Candida in Your Gut Is More Than a Nuisance. Here’s What Researchers Found

Fungi account for somewhere between 0.1% and 1% of fecal microbes, a sliver so small it was largely ignored for decades while researchers focused on bacteria. A 2023 review published in Mycopathologia by Irini Kreulen and colleagues at Amsterdam UMC argues that the oversight has real clinical consequences. Candida species in particular, often the most abundant fungi in the human gut, show up repeatedly at the scene of serious intestinal disease. Whether they are driving that disease or merely exploiting it is the central question the review sets out to examine.

Candida colonizes the gut from birth and expands under stress

Candida colonization does not wait for adulthood. The gut mycobiome of newborns is dominated by low-richness communities anchored by Candida, Saccharomyces, and Debaryomyces, and Candida species are especially prominent in preterm neonates. That early foothold becomes dangerous fast: preterm infants receiving broad-spectrum antibiotics face sharply increased susceptibility to fungal overgrowth, because the antibiotics remove bacterial competitors that would normally keep Candida in check.

The consequences are severe. Invasive candidiasis is a leading cause of mortality in extremely preterm neonates, with C. albicans responsible for 60.2% of such cases among European newborns. Increased Candida abundance is also linked to necrotizing enterocolitis, the most common acute neonatal intestinal disease, and to systemic sepsis. On a more encouraging note, the review notes that probiotic treatment significantly reduced the relative abundance of Candida species in extremely preterm infants, suggesting the bacterial-fungal balance is malleable even in the earliest weeks of life.

Inflammatory bowel disease and the contested role of C. albicans

The relationship between Candida and inflammatory bowel disease is complicated, and the review is careful not to overstate it. Elevated Candida or C. albicans abundance is observed frequently in adult IBD patients, and pediatric IBD patients show reduced fungal diversity alongside altered mycobiota profiles. In children, elevated C. parapsilosis correlates positively with Bacteroides fragilis, hinting at cross-kingdom interactions between gut bacteria and fungi that amplify or dampen inflammation together.

Genetics add another layer. Variants in CARD9, a gene associated with IBD susceptibility, are tied to fungal-related signaling pathways. Murine models using chemically induced colitis show that proper antifungal immune recognition is necessary to prevent fungi from making colitis worse. Anti-Saccharomyces cerevisiae antibodies, which also recognize mannans from C. albicans cell walls, are frequently detected in the serum of Crohn's disease patients, pointing to a fungal immune signature that clinicians can potentially measure.

One clinically striking finding: high pre-treatment Candida abundance in IBD patients correlated with a positive response to fecal microbiota transplantation. That association suggests the gut's fungal composition could one day help predict which patients will benefit from microbiome-based therapies before they undergo the procedure.

C. tropicalis links Candida to colorectal cancer and liver disease

Beyond IBD, the review maps Candida associations across two further disease areas. In colorectal carcinoma, where IBD patients already carry a two-to-three-fold elevated risk due to chronic inflammation, C. tropicalis is elevated while C. albicans is relatively decreased. CARD9-deficient mice in experimental models showed increased susceptibility to chemically induced tumors and a higher tumor burden, an effect linked specifically to C. tropicalis elevation. The authors are careful to frame this as associative rather than causal, but the convergence across genetic, animal, and human data is worth watching.

In primary sclerosing cholangitis, a serious inflammatory liver and bile-duct condition, biliary samples from patients contain C. albicans, C. glabrata, and C. tropicalis. The presence of biliary Candida species correlates with elevated C-reactive protein and reduced transplantation-free survival, and the review notes an association with increased frequency of bile duct cancer in this population.

Irritable bowel syndrome and the strain-level detail that sequencing misses

Irritable bowel syndrome adds a subtler dimension to the Candida story. Candida species appear more abundant in fecal samples from IBS patients compared to healthy controls. More intriguingly, culture-dependent analysis of C. albicans isolates from IBS patients revealed clonal expansion within individual patients and enhanced virulence traits, including an increased tendency toward hyphal formation. Hyphae are the filamentous structures that help Candida invade tissue, so their enrichment in IBS strains is biologically meaningful even if causality remains unproven.

That finding also points to a methodological gap that runs through the entire review. Standard metabarcoding approaches, the DNA-sequencing techniques that dominate microbiome research, classify fungi at the species level at best. They mask the sub-species strain variation that culture-based work can detect. A gut sample might read as uniformly C. albicans while actually harboring strains with dramatically different virulence profiles. Candida species that appear commensal in sequencing data may behave very differently depending on the specific strain and the host's immune state.

Why studying gut fungi is still technically hard

The review closes with a frank accounting of the field's limitations. Reference databases for fungal sequences remain incomplete, restricting species-level classification. Sequencing protocols vary across labs in ways that make studies difficult to compare. Culture-based techniques miss hard-to-grow fungi. Murine models used to study host-fungal interactions often lack fungi in the intestine to begin with, which limits how closely they can model human pathophysiology.

Perhaps most fundamentally, the studies reviewed are almost entirely associative. They show that Candida abundance correlates with disease states; they rarely establish that Candida causes those states. Disentangling cause from consequence, and commensalism from pathogenesis, will require longitudinal studies with strain-level resolution and functional readouts that current metabarcoding cannot provide.

The 1% of your microbiome that is fungal, it turns out, may be one of the harder fractions to actually understand.

Evidence rating

EMERGING — 80/100

Caveats:

• This is a narrative review — it synthesizes existing studies rather than generating new experimental data, so its conclusions are only as strong as the underlying literature.
• Most cited studies are observational or associative; the review explicitly notes that causality has rarely been established in human contexts.
• Methodological inconsistencies across studies (varying sequencing protocols, incomplete fungal reference databases, culture bias) limit direct comparisons.
• Funding for this review was not disclosed by the authors.

Narrative review synthesizing observational and experimental studies on intestinal Candida spp. across multiple disease contexts. The majority of cited human evidence is associative, and the authors explicitly acknowledge that causal relationships have rarely been established. Methodological heterogeneity across included studies — including variable sequencing approaches and incomplete fungal reference databases — limits the strength of cross-study comparisons.

References

1. Irini A. M. Kreulen, Wouter J. de Jonge, René M. van den Wijngaard, Isabelle A. M. van Thiel (2023). Candida spp. in Human Intestinal Health and Disease: More than a Gut Feeling. Mycopathologia. https://doi.org/10.1007/s11046-023-00743-z
2. J. Christian Pérez (2021). The interplay between gut bacteria and the yeast Candida albicans. Gut Microbes. https://doi.org/10.1080/19490976.2021.1979877
3. Jieyu Song, Xianglan Yang, Xiaoyu Liu, Jun Li (2025). Gut bacteria: protective mediators, pathogenic contributors and novel therapeutic targets in Candida albicans infections. Gut Pathogens. https://doi.org/10.1186/s13099-025-00755-8
4. Benoît Marsaux, Frédéric Moens, Gies Vandevijver, Massimo Marzorati, Tom van de Wiele (2024). Candida species-specific colonization in the healthy and impaired human gastrointestinal tract as simulated using the Mucosal Ileum-SHIME® model. FEMS Microbiology Ecology. https://doi.org/10.1093/femsec/fiae113