Multi-kingdom microbiota analyses identify bacterial–fungal interactions and biomarkers of colorectal cancer across cohorts

Abstract

Despite recent progress in our understanding of the association between the gut microbiome and colorectal cancer (CRC), multi-kingdom gut microbiome dysbiosis in CRC across cohorts is unexplored. We investigated four-kingdom microbiota alterations using CRC metagenomic datasets of 1,368 samples from 8 distinct geographical cohorts. Integrated analysis identified 20 archaeal, 27 bacterial, 20 fungal and 21 viral species for each single-kingdom diagnostic model. However, our data revealed superior diagnostic accuracy for models constructed with multi-kingdom markers, in particular the addition of fungal species. Specifically, 16 multi-kingdom markers including 11 bacterial, 4 fungal and 1 archaeal feature, achieved good performance in diagnosing patients with CRC (area under the receiver operating characteristic curve (AUROC) = 0.83) and maintained accuracy across 3 independent cohorts. Coabundance analysis of the ecological network revealed associations between bacterial and fungal species, such as Talaromyces islandicus and Clostridium saccharobutylicum. Using metagenome shotgun sequencing data, the predictive power of the microbial functional potential was explored and elevated D-amino acid metabolism and butanoate metabolism were observed in CRC. Interestingly, the diagnostic model based on functional EggNOG genes achieved high accuracy (AUROC = 0.86). Collectively, our findings uncovered CRC-associated microbiota common across cohorts and demonstrate the applicability of multi-kingdom and functional markers as CRC diagnostic tools and, potentially, as therapeutic targets for the treatment of CRC.

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

“…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. Notably, a recent study using a CRC metagenomic dataset, analyzing 1,368 samples from 8 distinct geographical cohorts, also showed an excellent diagnostic value of gut fungi for CRC ( Liu N. N. et al, 2022 ). Therefore, the study of gut mycobiome offers new ideas for diagnosing CRC.…”

Bacterial-fungal metabolic interactions within the microbiota and their potential relevance in human health and disease: a short review

“…Two studies on colorectal cancer have demonstrated modifications in the fungal microbiota community and in the networks of inter-kingdom interactions suggesting a possible link between disease and the equilibrium of these two microbial communities. 133 , 134 However, the mechanisms behind these interactions are not yet fully understood, but can be the results of a complex exchange of metabolites. Although, specific bacterial-fungal metabolic interactions have been related to the occurrence of pathologies in several studies.…”

Cancer as microenvironmental, systemic and environmental diseases: opportunity for transdisciplinary microbiomics science

“…In addition to bacteria, non-bacterial microorganisms, including viruses, fungi, archaea and parasites, likely play pathogenic roles in various cancer types, including CRC 33 34. Viruses represent an essential component of the intestinal microbial community and have been implicated in inflammatory bowel diseases35 36 and CRC 34 37 38.…”