Gut Microbiota, Metabolome, and Body Composition Signatures of Response to Therapy in Patients with Advanced Melanoma
Abstract
:1. Introduction
2. Results
2.1. Demographic, Anthropometric, Body Composition, Physical Activity, Dietary, and Clinical Characteristics of the Study Population
2.2. Gut Microbiota Profiling
2.3. Fecal Metabolomic Profile
2.4. Integration of Omics (Microbiomics and Metabolomics) Data and Patient Metadata
3. Discussion
4. Materials and Methods
4.1. Patient Enrollment and Sample Collection
4.2. Nutritional Status Assessment
4.3. Physical Activity and Dietary Questionnaires
4.4. Immune Profile
4.5. Microbial DNA Extraction and 16S rRNA Amplicon Sequencing
4.6. Fecal Metabolomics
4.7. Bioinformatic and Statistical Analysis
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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Characteristic | Overall (n = 31) | Responders (n = 18) | Non-Responders (n = 13) | p Value |
---|---|---|---|---|
Age (years), mean (SD) | 62 (11) | 62 (11) | 61 (12) | 0.5748 |
Sex, n (%) | 0.4120 | |||
Male | 23 (74) | 12 (52) | 11(48) | |
Female | 8 (26) | 6 (75) | 2 (25) | |
Stage, n (%) | 0.6207 | |||
IIIC | 4 (13) | 3 (75) | 1 (25) | |
IV | 27 (87) | 15(56) | 12 (44) | |
ECOG performance status, n (%) | 0.1337 | |||
0 | 26 (84) | 17 (65) | 9 (35) | |
1–2 | 5 (16) | 1 (20) | 4 (80) | |
Planned anti-PD-1 treatment, n (%) | 0.7777 | |||
Nivolumab | 19 (61) | 12 (63) | 7 (37) | |
Pembrolizumab | 5 (16) | 3 (60) | 2 (40) | |
Targeted therapy, n (%) | 0.4130 | |||
Dabrafenib and trametinib | 7 (23) | 3 (43) | 4 (57) | |
NLR a, mean (SD) | 5.5 (7.5) | 2.8 (1.6) | 9.0 (10.4) | 0.0034 |
NLR a | 0.0196 | |||
<4, n (%) | 21 (70) | 15 (71) | 6 (29) | |
≥4, n (%) | 9 (30) | 2 (22) | 7 (78) | |
Medication use b, n (%) | ||||
Antibiotics a | 10 (33) | 5 (50) | 5 (50) | 0.4611 |
Probiotics a | 6 (20) | 3 (50) | 3 (50) | 0.6599 |
Proton-pump inhibitors | 7 (23) | 2 (29) | 5 (71) | 0.0994 |
Corticosteroids | 6 (19) | 2 (33) | 4 (66) | 0.2076 |
Characteristic | Overall (n = 31) | Responders (n = 18) | Non-Responders (n = 13) | p Value |
---|---|---|---|---|
Anthropometry | ||||
Height (m), mean (SD) | 1.71 (0.1) | 1.72 (0.1) | 1.71 (0.1) | 0.6591 |
Weight (kg), mean (SD) | 77.9 (17.4) | 84 (18.1) | 69.5 (12.5) | 0.0291 |
BMI (kg/m2), mean (SD) BMI, n (%) | 26.5 (4.8) | 28.5 (4.9) | 23.8 (3.2) | 0.0073 0.0275 |
<30 kg/m2 | 25 (81) | 12 (48) | 13 (52) | |
≥30 kg/m2 | 6 (19) | 6 (100) | 0 (0) | |
CT a | ||||
Sarcopenic | 14 (56) | 6 (43) | 8 (57) | 0.0029 |
Non-sarcopenic | 11 (44) | 11 (100) | 0 (0) | |
SM (cm2/m2), mean (SD) | 135.2 (29.4) | 139.5 (32.5) | 126.0 (20.0) | 0.3983 |
TAT (cm2/m2), mean (SD) | 125.21 (118.63) | 149.18 (131.2) | 74.28 (62.1) | 0.0018 |
