Do HMOs inhibit Candida Invasions?

May 28, 2023 7 min read

Do HMOs inhibit Candida Invasions?

Introduction

The human body is a remarkable feat of engineering but like all structures, it is vulnerable to nature, specifically opportunistic pathogens, and infections. It’s host to billions of tiny organisms, that for the most part, are often harmless. Or at least until they’re not.

Candida albicansis an example of a fungus that lives on the skin and within the body. Most of the time, it causes no harm. Yet, in the right conditions, these cells can chain together forming long, branching arms or filaments to invade the body’s tissues. Vulnerable individuals are most at risk, and one group in particular is pre-term babies.

A study by Gonia et al. (2015) looked to find out if human milk oligosaccharides (HMOs) could protect premature babies from the nasty invasion of C.albicans. In this article, we’ll investigate the outcome of the study and what this could mean for the future health of pre-term infants. 

What are HMOs?

Before we do that, though, let’s quickly recap what HMOs are:

  • The third most abundant component of human breast milk.
  • Oligosaccharides are a type of carbohydrate.
  • There are over 200 characterised HMOs.
  • HMOs are virtually absent from cow’s milk and formula milk.
  • There are three major types: fucosylated, sialylated, and non-fucosylated.
  • HMOs are associated with a wide range of health benefits, especially through their modulation of the human gut microbiome[i].

Want to know more? Check out our blog.

What is Candida albicans?

Candida albicansis a naturally present fungus on and in your body. Yet, it is also the most prevalent source of fungal infection in humans, called candidiasis.For most of the time, C. albicanslives in harmony with you, causing little issue if you are otherwise healthy and have a strong immune system.

However, they also thrive in people with weakened immunity and in moist environments – only becoming pathogenic when the right conditions are met. A particularly vulnerable group that is susceptible to the devastating effects of C. albicansinfection is pre-term babies.

Candidaspecies are renowned fungal inhabitants of the infant gut microbiome and its invasion can lead to dissemination and systemic infection. In infants who have an extremely low birth weight of less than 1000g, disseminated candidiasis is a frequent life-threatening infection, with incident rates as high as 23%[ii].

What’s the difference between disseminated and systemic infection?

Disseminated candidiasis is a type of Candidainfection that affects the liver and spleen, particularly in patients with acute leukaemia[iii].

Systemic candidiasisis an infection of the blood where there is an invasion of Candidaspecies, often causing symptoms that include:

  • Fever
  • Low blood pressure
  • High white blood cell count[iv]

What conditions can C. albicanscause?

The infections that C. albicans cause can be classified into two types:

  • Mucocutaneous candidiasis – includes diseases such as oral thrush and vaginal yeast infections.
  • Invasive candidiasis – causes a bloodstream infection called Candidemia and infections within deeper organs, such as the liver. These illnesses often have high morbidity and mortality rates[v].

Candida albicans and the gut

C. albicansis described as a common commensal microbe of the gut. Commensal microorganisms are those that have a neutral relationship with their host, in this case humans. It means that by living in and on us, neither we or the fungal cells receive any benefits or cause harm to the other[vi].

However, C. albicansis an opportunistic pathogen, responsible for both mild and severe, often life-threatening illness. The latter can occur when the conditions in the body are right for C. albicansto thrive, such as a disturbed gut microbiome and compromised immune defences. Many scientific studies demonstrate that the gastrointestinal tract is where systemic infections begin, with C. albicansable to move through the intestinal barrier and initiate blood infections.

Yet, some research suggests that the presence of this fungus as part of the gut mycobiome could have some beneficial effects, particularly for Clostridioides difficile infection. And, it may also have protective benefits against microbial infections of the blood[vii].

Therefore, there is some speculation that C. albicansmay have potential beneficial effects, but its colonisation can trigger immune responses by the body, resulting in infection.

What was the research by Gonia et al. about?

The study by Gonia et al. (2015) looked to determine if HMOs can protect human premature intestinal epithelial cells (pIECs) from a C. albicansattack. This study could be used to inform whether HMOs can protect the premature infant from infection.

How did Gonia et al. (2015) conduct their research?

The study by Gonia et al. (2015) was carried out in the laboratory. An immunocytochemical assay was used to determine invasiveness of the fungal cells. Non-invading C. albicanscells could be identified because they become fluorescently tagged, while invasive cells cannot be reached by the primary antibody, and as such are left untagged. These assays were carried out with and without the presence of human milk oligosaccharides.

To comprehend how HMOs affect C. albicansinvasion, specific virulence traits that are vital for attack, were quantified by the researchers. These traits include hyphal morphogenesis or the growth of long, filamentous structures called hyphae[viii]. Researchers also quantified the ability of the fungus to associate with the host cells. In this case, an association was defined by any morphological fungal cell being in the same plane of view as a host cell.

What were the results?

Many research studies have demonstrated that HMOs are capable of protecting the colon from pathogenic bacteria and viruses through modulation of the gut immune response and acting like decoy receptors[ix]. This study, however, aimed to investigate whether HMOs could prevent interaction between fungal cells and the host.

At present, drug therapy, such as fluconazole can be effective at lowering the risk of C. albicans infection in premature babies who are at high risk of candidiasis. Although it has no increased risk of short-term side effects, Zhang et al. (2021) showed that the minimum inhibitory concentration of fluconazole rose. This means more research needs to be carried out to ensure sensitivity of the drug[x].

