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In vitro inhibitory assessment of Lactobacillus spp. supernatant on the growth of Candida glabrata and Cryptococcus neoformans yeasts.

This study demonstrates that cell-free supernatants from *Lactobacillus* spp., particularly *L. reuteri*, effectively inhibit the growth of pathogenic yeasts *Candida glabrata* and *Cryptococcus neoformans* through organic acid production, suggesting their potential as safe and cost-effective adjuncts to conventional antifungal therapies.

Original authors: Caroline Araujo, Thalita Noemi Gomes da Silva, Fabiana Brandão

Published 2026-10-28
📖 5 min read🧠 Deep dive

Original authors: Caroline Araujo, Thalita Noemi Gomes da Silva, Fabiana Brandão

Original paper licensed under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). ⚕️ This is an AI-generated explanation of a preprint that has not been peer-reviewed. It is not medical advice. Do not make health decisions based on this content. Read full disclaimer

In the quiet corners of the human body, a constant, invisible struggle takes place between beneficial bacteria and harmful fungi. For decades, scientists have known that certain bacteria, specifically those in the Lactobacillus family, act as guardians. These microbes, often found in the gut and other parts of the body, produce a cocktail of natural chemicals as they eat and grow. When these bacteria are removed from their environment, the liquid they leave behind—known as cell-free supernatant—is rich with these bioactive compounds. Think of this liquid as the chemical exhaust of a factory that happens to be very good at keeping intruders at bay. Meanwhile, two types of yeast, Candida glabrata and Cryptococcus neoformans, represent a growing threat to human health. These fungi can cause severe infections, particularly in people with weakened immune systems, and they are becoming increasingly difficult to kill with standard medicines. The challenge for modern medicine is finding new ways to stop these resilient invaders without relying on drugs that can be toxic or that the fungi have learned to ignore.

A team of researchers at the University of Brasília set out to test a simple but powerful idea: could the liquid left behind by these helpful bacteria stop the growth of these dangerous yeasts? They did not use the bacteria themselves, but rather the sterile liquid they produced, which contains the metabolic byproducts of fermentation. The team focused on three specific strains of Lactobacillus: L. casei, L. reuteri, and L. rhamnosus. They grew these bacteria in a nutrient-rich broth for two days, then spun the mixture in a centrifuge to separate the liquid from the bacterial cells. This clear liquid, now free of any living bacteria, was then tested against the two types of yeast in a laboratory setting. The researchers wanted to see if this liquid could slow down or stop the yeasts from multiplying, and they wanted to understand how different food sources for the yeast might change the outcome.

The results revealed that the liquid from these bacteria is indeed a potent inhibitor, but its effectiveness depends heavily on the environment. When the researchers placed the yeast in a standard, nutrient-rich liquid often used to grow fungi, the bacterial liquid sometimes failed to stop them, and in a few cases, it even seemed to help the yeast grow. This happened because the rich food source allowed the yeast to overcome the chemical barriers. However, when the experiment was moved to a simpler, more defined environment that mimics the conditions inside the human body, the story changed completely. In these settings, the liquid from the bacteria consistently slowed the growth of both C. glabrata and C. neoformans.

Among the three bacterial strains tested, the liquid from L. reuteri proved to be the most powerful. It was the only strain that managed to inhibit the growth of the yeasts even in the rich, difficult-to-control environments. The liquid from L. reuteri reduced the growth of C. glabrata by nearly 45 percent in one type of rich medium and by over 33 percent in another. For the other two bacterial strains, L. casei and L. rhamnosus, the results were more mixed in rich environments, but they still showed strong inhibitory effects in the simpler, body-like environments. In these controlled settings, the liquid from all three bacteria reduced the growth of the yeasts significantly, with the most concentrated liquid showing the strongest effect. The researchers also measured the acidity of the bacterial liquid and found that it had become quite acidic, dropping from a neutral level to a pH of around 4.0. This drop in pH, caused by the production of organic acids like lactic acid, is a key part of how the bacteria create an environment that is hostile to the yeast.

The study also looked at a specific chemical compound called sodium butyrate, which is produced by some gut bacteria and is known for its anti-inflammatory properties. The researchers tested this compound on its own to see if it contributed to the antifungal effects. They found that sodium butyrate did reduce the growth of the yeasts, but its behavior was complex. In a rich sugar-based liquid, it effectively stopped the growth of both yeast types. However, in a different, protein-rich liquid, it actually encouraged the growth of C. glabrata. This suggests that the chemical environment plays a critical role in how these substances work. For Cryptococcus neoformans, sodium butyrate was effective in both environments, though it was more potent in the sugar-rich liquid.

The researchers concluded that the liquid from Lactobacillus bacteria contains a mix of natural chemicals that can effectively suppress dangerous yeasts, but this power is not absolute; it is shaped by the nutritional landscape in which the yeast lives. The study highlights that while these bacterial byproducts are promising, their success depends on the specific conditions of the infection site. The liquid from L. reuteri stood out as the most reliable agent, capable of working across different environments. The findings suggest that these bacterial metabolites could serve as a valuable addition to current treatments, offering a way to fight resistant fungi with substances that are naturally produced by the body's own beneficial microbes. The research does not claim to have solved the problem of fungal resistance, but it provides a clear, measured demonstration that these natural compounds have the potential to be part of a new strategy for keeping these dangerous infections in check.

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