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.

The fungal microbiome may be associated with colon cancer

We don’t write much about the fungal microbiome on this blog, but it may be every bit as important as the bacterial microbiome (and let’s not forget about the archaeal and eukaryotic microbiomes, and virome as well!).   Fungi are not as abundant in the microbiome as bacteria, which is probably why they are not as heavily researched, but they are known to cause diseases.  For example, vaginal yeast infections and oral thrush are caused by fungi belonging to the Candida genus.    

We recently wrote about a study that linked bacterial biofilm formation with colorectal cancer.  In this blog we mentioned that colorectal cancer is likely to have environmental causes.  Researchers from China hypothesized that fungi may be one of these risk factors, so they conducted an experiment to find out.  They recently published their results in Nature Scientific Reports.

The researchers first sampled the microbiomes of 27 patients with various stages of colorectal tumors, in addition to other, healthy areas of those patients’ guts adjacent to the tumors.  They then sequenced the genomes of the samples to determine which fungi existed, and where.  They discovered that fungal diversity was lower on tumors compared to other areas of the colon.  In addition, two known pathogenic fungi, Candida and Phoma existed in higher levels on tumors compared to the adjacent areas.  Finally, they found distinct differences between individuals with advanced and non-advanced tumors.  Those with advanced tumors had a higher abundance of two other known pathogenic fungi, Fusarium, which has been associated with intestinal disease in the past, and Trichoderma, which has been associated with infections of various organs. 

This study did not involve any healthy patient controls, and its sample size was somewhat limited.  Still, the results are intriguing because gut fungi that are known to cause inflammation elsewhere in the body are being found at the site of tumors.  Even if these fungi are not causing the tumors, they could at least be potentially used as a diagnostic or biomarker for tumors.  While we know that some fungi can be dangerous, we note that even specific genera are not always pathogenic, and sometimes they can exist normally in a host and only turn pathogenic at a later time.  Like other aspects of the microbiome, the story is complicated, but we would be willing to bet there is at least one beneficial fungus among us.