Alterations of Gut Mycobiota Profiles in Adenoma and Colorectal Cancer

Abstract

Accumulating evidence indicates that gut microbiota dysbiosis contributes to colorectal cancer and adenoma. However, a few studies revealed the altered gut mycobiota architecture in colorectal cancer. The present study characterized the gut mycobiota profiles in adenoma and colorectal cancer patients by metagenomic sequencing. Malassezia restricta increased, while Leucoagaricus_sp_SymCcos and fungal_sp_ARF18 significantly decreased in adenoma. Phanerochaete_chrysosporium, Lachancea_waltii, and Aspergillus_rambellii were the top 3 fungi that were significantly enriched in colorectal cancer, while Candida_versatilis, Pseudocercospora_pini_densiflorae, and Candida_sp_JCM_15000 were dominant in the healthy controls. Thirteen fungi, ranked as critical biomarkers in diagnosing colorectal cancer, showed positive associations among all samples. Lachancea_waltii and Phanerochaete_chrysosporium showed the most significant association within CRC. The values of area under the receiver-operating characteristics curve (AUROC) of selected 13 mycobiota were 0.926 in the training model and 0.757 in the 10-fold validation model. Our study provided a reliable investigation of the alterations of gut mycobiota in the development of colorectal cancer and established a convincing diagnostic model for colorectal cancer, which might improve the treatment strategy for colorectal cancer in the future.

Mycobiota and C-Type Lectin Receptors in Cancers: Know thy Neighbors

“…SymCcos and fungal sp. ARF18 significantly decreased in patients with adenoma compared to healthy controls ( Gao et al, 2022 ). Similarly, Wang et al (2021) also estimated differences in intestinal fungi between 24 patients with CRC, 31 patients with colorectal polyps, and 18 normal controls using intergenic spacer (ITS) sequencing ( Figure 2C ).…”

“…(B) Zhong et al (2021) and Zhang et al (2022) revealed the differences of the mycobiome in the tumor tissues compared to adjacent non-tumor tissues from patients with gastric cancer; Yang et al (2022) revealed the differences of the mycobiome in the tumor tissues from patients with gastric cancer compared to normal tissue from healthy controls. (C) Coker et al (2019) and Gao et al (2022) revealed the differences of the mycobiome in the stool samples from patients with colorectal cancer compared to healthy controls. (D) Aykut et al (2019) revealed the differences of the mycobiome in the tumor specimens compared to gut specimens from patients with pancreatic ductal adenocarcinoma.…”

“…Subsequent analyses regarding tumor stage showed that patients with late-stage CRC possessed a higher diversity of mycobiota and a higher abundance of Microbotryomycetes, Sordariomycetes, Microascaceae, Sordariales unidentified, Lasiosphaeriaceae unidentified, Sordariales unidentified 1 , and Microascales , and a lower abundance of Pleosporaceae and Alternaria compared to those with early stage CRC ( Gao et al, 2017 ). Next, the team re-analyzed 71 patients with CRC, 63 patients with adenoma, and 91 healthy controls for fecal fungi using metagenomic sequencing ( Gao et al, 2022 ; Figure 1C ), and found that there were no significant differences in alpha diversity, beta diversity, and the ratio of Basidiomycota / Ascomycota among the three groups. Phanerochaete chrysosporium, Lachancea waltii , and Aspergillus rambellii were dominant in patients with CRC, while Candida versatilis, Pseudocercospora pini densiflorae , and Candida sp.…”

“…Independent Chinese and European cohorts validated these findings, respectively ( Coker et al, 2019 ). The model constructed by Gao et al (2022) using 13 fungal species ( Taxomyces andreanae, Aspergillus rambellii, Lachancea waltii, fungal sp. ARF18, Phanerochaete chrysosporium, Aspergillus flavus, Fusarium pininemorale, Raffaelea quercus mongolicae, Tilletia controversa, Candida versatilis, Exophiala mesophila, Pseudocercospora pini densiflorae , and Brettanomyces anomalus ) also displayed strong diagnostic performance.…”

Effects of Long Non-Coding RNAs Induced by the Gut Microbiome on Regulating the Development of Colorectal Cancer

“…Enrichment of pathogenic bacteria in the gut can cause DNA damage, promote inflammation, induce tumor cell proliferation, and shield the tumor from immune attack [ 29 ]. Intestinal ecological dysregulation has been identified in several macrogenomic studies on CRC as a crucial risk factor for the development of colorectal malignancies [ 30 , 31 , 32 ]. The Alpha-bugs and the bacterial driver-passenger models are widely accepted theories for how dysregulated gut microbiota triggers the development and progression of CRC [ 33 , 34 ].…”