When an imbalance occurs in the gut microbiome, due to antibiotics or other environmental influences, individual microbial species can spread and lead to infection. Fungi of the Candida genus, for example, are present in the intestines of many healthy people. They are usually harmless but can also cause dangerous systemic infections.

New research shows that the bacteria present in the intestine provide information about the quantities of fungi, specifically of the Candida genus. Among them, surprisingly, are lactic acid bacteria that are known for their protective effect against fungal infections.

This work is published in Nature Communications in the paper, “Candida expansion in the gut of lung cancer patients associates with an ecological signature that supports growth under dysbiotic conditions.”

Researchers integrated cross-sectional mycobiome and shotgun metagenomics data from stool samples taken from 75 cancer patients who were at risk but without systemic candidiasis. They found that certain bacterial species always appear in greater numbers when the amount of fungi from the Candida genus is also high. “With these data, we developed a computer model that was able to predict the amount of Candida in another group of patients with an accuracy of about 80% based on bacterial species and amounts alone,” explained Bastian Seelbinder, a researcher at Microbiome Dynamics, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Jena, Germany.

What surprised the researchers was not only how successful the prediction of the amount of fungi based on the bacterial species present was, but also which bacteria correlated with high amounts of fungi. “We found an increased number of bacterial species that produce lactic acid, including Lactobacillus species,” Seelbinder explained. “I could hardly believe it at first, so I checked several times, always with the same result.”

The reason for his surprise: Several studies have attested to the protective effect of lactic acid bacteria against fungal infections.

The researchers’ hypothesis is that lactic acid bacteria, particularly of the genus Lactobacillus, favor Candida proliferation but at the same time make the fungus less virulent. This could be due to the fact that Candida species can switch their metabolism to be able to use the lactate produced by lactic acid bacteria. The researchers found that this gives them a competitive advantage over other fungi such as Saccharomyces cerevisiae. However, the metabolic switch also causes Candida to remain in its (usually harmless) spherical yeast form instead of forming fungal hyphae that could invade the intestinal mucosa.

In the paper, they 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, they write, “the ability of Candida to harness lactate as a nutrient source may enable Candida to outcompete other fungi in the gut.”

“There is also a suggestion that certain groups of Lactobacillus species might have different effects,” Seelbinder said. To investigate this, the next step will be to perform more detailed genomic analyses of the bacteria. In addition, the researchers want to investigate samples from healthy subjects to develop long-term strategies for at-risk patients based on their microbiome, rather than stool samples from cancer patients who are particularly at risk for fungal infections.

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