Human milk oligosaccharides, on the other hand, are natural sugars present in human breast milk and could help to avoid the disadvantages of drug therapy. The results of the Gonia et al. (2015) study showed that HMOs can disrupt the early association of fungal C. albicanscells with the host.

The researchers demonstrated that HMOs significantly reduced the invasion of C. albicanson pIECs, with just 5g HMOs/L. The inhibition increased as the concentration of HMOs increased.

Next, the researchers investigated whether the inhibitory effect of HMOs was because they could reduce hyphal growth. The results showed that although HMOs didn’t have any effect on the growth or width of the C. albicansprotrusions or hyphae, they did have an impact on hyphal length.

After 75 minutes, hyphal lengths were 30% shorter in the HMO-containing media compared to the media alone. Equally, the presence of HMOs reduced the initial emergence of hyphae by 40% and also resulted in a 50% reduction in yeast cells forming hyphae after one hour.

It means that even though HMOs do not stop the hyphal initiation of C. albicans,they do delay the time it takes for them to emerge as well as the length.

Overall, this study gives a clear insight into how HMOs could protect the intestinal environment of premature babies from C. albicansinvasion and subsequent damage caused by the fungal cell’s hyphae. Future research needs to be conducted to determine the specific HMO structures that could protect pIECs from an attack by C. albicans. Doing so, could, in the future, help to devise an effective therapy to protect groups who are at risk of microbial-associated gut-mediated disease.

Conclusion

Despite numerous studies proving that HMOs can prevent infection from pathogenic bacteria and viruses, research into their effects on fungi are limited. The focus study in this article indicated that HMOs could lower the harmfulness of C. albicans in the gut. The study suggests that in the future HMOs could be an effective preventative measure for protecting the premature infant colon from attack and damager caused by this fungus.

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Written byLeanne Edermaniger, M.Sc. Leanne is a professional science writer who specializes in human health and enjoys writing about all things related to the gut microbiome. 

References

[i] Hegar, B., Wibowo, Y., Basrowi, R. W., Ranuh, R. G., Sudarmo, S. M., Munasir, Z., Atthiyah, A. F., Widodo, A. D., Supriatmo, Kadim, M., Suryawan, A., Diana, N. R., Manoppo, C., & Vandenplas, Y. (2019). The Role of Two Human Milk Oligosaccharides, 2'-Fucosyllactose and Lacto-N-Neotetraose, in Infant Nutrition. Pediatric gastroenterology, hepatology & nutrition22(4), 330–340. https://doi.org/10.5223/pghn.2019.22.4.330

[ii] Gonia S, Tuepker M, Heisel T, Autran C, Bode L, Gale CA. Human milk oligosaccharides inhibit candida albicans invasion of human premature intestinal epithelial cells ,. The Journal of Nutrition. 2015;145(9):1992–8. doi:10.3945/jn.115.214940 

[iii] Chen C-Y, Cheng A, Tien F-M, Lee P-C, Tien H-F, Sheng W-H, et al. Chronic disseminated candidiasis manifesting as hepatosplenic abscesses among patients with hematological malignancies. BMC Infectious Diseases. 2019;19(1). doi:10.1186/s12879-019-4260-4 

[iv] Tesini BL. Systemic candidiasis [Internet]. BMJ; [cited 2023 May 16]. Available from: https://bestpractice.bmj.com/topics/en-us/1062#:~:text=Definition,hypotension%2C%20and%2For%20leukocytosis. 

[v] Arsenault AB, Bliss JM. Neonatal Candidiasis: New Insights into an Old Problem at a Unique Host-Pathogen Interface. Curr Fungal Infect Rep. 2015 Dec 1;9(4):246-252. doi: 10.1007/s12281-015-0238-x. Epub 2015 Sep 7. PMID: 26779297; PMCID: PMC4712708.

[vi] Commensal (bacteria) [Internet]. 2020 [cited 2023 May 17]. Available from: https://www.gutmicrobiotaforhealth.com/glossary/commensal-bacteria/#:~:text=The%20term%20commensalism%20refers%20to,is%20therefore%20a%20neutral%20relationship. 

[vii] Alonso-Monge R, Gresnigt MS, Román E, Hube B, Pla J. Candida albicans colonization of the gastrointestinal tract: A double-edged sword. PLoS Pathog. 2021 Jul 22;17(7):e1009710. doi: 10.1371/journal.ppat.1009710. PMID: 34293071; PMCID: PMC8297749.

[viii] Harris SD. Hyphal morphogenesis: An evolutionary perspective. Fungal Biology. 2011;115(6):475–84. doi:10.1016/j.funbio.2011.02.002 

[ix] Singh RP, Niharika J, Kondepudi KK, Bishnoi M, Tingirikari JM. Recent understanding of human milk oligosaccharides in establishing infant gut microbiome and roles in immune system. Food Research International. 2022 Jan;151:110884. doi:10.1016/j.foodres.2021.110884 

[x] Zhang D, Xie D, He N, Wang X, Dong W, Lei X. Prophylactic Use of Fluconazole in Very Premature Infants. Front Pediatr. 2021 Oct 1;9:726769. doi: 10.3389/fped.2021.726769. PMID: 34660487; PMCID: PMC8517516.


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