Alexey S. Zhivotovskiy

To perform the first concurrent characterization of gut and respiratory microbiome profiles in colorectal cancer patients from Western Siberia, Russia. We analyzed synchronous fecal and sputum samples from 40 treatment-naive colorectal cancer patients and 45 healthy controls using 16S rRNA gene (V3-V4) sequencing and QIIME 2-based bioinformatic workflows. While alpha-diversity indices did not differ significantly between groups, beta-diversity analysis revealed substantial compositional differences for both ecosystems. Colorectal cancer patients exhibited gut enrichment of Proteobacteria, Fusobacteria, Fusobacterium, Odoribacter, Lachnospiraceae_UCG-010, Erysipelatoclostridium, Parvimonas, Finegoldia, Clostridium and Bacteroides (Bacteroides fragilis), alongside sputum enrichment of phyla Bacteroidetes and Actinobacteria, as well as genera Neisseria, Prevotella, Lactobacillus, Rothia, Nocardia, Leptotrichia, Campylobacter, and Helicobacter. Stage-associated shifts included elevated Akkermansia in gut microbiomes of patients with advanced-stage disease and higher Campylobacter in early-stage sputum. These findings identify distinct gut–respiratory dysbiotic signatures in a previously understudied population. Our results underscore the potential of dual-compartment microbiome profiling for developing non-invasive biomarkers and require validation in larger, multicenter cohorts to elucidate mechanistic links between respiratory dysbiosis and colorectal carcinogenesis.

Formation of DNA adducts of chemical carcinogens is a trigger for carcinogenesis. Adducts of benzo[a]pyrene metabolites and estradiol metabolites with DNA have been found in normal and tumor cells in healthy women and patients with breast and colorectal cancer. These low-weight compounds in macromolecular complexes induce the synthesis of specific antibodies. Previously, the presence of specific antibodies against benzo[a]pyrene (IgA-Bp), estradiol (IgA-Es) and progesterone (IgA-Pg) was revealed in breast cancer patients. The aim of this study is to identify the putative features of the IgA-Bp, IgA-Es, and IgA-Pg formation in postmenopausal women with colorectal cancer, in comparison with healthy and breast cancer patients. Using a noncompetitive enzyme-linked immunosorbent assay, the content of these antibodies was studied in the blood serum of healthy women (n = 401), patients with colorectal cancer (n = 219) and breast cancer (n = 1469) using conjugates of Bp, Es, and Pg with bovine serum albumin as adsorbed antigens. When compared with healthy people, the patients with colorectal cancer exhibited higher incidence of IgA-Bp > 3 (75% vs 37%, p < 0.0001, OR = 5.0), as well as more common levels of individual antibody ratios: IgA-Bp/IgA-Es > 1 (82% vs 41%, p < 0.0001, OR = 6.5); IgA-Bp/IgA-Pg > 1.5 (77% vs 20%, p < 0.0001, OR = 13.4); IgA-Es/IgA-Pg > 1 (89% vs 48%, p < 0.0001, OR = 8.7). In breast cancer patients, compared with healthy people, high IgA-Bp values ( > 3) were more common (45% vs 37%, p < 0.004, OR = 1.4), as well as increased IgA-Bp/IgA-Es ratio > 1 (57% vs 41%, p < 0.0001, OR = 1.9), IgA-Bp/IgA-Pg > 1.1 (71% vs 36%, p < 0.0001, OR = 4.4) and IgA-Es/IgA-Pg > 1.1 (71% vs 41%, p < 0.0001, OR = 3.5). In patients with colorectal cancer, compared with patients with breast cancer we have found higher incidence of increased IgA-Bp values ( > 3) (75% vs 45%, p < 0.0001), IgA-Es > 3 (53% vs 39%, p < 0, 0001), and of IgA-Pg > 2 (52% vs 44%, p = 0.025), as well as IgA-Bp/IgA- Es > 1 (82% vs 57%, p < 0.0001, OR = 50.8 ); IgA-Bp/IgA-Pg > 1.5 (77% vs 49%, p < 0.0001); IgA-Es/IgA-Pg > 1.1 (85% vs 71%, p < 0.0001). The apparently high serum IgA-Bp levels reflect the formation of DNA-Bp adducts at large scale in target cells in colorectal cancer compared with healthy women and breast cancer patients, due to direct exposure of colon epithelium to Bp from food. Immunoassay for IgA-Bp, IgA-Es and IgA-Pg is proposed for assessing individual risk of colorectal cancer in postmenopausal women. The ratios of IgA Bp/IgA-Pg levels > 1.5 represent the most informative marker of individual risk for colorectal cancer.