Thursday, October 9, 2014

Candida Albicans: Fact vs Fiction

The internet is filled with tons of information on the fungus Candida albicans.  While I love that information is much more accessible now than it has been in the past thanks to the internet, there is a problem with being able to put out and receive any information you like: It's difficult to determine fact from fiction.  In this blog I will go over some of the intricacies of Candida albicans and help create a better understanding of what this crazy commensal critter is up to.

What is Candida albicans?

Candida albicans is often referred to as a yeast because overgrowth in the vaginal wall is referred to as a yeast infection, but this is a misnomer.  Candida albicans is a fungus that can grow as either single cell yeast or multicelluar filamentous cells.  Since it's found in 80% of the human population(1) and more often than not causes no harm to us, it's considered a commensal organism.  Candida albicans can convert back and forth between both yeast and hypha depending on the environment it's in, thus it is highly adaptable.  The yeast form of Candida albicans is typically benign, it's the filamentous cells that more often than not tend to become problematic, but conversion to filamentous hypha doesn't necessarily have to occur for Candida albicans to cause problems.  It is believed that the ability to switch forms and, therefore, adapt to the environment may be the most important factor in the ability of Candida albicans to infect a host rather than just one specific form(2).

Since the yeast form is unicellular, it typically spreads out within an environment which causes cells to compete with daughter cells as well as other bacteria found there for real estate and nutrients.  Filamentous cells, on the other hand, form hypha that are able to invade host tissues, find nutrients, and help grow biofilms(3).  This allows the cells to grow out in to what is more or less a root network, meaning real estate isn't as big of an issue and it can acquire resources in remote areas where other bacteria can't.  Even though Candida albicans is considered a commensal organism, it is a frequent cause of infection in patients with a compromised immune system.  Below is a picture of Candida albicans in yeast(L) and hyphal(R) form.

Yeast to hypha conversion

While conversion from yeast to filamentous hyphae is not necessary for invasion, this is the most common route due to high expression of the hyphal wall protein-1 gene.  When activated, this gene allows the filamentous cells to bind heavily to host tissues, providing stability so that they can form filaments that can puncture and invade host tissues, primarily to scrounge for nutrients.  Think of it like outriggers on a drill, without outriggers the drill will topple as it tries to drill in to the ground.  When anchored to the ground, stability allows the drill to puncture the ground and the same happens with Candida hyphae.  Without adhering to tissue, the hypha would merely push itself away from the tissue rather than puncture through it.  Hyphal wall protein-1 is either non-existent or barely expressed in the yeast form of the fungus, but highly expressed in the hyphal form(4).

Many people believe high sugar/carbohydrate intake to be the primary culprit in Candida albicans invasion, but the science doesn't support this.  In fact, high levels of glucose tend to prevent conversion of yeast to hypha while increased amino acid availability tends to promote it(5).  Another factor that tends to promote yeast to hypha conversion is an increased environmental pH, which is promoted through the formation of ammonia when hypha metabolize amino acids.  When the yeast form metabolizes glucose, this increases acidity which lowers pH and makes the environment less hospitable to the hyphal form.

If sugar intake is involved at all, it may increase the amount of yeast found within the GI tract.  This could indirectly increase the risk of hyphal conversion if the proper conditions present themselves by providing more yeast that could turn in to hyphae, but it doesn't in and of itself promote virulence of Candida albicans under most conditions. Another indirect way sugar intake can promote virulence is through inflammation, which animal models show promotes colonization of Candida albicans(6).  This wouldn't be a result of carbohydrate intake, per se, but more likely caused by specific types of food. 

Gluten and Candida

When you look at potential dietary issues that may promote Candida albicans invasion, carbohydrate intake does not appear to be directly linked.  However, something often found in foods that contain carbohydrate may have a direct effect on Candida albicans yeast to hypha conversion, which increases the likelihood of invasion.  Gluten, a protein found in grains, is not completely digested by humans because of it's high content of the amino acids L-Proline and L-Glutamine.  This allows gluten to interact with the resident flora within our digestive tract, of which Candida albicans is a member.

Studies have shown L-Proline(7, 8) and L-Glutamine(8) to be potent drivers of yeast to hypha conversion, with L-Proline having the biggest effect of any amino acid(9).  Candida albicans is also able to bind to free amino acids as well as amino acids that are part of larger proteins(10), as would be the case for a large protein like gluten.  Since Candida albicans makes the enzyme needed to break apart proteins high in L-Proline, it could bind to larger proteins and take in L-Proline to induce conversion from yeast to hypha.  In addition, gluten is also known to cause inflammation in the GI tract which is another way it may promote the virulence of Candida albicans. 

Candida and the immunocompromised

For the most part, the assumption has been that people who are not immunocompromised don't tend to have issues with Candida albicans or other Candida species.  However, this is not necessarily true.  First, Candida albicans may team up with Streptococcus mutans to form biofilms and cause cavities in the mouths of children(11).  Second, a recent study looking post mortem at people who died of heart disease found fungi of the species Candida in plaques from the blood vessel walls during autopsy(12).  Another study found significant levels of Candida albicans in the healthy wall of the aorta in patients with coronary artery disease and in the aorta of those with aortic valve stenosis (13).  This by no means implies that Candida albicans causes any of these issues, but to say that it is benign in people with a functioning immune system isn't quite true.

Up until recently, the model for Candida albicans invasion has required the host to be immunocompromised.  However, in 80% of people with disseminated Candida albicans, there is no evidence that they are immunocompromised.  In most people, Candida disseminates due to a break down in the permeability of the skin or GI tract or via a change in the gut microbiota.  These changes can come about due to surgery, nutrition, and/or antibiotic/antimicrobial usage(14). Even within the GI tract, Candida can become problematic if it overgrows due to its ability to alter hormonal status.  This is due to its ability to bind endogenous hormones. 

Candida and hormones

Candida albicans can bind female sex hormones, including estrogen(15, 16), and possesses a receptor for corticosteroids that can bind endogenous hormones as effectively as the native corticosteroid receptor(17, 18).  Corticosteroids are steroid hormones such as cortisol, corticosterone, and aldosterone that play a significant role in human physiology.  Cortisol and corticosterone are glucocorticoids, hormones that prepare the body to deal with stress by increasing blood glucose and suppressing the immune system, among other things.  While cortisol is the primary glucocorticoid in humans, corticosterone has a limited role in the human stress response but plays a role in human skin physiology that is just recently being explored.  It is also a precursor to aldosterone, a mineralocorticoid that helps regulate electrolyte balance by causing sodium and water to be retained.  In addition to binding corticosteroids, the same receptor is capable of binding to progesterone, a precursor to aldosterone and cortisol(19). 


The ability of Candida albicans to bind to hormones indicates it may have the ability to alter hormonal balance if it overgrows and invades a host.  In part 2 of this blog, I will go over how an overgrowth of Candida albicans can cause symptoms ranging from:

  1. HPA axis dysregulation
  2. Skin sensitivity reactions(Cosmetic sensitivities, hair loss, fungal nail infections)
  3. Digestive issues
  4. Hormonal issues
 From there, we will explore therapeutic strategies for fixing an overgrowth of Candida Albicans.