C.Difficle Infections…A Case of the “omes” Working Together?

As my regular readers know, I am particular interested in science that looks at how the various kingdoms of the human biome interact to promote health or disease.  Another interesting article came out recently that looks at how yeasts and bacteria work together to perpetuate Clostridia difficile infections (CDI).[i]  In this case, researchers have found that various yeast (mycobiome) species flourish in people infected with the pathogen. They believe, in fact, that these yeasts, along with other pathogenic species of bacteria (bacterial microbiome), play a role in perpetuating this life-threatening infection.

To give you some idea of the severity of a CDI:  according to the US CDC, nearly half a million Americans suffer from such an infection every year.  Believe it or not, an infection is so virulent that 29,000 patients die within 30 days of the initial diagnosis of C. difficile.[ii]

These researchers looked at 49 stool samples collected from hospitalized patients, 18 of whom had tested positive for C.difficile infection (CDI).  Initially, they found that 2 fungal species and 9 bacterial were markedly higher in those with the infection. Upon further analysis, they found that other fungal species were also elevated, and that these elevated levels of yeasts were associated with decreased levels of probiotic bacteria:  there were “…negative cooccurring relationships between fungi and commensal gut bacteria. Candida and Byssochlamys were present at relatively high abundances within CDI⁺ individuals and formed strong negative relationships with several bacterial taxa…”  These fungi may be critical to the perpetuation of the CDI.  Their findings lend “…further support to the concept that the dysbiosis associated with CDI has an important contribution from fungal organisms.”

The presence of pathogenic yeasts and bacteria, especially E.coli and another bacterial species, Pseudomona, led to biofilm production: “…the causal dysbiosis of CDI my self-perpetuate, potentially contributing to treatment failure.”  For those who are unfamiliar with the term biofilm, it’s defined as a mass of organisms that stick together to form a slimy matrix. (Think of plaque on your teeth.)  Organisms are able to hide in the thick biofilm, making them harder to kill.  What these researchers are saying then is that the C.difficile works with yeasts and pathogenic bacteria to perpetuate the state of dysbiosis – and their own survival –by working together to form a biofilm.  If their findings are replicated, it would certainly go a long way toward explaining why treating CDI is so incredibly difficult and why it recurs so often.

By the way, none of this was found in the people without C.difficile infections.

Their next steps are to determine which of these altered species is particularly significant to perpetuating a CDI.  As C.difficile infection is highly associated with antibiotic use, it’s possible that if, for example, a particular yeast is found to help initiate and perpetuate an infection, it would be possible to treat CDI without using antibiotics but instead, perhaps treating with antifungals, which is much safer for the biome: “The researchers believe it’s a research question worth pursuing. C. difficile infection is difficult to control, largely because it affects patients who have already been treated with antibiotics. If researchers pin down a clear cause-and-effect relationship between fungal species and C. difficile infection, they might be able to develop treatments that don’t involve antibiotics.”[iii]

That would be a pretty critical finding.

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[i] David B. Stewart, Justin R. Wright, Maria Fowler, Christopher J. McLimans, Vasily Tokarev, Isabella Amaniera, Owen Baker, Hoi-Tong Wong, Jeff Brabec, Rebecca Drucker, Regina Lamendella. Integrated Meta-omics Reveals a Fungus-Associated Bacteriome and Distinct Functional Pathways in Clostridioides difficile Infection. mSphere, 2019; 4 (4) DOI: 10.1128/mSphere.00454-19

[ii] https://www.cdc.gov/media/releases/2015/p0225-clostridium-difficile.html

[iii] https://www.sciencedaily.com/releases/2019/08/190828140108.htm