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.

Could ice cream prevent cavities?

We know that the oral microbiome hosts a wide variety of bacteria, some good, and some that cause cavities.  Those that cause cavities do so by producing acid as they break down the food in our mouths.  Researchers in India are trying to discover if probiotics could help alter the oral microbiome so there is a decrease in the bacteria that commonly cause cavities.  In their study they investigated a type of ice cream sold in India that has the probiotics Bifidobacterium bifidum and Lactobacillus acidophilus mixed in with the ice cream.  The researchers were interested in the effects the probiotic ice cream on the levels of bacteria and fungi in saliva, namely Streptococcus mutans, Lactobacillus acidophilus, and Candida albicans, because these three bacteria are the main causes of tooth decay.  The results were recently published in the Journal of Dental and Medical Sciences.

In the study, the researchers gave 20 participants one dish of ice cream each day for 10 days that either contained the probiotics or did not.  The researchers examined the bacteria in the participants’ saliva both before and after the ice cream intervention.  The results showed that consumption of probiotic ice cream caused a significant reduction of both S. mutans and C. albicans, and an increase in the number of L. acidophilus when compared to controls.  The increase in L. acidophilus is not surprising because the ice cream contained L. acidophilus. The researchers highlighted that in other studies of people eating Lactobacillus acidophilus, it did not persist in the individuals’ mouths.  Overall, two of the cavity causing bacteria decreased in abundance and one, which was in the probiotic ice cream, increased in abundance.

We must admit that the rigor of this study was highly lacking, so we don’t want anyone to take these results too seriously. While more research needs to be done to determine if probiotic ice cream can actually help prevent cavities and tooth decay, any study that recommends eating it is fine by me.  It’s obviously important to brush your teeth every day, but it’s definitely more fun to eat ice cream than to floss!