Microbiome and Candida

Posted: May 2023

Author: Katie Donnelly, Adv Dip HSc Naturopathy

Microbiome and Candida

Candida albicans (candida) is a well-known commensal fungi that exists symbiotically within the microbiome. It is predominantly prevalent in the oropharynx, gastrointestinal tract, and urogenital tract, in approximately 70% of healthy individuals.¹ Candida replication and cellular invasion is typically associated with microbiome change, compromised immunity, and altered environmental pH. It enables opportunistic polymorphism and the development of pseudo-hyphae, hyphae, and biofilms.

Candia presents a growing anti-fungal resistance against current pharmaceutical treatments, phytomedicine offers an effective approach to managing acute and chronic candida balance.²

The mIcrobiome influence

As a eukaryotic organism, candida prevalence is largely regulated by bacteria. The peptide secretion from beneficial bacteria and toxins within the gastrointestinal system, then further prevent hyphae filaments from developing and subsequent biofilm formation.³ Similarly, lactic acid and peroxide released by vaginal bacteria maintain a low pH. This then creates an inhospitable environment for candida. When microbial variation becomes reduced, candida morphology is further enabled.

Hyphal growth prompts the production of hydrolytic enzymes, damaging human cellular membranes. The presence of adhesive factors including hyphal wall protein 1 (HWP1) and agglutinin-like sequence (ALS) proteins, enable binding. Therefore, increasing the chance of candida development.⁴

A potent anti-inflammatory and antioxidant, Curcuma longa (turmeric) constituent curcumin, has shown to inhibit and break down candida biofilm formation. This action has primarily been noted in relation to adhesion prevention, acting to reduce ALS-3 and HWP1. Further studies on curcumin displayed reduced gene expression that enables morphology and reduce enzyme releases. These actions typically are used to break down host cells and damage tissues. This phytochemical has also been successfully used in combination with fluconazole to reduce hyphae development and biofilm formation, in strains identified as resistant to the antifungal treatment. Host cells also became less permeable.⁵

Also, Commiphora molmol (myrrh) displayed strong antimicrobial actions against C.albicans in studies, when used topically in comparison to Gentamycin. Myrrh has been traditionally used as a treatment for fungal conditions since ancient times. With recent studies identifying noted actions against candida, even with long-term use. Sesquiterpenoids were highlighted as playing an important role in this antimicrobial activity, also influencing adhesive cell markers. These constituents also offer protection of the gastrointestinal system against inflammation as an antioxidant, with polysaccharides offering potential benefits to the microbiome diversity.⁶

Another herb traditionally used as an antimicrobial is Cinnamomim verum (cinnamon). This has exhibited promising results in studies on oral candidiasis. Cinnamaldehyde extract was examined against the anti-fungal Nystatin to monitor the growth of various candida strains, including C.albicans. Results showed cinnamon to alter the cellular wall of the yeasts and prevent growth when higher doses were used.⁷ Separate studies suggested that the combination of constituents, including cinnamaldehyde, eugenol, and linalool, among others, work in synergy to alter the yeast cell wall and reduce virulence.⁸

When the microbiome is depleted, candida becomes more virulent. Common factors influencing microbiome balance include increased oestrogen from the oral contraceptive pill, highly refined diet, alcohol use, high sugar intake, antibiotic use, and pregnancy. These factors alter the pH of the stomach, encouraging candida replication. Berberine containing herbs can offer beneficial support here. With known actions against small intestinal bacterial overgrowth, polysaccharides benefiting helpful microbiome variants, and in vitro studies showing activity against candida proliferation.⁹

Animal model studies have identified that beta-lactam antibiotic use, including penicillin and amoxycillin, increased hyphae development. It acts through the breakdown of peptidoglycans from the bacterial cell wall. N-acetylglucosamine, an amino cell wall sugar, also encourages hyphae growth, which penetrate cells or between cell junctions as the dominant method of infiltration. Chronic cellular stress can result in damaged gastrointestinal junctions and act as the precursor to conditions like leaky gut.¹⁰ This can also enable the movement of C. albicans to other body systems and into the bloodstream, resulting in candidiasis.

