Disrupted gut fungi tied to colorectal cancer

Alterations in normal gut mycobiota profile, particularly the enrichment of the pathogenic Aspergillus rambellii, appear to aggravate the risk of colorectal cancer (CRC), according to a recent study.

“Here, we revealed the alteration of enteric mycobiota in CRC patients from different populations, and our results clearly showed the occurrence of fungal dysbiosis along CRC progression—from healthy subjects, patients with adenoma, and to CRC patients,” the researchers said.

The present study used faecal metagenomic datasets retrieved from seven prior publications and added an in-house cohort for the present analysis. The total study sample included 1,329 metagenomes, of which 454 were of CRC, 350 of adenoma, and 525 of healthy controls. DNA sequencing analysis was used to assess the mycobiota profile of the in-house cohort.

Pooled analysis of the in-house and literature cohorts revealed significant disruption of normal enteric mycobiota in CRC progression. In particular, fungal richness, as quantified by alpha diversity, was significantly reduced in CRC patients vs healthy controls (p<0.05). [Gastroenterology 2022;doi:10.1053/j.gastro.2022.06.038]

Of note, this trend reached significance in only three cohorts, suggesting substantial inter-cohort variation. Principal coordinates analysis revealed that such heterogeneity could be attributed to population geography, sex distribution, or disease stage.

Comparing fungal abundances in CRC patients with controls, the researchers identified 33 species that could differentiate the two patient subgroups. Of note, the pathogenic A. rambellii was the top enriched species in CRC patients, while A. kawachii was the top depleted species.

A. rambellii was three times more abundant in CRC patients than in controls, while A. kawachii saw a twofold depletion (p<0.0001 for both). As with fungal richness, species abundance values differed greatly across the cohorts, suggesting strong variations depending on cohort characteristics, though findings for A. rambellii were consistent in seven of the eight included cohorts.

Aside from A. rambellii and A. kawachii, the researchers identified 16 more species whose enteric abundances were significantly altered between CRC patients and controls. Of these, six were enriched, including Erysiphe pulchra and Elsinoe australis; on the other hand, 10 were depleted, including Trichophyton mentagrophytes and Pseudocercospora fijiensis.

Despite substantial inter-cohort heterogeneity, the alteration in abundance of these 18 species was generally consistent.

These analyses were repeated in patients with adenoma, revealing 10 CRC-enriched and 23 CRC-depleted fungi species. A. rambellii was again the top enriched species, with a threefold increase relative to controls; A. kawachii was likewise the most depleted species, representing a twofold decrease compared with healthy participants (p<0.0001 for both).

“It is therefore worth further mechanistic investigation to depict the consequences of dysbiotic mycobiota and to evaluate whether CRC-enriched fungal species are the cause of CRC,” the researchers said. “Our results also highlighted the potential of fungi as biomarkers for CRC diagnosis.”

“Clinical assessment of diagnostic panels with combined fungal and bacterial biomarkers for CRC is warranted, which may improve the performance of current biomarker panels that are based on a single kingdom of bacteria,” they added.