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Candida albicans is one of the fungi found in the microbiomes that exist all over the hu- man body, coexisting alongside other fungi, bacteria and viruses. Diversity and balance are the hallmarks of a healthy microbiome, which enables it to keep any opportunistic species in check, but when either of these qualities is lost, Candida, and in particular, Candida albicans, can start to overgrow and cause a wide range of symptoms. These can include digestive issues, fungal skin infections, vaginal infections, brain fog, mood swings, sugar cravings, seasonal allergies, fatigue, sinus disruption and eventually more serious problems such as fibromyalgia, autoimmune disease and chronic fatigue syn- drome.

One of the reasons for such a wide range of symptoms is that the breakdown products of Candida can compromise many of our enzyme and detox pathways by blocking or over- whelming them. Another is that a chronic Candida overgrowth will create roots called hy- phae to anchor it in the body and to increase its ability to find food. These hyphae active- ly invade tissues, including the intestinal lining, causing them to become permeable, or ‘leaky’ so that endotoxins from the intestinal lumen (such as lipopolysaccharides or LPS) start directly entering the circulation. This metabolic endotoxemia triggers innate immune responses that result in systemic sub-clinical, low-grade inflammation and numerous symptoms.

This article considers the evidence for some novel natural therapies to approach a Candi- da problem as an alternative to the 5Rs or the use of harsh anti-fungals.

Using certain probiotics to restore gut integrity & microbiome diversity

MegaSporeBiotic, which consists of 5 Bacillus spores, was shown in a 2017 double-blind placebo-based published study to drastically reduce metabolic endotoxemia (by 60% compared to placebo) in just 30 days by shifting users to a more protective microbiome. This also lead to significant reductions in many systemic inflammatory markers: IL-6, IL-8, MCP-1, IL-1B and IL-12. This suggests that these spores have the ability to rebalance and re-diversify the microbiome and to restore the gut lining’s integrity. In one study, where the spores were used in conjunction with prebiotics, there was a clear increase in the Simpson reciprocal index, a scientific measure of healthy microbial diversity. One of the reasons spores are so effective are that they naturally survive the harsh gastric pas- sage and enter the intestines completely viable, unlike most other probiotic strains. Bacillus spores used in combination with the probiotic yeast strain, Saccharomyces boul- ardii, can be even more effective where there is a Candida overgrowth. By competing for space with Candida, S. boulardii can reduce pathogenic fungal overgrowths, such as Candida and in a mouse model of colitis, S. boulardii was able to decrease both inflam- mation and Candida albicans colonisation of the intestine. Another study showed it to re- duce the translocation of C. albicans from the intestinal tract into the lymphatic tissues. Furthermore, a prospective study of 181 infants found that prophylactic S. boulardii sup- plementation was just as effective as Nystatin in reducing fungal colonisation and invas- ive fungal infections. Spores can be applied orally or vaginally, by inserting the capsule intact or by opening it and using the spores directly on any infected areas.

Natural anti-candida compounds: Bee Propolis and Undecylenic Acid

The best compounds to use against a Candida overgrowth need to be able to control its replication, reduce the formation of hyphae and disrupt the biofilms it creates, without causing any further imbalances or harm to the host. Two natural products worth consid- ering are bee propolis and undecylenic acid.

Bee propolis is the resinous material used to line the inside of beehives. This substance is able to successfully protect each honey-filled hive from fungal, bacterial and viral infec- tion in a wide range of temperature and humidity levels. A study in the Journal of Medi- cinal Food found that bee propolis inhibits the growth of Candida albicans, Candida glab- rata, and Candida krusie in vitro, with its anti-fungal activity attributed to lysozyme, phen- olic acids, and flavonoids. Another in vitro study, published in the Journal of Medical My- cology, found that propolis, in adequate concentration, has the ability to break down Candida biofilms.

A human study published in Phytotherapy Research, found that oral candidiasis patients who applied an ethanol propolis extract to the oral cavity for 7 days experienced lesion

remission comparable to those patients receiving conventional Nystatin treatments. It appears that propolis is able to fight foreign infections without recruiting the immune sys- tem, which not only spares energy, but also prevents macrophagic, inflammatory reactions that can cause irritation and pain.

Undecylenic acid is a monounsaturated fatty acid with documented anti-fungal proper- ties. One study demonstrated that the greater the number of carbon atoms in an unsatur- ated fatty acid chain, the greater the fungicidal activity. With eleven carbons, undecylenic acid is long, and has been shown to be approximately six times more effective as an anti- fungal than caprylic acid.

Its topical use is safe even on the most sensitive places, such as skin, mouth, and vaginal cavities. In fact, a multi-centre, placebo-controlled study found that applying a 15% un- decylenic acid cream to vaginal areas affected by herpes labialis significantly reduced the incidence and duration of viral shedding with no adverse effects. Similarly, another study published in the Journal of Pharmacology and Therapeutics found undecylenic acid to be highly effective in treating fungal Tinea pedis, or athletes’ foot.

