Candida expansion in the gut of lung cancer patients associates with an ecological signature that supports growth under dysbiotic conditions

• Published in: Nature communications 2023-05, Vol.14 (1), p.2673-15, Article 2673
• Main Authors: Seelbinder, Bastian, Lohinai, Zoltan, Vazquez-Uribe, Ruben, Brunke, Sascha, Chen, Xiuqiang, Mirhakkak, Mohammad, Lopez-Escalera, Silvia, Dome, Balazs, Megyesfalvi, Zsolt, Berta, Judit, Galffy, Gabriella, Dulka, Edit, Wellejus, Anja, Weiss, Glen J., Bauer, Michael, Hube, Bernhard, Sommer, Morten O. A., Panagiotou, Gianni
• Format: Article
• Language: English
• Subjects: 49/22; 49/23; 631/114/1305; 631/114/2401; 631/326/193/2539; 631/326/2565/2142; 631/553/2695; Bacteria; Cancer; Candida; Candidiasis; Cross-Sectional Studies; Digestive system; Dysbacteriosis; Dysbiosis; Fatty acids; Female; Flexibility; Gastrointestinal tract; Humanities and Social Sciences; Humans; Lactic Acid; Learning algorithms; Lung cancer; Lung Neoplasms; Machine learning; Male; Metagenomics; multidisciplinary; Science; Science (multidisciplinary)
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-38058-8

Candida species overgrowth in the human gut is considered a prerequisite for invasive candidiasis, but our understanding of gut bacteria promoting or restricting this overgrowth is still limited. By integrating cross-sectional mycobiome and shotgun metagenomics data from the stool of 75 male and female cancer patients at risk but without systemic candidiasis, bacterial communities in high Candida samples display higher metabolic flexibility yet lower contributional diversity than those in low Candida samples. We develop machine learning models that use only bacterial taxa or functional relative abundances to predict the levels of Candida genus and species in an external validation cohort with an AUC of 78.6–81.1%. We propose a mechanism for intestinal Candida overgrowth based on an increase in lactate-producing bacteria, which coincides with a decrease in bacteria that regulate short chain fatty acid and oxygen levels. Under these conditions, the ability of Candida to harness lactate as a nutrient source may enable Candida to outcompete other fungi in the gut. Here, Seelbinder et al . show high Candida levels in cancer patients’ stool to correlate with greater metabolically flexibility but less robust bacterial communities and, combined with machine learning models to predict Candida levels from bacterial data, suggest that lactate producing bacteria may fuel Candida overgrowth in the gut during dysbiosis.