Exploring Connections between Oral Microbiota, Short-Chain Fatty Acids, and Specific Cancer Types: A Study of Oral Cancer, Head and Neck Cancer, Pancreatic Cancer, and Gastric Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Subject Characteristics
2.2. Saliva and Blood Sampling
2.3. DNA Isolation, 16S rRNA Gene Sequencing, and Analysis
2.4. Measuring SCFA, FFAR2, and Chemokine/Cytokine-Related Cancer Associations with Oral Microbial Signals
2.5. Oral Microbiota Key Metabolic Pathways Prediction
2.6. Machine Learning and Statistical Analyses
3. Results
3.1. Demographic and Lifestyle Characteristics of Study Participants
3.2. Taxonomic Analyses and the Identification of Genera Potentially Associated with Cancer Risk
3.3. Oral Microbiota Profiles Are Switched in All Cancer and Control Groups
3.4. Identification of Potential Correlation between Specific KOs in Oral Microbiota and Increased Cancer Risk
3.5. Oral Microbiota Modified Systemic Inflammation and Cancer Initiation
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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Variable | Control | Cancer | p Value a |
---|---|---|---|
(n = 745) | (n = 309) | ||
Age a | 57.3 ± 9.20 | 63.2 ± 12.2 | <0.0001 |
Sex a | <0.0001 | ||
Female | 434 (58.3%) | 116 (37.5%) | |
Male | 311 (41.7%) | 193 (62.5%) | |
BMI (kg/m2) | 24.0 ± 3.03 | 23.6 ± 3.67 | <0.0001 |
<18.5 | 17 (2.28%) | 24 (7.77%) | 0.002 |
18.5~22.9 | 272 (36.5%) | 101 (32.7%) | |
23.0~24.9 | 197 (26.4%) | 78 (25.2%) | |
25.0~29.9 | 226 (30.3%) | 90 (29.1%) | |
30≥ | 27 (3.62%) | 11 (3.56%) | |
Smoking b | <0.0001 | ||
Non-smoker | 447 (60.0%) | 152 (49.2%) | |
Former smoker | 202 (27.1%) | 85 (27.5%) | |
Current smoker | 71 (9.53%) | 66 (21.4%) | |
Drinking c | <0.0001 | ||
Non-drinker | 179 (24.0%) | 118 (38.2%) | |
Former drinker | 85 (11.4%) | 56 (18.1%) | |
Current drinker | 441 (59.2%) | 129 (41.8%) | |
Stage d | |||
1 | 89 (28.8%) | ||
2 | 43 (13.9%) | ||
3 | 43 (13.9%) | ||
4 | 101 (32.7%) | ||
T Stage e | |||
T1 | 96 (31.1%) | ||
T2 | 57 (18.5%) | ||
T3 | 36 (11.7%) | ||
T4 | 63 (20.4%) | ||
N Stage f | |||
N0 | 141 (45.6%) | ||
N1 | 40 (12.9%) | ||
N2 | 32 (10.4%) | ||
N3 | 14 (4.53%) |
Taxon Name | Logistic Regression | Number of Subjects a | OR b (95% CI) | p Value c | |
---|---|---|---|---|---|
Control | Cancer | ||||
Streptococcus | Continuous scale | 745 | 309 | 3.13 (2.51, 3.94) | 3.33 × 10−23 |
Quartile 1 | 187 | 33 | ref | ||
Quartile 2 | 186 | 36 | 1.09 (0.65, 1.83) | 0.72 | |
Quartile 3 | 186 | 57 | 1.73 (1.08, 2.81) | 0.02 | |
Quartile 4 | 186 | 183 | 5.57 (3.69, 8.62) | 1.60 × 10−15 | |
Haemophilus | Continuous scale | 745 | 309 | 0.42 (0.35, 0.51) | 3.30 × 10−19 |
Quartile 1 | 187 | 165 | ref | ||
Quartile 2 | 186 | 46 | 0.28 (0.18, 0.40) | 9.15 × 10−11 | |
Quartile 3 | 186 | 38 | 0.23 (0.15, 0.34) | 1.83 × 10−12 | |
Quartile 4 | 186 | 60 | 0.36 (0.25, 0.52) | 3.76 × 10−8 | |
Prevotella | Continuous scale | 745 | 309 | 0.51 (0.42, 0.62) | 1.62 × 10−11 |
Quartile 1 | 187 | 131 | ref | ||
Quartile 2 | 186 | 70 | 0.53 (0.37, 0.76) | 0.00 | |
Quartile 3 | 186 | 60 | 0.46 (0.31, 0.66) | 3.42 × 10−5 | |
Quartile 4 | 186 | 48 | 0.36 (0.24, 0.53) | 4.55 × 10−7 | |
Leuconostoc | Continuous scale | 745 | 309 | 2.23 × 1041 (1.24 × 1026, 2.06 × 105) | 3.06 × 10−6 |
=0 | 715 | 207 | ref | ||
>0 | 30 | 102 | 11.74 (7.69, 18.42) | 1.45 × 10−28 | |
