The fungal microbiome in obese individuals

We hear mostly about the bacterial microbiome but there are other microbiomes out there like the virome (virus microbiome) and mycobiome (fungal microbiome). The mycobiome is an important part of the gastrointestinal tract and fungal microorganisms make up between .03-2% of the total microorganisms in the gut. A recent study out of Spain characterized the mycobiome of obese individuals and compared them to non-obese individuals.

The scientists used sequencing technologies to analyze the diversity of fungal organisms in the gut of 52 Caucasian individuals who were recruited for the study. After fecal sampling and sequencing, they found that diversity was lower in obese subjects than in non-obese subjects and they could be stratified depending on their mycobiome composition. Ascomycota and Basidiomycota were not significantly different between the two groups, however, the minor phylum Zygomycota was represented less in obese patients.

Interestingly, they found that the relative abundance of fungus in the Eurotiomycetes class of the Ascomycota phylum were similar between obese individuals and non-obese individuals but obese subjects with low levels of Eurotiomycetes had worse metabolic profiles. These subjects were identified as more “unhealthy” obese subjects than those with a higher abundance of Eurotiomycetes. 

This was the first study to look at the human mycobiome in relation to obesity and associated metabolic disorders. Further knowledge of these interactions between the mycobiome, microbiome, and metabolic disorders may elucidate new methods for treating obesity and metabolic syndromes.  

Fungal infection in brain highly associated with Alzheimer’s disease

Common example of fungi hyphae

Alzheimer’s disease is a brain disease in which slow and irreversible neuronal deterioration occurs. It is characterized by the accumulation and aggregation of proteins in the brain and central nervous system (CNS), although no one knows the cause of this protein aggregation, or if these amyloids are even responsible for the neurodegeneration that occurs, rather than just associated with it.  More recently, some scientists believe that Alzheimer’s is a disease caused by inflammation, because sufferers of the disease have high levels of many inflammatory signals in their brains.  Indeed, some infections that would drive inflammation have been found in Alzheimer’s patients, but nothing convincing as of yet.  This week though, scientists from Spain discovered that a fungal infection in the brain is highly associated with the disease.  They published their results in Nature Scientific Reports.

The scientists made histological sections from the brains of 10 patients with Alzheimer’s and 10 healthy controls, and stained them for the presence of fungi.  Remarkably, all 10 of the patients with Alzheimer’s showed signs of various fungi, whereas none of the healthy controls did.  The fungi were seen both intracellularly and extracellularly, meaning that in some cases the fungi actually entered the neurons in the brain.  The fungi included both yeasts, such as Sachromyces cerevisae, as well hyphae forming fungi such as Neosartorya hiratsukae. In addition, the scientists found traces of these fungi in the blood of the Alzheimer’s patients as well, suggesting that they may originate through common pathways, and spread into the brain.

While this study does not in any way prove these fungi are causing the disease, it certainly is compelling data that they are primary culprit for the disease.  As the authors state, if one were to assume that the etiology of the disease is caused by the fungi, all the symptoms of the disease can be explained.  For example, the slow progression and inflammatory nature of the disease.  Fortunately, If the fungi are responsible there could be many possible therapeutic approaches, including antifungals.

Fungi associated with enterocolitis for those with Hirschsprung's disease

Plot of the fungal populations in the stool of children without enterocolitis (left), and those with enterocolitis (right).  Notice the substantially larger population of Candida, and Candida albicans in the population with enterocolitis.

Hirschsprung's disease (HD) occurs when an infant is born without ganglion cells in their colon.  The result is that the portion of the colon that lacks these cells cannot relax and pass stool.  It is normally treated surgically by bypassing this portion of the colon with a normally functioning part of the colon.  Unfortunately, around 25% of patients that undergo this procedure eventually get enterocolitis (i.e. colon infection), which can be life threatening. 

Researchers have long believed there to be a bacterial cause for this type of Hirschsprung's associated enterocolitis (HAEC), however the connection has remained elusive.  Researchers, primarily from Cedars-Sinai, published the results of a study this week that suggests fungi, not bacteria, are primarily responsible for causing HAEC.  They published their results in the journal PLoS ONE.

The researchers developed a cohort of seventeen children that suffered from HD as an infant, and who had surgery to correct it.  Eight of these children developed HAEC, while the other nine remained healthy.  The researchers took stool samples from each of the children and measured their bacterial and fungal populations.  Surprisingly to the researchers, there was no statistical difference in the abundance of various bacteria between the two groups.  However, there was a much different story with the fungi.  The normal HD patients had a higher diversity of fungi than the HAEC patients.  In addition, HAEC patients were dominated by Candida species, while the others were not.  Moreover, an average of 90% of the Candida was Candida albicans, a pathogenic fungus that we have written about on the blog in the past.

The scientists were not able to say whether or not Candida albicans was responsible for causing the enterocolitis in these patients, however they do suggest it as a possibility.  To that end, they suggest that perhaps antifungals, rather than antibiotics, should be used to combat HAEC, especially given the fact that antibiotics can lead to ‘blooms’ in fungal species.  We often discuss the importance of all the aspects of the microbiome beyond just the bacteriome (bacteria), such as the virome (viruses), and mycobiome (fungi), and this paper shows another example of why these various ‘omes’ should not be neglected during microbiome research.