This Month in Blastocystis Research (APR 2016)

I thought I’d give examples of some of the Blastocystis-related activities in which I was involved in April.

I was lucky to be invited as part of the faculty for this year’s ECCMID conference in Amsterdam. I had an opportunity to give a talk on Detection of protozoans using molecular techniques in routine clinical practice (click link to watch it). I also co-authored a poster with the title Blastocystis colonization correlates with gut bacterial diversity which is one of several studies recently performed by our group that suggest that Blastocystis is a biomarker – or an indicator if you wish – of a healthy gut microbial environment and high gut microbiota diversity. 

This very topic was one of the two major topics of my colleague Lee O’Brien Andersen’s PhD work; Lee just defended his thesis this Friday and being involved in his work is some of the most interesting, rewarding, and challenging professional activities I’ve experienced so far. I will soon provide a link to an electronic version of his thesis here on this site. I hope that we will be able to fund his post doc aiming to expand his work on comparative Blastocystis genomics, since he only just started this work. Also, I hope that we will be able to do much more research on Blastocystis’ impact on host immunity and gut microbiota using in vitro and in vivo models. We need to know much more about to which extent Blastocystis can actually induce changes in bacterial communities and what these changes are. We also need to know whether manipulation of gut bacteria in a Blastocystis carrier can lead to eradication of the organism. 

Last week, I was so fortunate to oversee the production of an e-learning course in faecal microbiota transplantation (FMT) for Unite European Gastroenterology (UEG), which will probably appear online already in June. FMT is currently used primarily for treating recurrent Clostridium difficile infections, but the application range may extend far beyond this. The presentations included both theoretical and live sessions, and it was a lot of fun to do, not only because of the topic, but also because my colleagues at the Agostino Gemelli University Hospital in Rome were extremely professional, enthusiastic and well-organised. The reason why FMT is interesting in a Blastocystis context includes the fact that while there are quite standardized guidelines as to what is not allowed in donor stool, there is no consensus on what is actually allowed in the stool. Obviously, Blastocystis will often be present in donor stool, and when conventional microbiological methods are used to screen donor stool for pathogens, Blastocystis will only rarely be picked up. Hence recipients may receive stool containing Blastocystis. And so of course we would like to know whether to recommend using or excluding stool positive for Blastocystis (and other common parasites such as Dientamoeba) for FMT.

This Month in Blastocystis Research (AUG 2015)

I would like to highlight a comment that we published in PLoS Pathogens, - a paper that is free for download here. It gained some attention on Twitter, and it was recently reviewed in the Faculty of 1000.

We basically highlight the tricky situation that we so often encounter in the field of clinical microbiology, namely the one in which all non-fungal organisms isolated from the human intestinal tract are being referred to collectively as 'parasites'. The word 'parasite' has a negative connotation, indicating that the organism exploits the host with detrimental effects on the host. While this is true for some ciliates, for instance Giardia, other ciliates may in fact be mutualists, which means that these organisms have adapted to a life within a host, providing the host with one or more advantages. One such example is seen in herbivores, where ciliates and flagallates break down cellulose.

In the clinical microbiology lab we face different types of organisms when dealing with stool samples: Giardia, Cryptosporidium and Entamoeba histolytica are considered true parasites, i.e. organisms benefitting from the environment of a host, at the expense of the host, and symptoms such as diarrhoea may develop, indicating host damage. Parasites such as Cryptospordium are usually infecting an individual for a short while, with immunity developing. Meanwhile, we also encounter eukaryotic organisms that are known to be able to colonise the intestine for a very long time, - decades, without being expelled by the host; Blastocystis belong to this group. For some reason it is as if the body 'tolerates' the presence of the organism. Maybe Blastocystis is good at evading local immune responses, or maybe the body wishes to 'keep' Blastocystis for some reason and so  developed a way to tolerate it... as I've hinted at before on this blog, maybe Blastocystis may assist us in one or more metabolic processes, for instance, either directly or indirectly, maybe by selecting for or influencing bacterial communities. Indeed, we recently found evidence of Blastocystis being specifically related to certain groups of bacteria, which, if confirmed, opens up for a whole new line of research, including the use of Blastocystis as a probiotic.

