Intestinal Candidiasis

Fungi make up a very small portion of the gut microbiome, with a population estimated at around 1 billion out of the 10 trillion microbes residing there.^[13] Most fungi in the gut are forms of yeast, such as Candida, Saccharomyces, and Malassezia. The genus Candida includes many species, but the most common is C. albicans. Depending on the sampling site and preparation, yeasts are detected in the feces of 4–97% of healthy people.^[1][16]

The fungal microbiome, or mycobiome, of the human gut is poorly understood. It is much lower in abundance, diversity, and stability than the bacterial microbiome but more unique to each individual.^[16] Some evidence suggests that most fungi aren’t inhabitants of the gut at all, but rather ingested with food and saliva (from the oral mycobiome).^[13]

To further complicate matters, fungi are dimorphic, meaning they can exist in different forms, and can change to a hyphal form, which is less adapted to the human gastrointestinal (GI) tract and potentially more pathogenic (likely to cause disease). Because gene expression differs between the fungal and hyphal forms of the same species, accurate identification and quantification (measuring the number) is challenging.^[16]

The role of the mycobiome in human health and disease is largely unknown. Some yeast species, such as C. albicans, exist as pathobionts, which are potential pathogens that remain harmless or even beneficial under normal conditions. Others, such as Saccharomyces boulardii, have known probiotic effects.^[17]

Though intestinal colonization is normal and harmless in healthy individuals, certain species of yeast can cause disease in immunocompromised individuals, premature newborns, and cases of surgery or inflammatory bowel disease (IBD) that damage the physical barrier of the intestinal wall.^[18][19][20] In these cases, microbes that reside in the gut can easily overcome the cellular or physical defenses of the immune system, escaping the intestines and entering the circulatory system. Yeast may also play a role in the development of antibiotic-associated diarrhea and certain respiratory and skin allergies, but more research is needed to establish causality.^[1]

Many microbes in the intestines are potentially pathogenic, which means they could cause disease in certain circumstances. Their potential for causing disease is controlled by immune cells, the physical barrier of the intestinal walls, and other resident microbes of the GI tract.^[1][23]

In healthy people, the innate immune system controls Candida colonization by initiating the production of antimicrobial peptides (amino acid chains), and neutrophils (cells of the innate immune system) prevent Candida from escaping the GI tract and causing infection. Other microbes may communicate with the innate immune system to induce an antimicrobial response or produce metabolites, which suppress Candida growth.^[23]

There is also some evidence that the GI tract in mammals induces specific characteristics in Candida that make it less likely to cause disease. In other words, it trades its virulence (or ability to cause disease) for better chances of survival in the human gut.^[23]

Candidiasis can occur in the mouth and throat (often referred to as thrush), esophagus, or vagina (commonly called a yeast infection). Invasive candidiasis is an infection of other parts of the body, including the brain, blood, and heart. Candidemia, or a blood infection, is the most common form of invasive candidiasis. Candiduria, or Candida in the urine, is also a sign of invasive infection.

Though it’s unclear whether Candida plays a causal role, researchers have found low or altered fungal diversity in patients with inflammatory bowel disease (IBD),^[26] and emerging evidence indicates that Candida species tend to predominate in the mycobiomes of patients with IBD.^[27]

Some species of Candida can colonize and delay the healing of gastric and intestinal ulcers. One small observational study found that certain species were detectable in inflamed regions of the intestines in Crohn’s disease but absent from the non-inflamed areas.^[18] One nonrandomized, uncontrolled study reported that two weeks of antifungal treatment in patients with ulcerative colitis and significant fungal colonization reduced disease activity and mucosal inflammation.^[28]

Without diagnostic criteria or the quantification of Candida colonization in these studies, however, it’s impossible to determine whether these cases would be characterized as IC or some form of fungal imbalance. Patients with IBD often use certain medications that increase the risk for fungal disease, which could also explain these findings.^[19]

Candida abundance is also associated with visceral hypersensitivity (a heightened sense of pain in response to normal gut functions) in a subgroup of IBS that responds well to antifungal treatment.^[29] Exploratory studies have noted that higher Candida abundance is associated with more severe bloating.^[30] Though Candida species are present in people with and without IBS, other emerging evidence suggests that C. albicans in people with IBS is genetically distinct from the same species in healthy people. The correlations between Candida and certain bacteria also differ between people with IBS-D and healthy controls.^[31] There is still no conclusive link between IBS and Candida, though. Despite some unique variations in IBS versus healthy controls, the mycobiome isn’t a useful biomarker for IBS due to high levels of individual variability and lack of any causal relationships.

