Showing posts with label co-evolution. Show all posts
Showing posts with label co-evolution. Show all posts

Saturday, May 10, 2014

Parasite-Microbiota-Host Interactions

One of the current mantras in microbiology is that 'bacterial cells in the human body outnumber human cells 10 to one'. This has been known for a long time, but I guess that the main reason why this is being hyped nowadays is due to the fact that current technologies now enable us to look at entire microbial communities in a given ecological niche at any time point and how for instance they relate to health and disease.

Casadevall and Pirofski already made this point clear back in 2000 in their great minireview in the journal Infection and Immunity on 'Host-Pathogen Interactions: Basic Concepts of Microbial Commensalism, Colonization, Infection, and Disease'. This is a great paper that helps us understand and distinguish between the many ways microbes impact on our body. First and foremost, it allows us to understand that microbes can be commensals in some hosts but cause disease in other hosts, and that very few microbes are obligate pathogens.

Anatomical drawing of abdomen, ca. 1900 (Elisa Schorn). Source.

Commensalism is defined by these authors as 'a state of infection that results in either no damage or clinically inapparent damage to the host, though it can elicit an immune response'. And a commensal is a 'microbe that induces either no damage or clinically inapparent damage after primary infection; a state that is thought to be established early in life'. In terms of the antibody response, 'it is not known whether these immune responses reflect the occurrence of an unidentified form of damage to the host'. Importantly, 'commensals also synthesise metabolites that are essential nutrients for the host'.

According to Casadevall and Pirofski, colonisation is 'a state of infection that results in a continuum of damage from none to great, with the latter leading to the induction of host responses that could eliminate or retain the microbe, or progress to chronicity or disease; for organisms that induce no damage during infection this state is indistinguishable from commensalism'.

I guess that to this end comes the concept of tolerance...Some single-celled parasites are common in young mammals such as calves and lambs (for instance Cryptosporidium and - it appears - microsporidia (unpublished data)), but appear to be cleared by host immune response mechanisms, while other parasites are establishing chronic colonisation, - parasites such as Entamoeba and Blastocystis. The latter parasites may also colonise humans for years on end... So why do we not eliminate these parasites? Blaser writes back in 1997: 'Failure to eliminate the parasite implies that the cost to the host is greater than the benefit. This may be due to high costs (e.g., loss of vital (...) functions), or significant benefits (e.g., protection against lethal diseases), or that both cost and benefit are relatively low'.

In Blastocystis research most scientists appear to be preoccupied by identifying a role for Blastocystis in disease, driven by the black and white concept that either it's pathogenic or not... or at least that if it can cause disease, it's by definition a pathogen! I think the paper by Casadevall and Pirofski shows with great clarity why we should try and take a much more differentiated view on Blastocystis and it's role in health and disease.

As mentioned in a previous blog post, Blastocystis is practically an obligate finding in some societies, while more rare in others. In some communities it may be common to contract it in very early childhood (infants/toddlers), while in other communities you may not be infected or infected only in adulthood. In Denmark, the prevalence in the healthy adult population is about 30%, and there may be countries where the prevalence is even lower - typically in regions, where the general population has been 'intestinally defaunated' (presumably due to excessive hygiene combined with a Westernised diet). And so, in some places this parasite is getting so uncommon that it may at some point become a cause of disease, a so-called 'emerging pathogen'... Conjectural maybe, but still not far fetched.

Simultaneously, evidence is emerging that intestinal microbial eukaryotes (Blastocystis and Dientamoeba fragilis) are significantly more common in healthy individuals than in patients with gastrointestinal disease such as IBS and - especially - IBD, suggesting that these parasites are protective of functional and organic bowel disease. Do they prime our immune system in a beneficial way? Do they select for beneficial bacteria? Do they keep potential harmful microbial intruders at bay? Could they be synthesising metabolites beneficial to the host just like ciliates involved in fermentation processes in the large intestine of various herbivorous mammals?

This is why the exploration of the structure and function of intestinal pro- and eukaryotic communities is so important. For instance, can we link Blastocystis to any intestinal microbial patterns? At our lab, we think we can, and it's something that we will try and explore further (if funding can be obtained). Our null hypotheses include the following:

1) The distribution of pro- and eukaryotes is random (for instance: Blastocystis is not statistically associated with the presence of particular bacteria or other eukaryotes (fungi, parasites)).

2) The introduction of a Blastocystis strain into an intestinal microbial niche does not cause alteration of the composition of the pro- and eukaryotic flora. This can be studied using an animal model, and it is tempting to try and study host immunological parameters during and after challenge with Blastocystis. Also gene expression in both host and microbial communities could be studied.

Take home message is that we should be cautious with regard to deeming a parasite as being either 'pathogenic' or 'non-pathogenic'... parasites may have a multitude of functions and may impact their hosts in a variety of ways that together with all other types of impact from and interactions with other microorganisms (microbiota) results in a health/disease matrix in every single individual.

Finally: Here's to pageview # 200,000! See you in Boston on Sunday morning at the #ASM2014 conference: Passion for Parasites !

