Mucosal microbial parasites/symbionts in health and disease: an integrative overview

Abstract

Microbial parasites adapted to thrive at mammalian mucosal surfaces have evolved multiple times from phylogenetically distant lineages into various extracellular and intracellular life styles. Their symbiotic relationships can range from commensalism to parasitism and more recently some host-parasites interactions are thought to have evolved into mutualistic associations too. It is increasingly appreciated that this diversity of symbiotic outcomes is the product of a complex network of parasites-microbiota-host interactions. Refinement and broader use of DNA based detection techniques are providing increasing evidence of how common some mucosal microbial parasites are and their host range, with some species being able to swap hosts, including from farm and pet animals to humans. A selection of examples will illustrate the zoonotic potential for a number of microbial parasites and how some species can be either disruptive or beneficial nodes in the complex networks of host-microbe interactions disrupting or maintaining mucosal homoeostasis. It will be argued that mucosal microbial parasitic diversity will represent an important resource to help us dissect through comparative studies the role of host-microbe interactions in both human health and disease.

Keywords: Bacteria; extracellular and intracellular parasites; innate and adaptive immune responses; microbiota; mucosa; parasitic protists; parasitic protozoa; pathobionts; viruses.

Fig. 1

The now generally accepted new paradigm of microbe-microbe / host-microbe complex network of interactions that can contribute to health (maintaining homeostasis) or disease (inducing excessive inflammation through time and space) status of the animal/human host. The terms eubiosis and dysbiosis relate to the microbiota functional activities associated with respectively health through maintaining mucosal homeostasis (ensuring optimal mucosal functionality) or pathologies due to excess inflammation leading to damage mucosal surfaces and that can also contribute to disrupt systemic physiology and sub-optimal cognitive capacities. See main text and cited references for the conceptual limitations on the use of eubiosis and dysbiosis.

Fig. 2

The complex network of interactions at mucosal surfaces between microbes, epithelial cells and immunocytes modulating the immunological and inflammatory status of the mucosal surfaces. Optimal interactions ensure adequate responses to the presence of members of the microbiota and robust challenges to pathogens and at the same time tolerance to innocuous antigens required to maintain long term functionality of the mucosal surface underlying optimal digestion and nutrient uptake, breathing, or reproduction. Arrows indicate direct (e.g. physical contact) and indirect (e.g. metabolites or signalling molecules) interactions such as infection of epithelial cells by intracellular pathogens (viruses or Microsporidia, both illustrated) and doted arrows indicate indirect (e.g. though metabolites) interactions between illustrated cells. Note in particular the central node/role of epithelial cells that integrate, and in effect coordinate/orchestrate the complex network of interactions between microbes and immunocytes. A virus (several green “stars”) infected epithelial cell is illustrated as is a virus infected trichomonad (one green “star”, see example in the text). In addition, some viruses/phages infect bacteria also contributing to the overall functional properties of the mucosa microbial ecology. Intracellular bacteria (black rectangles) and Microsporidia (blue cell and spores) are also illustrated within epithelial cells. ZO, Zonula occludens - tight junction; ECM, extra cellular matrix. For simplicity the presence of mucus and the glycocalyx interacting with luminal microbes are not shown and only a monolayer of epithelial cells (e.g. as in the intestine) is illustrated.

Fig. 3

Potential role of MMPS in inducing dysbiosis or eubiosis at mucosal surfaces. In the context of dysbiosis this would contribute to the loss of mucosal homeostasis, and by doing so to a number of potential pathologies that eventually will translate in dysfunctional mucosa leading to disease both locally, e.g. mucosa inflammation, or more distal impacts. The illustrated examples include: Trichomonas vaginalis (Tv) contributing to increasing the vaginal bacterial diversity associated with bacterial vaginosis, a form of pro-inflammatory dysbiosis of the urogenital tract (UGT). T. vaginalis infections are also associated with the loss of mutualists in the UGT. Entamoeba histolytica (Eh) can contribute to colitis, mucosa perforation and translocation of both parasites and some member of the gut microbiota into the portal vein and systemic tissues that can contribute to highly damaging systemic and local inflammations in the digestive tract (DT) and beyond. In contrast, the loss of some microbial eukaryotes, including potentially Blastocystis hominis (Bh) and some Entamoeba spp. (especially, non-histolytica species), could contribute to the gut microbiota reduced bacterial diversity associated with a dysbiotic state. Similarly, metronidazole treatments aiming at eradicating anaerobic mucosal microbial parasites such as Giardia and Trichomonas species, will also contribute at disrupting the mucosal microbiota by killing important bacterial anaerobes and can favour the expansion of bacterial pathobionts in the DT and the respiratory tract (RT). See main text for examples and citations. MMPS can also influence the RT - e.g. (Maritz et al., 2014) - but this is not covered here.