The Science Behind Probiotics and Antifungals: Delving Deep into Mechanisms and Synergy

Probiotics are living organisms that provide health benefits when consumed. They function to support a healthy microbiota in the gut which can benefit health overall. Antifungals on the other hand, are medicines that treat fungal infections. Whether it be in humans, animals, or crops, they generally target the cell membrane of fungi and kill them or stop them from colonizing. Due to growing resistance to common antifungals, and how helpful probiotics can be, there is new interest in how they may work together. Probiotics as adjunct therapy could be very beneficial in healthcare in regard to growing resistance and increasing healthcare costs.

Understanding Probiotics: The Basics

Definition and Types

A probiotic is a microorganism that contains one or more beneficial qualities when introduced to the body. If consumed in the correct quantity, there are a multitude of health benefits that come from probiotics. Some of the most common types are Lactobacillus, Bifidobacterium, Saccharomyces boulardii, Streptococcus thermophilus, and Escherichia coli Nissle 1917.

Lactobacillus is the most common probiotic strain. It is generally found in fermented foods. Bifidobacterium is found naturally in the gut and is crucial in maintaining gut health. Saccharomyces boulardii is a type of probiotic called a yeast probiotic. It is different because it is a yeast, not a bacteria. It is used for the treatment of diarrhea that is a result of GI infections or antibiotic usage. Streptococcus thermophilus is used in making yogurt and fermented dairy. E. coli Nissle 1917 is a nonpathogenic strain of E. coli. It could have benefits in regard to digestive disorders.

The Role and Mechanism of Action of Probiotics in the Gut

Probiotics are extremely helpful for maintaining gut health and a balanced microbiota. These “good” bacteria compete with “bad” bacteria for space and nutrients in the gut. The greater the amount of good bacteria an individual has, the less space there is for bad bacteria to gain footing and thus colonize and take over the gut. These beneficial microorganisms produce antimicrobial substances, vitamins, and short-chain fatty acids, all of which make the gut a place for good bacteria to thrive and not supportive of bad bacteria. They also can help to balance the immune response. A balanced immune system helps the body fight off invaders well. Probiotics are inflammation-lowering substances and can prevent intense immune responses that are harmful to the gut microbiota.

When a person’s intestinal barrier is weak, they have a greater likelihood of having gut-associated problems. This is because a weak gut lining allows harmful substances and even pathogens from the colon to reach the bloodstream. Probiotics can strengthen the gut lining, thus reducing the risk of these issues. Often after antibiotic use, the gut environment is imbalanced. Probiotics can help to restore the natural balance by adding in beneficial bacteria.

Some probiotic strains like Lactobacillus rhamnosus GG, Lactobacillus acidophilus, Bifidobacterium breve, and Saccharomyces boulardii are remarkably antifungal in nature. For example, Lactobacillus acidophilus causes the gut to be more acidic, which does not allow fungi like Candida to grow.

Antifungals: More than Just Killing Fungi

What are Antifungals?

Antifungals on the other hand are either a substance or treatment that destroys fungi, or at least inhibits fungi/fungal infections. In addition to treating fungal infections in humans and animals, they may also be used for crop protection and preservation of food. The most common types of antifungal medicines are azoles, polyenes, echinocandins, and flucytosine.

Azoles, commonly recognized as ketoconazole or fluconazole, are used to combat fungal infections such as oral thrush, vaginal yeast infections, and systemic infections. Polyenes, like nystatin, are used for more severe fungal infections. Echinocandins are used for aspergillosis and invasive candidiasis. These are commonly recognized as medications such as caspofungin and anidulafungin. Flucytosine is used for severe systemic infections and generally in combination with other drugs.

Mechanisms of Action

Antifungals ultimately are seeking a way to exact cell death within the cells of fungi. They have to find a way to break down the cell wall or a way into the cell itself and disrupt the functions it takes for a cell to survive. Polyenes and azoles are examples of antifungals that seek to destroy the cell wall. Either by making holes in the membrane so that essential components escape, or by disrupting the synthesis of ergosterol, the actual structure of the cell is threatened and should lead to cell death. Ergosterol works within fungal cells to reinforce the cell wall, and without adequate amounts, the cell will fall to antifungals.

Echinocandins work by seeking out beta-glucan and interfering with its production. This causes the cell to be more at risk of stress and rupture because of the weakened cell wall that results from decreased beta-glucans. Flucytosine works against the production of fungal DNA and RNA which causes the fungus to not be able to reproduce and colonize.

