Biofilms and the Mycobiome/IBD Connection: A Refresher and a Probiotic Treatment Finally?!

I’ve decided to start this week with some good news.

A few days ago, the headline of a little op-ed sort of piece on a science-devoted website caught my eye:  “It’s Time to Highlight Our Fungus Friends in Our Microbiomes.”[i]  The author gives a short explanation of the diversity of the human microbiome – a diversity which is in sharp contrast to what seems to be the research world’s single-minded focus on the bacterial element alone:  “…focusing solely on this one facet of the microbiome contributes to the misconceptions that only bacteria inhabit our guts and that bacteria are exclusively what gut microbes should look like….fungi, protists [ie. protozoa], and bacteria inhabit the same spaces in our guts and share and compete for resources. And even though studying all members of the microbiome is extremely challenging, it is the only way that we will begin to understand the complex interactions among them and do better science.”

Hear!  Hear!

Unfortunately, this author too only focuses in on the microbiome, neglecting to  mention our missing macrobiomes.  Still, I very much appreciated her vehemence in pointing out that science absolutely must look at the role other organisms play in the gut and in the development of disease. I have written about both fungi (mycobiome) and protists before on this blog but unfortunately, not nearly as much as I’d like, as there really is so little research happening out there.  Anyway, she points out – as I have  – that Crohn’s disease, for example, certainly seems to be associated with increases of fungi in the gut.

Which leads to me to a 2^nd article[ii] that appeared the same day, this one describing a National Institute of Health grant just given to Dr. Mahmoud A. Ghannoum, a professor and researcher at Case Western Reserve School of Medicine and Cleveland Medical Center, to continue his research into this very association.   Several times, I’ve written about the increase in the yeast, C. tropicalis, being associated with flare ups in IBD.  (For example, here and here.)  In this latter post, I wrote about Dr. Ghannoum’s recent research:  “In a mouse model, fungi have been shown to aggravate the severity of inflammation in IBD.  This research supports the idea that the fungi work with the bacteria in such a way as to worsen IBD symptoms. In fact, another study in humans… showed that the fungi, C. tropicalis, and the bacteria E. coli and S. marcescens, work together to form a biofilm (kind of a slimy mass that protects the organisms inside – think about the plaque on your teeth) that evokes an inflammatory immune response.”  Dr. Ghannoum was will be looking at this in much greater depth, to figure out exactly how this yeast interacts with the gut bacteria to trigger Crohn’s.

1. Dr. Ghannoum will look at the genes of these 3 organisms alone and then together, to see which increase in expression when they are together. He’ll then delete those genes to see if the biofilm still forms.
2. Secondly, he’ll look at the metabolites secreted by the biofilm so see if this is the factor that leads to the increase in fungi.
3. Finally, he’ll see how these 3 organisms in isolation, and together, affect inflammation levels. Plus, does giving anti-bacterial, antifungal, etc. agent affect inflammation levels?

Says Dr. Ghannoum, “”The long-term goal of this project is to develop novel antifungal and probiotic strategies that can be tested in pre-clinical and clinical studies to decrease the occurrence and duration of symptoms in patients…”

In fact, Dr. G and colleagues are already working on a probiotic mix to treat this overgrowth of C. tropicalis and the ensuing biofilm it forms.  They published a paper[iii] in April, in which they tested a mixture “…consisting of Saccharomyces boulardii, Lactobacillus acidophilus, Lactobacillus rhamnosus, and Bifidobacterium breve…that would prevent and treat PMB [biofilm].”  And yes, this probiotic mix successfully and significantly reduced the thickness of the biofilm.  In their concluding paragraph, the authors state, “The antibiofilm activity of our probiotic has significant health implications given that biofilms are increasingly being recognized as primary contributors to host infections and certain GI diseases (e.g., Crohn’s disease and colorectal cancer). According to the World Health Organization, biofilms are implicated in 65 to 80% of microbe-based diseases.”

Holy smokes, right?!

Hopefully, human clinical trials are on the near horizon.  Stay tuned.

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[i] https://massivesci.com/articles/fungi-protists-in-microbiome-research-mycobiome/

[ii] https://www.eurekalert.org/pub_releases/2019-07/cwru-hdi072519.php

[iii] Hager, CL, etc.  Effects of a Novel Probiotic Combination on Pathogenic Bacterial-Fungal Polymicrobial Biofilms.  mBio.  2019.  10(2).  doi: 10.1128/mBio.00338-19