I know that this last sentence may sound harsh in some people's ears; nevertheless, most research involving Blastocystis so far has been quite static and unimaginative, and it's about time that food microbiologist and the like start taking an interest in the micro-eukaryotes that tend to be common and stable conolisers of our guts.

If YOU take an interest in this topic, I suggest you look up the articles cited below.

References and further reading:

Andersen LO, Bonde I, Nielsen HB, & Stensvold CR (2015). A retrospective metagenomics approach to studying Blastocystis. FEMS Microbiology Ecology, 91 (7) PMID: 26130823

Lukeš J, Stensvold CR, Jirků-Pomajbíková K, & Wegener Parfrey L (2015). Are Human Intestinal Eukaryotes Beneficial or Commensals? PLoS Pathogens, 11 (8) PMID: 26270819

Parfrey LW, Walters WA, & Knight R (2011). Microbial eukaryotes in the human microbiome: ecology, evolution, and future directions. Frontiers in Microbiology, 2 PMID: 21808637

Scanlan PD, Stensvold CR, Rajilić-Stojanović M, Heilig HG, De Vos WM, O'Toole PW, & Cotter PD (2014). The microbial eukaryote Blastocystis is a prevalent and diverse member of the healthy human gut microbiota. FEMS Microbiology Ecology, 90 (1), 326-30 PMID: 25077936

This Month in Blastocystis Research (JUN 2015)

I started developing this blog more than three years ago. After a bit more than a year, I collected a bunch of the posts, edited them and published them as a book on Amazon. Recently, I logged into my Amazon profile to see how the book was doing, and I was very pleased to notice that there were no less than four reviews of the book, and very positive ones too! Thank you to everyone who read/browsed it.

Blastocystis research is currently a quickly moving field, and I'm please to be able to inform you that one of the most interesting contributions to Blastocystis research coming out from our intstitute has just been published in Fems Microbiology Ecology. The article appearing in this journal was first-authored by PhD student Lee O'Brien Andersen (Statens Serum Institut) and post doc Ida Bonde (Danish Technical University) and describes how Lee and Ida took a retrospective approach to analysing metagenomics data originally generated by the MetaHIT Consortium and published in the often cited paper by Arumugam et al. (2012).

The abstract reads as follows:

Blastocystis is a common single-celled intestinal parasitic genus, comprising several subtypes. Here, we screened data obtained by metagenomic analysis of faecal DNA for Blastocystis by searching for subtype-specific genes in co-abundance gene groups, which are groups of genes that co-vary across a selection of 316 human faecal samples, hence representing genes originating from a single subtype. The 316 faecal samples were from 236 healthy individuals, 13 patients with Crohn's disease (CD), and 67 patients with ulcerative colitis (UC). The prevalence of Blastocystis was 20.3% in the healthy individuals and 14.9% in patients with UC. Meanwhile, Blastocystis was absent in patients with CD. Individuals with intestinal microbiota dominated by Bacteroides were much less prone to having Blastocystis-positive stool (Matthew's correlation coefficient = -0.25, P < 0.0001) than individuals with Ruminococcus- and Prevotella-driven enterotypes. This is the first study to investigate the relationship between Blastocystis and communities of gut bacteria using a metagenomics approach. The study serves as an example of how it is possible to retrospectively investigate microbial eukaryotic communities in the gut using metagenomic datasets targeting the bacterial component of the intestinal microbiome and the interplay between these microbial communities.

As far as we know this is the first study to sift out data on Blastocystis from data originally intended for analysis of bacterial communities only, and in the paper we describe how this was done. We believe that this approach has imminent potential for quickly advancing our knowledge on Blastocystis in a gut ecology context, including knowledge on the role of Blastocystis in terms of impacting/manipulating one or more types of intestinal bacteria.