Side Effects and Resistance

Side effects of antifungal usage can vary from person to person, based on dosage, specific drug used, treatment duration, and an individual’s overall health. However, there are common side effects a person may experience. GI symptoms including abdominal pain, nausea, vomiting, and diarrhea are common. In addition, individuals may experience headaches, itching or rashes, and altered taste. When taking azoles, preexisting liver conditions should be considered, because these can affect liver function. Individuals may experience hypertension or hormone disruption when taking some antifungals, namely Ketoconazole. Some antifungals can even cause sensitivity to the sun. Rarely, people can be allergic to antifungals and may have swelling, hives, or difficulty breathing. This would warrant immediate medical attention. Consult your physician if you experience any of these side effects, particularly if they are severe.

Due to overuse or misuse of antifungals, insufficient dosing or treatment duration, not being specific enough, and minimal new antifungals being developed, there is some concern for antifungal resistance. This is bad news for humans, animals, and crops alike. Antifungal resistance is where for one reason or another, antifungals are unable to carry out their mechanism of action against fungi and less effective in its eradication. Overuse, inadequate dosing, inadequate treatment duration, and broad-spectrum antifungal use have led to favoring the survival of drug-resistant strains of fungi. In nature, antifungals may be encountered in agricultural runoff, causing spores to develop naturally occurring resistance from the exposure. It is possible for some fungi to develop a biofilm, which is protective of the cell wall.

It is important for those prescribing antifungals to be specific to the type of infection and for individuals to follow the treatment plan. Individuals should immediately inform their care provider if they are not improving during treatment duration. Resistance can cause treatment to fail, increased disease burden and mortality, more medical care, longer hospital stays, and limited options for treatment. Healthcare costs can also be increased. The possibility of global spread can also be difficult to control.

The Synergy Between Probiotics and Antifungals

Probiotics Enhancing Antifungal Efficacy

Fortunately, there is a way to enhance antifungal effectiveness. As discussed above, probiotics support gut health. Antifungals may cause the gut microbiota to become imbalanced, but when used with probiotics this is less severe. In a 2022 study of probiotics and vaginal candida infections, it was shown that probiotics increased the effectiveness of the antifungals used. A study from the Frontiers in Cellular and Infection Microbiology suggests probiotics have an antifungal effect and could have an enormous impact on the efficacy of antifungal treatments.

Probiotics Mitigating Side Effects of Antifungals

Unfortunately, antifungals target both good bacteria and harmful fungi. Probiotics can help to restore this balance. Using probiotics in conjunction with antifungals can lower the risk of antifungal gastrointestinal side effects. Probiotic, “good” bacteria can lower gastrointestinal side effects by competing with and crowding out fungi that would cause GI side effects. Gut motility can also be influenced by probiotics. This can help with easier digestion of food and reduce the risk of constipation or diarrhea that may come from antifungals. Probiotics are also protective of the gut lining in that they reduce oxidative stress caused by antifungals.

Mechanisms Behind the Synergy

Probiotics enhance immune function which helps fight off fungal infections and works together with the action of antifungals. When the gut is disturbed by antifungal medication, individuals may contract infections like Clostridium difficile. This is especially a risk when antifungals are taken alongside antibiotics. Probiotics can reduce this risk. Probiotics aid the body’s “surveillance system” in that they help the body respond to invaders. Some emit short-chain fatty acids which are antimicrobial in nature. This creates an environment that is uninviting to fungi. Probiotics balance the immune response, which is crucial for fighting off fungal infections. They may help support mucosal defenses in areas that are more likely to acquire a fungal infection, like vaginal and oral mucosa. Maintaining balance in these microbiota reduces the risk of overgrowth. All in all, it appears probiotics help to make an environment supportive of antifungal medications working effectively.

Finding a high-quality, effective probiotic is key to promoting the effectiveness of antifungals and mitigating the side effects. To decide whether a supplement is high-quality or not, three things to look for are the GMP seal (good manufacturing practices), third-party testing, and transparency of ingredients. Fortunately, CanXida checks all these boxes, and the products would be a great addition to an antifungal regimen.  CanXida’s Restore capsules are a blend of enzymes and probiotics that help to restore gut health. CanXida’s Remove capsules are designed to target and reduce fungi in the body and eliminate overgrowth. Taking Restore and Remove in conjunction with one another will yield the best results. For more detailed information on these, see their linked product guides.