Interestingly, a 2016 study in the International Journal of Clinical Pharmacology high- lighted its most promising quality; the ability to inhibit the switch from yeast to hyphae in Candida yeasts, and even abolish it at high enough concentrations, by down-regulating hyphae formation genes such as HWP1. This leads to “a poorly organised biofilm in un- decylenic acid treated environments”. (McLain et al., 2000) This quality is well known in the management of denture biofilms where undecylenic acid is widely used. Undecylenic acid has also been shown to control fungal overgrowths in the gut and is nontoxic to hu- man cells.

Conclusion

Natural treatments are becoming more important as fungi, including Candida albicans, are becoming increasingly resistant to anti-fungal drugs. Whilst propolis and undecylenic acid are useful in tackling Candida overgrowths in themselves, they become much more effective when used in conjunction with probiotic strains, such as Bacillus spores and Saccromyces

boulardii. These manage the Candida by supporting and rebalancing the whole microbio- me, and reduce metabolic endotoxemia, the underlying cause of many of the symptoms.

This multi pronged approach targets the Candida from every angle, affecting its reproduc- tion, hyphae growth, biofilm formation, whilst also correcting the imbalance and lack of di- versity within the microbiome that allowed for the overgrowth in the first place, which then helps to prevent any reoccurrence.

References

Berg, R. et al. (1993) Inhibition of Candida albicans Translocation from the Gastrointestinal Tract of Mice by Oral Ad- ministration of Saccharomyces boulardii. Journal of Infectious Diseases. [Online] 168 (5), 1314-1318.

Chretien, J. et al. (1980) Efficacy of Undecylenic Acid–Zinc Undecylenate Powder in Culture Positive Tinea Pedis. In- ternational Journal of Dermatology. [Online] 19 (1), 51-54.

Demirel, G. et al. (2013) Prophylactic Saccharomyces boulardii versus nystatin for the prevention of fungal coloniza- tion and invasive fungal infection in premature infants. European Journal of Pediatrics. [Online] 172 (10), 1321-1326.

Duysburgh, C. et al. (2019) A synbiotic concept containing spore-forming Bacillus strains and a prebiotic fiber blend consistently enhanced metabolic activity by modulation of the gut microbiome in vitro. International Journal of Phar- maceutics: X. [Online] 100021.

Freires, I. et al. (2016) Chemical composition and antifungal potential of Brazilian propolis against Candida spp. Journ- al de Mycologie Médicale. [Online] 26 (2), 122-132.

Gu, M. et al. (2014) Bacillus subtilis Protects Porcine Intestinal Barrier from Deoxynivalenol via Improved Zonula Oc- cludens-1 Expression. Asian-Australasian Journal of Animal Sciences. [Online] 27 (4), 580-586.

Hong, H. et al. (2005) The use of bacterial spore formers as probiotics. FEMS Microbiology Reviews. [Online] 29 (4), 813-835.

Jawhara, S. & Poulain, D. (2007) Saccharomyces boulardii decreases inflammation and intestinal colonization by Can- dida albicans in a mouse model of chemically-induced colitis. Medical Mycology. [Online] 45 (8), 691-700.

Koç, A. et al. (2011) Antifungal Activity of the Honeybee Products Against Candida spp. and Trichosporon spp. Journal of Medicinal Food. [Online] 14 (1-2), 128-134.

McFarlin, B. et al. (2017) Oral spore-based probiotic supplementation was associated with reduced incidence of post- prandial dietary endotoxin, triglycerides, and disease risk biomarkers. World Journal of Gastrointestinal Patho- physiology. [Online] 8 (3), 117.

McLain, N. et al. (2000) Undecylenic Acid Inhibits Morphogenesis of Candida albicans. Antimicrobial Agents and Chemotherapy. [Online] 44 (10), 2873-2875.

Santos, V. et al. (2005) Oral candidiasis treatment with Brazilian ethanol propolis extract. Phytotherapy Research. [On- line] 19 (7), 652-654.

Sardana, D. et al. (2013) Role of propolis in dentistry: review of the literature. Focus on Alternative and Complement- ary Therapies. [Online] 18 (3), 118-125.

Shafran, S. et al. (1990) Topical 15% undercylenic acid (UDA) cream vs placebo (PLB): A Canadian, randomized, mul- ticenter, patient-initiated (PI) trial in patients with recurrent oral-labial (OL) herpes simplex virus (HSV) infections. Antiviral Research. [Online] 13102.

Shi, D. et al. (2016) Antifungal effects of undecylenic acid on the biofilm formation of Candida albicans. Int. Journal of Clinical Pharmacology and Therapeutics. [Online] 54 (05), 343-353.

Tomičić, Z. et al. (2016) Probiotic yeast Saccharomyces boulardii (nom. nud.) modulates adhesive properties of Can- dida glabrata. Medical Mycology. [Online] 54 (8), 835-845.

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