I have a feeling that this is the first study in a string of similar studies that will soon hit PubMed, and within a year or two, we should be able to with confidence to hypothesise on the relationship between the structure and function on of the gut microbiota and Blastocystis, and–hopefully–other intestinal micro-eukaryotes.

Lastly, it was very interesting to note the article by Paramsothy et al. on donor recruitment for faecal microbiota transplantation (FMT; never heard of this? Watch the video below to learn more), recently appearing in the journal Inflammatory Bowel Disease. The study is interesting because it shows that most FMT donors are seemingly ineligible due to a variety of reasons, including colonisation by intestinal parasites such as Blastocystis... Given emerging data suggesting that Blastocystis is more common in healthy invididuals than in patients with gastrointestinal disease, the question remains whether Blastocystis-positivity should be a limiting factor for stool donation?

References:

Andersen LO, Bonde I, Nielsen HB, Stensvold CR. A retrospective metagenomics approach to studying Blastocystis. Published online 30 June 2015. DOI: http://dx.doi.org/10.1093/femsec/fiv072

Paramsothy S, Borody TJ, Lin E, Finlayson S, Walsh AJ, Samuel D, van den Bogaerde J, Leong RW, Connor S, Ng W, Mitchell HM, Kaakoush N, & Kamm MA (2015). Donor Recruitment for Fecal Microbiota Transplantation. Inflammatory bowel diseases, 21 (7), 1600-6 PMID: 26070003

This Month in Blastocystis Research (APR 2015)

#ECCMID2015 took place in Copenhagen. It was a great venue with a lot of interesting sessions. My favourite presentation was by Dr Paul D Cotter. We have had the pleasure of doing some work together with Dr Pauline D Scanlan as the main driving force. In his talk, Dr Cotter highlighted the emergence of research exploring whether certain organisms are pathobionts or probionts; among these, Blastocystis. Among many things, Dr Cotter reviewed the two recent Blastocystis-specific publications by Scanlan et al. focusing on the commonness and stability of Blastocystis colonisation [1] and on the need to use subtype-specific PCRs to detect and identify mixed subtype colonisation/infection [2].

Based at TEAGASC - Ireland, the Cotter/Scanlan group is one of the teams interested in looking into the ecology of Blastocystis (and other microbial eukaryotes of the gut), including its influence of the parasite on gut microbiota/microbiome (structure and function of our all gut organisms) and vice versa, and I'm sure that there will be a lot of interesting data coming out from their lab in the near future.

Cotter mentioned that Blastocystis has been subject to bad science. This may be due to a number of reasons. When developing hypotheses, we have a tendency of opting for dichotomous outcomes - either it is this or that, - maybe that's the very nature of hypotheses. If the clinical significance of Blastocystis is dependent on a number of different things such as co-colonising microbes (cross-talk), differences in host immunity response, Blastocystis subtype, and host diet for instance, then the true tapestry of physiological/biological/clinical mechanisms is likely to be extremely difficult to uncover. Moreover, despite the fact that so many people are curious about the public health significance of Blastocystis, apparently very little funding for targeted Blastocystis research exists. This means that mostly minor and not so significant studies ("cheap studies") on Blastocystis are available. Relatively little seminal research has been done in the clinical field (including the field of gastroenterology), and most studies on Blastocystis are cross-sectional and descriptive and usually not very well designed/carried out (use of diagnostic tools with limited sensitivity, for instance).

Maybe things will change when more and more people realise that we might be able to use Blastocystis as a biomarker/surrogate marker of intestinal homeostasis...