IC may lead to invasive candidiasis in susceptible individuals, such as critically ill or immunosuppressed patients and premature babies. This occurs when fungi — most commonly the Candida species — escape the intestinal tract and infect other areas, such as the blood, brain, or heart. This leads to a fever that doesn’t go away after treatment with antibiotics, and can eventually progress to sepsis (a life-threatening immune system response) and death if untreated.

The mortality rate of candidemia (a Candida infection in the bloodstream) is estimated to be over 25% in premature infants and roughly 58% in adults who don’t receive timely treatment.^[21]

Small Intestinal Fungal Overgrowth (SIFO) is characterized by high numbers of fungi in the small intestine, while Small Intestinal Bacterial Overgrowth (SIBO) is caused by elevated numbers of bacteria. Much more is known about bacterial overgrowth, but it’s still poorly understood. It is thought that microbial overgrowth could play a role in unexplained GI symptoms such as gas, bloating, and abdominal pain.

Recent studies have used more accurate sampling and quantification methods to detect Candida and other forms of fungi in the small intestine. Though sampling this way can accurately detect intestinal overgrowth of bacteria and fungi, these studies found that the rates of unexplained GI symptoms were similar in participants regardless of their fungal colonization. In a study that sampled the gastric (stomach) mucosa of people with dyspepsia (indigestion) or ulcer complaints, Candida was present in approximately 27% of the participants (with no control samples for comparison). A follow-up study compared participants with and without SIFO, and found no differences in the severity of the participants’ GI symptoms. In that study, 25% of the participants with unexplained digestive complaints also had SIFO.

Though prescription antacid medications and altered gut motility (organized muscular contractions) may increase the risk of developing SIBO, they aren’t associated with SIFO.^[2]

Controversial publications from the 1970s and ’80s claimed that intestinal C. albicans overgrowth impaired immune, thyroid, digestive, and adrenal function. This “Candidiasis Hypersensitivity Syndrome” allegedly led to a long list of ailments, including chronic fatigue, GI discomfort, recurrent vaginal yeast infections, arthritis, acne, migraines, menstrual symptoms, and heart issues.^[1]

An observational study of 26 participants with chronic fatigue syndrome and 50 healthy controls revealed no differences in the concentration of Candida antibodies in their blood samples, which indicates that Candida infections don’t play a role in chronic fatigue.^[24]

A more informative study compared antifungal treatment to a placebo in 42 women with alleged Candidiasis Hypersensitivity Syndrome and recurring vaginal yeast infections. Though the antifungal treatment resolved the vaginal yeast infections much more effectively than the placebo did, both were equally effective in reducing the systemic symptoms, such as fatigue, and psychological effects. This evidence strongly suggests that Candida colonization played no role in their physical symptoms.

The Executive Committee of the American Academy of Allergy, Asthma & Immunology released a position statement about this syndrome, critiquing the lack of evidence for any of its claims and the potential dangers of long-term antifungal drugs recommended by the program.^[25]

Most cases of IC (and subsequent invasive infection) are seen in preterm infants and critically ill or immunocompromised individuals. Certain medications, such as antibiotics and steroids, can also increase the risk of developing IC.

Immature immune systems, permeable intestines, invasive surgical procedures, hospitalization, and the use of broad-spectrum antibiotics make premature infants more prone to IC and invasive infections.^[3] (A suppressed immune system also increases the risk of oral and esophageal candidiasis in people with HIV or cancer, but whether this translates to IC is unknown.)

Emerging research suggests that people with diabetes may also be more prone to IC, but these findings are complicated by the participants’ use of antifungals, antibiotics, and steroids (to control inflammation). Intestinal Candida counts can also be elevated as a result of swallowing oral Candida, and oral candidiasis (overgrowth of yeast in the mouth and throat) can occur in people who wear dentures or take the aforementioned medications.^[14][15][13]

Healthy people may experience a relative increase in Candida compared to bacteria while taking antibiotics, but the actual numbers of Candida may not reach abnormally high levels consistent with IC. This has been connected to antibiotic-associated diarrhea, but a causal relationship hasn’t been established. Early studies detected Candida in the stools of people with antibiotic-associated diarrhea, but they lacked a control group, so no conclusions could be drawn. Evidence from a small, uncontrolled study showed that antibiotic-associated diarrhea occurred in patients regardless of Candida colonization. Though antifungal medications resolved diarrhea in five of the seven colonized patients, diarrhea also resolved without treatment in two patients and didn’t resolve until after antibiotics were ceased in the non-colonized patients.^[1][22]