Osmoregulation and the human mycobiome

INTRODUCTION The last one-and-a half decades have made it amply clear that the human microbiota have a very significant role to play in health and disease. The human body can (or should) be better viewed as a complex ecosystem inhabited by micro-organisms that outnumber human cells 10 to 1 (Ley et al., 2006). However, most research in this field has been focused on the prokaryotic (specifically, bacterial) component of the microbiota. Sampling, in turn, is carried out mostly from sites that are readily accessible (Human Microbiome Project Consortium, 2012). Such sampling might not be genuinely representative of the situation in vivo, even for the bacteria under study. The human alimentary tract is a complex entity that exhibits extensive variation in biological characteristics such as tissue/cell types and secretions, as well as parameters such as temperature, pH, oxygen levels and osmolarity along its entire length. A proteomic study sampling mucosal lavages at multiple colonic sites indicated significant differences in protein profiles between the proximal and distal colon, which was supportive of the concept of their functional and developmental distinctness (Li et al., 2011). The colonization of the human infant by microbes, initially during the process of birth, exhibits an ecological succession of microbial species over time, and plays a prominent role in the maturation of the immune system as well (reviewed in Costello et al., 2012). The fungal members of the microbiota are not very numerous compared to bacteria. Large-scale metagenomic sequencing of fecal samples of 124 individuals found that only about 0.1% of genes detected were of eukaryotic origin (Qin et al., 2010). The most commonly encountered genera constituting the fungal microbiota or “mycobiome” (Huffnagle and Noverr, 2013) are Candida, Saccharomyces and Cladosporium (Hoffmann et al., 2013). The bacterial microbiota and a functional immune system are thought to keep the numbers of opportunistic fungal pathogens, such as Candida spp., under check in the absence of any perturbations. However, information from studies of polymicrobial diseases points to subtler adjustments, dependent on environmental conditions and cross-kingdom signals that eventually influence (positively and negatively) modes and rates of growth (reviewed in Peleg et al., 2010). The sensing of, and responses to, biotic and abiotic stimuli by fungi (as in other organisms) involves multiple signaling pathways that can interact to either augment or attenuate one another, as will be discussed below.