Colorectal cancer (CRC) is a major cause of cancer mortality in the world. One of the most widely used screening tests for CRC is the immunochemical fecal occult blood test (iFOBT), which detects human hemoglobin from patient's stool sample. Although it is highly efficient in detecting blood from patients with gastro-intestinal lesions, such as polyps and cancers, the iFOBT has a high rate of false positive discovery. Recent studies suggested gut bacteria as a promising noninvasive biomarker for improving the diagnosis of CRC. In this study, we examined the composition of gut bacteria using iFOBT leftover from patients undergoing screening test along with a colonoscopy. After collecting data from more than 800 patients, we considered 4 groups for this study. The first and second groups were respectively “healthy” in which the patients had either no blood in their stool or had blood but no lesions. The third and fourth groups of patients had both blood in their stools with precancerous and cancerous lesions and considered either as low-grade and high-grade lesion groups, respectively. An amplification of 16S rRNA (V4 region) gene was performed, followed by sequencing along with various statistical and bioinformatic analysis. We analyzed the composition of the gut bacteriome at phylum, class, genus, and species levels. Although members of the Firmicute phylum increased in the 3 groups compared to healthy patients, the phylum Actinobacteriota was found to decrease. Moreover, and from the phylum Firmicutes were increased and from phylum Actinobacteriota was found decreased when healthy group is compared to the patients with high-grade lesions. Finally, among the 5 machine learning algorithms used to perform our analysis, both elastic net (AUC > 0.7) and random forest (AUC > 0.8) performs well in differentiating healthy patients from 3 other patient groups having blood in their stool. Our study integrates the iFOBT screening tool with gut bacterial composition to improve the prediction of CRC lesions.

中文翻译：

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使用肠道细菌组作为生物标志物优化粪便潜血测试 (FOBT) 结直肠癌筛查

结直肠癌（CRC）是世界上癌症死亡的主要原因。最广泛使用的 CRC 筛查测试之一是免疫化学粪便潜血测试 (iFOBT)，它可检测患者粪便样本中的人类血红蛋白。尽管 iFOBT 在检测息肉和癌症等胃肠道病变患者的血液方面非常有效，但其假阳性发现率很高。最近的研究表明肠道细菌是一种很有前途的非侵入性生物标志物，可以改善结直肠癌的诊断。在这项研究中，我们使用接受筛查测试和结肠镜检查的患者剩余的 iFOBT 检测了肠道细菌的组成。在收集了 800 多名患者的数据后，我们考虑了 4 组进行这项研究。第一组和第二组分别为“健康”，即患者大便中无血或有血但无病变。第三组和第四组患者的便血均伴有癌前病变和癌病变，分别被认为是低级别病变组和高级别病变组。对 16S rRNA（V4 区）基因进行扩增，然后进行测序以及各种统计和生物信息分析。我们在门、纲、属和种水平上分析了肠道细菌组的组成。尽管与健康患者相比，三组中厚壁菌门的成员有所增加，但放线菌门却有所减少。此外，与患有高度病变的患者相比，健康组中厚壁菌门的含量增加，放线菌门的含量减少。最后，在用于执行我们分析的 5 种机器学习算法中，弹性网络 (AUC > 0.7) 和随机森林 (AUC > 0.8) 在区分健康患者和其他 3 个便血患者组方面均表现良好。我们的研究将 iFOBT 筛查工具与肠道细菌组成相结合，以改善 CRC 病变的预测。