Microbial and metabolic gut profiling across seven malignancies identifies fecal Faecalibacillus intestinalis and formic acid as commonly altered in cancer patients

The key association between gut dysbiosis and cancer is already known. Here, we used whole-genome shotgun sequencing (WGS) and gas chromatography/mass spectrometry (GC/MS) to conduct metagenomic and metabolomic analyses to identify common and distinct taxonomic configurations among 40, 45, 71, 34, 50, 60, and 40 patients with colorectal cancer, stomach cancer, breast cancer, lung cancer, melanoma, lymphoid neoplasms and acute myeloid leukemia (AML), respectively, and compared the data with those from sex- and age-matched healthy controls (HC). Alpha-diversity differed only between the lymphoid neoplasm and AML groups and their respective HC, while Geta-diversity differed between all groups and their HC. Of 203 unique species, 179 and 24 were under- and over-represented, respectively, in the case groups compared with HC. Of these, Faecalibacillus intestinalis was under-represented in each of the seven groups studied, Anaerostipes hadrus was under-represented in all but the stomach cancer group, and 22 species were under-represented in the remaining five case groups. There was a marked reduction in the gut microbiome cancer index in all case groups except the AML group. Of the short-chain fatty acids and amino acids tested, the relative concentration of formic acid was significantly higher in each of the case groups than in HC, and the abundance of seven species of Faecalibacterium correlated negatively with most amino acids and formic acid, and positively with the levels of acetic, propanoic, and butanoic acid. In conclusion, we found more differences than similarities between the studied malignancy groups, with large variations in diversity, taxonomic/metabolomic profiles, and functional assignments. While the results obtained may demonstrate trends rather than objective differences that correlate with different types of malignancy, the newly developed gut microbiota cancer index did distinguish most of the cancer cases from HC. We believe that these data are a promising step forward in the search for new diagnostic and predictive tests to assess intestinal dysbiosis among cancer patients.

肠道菌群失调与癌症之间的关键关联已为学界所熟知。本研究采用全基因组鸟枪测序（whole-genome shotgun sequencing, WGS）与气相色谱-质谱联用（gas chromatography/mass spectrometry, GC/MS）开展宏基因组与代谢组学分析，分别纳入结直肠癌、胃癌、乳腺癌、肺癌、黑色素瘤、淋巴组织肿瘤及急性髓系白血病（acute myeloid leukemia, AML）患者各40、45、71、34、50、60及40例，并将所得数据与性别、年龄匹配的健康对照（healthy controls, HC）进行对比。α多样性仅在淋巴组织肿瘤组、急性髓系白血病组与其各自健康对照间存在显著差异，而β多样性在所有癌症组与其健康对照间均存在显著差异。在203个独特菌种中，与健康对照相比，病例组内分别有179个菌种丰度下调、24个菌种丰度上调。其中，肠道粪杆菌（Faecalibacillus intestinalis）在全部7个研究癌症组中丰度均显著下调；哈氏厌氧杆菌（Anaerostipes hadrus）除胃癌组外，在其余所有癌症组中丰度均显著下调；另有22个菌种在剩余5个癌症组中丰度显著下调。除急性髓系白血病组外，所有癌症组的肠道微生物组癌症指数均出现明显降低。在所检测的短链脂肪酸与氨基酸中，所有癌症组的甲酸相对浓度均显著高于健康对照；7种粪杆菌属（Faecalibacterium）菌种的丰度与多数氨基酸及甲酸水平呈负相关，而与乙酸、丙酸及丁酸的水平呈正相关。综上，本研究发现所分析的各类恶性肿瘤组间相似性有限、差异更为显著，其多样性、分类学/代谢组学特征及功能注释均存在较大变异。尽管本研究所得结果或仅能反映不同恶性肿瘤相关的趋势性差异而非绝对差异，但新构建的肠道微生物组癌症指数仍可有效区分多数癌症病例与健康对照。我们认为，本研究数据为开发用于评估癌症患者肠道菌群失调的新型诊断与预测检测手段提供了极具前景的研究基础。