VAT (cm2/m2), mean (SD) | 172.2 (123.4) | 207.8 (131.1) | 96.7 (57.7) | 0.0113 |
SAT (cm2/m2), mean (SD) | 191.0 (89.4) | 225.3 (86.2) | 118.1 (38.7) | 0.0010 |
IMAT (cm2/m2), mean (SD) | 12.4 (10.1) | 14.5 (10.7) | 8.0 (7.7) | 0.0510 |
VATSAT, mean (SD) | 0.88 (0.45) | 0.93 (0.47) | 0.77 (0.41) | 0.3983 |
FFM (kg), mean (SD) | 46.6 (8.8) | 47.9 (9.8) | 43.0 (5.9) | 0.4025 |
Physical activity, n (%) b | 0.1516 | |||
Low | 14 (45) | 6 (43) | 8 (57) | |
Moderate | 11 (36) | 9 (82) | 2 (18) | |
High | 6 (19) | 3 (50) | 3 (50) | |
Fiber: EPIC FFQ c | 1.000 | |||
<25 g/die | 17 (65) | 12 (71) | 5 (29) | |
≥25 g/die | 9 (35) | 6 (67) | 3 (33) | |
Italian Mediterranean Index c | 0.0838 | |||
0–3 | 11 (42) | 10 (91) | 1 (9) | |
4–11 | 15 (58) | 8 (53) | 7 (47) |
Metabolite | Non-Responders | Responders | p Value |
---|---|---|---|
Butanoic acid, methyl ester | 0.47 ± 0.1 | 0.013 ± 0.0063 | 0.002 |
1-Hexanol, 2-ethyl- | 0.034 ± 0.01 | 0.15 ± 0.015 | 0.003 |
2-Heptanone, 6-methyl- | 0.031 ± 0.0045 | 0.0069 ± 0.0025 | 0.006 |
Cyclohexanecarboxylic acid, ethyl ester | 0.41 ± 0.12 | 0.0082 ± 0.0029 | 0.007 |
Butanoic acid | 25 ± 4.3 | 5.7 ± 0.63 | 0.02 |
Butanoic acid, propyl ester | 1.3 ± 0.36 | 0.1 ± 0.035 | 0.02 |
2H-Indol-2-one, 1,3-dihydro- | 0.11 ± 0.037 | 0.12 ± 0.011 | 0.02 |
2-Hexanone | 0.076 ± 0.022 | 0.18 ± 0.021 | 0.04 |
5,9-Undecadien-2-one, 6,10-dimethyl- | 0.13 ± 0.024 | 0.34 ± 0.047 | 0.04 |
Anethole | 0.14 ± 0.05 | 0.86 ± 0.26 | 0.05 |
Propanoic acid, ethyl ester | 0.12 ± 0.037 | 0.007 ± 0.0035 | 0.05 |
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Vandoni, G.; D'Amico, F.; Fabbrini, M.; Mariani, L.; Sieri, S.; Casirati, A.; Di Guardo, L.; Del Vecchio, M.; Anichini, A.; Mortarini, R.; et al. Gut Microbiota, Metabolome, and Body Composition Signatures of Response to Therapy in Patients with Advanced Melanoma. Int. J. Mol. Sci. 2023, 24, 11611. https://doi.org/10.3390/ijms241411611
Vandoni G, D'Amico F, Fabbrini M, Mariani L, Sieri S, Casirati A, Di Guardo L, Del Vecchio M, Anichini A, Mortarini R, et al. Gut Microbiota, Metabolome, and Body Composition Signatures of Response to Therapy in Patients with Advanced Melanoma. International Journal of Molecular Sciences. 2023; 24(14):11611. https://doi.org/10.3390/ijms241411611
Chicago/Turabian StyleVandoni, Giulia, Federica D'Amico, Marco Fabbrini, Luigi Mariani, Sabina Sieri, Amanda Casirati, Lorenza Di Guardo, Michele Del Vecchio, Andrea Anichini, Roberta Mortarini, and et al. 2023. "Gut Microbiota, Metabolome, and Body Composition Signatures of Response to Therapy in Patients with Advanced Melanoma" International Journal of Molecular Sciences 24, no. 14: 11611. https://doi.org/10.3390/ijms241411611