Alteration of Colonic Bacterial and Fungal Composition and Their Inter- and Intra-Kingdom Interaction in Patients with Adenomas with Low-Grade Dysplasia

Abstract

Colorectal cancer (CRC) develops from pre-cancerous cellular lesions in the gut epithelium and mainly originates from specific types of colonic adenomas with dysplasia. However, gut microbiota signatures among sampling sites in patients with colorectal adenomas with low-grade dysplasia (ALGD) and normal control (NC) remain uncharacterized. To characterize gut microbial and fungal profiles in ALGD and normal colorectal mucosa tissues. We used 16S and ITS1-2 rRNA gene sequencing and bioinformatics analysis on the microbiota of ALGD and normal colorectal mucosa from 40 subjects. Bacterial sequences in the ALGD group showed an increase in Rhodobacterales, Thermales, Thermaceae, Rhodobacteraceae, and several genera, including Thermus, Paracoccus, Sphingobium, and Pseudomonas, compared to the NC group. Fungal sequences in the ALGD group showed an increase in Helotiales, Leotiomycetes, and Basidiomycota, while several orders, families, and genera, including Verrucariales, Russulales, and Trichosporonales, were decreased. The study found various interactions between intestinal bacteria and fungi. The bacterial functional analysis showed increased glycogen and vanillin degradation pathways in the ALGD group. Meanwhile, the fungal functional analysis showed a decrease in pathways related to the biosynthesis of gondoate and stearate, as well as degradation of glucose, starch, glycogen, sucrose, L-tryptophan, and pantothenate, and an increase in the octane oxidation pathway in the ALGD group. The mucosal microbiota in ALGD exhibits altered fungal and microbial composition compared to the NC mucosa, potentially contributing to the development of intestinal cancer by regulating specific metabolic pathways. Therefore, these changes in microbiota and metabolic pathways may be potential markers for diagnosing and treating colorectal adenoma and carcinoma.