Literature:

Blaser, M. (1997). Ecology of Helicobacter pylori in the human stomach. Journal of Clinical Investigation, 100 (4), 759-762 DOI: 10.1172/JCI119588  

Casadevall, A., & Pirofski, L. (2000). Host-Pathogen Interactions: Basic Concepts of Microbial Commensalism, Colonization, Infection, and Disease. Infection and Immunity, 68 (12), 6511-6518 DOI: 10.1128/IAI.68.12.6511-6518.2000

Sunday, March 16, 2014

What's In A Name?

When people have had their stools examined and are told that they have Blastocystis, most of them will not have a clue about what that is. And eventually they'll be told that it's a parasite. A parasite? As in tapeworm? Ok it's not. But then what? As in malaria? Oh... ok, I see... So it's....? Huh? As in ... what???

Now, which are those parasites in and on your body, and what in fact makes a parasite? Depends on who you ask. For parasitologists and public health/clinical microbiologists, a parasite means something along the lines of a eukaryotic organism (i.e. not a bacterium and not a virus) that is not a fungus and that is capable of living and maybe even multiplying on or inside another organism. Some organisms are considered somewhere in between parasites and fungi, such as microsporidia and Pneumocystis. But whether an organism is a fungus or a parasite is not important in most cases. You will also sometimes see that 'parasite' is used as a term meant to cover living organisms causing disease, and in this sense the term may include for instance bacteria and viruses; for instance. A lot of research deals with 'host-parasite' relationships, evolution of virulence and tolerance in parasites and hosts, respectively; also here, bacteria may be referred to as parasites.

 Mosquitos are practically parasites that may transmit other parasites. Source (eyeweed on Flickr).

The word 'parasite' stems from Greek, and means something like 'eating beside' or 'eating at someone else's table'. Parasitism is a non-mutual symbiotic relationship where one organism (the parasite) benefits at the expense of another (the host).

People like me usually divide parasites (sensu stricto) into protozoa (single-celled) and helminths (multi-cellular; worms). Effectively, this should be protists and helminths, since not all single-celled parasitic eukaryotes are protozoa. Please note that most protists and helminths (the nematode fraction) are free-living, - but some have adapted a parasitic life style and very effectively so.

So, when we're told by doctors that we are in fact hosting parasites, - how do we react? I guess  some of us will be quite alarmed: Creatures eating defenseless hosts from within, castrating them and turning them into zombies come to our minds, for instance Sacculina, Dicrocoelium, and Leucochloridium, just to mention a few ones (if you're not familiar with these ones, I suggest you look them up - you will hardly believe what they are capable of doing, and despite the horrifying subtlety and cold-bloodedness with which these creatures operate, one can hardly help marveling on how cunningly evolution makes way for some organisms' ability to exploit others). Other parasites are known to cause less spectacular phenotypic changes while having huge consequences for human health and disease: Malaria continues to be a significant cause of morbidity and mortality in many larger regions, and recently, diarrhoea caused by species of Cryptospordium was recognised as one of the most significant health issues in infants and toddlers in select sentinel areas sub-Saharan Africa and South Asia.

Some parasites, however, are commensals (ie. they just sit there with a more or less neutral outcome) or even beneficial to the host; for instance, there's evidence of ciliates assisting herbivores in metabolising cellulose. So while, these organisms from one point of view are parasites, the hole symbiotic relationship between these protozoa and herbivores may be seen as mutualistic. Maybe this particular relationship started out as 'parasitsm' but developed into 'mutualism'? There may be a lot more examples of this. Animals usually host various types of parasites, and humans probably used to host a much larger zoo of parasites than many of us do today; what is the public health significance of the recent and rapid 'defaunation' of humans in certain parts of the world?

At least technically, Blastocystis is also a parasite: Sitting in the colon, it lives on food delivered by its host, and thereby it certainly eats at someone else's table. Moreover, the parasite is probably not capable of completing its life cycle without a host. But what does it do apart from eating? Does it do us any good just like the ciliates in the herbivores? Blastocystis has co-evolved with humans (and other host species) and maybe humans have learned to exploit Blastocystis so that it's not only Blastocystis exploiting us? Does Blastocystis compete with other organisms in the gut? Does it secrete substances that impact other organisms including the host, and if so, in what way? What's its impact on the immune system? Etc.

I guess the take-home message here is that 'parasite' is just a word, - a name for something, and there are examples of parasitism turning into mutualism. Not all parasites induce disease, and parasites are not always organisms that should be sought eradicated.

Literature:

Kotloff KL, Nataro JP, Blackwelder WC, Nasrin D, Farag TH, Panchalingam S, Wu Y, Sow SO, Sur D, Breiman RF, Faruque AS, Zaidi AK, Saha D, Alonso PL, Tamboura B, Sanogo D, Onwuchekwa U, Manna B, Ramamurthy T, Kanungo S, Ochieng JB, Omore R, Oundo JO, Hossain A, Das SK, Ahmed S, Qureshi S, Quadri F, Adegbola RA, Antonio M, Hossain MJ, Akinsola A, Mandomando I, Nhampossa T, Acácio S, Biswas K, O'Reilly CE, Mintz ED, Berkeley LY, Muhsen K, Sommerfelt H, Robins-Browne RM, & Levine MM (2013). Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study. Lancet, 382 (9888), 209-22 PMID: 23680352

Veira DM (1986). The role of ciliate protozoa in nutrition of the ruminant. Journal of Animal Science, 63 (5), 1547-60 PMID: 3098727