Neisseria | Continuous scale | 745 | 309 | 0.72 (0.63, 0.83) | 4.86 × 10−6 |
Quartile 1 | 187 | 111 | ref | ||
Quartile 2 | 186 | 74 | 0.67 (0.46, 0.95) | 0.02 | |
Quartile 3 | 186 | 63 | 0.57 (0.39, 0.82) | 0.00 | |
Quartile 4 | 186 | 61 | 0.55 (0.37, 0.79) | 0.00 | |
Abiotrophia | Continuous scale | 745 | 309 | 658.08 (98.59, 5651.18) | 3.24 × 10−10 |
=0 | 368 | 104 | ref | ||
>0 | 377 | 205 | 1.92 (1.46, 2.54) | 3.42 × 10−6 |
Function Name | Abundance Median | Fold Change | Univariate Logistic Regression | OR (95% CI) b | p Value c | AUC | ||
---|---|---|---|---|---|---|---|---|
Control (n = 750) | Cancer (n = 313) | p Value a | Cancer/ Control | |||||
G protein-coupled receptor kinase (K08291) | 3.1 × 10−8 | 1.7 × 10−7 | 1.5 × 10−16 | 5.40 | Continuous Scale | 1.75 (1.54–1.98) | 7.2 × 10−18 | 0.73 |
Quartile 1 | ref | 7.1 × 10−25 | ||||||
Quartile 2 | 1.37 (0.87–2.15) | |||||||
Quartile 3 | 2.34 (1.57–3.49) | |||||||
Quartile 4 | 3.13 (2.20–4.45) | |||||||
Futalosine hydrolase (K11783) | 2.3 × 10−8 | 1.2 × 10−7 | 6.9 × 10−8 | 5.20 | Continuous Scale | 1.39 (1.24–1.56) | 1.9 × 10−8 | 0.76 |
Quartile 1 | ref | 6.8 × 10−19 | ||||||
Quartile 2 | 2.35 (1.58–3.51) | |||||||
Quartile 3 | 3.06 (2.09–4.48) | |||||||
Quartile 4 | 4.61 (3.24–6.57) | |||||||
H+-transporting ATPase (K01535) | 5.1 × 10−8 | 2.5 × 10−7 | 8.5 × 10−23 | 5.00 | Continuous Scale | 1.74 (1.56–1.94) | 1.2 × 10−23 | 0.73 |
Quartile 1 | ref | 3.1 × 10−25 | ||||||
Quartile 2 | 1.66 (1.07–2.60) | |||||||
Quartile 3 | 1.78 (1.15–2.76) | |||||||
Quartile 4 | 6.74 (4.71–9.66) |
Name | Leuconostoc | Streptococcus | Abiotrophia | Prevotella | Haemophilus | Neisseria | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
r a | p b | r a | p b | r a | p b | r a | p b | r a | p b | r a | p b | |
G protein-coupled receptor kinase (K08291) | 0.16 | <0.0001 | 0.16 | <0.0001 | 0.05 | 0.13 | −0.07 | 0.02 | −0.10 | 0.001 | −0.12 | 0.000 |
Futalosine hydrolase (K11783) | 0.13 | <0.0001 | 0.16 | <0.0001 | 0.12 | 0.000 | −0.14 | <0.0001 | −0.10 | 0.001 | −0.01 | 0.79 |
H+−transporting ATPase (K01535) | 0.22 | <0.0001 | 0.21 | <0.0001 | 0.07 | 0.02 | −0.12 | <0.0001 | −0.18 | <0.0001 | −0.14 | <0.0001 |
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Share and Cite
Nouri, Z.; Choi, S.W.; Choi, I.J.; Ryu, K.W.; Woo, S.M.; Park, S.-J.; Lee, W.J.; Choi, W.; Jung, Y.-S.; Myung, S.-K.; et al. Exploring Connections between Oral Microbiota, Short-Chain Fatty Acids, and Specific Cancer Types: A Study of Oral Cancer, Head and Neck Cancer, Pancreatic Cancer, and Gastric Cancer. Cancers 2023, 15, 2898. https://doi.org/10.3390/cancers15112898
Nouri Z, Choi SW, Choi IJ, Ryu KW, Woo SM, Park S-J, Lee WJ, Choi W, Jung Y-S, Myung S-K, et al. Exploring Connections between Oral Microbiota, Short-Chain Fatty Acids, and Specific Cancer Types: A Study of Oral Cancer, Head and Neck Cancer, Pancreatic Cancer, and Gastric Cancer. Cancers. 2023; 15(11):2898. https://doi.org/10.3390/cancers15112898
Chicago/Turabian StyleNouri, Zahra, Sung Weon Choi, Il Ju Choi, Keun Won Ryu, Sang Myung Woo, Sang-Jae Park, Woo Jin Lee, Wonyoung Choi, Yuh-Seog Jung, Seung-Kwon Myung, and et al. 2023. "Exploring Connections between Oral Microbiota, Short-Chain Fatty Acids, and Specific Cancer Types: A Study of Oral Cancer, Head and Neck Cancer, Pancreatic Cancer, and Gastric Cancer" Cancers 15, no. 11: 2898. https://doi.org/10.3390/cancers15112898