Enter the mycobiota

I have found the publication that focus on pretty much unexplored subject which is the presence and role of commensal fungi in the mammalian gastrointestinal tract. As far as I know there is no information on whether the intestinal fungi community (similarly the bacterial microbiome) has any influence on the basic metabolic functions of their hosts. The discussed paper does not provide such knowledge either. Instead it attempts to establish a link between the increased susceptibility to colitis and the inability to respond properly to fungal wall components (through the lack of the innate receptor Dectin-1) as well as it makes the initial analysis of murine mycobiome. Although it is probably too early to draw such conclusion, my impressions are that there might be differences in the very basics rules of cohabitation between mammals and intestinal fungi compared to mammals/commensal bacteria interactions.

The link: http://www.sciencemag.org/content/336/6086/1314.abstract

Authors confirm the presence of fungi in the gastrointestinal tract with two methods – the first detects the specific fungal RNA whereas the second visualizes fungal cells with soluble Dectin-1 probe (Dectin-1 recognizes β-1,3-glucans from fungal cell wall). The biggest fungal concentration is found in the colon which is also the place where commensal bacteria reach their highest density. However, the bulk of data is devoted to the analysis how the absence of Dectin-1 (which as mentioned above is the fungi-specific innate receptor linked to the inflammasome pathway) may influence the colitis development. The most important finding in that aspect is that the lack of Dectin-1 procures significantly worse colitis outcome in the mouse model that applies DSS-induced injury. Also the polymorphism in human gene encoding Dectin-1 is linked to the severe form of disease recognized as MRUC (medically refractory ulcerative colitis).

The publication contains other interesting data that allow very initial comparison between the characteristics of microbiome and mycobiome. One of important terms that describe a specific interaction between intestinal bacteria and their host is “dysbiosis”. The dysbiosis occurs when the gastrointestinal tract holds the abnormal microflora composition which appears to be able to influence the predisposition to maladies like gut inflammation or metabolic syndrome malfunctions. An interesting example of dysbiosis develops when animals are deficient for the innate receptor that recognizes bacterial flagellin (TLR5) which is a dominant immune activator in the gut. Remarkably, in some cases this pathogenic microflora setup has been shown to be transferable between different specimens as the sheer cohabitation of experimental animals (which is meant to expose them to each other microbiota) may change their susceptibility to certain diseases (consult the following report for an example: Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature; 2012. 482: 179-85). Authors test whether the absence of Dectin-1 could trigger any disease-facilitating microflora variations by crisscross transferring of microflora (not discriminating between bacteria and fungi) from either wild type animals or animals with Dectin-1 deficiency. However, such exchange does not influence the severity of DSS-provoked colitis which in this case looks to be determined by the host genetic background only.

The key in the understanding of the unique interactions between microbiota and immune system is the mutual interdependence of bacteria and their hosts. Nobody knows if this is the case for intestinal fungi; however, the initial data (with the emphasis on “initial”) coming from this report suggest something else. Investigators perform the assessment of murine intestinal mycobiome by sequencing and find that although there is enough diversity in the species arrangement, most data derive from a single organism – Candida tropicalis. This fungus is an opportunistic pathogen and authors confirm that it can play a role in the colitis development. Could intestinal fungi be just free riders?

Iliev ID, Funari VA, Taylor KD, Nguyen Q, Reyes CN, Strom SP, Brown J, Becker CA, Fleshner PR, Dubinsky M, Rotter JI, Wang HL, McGovern DP, Brown GD, & Underhill DM (2012). Interactions between commensal fungi and the C-type lectin receptor Dectin-1 influence colitis. Science (New York, N.Y.), 336 (6086), 1314-7 PMID: 22674328