A, KRAS-mutant tumors use glucose or glutamine to fuel their metabolism, while KRAS/LKB1/KEAP1 mutant tumors preferentially use glutamine. B, Blocking glutaminolysis using GLSi impairs proliferation of KRAS/LKB1/KEAP1-mutant tumors as they are unable to maintain the TCA cycle.

Microbiota refers to a colony of microorganisms, and they are found in all multicellular organisms. This colony plays a major role in both the physiology and disease of the organism it inhabits. Much attention has been paid to host-microbiota interactions, but there has been little investigation on its role in carcinogenesis. In this study, we characterized a fecal mycobiota, also known as fungal signature, for the first time with 131 subjects, comprising polyp and colorectal cancer (CRC) patients, as well as a healthy control population. The data obtained were analyzed to assess the biodiversity and composition of the fungi. The impacts of anatomic position and tumor stage on the mycobiota were also evaluated. Correlations between fungi were investigated using the Spearman test. We observed fungal dysbiosis in colon polyps and CRC, including decreased diversity in polyp patients, an increased Ascomycota/Basidiomycota ratio, and an increased proportion of opportunistic fungi Trichosporon and Malassezia, which might favor the progression of CRC. Subsequent analysis with regard to tumor stage demonstrated a lower diversity and significant mycobiota alteration in early-stage tumors. Finally, the fungal correlation showed a close relationship within the community and concomitantly revealed a dramatically structured discrepancy in each clinical phenotype. In conclusion, our study has uncovered a distinct fungal dysbiosis and an alteration in the fungal network, which could play important roles in polyp and CRC pathogenesis.

The aim of this study was to explore the gut microbiota profiles of colorectal cancer (CRC) patients and to examine the relationship between gut microbiota and other key molecular factors involved in CRC tumorigenesis. In this study, a 16S rDNA sequencing platform was used to identify possible differences in the microbiota signature between CRC and adjacent normal mucosal tissue. Differences in the microbiota composition in different anatomical colorectal tumor sites and their potential association with KRAS mutation were also explored. In this study, the number of Firmicutes and Actinobacteria decreased, while the number of Fusobacteria increased in the gut of CRC patients. In addition, at the genus level, Fusobacterium was identified as the key contributor to CRC tumorigenesis. In addition, a different distribution of gut microbiota in ascending and descending colon cancer samples was observed. Lipopolysaccharide biosynthesis-associated microbial genes were enriched in tumor tissues. Our study suggests that specific mucosa-associated microbiota signature and function are significantly changed in the gut of CRC patients, which may provide insight into the progression of CRC. These findings could also be of value in the creation of new prevention and treatment strategies for this type of cancer.