Department of Pathology and Clinical Bioinformatics, The Tumor Immuno-Pathology Laboratory, Erasmus University Medical Center, Rotterdam, the Netherlands.
Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
Cancer Med. 2024 Feb;13(3):e6860. doi: 10.1002/cam4.6860. Epub 2024 Feb 17.
The immune response-gut microbiota interaction is implicated in various human diseases, including cancer. Identifying the link between the gut microbiota and systemic inflammatory markers and their association with cancer will be important for our understanding of cancer etiology. The current study was performed on 8090 participants from the population-based Rotterdam study. We found a significant association (false discovery rate [FDR] ≤0.05) between lymphocytes and three gut microbial taxa, namely the family Streptococcaceae, genus Streptococcus, and order Lactobacillales. In addition, we identified 95 gut microbial taxa that were associated with inflammatory markers (p < 0.05). Analyzing the cancer data, we observed a significant association between higher systemic immune-inflammation index (SII) levels at baseline (hazard ratio (HR): 1.65 [95% confidence interval (CI); 1.10-2.46, p ≤ 0.05]) and a higher count of lymphocytes (HR: 1.38 [95% CI: 1.15-1.65, p ≤ 0.05]) and granulocytes (HR: 1.69 [95% CI: 1.40-2.03, p ≤ 0.05]) with increased risk of lung cancer after adjusting for age, sex, body mass index (BMI), and study cohort. This association was lost for SII and lymphocytes after additional adjustment for smoking (SII = HR:1.46 [95% CI: 0.96-2.22, p = 0.07] and lymphocytes = HR: 1.19 [95% CI: 0.97-1.46, p = 0.08]). In the stratified analysis, higher count of lymphocyte and granulocytes at baseline were associated with an increased risk of lung cancer in smokers after adjusting for age, sex, BMI, and study cohort (HR: 1.33 [95% CI: 1.09-1.62, p ≤0.05] and HR: 1.57 [95% CI: 1.28-1.92, p ≤0.05], respectively). Our study revealed a positive association between gut microbiota, higher SII levels, and higher lymphocyte and granulocyte counts, with an increased risk of developing lung cancer.
免疫反应-肠道微生物群相互作用与包括癌症在内的各种人类疾病有关。确定肠道微生物群与全身炎症标志物之间的联系及其与癌症的关联,对于我们理解癌症病因将是重要的。本研究在基于人群的鹿特丹研究中的 8090 名参与者中进行。我们发现淋巴细胞与三种肠道微生物群之间存在显著关联(错误发现率 [FDR] ≤0.05),即链球菌科、链球菌属和乳杆菌目。此外,我们还鉴定出 95 种与炎症标志物相关的肠道微生物群(p<0.05)。分析癌症数据时,我们观察到基线时较高的全身性免疫炎症指数(SII)水平(风险比 [HR]:1.65[95%置信区间 [CI]:1.10-2.46,p≤0.05])与较高的淋巴细胞计数(HR:1.38[95% CI:1.15-1.65,p≤0.05])和粒细胞计数(HR:1.69[95% CI:1.40-2.03,p≤0.05)之间存在显著关联,提示调整年龄、性别、体重指数(BMI)和研究队列后,肺癌发病风险增加。在进一步调整吸烟因素后,SII 和淋巴细胞之间的这种关联消失(SII=HR:1.46[95% CI:0.96-2.22,p=0.07]和淋巴细胞=HR:1.19[95% CI:0.97-1.46,p=0.08])。在分层分析中,调整年龄、性别、BMI 和研究队列后,基线时较高的淋巴细胞和粒细胞计数与吸烟者肺癌发病风险增加相关(HR:1.33[95% CI:1.09-1.62,p≤0.05]和 HR:1.57[95% CI:1.28-1.92,p≤0.05])。本研究揭示了肠道微生物群、较高的 SII 水平以及较高的淋巴细胞和粒细胞计数之间的正相关,与肺癌发病风险增加有关。