Caracterização da microbiota intestinal e de mediadores imunológicos solúveis de pacientes com câncer colorretal tratados em uma unidade terciária na Amazônia brasileira

Abstract

Introduction: Colorectal cancer (CRC) is the second most common malignancy and arises from the transformation of intestinal stem cells into malignant cells, influenced by genetic, epigenetic, and environmental factors, such as diet and gut microbiota. Alterations in microbiota composition, known as dysbiosis, have been associated with CRC and may promote chronic inflammation and tumor progression. Objective: To describe the intestinal microbiota profile and soluble immune mediators in patients with colorectal cancer treated at a tertiary care unit in the Brazilian Amazon. Materials and Methods: This was an observational, descriptive, and retrospective study with a quantitative approach, conducted at Fundação CECON with 60 patients with colorectal cancer recruited between 2023 and 2025. Clinical, sociodemographic, and lifestyle data were collected through questionnaires, and blood and fecal samples were analyzed. Immune mediators (CXCL8, IL-1β, IL-6, TNF, IL-12p70, IFN-γ, IL-17A, IL-4, IL-10, and IL-2) were quantified using Cytometric Bead Array (CBA), and the gut microbiota was characterized by next-generation sequencing (NGS, Ion Torrent). Results: Sixty patients with paired biological samples (blood and stool) were included, with the majority being female (60%), 86.7% over 51 years, and a mean age of 65 ± years. Risk factors included smoking (35%), alcohol consumption (43.3%), and regular intake of processed foods (50%). A family history of cancer was reported in 71.7%. Hypertension was present in 23.3% and combined with diabetes mellitus in 10%. Lesions predominated on the left side (81.7%), mostly rectal cancer (C20 – 41.7%). Most patients were in advanced stages (Stage III: 48.3%). The most common treatment was surgery combined with chemotherapy and radiotherapy (33.3%). Patients with right-sided CRC (CRC-RS) showed increased CXCL8 (p = 0.01) and IL-6 (p = 0.03), while IFN-γ and IL-2 were reduced (p = 0.009; 0.007) compared to left-sided CRC (CRC-LS). Stage III-IV tumors also exhibited increased CXCL8 (p = 0.04). Immune mediator signatures indicated that CRC-LS tumors tend to be more inflammatory, whereas CRC-RS and advanced-stage tumors showed higher expression of cytokines related to tumor progression and immunosuppression. Microbial diversity was generally similar, with some individuals showing lower complexity, as indicated by Shannon (p = 0.0043) and Simpson (p = 0.0035) indices. Conclusion: Clinical and lifestyle variables appear to influence patient profiles. Microbiota diversity was generally homogeneous, dominated by Bacteroides and beneficial genera, maintaining ecological function. Subgroups with Fusobacterium suggest dysbiosis and CRC association. Cytokine profiles, linked to tumor laterality and stage, indicate potential biomarkers and therapeutic targets. Right-sided tumors had higher CXCL8 and IL-6, while left-sided tumors had higher IFN-γ and IL-1β.