Recent studies have shown, however, that Bacteroides fragilis and Bacteroides vulgatus growth were encouraged by candida yeast, and the fungus also acted to protect against pathogenic infection via immune cell activation. This suggests that candida fungi in balance can have a protective role within the biome as a yeast.¹¹

Immune system regulation

Adequate immune cell presence is a crucial factor in managing candida, and relative infection is commonly associated to compromised immune function. As candida co-exists in the biome, it can obscure Pathogen-associated Molecular Patterns (PAMP) that would otherwise notify Pattern Recognition Receptors. This becomes visible once hyphal development occurs, triggering an innate inflammatory immune response in normal circumstances. In cases of compromised immunity, candida can impact cellular responses by damaging the mucosa, changing the levels of cytokines and antimicrobial peptides released. As such, candida can thrive.^12,13

A recent study identified a notable relationship between hospitalised Covid 19 patients and candida infection, relative to immune dysregulation, medication dispensed, and pre-existing health conditions. Covid patients also experience reduced CD4 and CD8 levels and increased corticosteroid and antibiotic intake, increasing susceptibility.¹⁴

Well utilised as an immune supporting herb, Thymus vulgaris (thyme) has also displayed antifungal activity against resistant candida strains. A combination of flavonoids, saponins, and phenols contribute to this herb’s actions, with particular interest in the essential oil and thymol, linalool, and carvacrol terpenes.¹⁵ Small quantities of thyme showed strong actions against C.albicans, preventing adhesion between cells, altering cellular formation. This prevents replication more effectively than Fluconazole. Thyme oils were also discovered to have penetrated the cell cytoplasm of candida and decreased biofilm by a minimum of 50% in separate studies.¹⁶

The powerful antioxidant and anti-inflammatory actions of Punica granatum (pomegranate) can be beneficial supporting the immune response and in repairing the gastrointestinal mucosa. This is particularly relevant to cases of recurrent fungal infections where dysbiosis is a factor. Resulting in altered gastrointestinal epithelial integrity triggering a dysfunctional immune response and increased damage. Pomegranate has shown to repair intestinal junctions via actions on immune cells, increasing interleukin-5, interleukin-10, and interferon gamma, while reducing pro-inflammatory markers. This regeneration prevents opportunistic microbe movement and infection, with polyphenols attributed also preventing biofilm development.¹⁷

Similarly, the wound-healing and antimicrobial topical actions of Calendula officinalis (calendula) has displayed beneficial results in cases of candida and vaginosis infection. When compared with Clotrimazole, calendula showed to work just as effectively to reduce symptoms of vaginal thrush, with activity noted specifically in the flowers and leaves.¹⁸

The native Leptospermum scoparium (mānuka) can also be utilised as an anti-inflammatory, reducing tumour necrosis factor, and an antifungal, acting on the cell wall and membrane. Increased levels of β-triketones have been attributed with many of these actions.¹⁹ Mānuka has more recently been recognised as having immune modulating properties. Therefore, stimulating an appropriate immune response to counteract pathogen proliferation, while down-grading inflammation where necessary, Making mānuka an appropriate herb for use in microbial and fungal infection.^19,20

Reference List

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2. Shariati A, Didehdar M, Razavi S, Heidary M, Soroush F, Chegini Z. Natural Compounds: A Hopeful Promise as an Antibiofilm Agent Against Candida Species. Front Pharmacol [Internet]. 2022 Jul 11;13:917787. Available from: https://doi.org/10.3389/fphar.2022.917787
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17. Rizzo G, Pineda Chavez SE, Vandenkoornhuyse E, Cárdenas Rincón CL, Cento V, Garlatti V, et al. Pomegranate Extract Affects Gut Biofilm Forming Bacteria and Promotes Intestinal Mucosal Healing Regulating the Crosstalk between Epithelial Cells and Intestinal Fibroblasts. Nutrients [Internet]. 2023;15:1771. Available from: https://doi.org/10.3390/nu15071771.
18. Pazhohideh Z, Mohammadi S, Bahrami N, Mojab F, Abedi P, Maraghi E. The effect of Calendula officinalis versus metronidazole on bacterial vaginosis in women: A double-blind randomized controlled trial. J Adv Pharm Technol Res [Internet]. 2018 Jan-Mar;9(1):15-19. Available from: https://doi.org/10.4103/japtr.JAPTR_305_17
19. Noites A, Araújo B, Machado J, Pinto E. Antifungal Potential of Some Herb Decoctions and Essential Oils on Candida Species. Healthcare [Internet]. 2022 Sep 21;10(10):1820. Available from: https://doi.org/10.3390/healthcare10101820.
20. Masad RJ, Nasser RA, Bashir G, Mohamed YA, Al-Sbiei A, Al-Saafeen BH, Fernandez-Cabezudo MJ, Al-Ramadi BK. Characterization of immunomodulatory responses induced by manuka honey. Front Immunol [Internet]. 2022 Nov 2;13:1020574. Available from: https://doi.org/10.3389/fimmu.2022.1020574.