5 ± 0.3 | 6.9 ± 0.6 | 8.2 ± 1.1 | 0.160 |
Neutrophils (103/µL) | 2.9 ± 0.2 | 3.6 ± 0.3 # | 5.9 ± 0.9 * | 0.027 |
INR | 0.98 ± 0.03 | 1.30 ± 0.17 | 1.38 ± 0.17 ** | 0.024 |
Demographic Parameters | Data |
---|---|
Age, mean ± SEM | 58 ± 2 |
Sex, n (%) | |
Men | 19 (43) |
Women | 27 (57) |
Samples recruitment, n/total (%) | Data |
Healthy controls | 10/46 (21.7) |
non-iDILI acute hepatitis | 12/46 (26.1) |
iDILI | 24/46 (52.2) |
iDILI-nonAC | 18/24 (75) |
iDILI-AC | 6/24 (25) |
iDILI liver damage, n/total (%) | Data |
Hepatocellular | 9/24 (37.5) |
Cholestatic | 11/24 (45.8) |
Mixed | 4/24 (16.7) |
iDILI causal agent, n/total (%) | Data |
Antibiotics | 14/24 (58.3) |
Amoxicillin–clavulanate | 6/14 (43) |
NSAIDs | 5/24 (20.8) |
Statins | 3/24 (12.5) |
Antifungals | 1/24 (4.2) |
Chemotherapeutics | 1/24 (4.2) |
Non-iDILI acute hepatitis causal agent, n/total (%) | Data |
Autoimmune hepatitis | 9/12 (75) |
Hepatitis C | 1/12 (8.3) |
Hepatitis B | 2/12 (16.7) |
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Román-Sagüillo, S.; Quiñones Castro, R.; Juárez-Fernández, M.; Soluyanova, P.; Stephens, C.; Robles-Díaz, M.; Jorquera Plaza, F.; González-Gallego, J.; Martínez-Flórez, S.; García-Mediavilla, M.V.; et al. Idiosyncratic Drug-Induced Liver Injury and Amoxicillin–Clavulanate: Spotlight on Gut Microbiota, Fecal Metabolome and Bile Acid Profile in Patients. Int. J. Mol. Sci. 2024, 25, 6863. https://doi.org/10.3390/ijms25136863
Román-Sagüillo S, Quiñones Castro R, Juárez-Fernández M, Soluyanova P, Stephens C, Robles-Díaz M, Jorquera Plaza F, González-Gallego J, Martínez-Flórez S, García-Mediavilla MV, et al. Idiosyncratic Drug-Induced Liver Injury and Amoxicillin–Clavulanate: Spotlight on Gut Microbiota, Fecal Metabolome and Bile Acid Profile in Patients. International Journal of Molecular Sciences. 2024; 25(13):6863. https://doi.org/10.3390/ijms25136863
Chicago/Turabian StyleRomán-Sagüillo, Sara, Raisa Quiñones Castro, María Juárez-Fernández, Polina Soluyanova, Camilla Stephens, Mercedes Robles-Díaz, Francisco Jorquera Plaza, Javier González-Gallego, Susana Martínez-Flórez, María Victoria García-Mediavilla, and et al. 2024. "Idiosyncratic Drug-Induced Liver Injury and Amoxicillin–Clavulanate: Spotlight on Gut Microbiota, Fecal Metabolome and Bile Acid Profile in Patients" International Journal of Molecular Sciences 25, no. 13: 6863. https://doi.org/10.3390/ijms25136863