Fungal Levels Spike 461,000-to-1 Below Bacteria, Yet Surge During UC Flares

Fungi make up a vanishingly small fraction of the gut microbiome: roughly one fungal gene copy for every 461,000 bacterial ones, according to a new prospective study published in Gut Pathogens. Yet despite that numerical insignificance, fungal abundance was markedly and significantly higher when ulcerative colitis patients were in active flare than when they were in long remission, pointing to a relationship between the gut mycobiome and disease activity that researchers are only beginning to map.

Fungal Load Rises Sharply During Active UC Flares

Herrera-deGuise and colleagues recruited 87 adults with ulcerative colitis and sorted them into three groups: 29 in long remission (UClr), 20 in short remission (UCsr), and 38 with active flare (UCfl). Using ITS2 amplification to target fungal DNA and 16S rRNA sequencing to target bacteria, the team performed absolute quantification of both kingdoms from fecal samples rather than simply reporting relative proportions.

The numbers are striking in their contrast. Median fungal abundance across all patients was 9.27 x 10^5 ITS2 gene copies per gram of stool. Median bacterial abundance was 4.28 x 10^11 copies per gram. That is a ratio of roughly 1:461,000. Even so, fungal abundance in the active-flare group was significantly higher than in the long-remission group (p = 0.0026), and the ITS2-to-16S ratio was elevated in flare patients compared to both remission groups (p < 0.01). Bacterial loads, by contrast, remained stable across all three disease states.

This asymmetry matters. It suggests that inflammation in UC does not simply disrupt all microbial residents equally; it appears to preferentially disturb the fungal compartment. Prior research has found that stool Candida increases during UC inflammation compared to remission, and that Candida albicans and Malassezia restricta are more prevalent during disease exacerbation than during quiescent periods. The current study adds a quantitative dimension: it is not merely species composition that shifts, but the total fungal burden.

Why the Mycobiome's Instability Could Matter for IBD Patients

For the roughly 5 million people worldwide living with inflammatory bowel disease, the gut microbiome is already central to clinical thinking. Bacterial dysbiosis is well-established in UC. The fungal microbiome, or mycobiome, has received far less attention, partly because fungi are numerically rare and methodologically harder to study.

What makes the Gut Pathogens findings clinically interesting is the suggestion of an altered inter-kingdom relationship during flares. When fungal abundance rises relative to bacteria during active inflammation, the ecological balance between these two kingdoms shifts. Whether fungi are responding to the inflamed environment, contributing to it, or both remains an open question. But the pattern is consistent enough across the study's patient groups to warrant serious attention.

The team also found that fungal abundance showed greater variability over time than bacterial abundance. In the remission groups, where two fecal samples were collected eight weeks apart, a modest but statistically significant decrease in the ITS2/16S ratio was observed at the second time point (p = 0.029). Bacterial loads did not shift comparably. This temporal instability suggests the mycobiome may be more sensitive to transient environmental signals, whether from diet, stress, or subclinical mucosal changes, than the bacterial compartment.

How Absolute Quantification Sharpens the Picture

Most microbiome studies report relative abundance: what percentage of detected sequences belong to a given taxon. That approach can mislead when the total microbial load itself changes. If fungi increase during flare while bacteria stay flat, a relative-abundance approach might detect the shift; if both changed in different directions, it could obscure or exaggerate the signal.

By amplifying both ITS2 (fungi) and 16S rRNA (bacteria) and expressing results as gene copies per gram of stool, Herrera-deGuise and colleagues anchored their comparisons to actual quantities. The design was prospective, and patients were categorized by validated disease-activity criteria. The UCfl group provided one sample at flare onset; the remission groups provided paired samples eight weeks apart, enabling assessment of short-term microbial stability within each disease state.

The 87-patient cohort is modest, and the study does not resolve which fungal species are driving the abundance increase, nor does it establish causality. A broader systematic review of mycobiome studies in IBD has already flagged heterogeneous methods and inconsistent results across the field, underscoring the need for standardized protocols from sample collection through data processing. This study's use of absolute quantification is a step toward that standardization, but replication in larger cohorts will be needed before firm clinical conclusions can follow.

Open Questions About Inter-Kingdom Dynamics in UC

The study frames its findings as preliminary evidence of an altered inter-kingdom relationship, the ecological interplay between bacteria and fungi, during UC inflammation. That framing is appropriately cautious. Fungi interact with bacteria through competition, metabolite exchange, and immune signaling, and dysregulation of those interactions could influence mucosal inflammation in ways that neither kingdom alone would predict.

What the data cannot yet tell us is whether elevated fungal load is a cause of flares, a consequence of the inflamed environment, or simply a correlated marker. The single time-point design for the flare group limits longitudinal interpretation. It is also unclear whether antifungal interventions, dietary changes, or restoration of the bacterial community would normalize fungal abundance and, if so, whether that normalization would track with clinical improvement.

Mycobiome Research Points Toward Precision Microbiome Therapies

The broader significance of this work lies in what it implies for treatment design. Efforts to develop microbiome-based therapies for ulcerative colitis, including fecal microbiota transplantation and defined microbial consortia, have focused almost entirely on the bacterial compartment. If the mycobiome is an active participant in UC disease activity rather than a passive bystander, next-generation interventions may need to account for it.

For now, the Gut Pathogens study adds a carefully measured data point to a field that has lacked them. Fungi may constitute 1 in 461,000 of the gut's microbial gene copies, but their behavior during ulcerative colitis flares suggests the ratio is not the whole story.

Evidence rating

EMERGING — 76/100

Caveats:

• Observational design: shows association between fungal abundance and UC flare, not causation — it is unclear whether elevated fungi contribute to flares or simply reflect intestinal inflammation.
• Modest sample size (n=87 across three groups); findings need replication in larger, independent cohorts before clinical conclusions can be drawn.
• Funding source was not disclosed in the published study.

Prospective observational study (n=87) comparing absolute fungal and bacterial abundance across three UC disease-activity states using ITS2 and 16S rRNA quantification. The study demonstrates an association between elevated fungal load and active disease but cannot establish causation, and the cross-sectional flare group (single sample) limits temporal interpretation. Findings have not yet been independently replicated.

References

1. Claudia Herrera-deGuise, Encarna Varela, Guillaume Sarrabayrouse, et al. (2026). Fungal abundance across flare and remission in ulcerative colitis patients. Gut Pathogens. https://doi.org/10.1186/s13099-026-00846-0
2. Sushrut Jangi, Katie Hsia, Naisi Zhao, et al. (2024). Dynamics of the Gut Mycobiome in Patients With Ulcerative Colitis. Clinical Gastroenterology and Hepatology. https://doi.org/10.1016/j.cgh.2023.09.023
3. Gabriela Świrkosz, Aleksandra Szczygieł, Katarzyna Logoń, Martyna Wrześniewska, Krzysztof Gomułka (2023). The Role of the Microbiome in the Pathogenesis and Treatment of Ulcerative Colitis—A Literature Review. Biomedicines. https://doi.org/10.3390/biomedicines11123144
4. Johannes D Füchtbauer, Olga Brovkina, Kostas Sivickis, et al. (2025). Gut Mycobiome in Inflammatory Bowel Disease: A Systematic Review of Case-Control Studies. Inflammatory Bowel Diseases. https://doi.org/10.1093/ibd/izaf217
5. Philippe Pinton (2026). Microbiome-Based Therapies in Ulcerative Colitis: Mechanisms, Clinical Evidence, and a Precision-Medicine Framework. Biomedicines. https://doi.org/10.3390/biomedicines14050969