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.  

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.

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.