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

Abstract

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.

Microbiota signatures associated with invasive Candida albicans infection in the gastrointestinal tract of immunodeficient mice

“…Among the gut microbiota, SCFA-producing bacteria are known probiotics for gut health and play an important role in inhibiting C. albicans colonization ( Fan et al., 2015 ) and morphogenesis ( Noverr and Huffnagle, 2004 ) and in suppressing C. albicans- induced mucosal inflammation ( Bhaskaran et al., 2018 ). In agreement with other findings regarding GI infections caused by C. albicans ( Mason et al., 2012b ; Seelbinder et al., 2023 ) or other pathogens ( Sohail et al., 2021 ), our data support the hypothesis that the introduction of C. albicans into the GI tract increased the gut bacterial alpha diversity and the abundance of SCFA-producing bacteria, especially butyrate-producing Lachnospiraceae and Ruminococcaceae , two abundant families in Firmicutes ( Louis et al., 2014 ). Contrary to the blockade of C. albicans colonization observed in immunocompetent mice ( Fan et al., 2015 ), the enrichment of Lachnospiraceae and Ruminococcaceae failed to prevent wild-type C. albicans colonization in Rag2γc mice.…”

Faecal microbial transfer and complex carbohydrates mediate protection against COPD

“…69 A limitation of this and other studies is the lack of assessment of viral and fungal components of the microbiome in COPD. While their role in COPD has not been clarified, gastrointestinal fungi, especially Candida, have been implicated in lung cancer 70 and murine models of allergic airway disease along with changes in lung and gut innate immune cell populations. 71 72 Fungi and viruses also activate TLRs, including recognition of β-glucans by TLR2, O-linked mannans by TLR4, fungal/viral RNA by TLR3 and 7 and DNA by TLR9, 73 74 and thus may overlap with several mechanisms identified in this study.…”

Functions and mechanisms of lactylation in carcinogenesis and immunosuppression

“…Panagiotou et al. ( 87 ) found that the excessive growth of intestinal Candida in patients with lung cancer was related to an increase in lactic-producing bacteria and a decrease in short-chain fatty acid production. Candida species use lactate as a nutrient source to compete with other fungi in the intestine.…”