In my opinion the following topics would make for good research projects:

1) Large studies of both diseased cohorts and healthy individuals, including Blastocystis subtype data and data on accompanying protists, bacteria and fungi (16S/18S/ITS profiling).
2) Manipulaton studies where Blastocytsis (cysts) are introduced in ecosystems (in vitro or in vivo) to monitor potential changes.
3) Animal models using cyst challenge (to look at microbiota profile changing upon challenge, and, if in vivo colitis models are used, impact on host immunity)
4) Longitudinal microbiome studies of patients with and without Blastocystis.
5) Investigation of Blastocystis as a biomarker/surrogate marker of microbiota profiles and gut microbiome homeostasis... similar to my recent blog post: 'Show me your gut bacteria, and I'll tell you if you have Blastocystis!'
6) Comparative genomics (virulence gene identification for instance).
7) Identification of Blastocystis-specific signatures in metagenomics data sets.
8) Identification of drugs that have anti-Blastocystis properties, since currently, there is no drug regimen that consistently enables eradication of Blastocystis.

Speaking of which: We just published data in Journal of Ethnopharmacology on the anti-Blastocystis activity of 24 plant parts from 21 medicinal plants from Ghana [3]. We performed in vitro challenge of 48 h Blastocystis cultured cells (subtype 4) using ethanolic, warm and cold water plant extracts. Screening of these 24 different plant parts showed significant anti-Blastocystis activity of six of the ethanolic extracts: Mallotus oppositifolius, IC₅₀, 24h 27.8 µg/mL; Vemonia colorata, IC₅₀, 24h 117.9 µg/mL; Zanthoxylum zanthoxyloides, cortex IC₅₀, 24h 255.6 µg/mL; Clausena anisata, IC₅₀, 24h 314.0 µg/mL; Z. zanthoxyloides, radix IC₅₀, 24h 335.7 µg/mL and Eythrina senegalensis, IC₅₀, 24h 527.6 µg/mL. The reference anti-protozoal agent metronidazole (MTZ) had an IC₅₀, 24h of 7.6 µg/mL. Since cultures were xenic, antimicrobial activity was tested against two Gram-positive and two Gram-negative bacteria for all 24 plant parts at a final concentration of 1 mg/mL. Only C. anisata showed antimicrobial activity at a concentration of 800 µg/mL.

Hence, M. oppositifolius showed nearly as good activity as the reference anti-protozoal drug MTZ. Historically, the active plants found in this study have been used against dysentery, diarrhoea or other stomach disorders. Nowadays they are not used specifically for dysentery, but they are being used as medicinal plants against various stomach disorders.

Our book 'Biology of Foodborne Parasites' is out and available for ordering.

Incidentally, Blastocystis earned a designated chapter in the book 'Biology of Foodborne Parasites' which is now out and available for ordering here. It was fun writing it up, and hope that the chapter will be of interest to health care professionals and students around the world. The book also contains  introductions to the public health importance of foodborne parasites, molecular biological techniques in studies of foodborne parasites, and detection of parasites in foods.

References:

[1] Scanlan PD, Stensvold CR, Rajilić-Stojanović M, Heilig HG, De Vos WM, O'Toole PW, & Cotter PD (2014). The microbial eukaryote Blastocystis is a prevalent and diverse member of the healthy human gut microbiota. FEMS Microbiology Ecology, 90 (1), 326-30 PMID: 25077936   

[2] Scanlan PD, Stensvold CR, & Cotter PD (2015). Development and application of Blastocystis subtype-specific PCR reveals that mixed subtype infections are common in a healthy human population. Applied and Environmental Microbiology PMID: 25841010

[3] Bremer Christensen C, Soelberg J, Stensvold CR, & Jäger AK (2015). Activity of medicinal plants from Ghana against the parasitic gut protist Blastocystis. Journal of Ethnopharmacology PMID: 25773490

This Month in Blastocystis Research - MAR 2015

"Show me your gut bacteria and I'll tell you if you're infected with Entamoeba"

One of my 'partners in crime', science reporter Jop de Vrieze, made me aware of a study just published now by Elise R Morton and colleagues. The study appeared in bioRxiv—The Preprint Server for Biology, operated by Cold Spring Harbor Laboratory. The study is totally in line with one of the research foci in our lab.

The paper is called 'Variation in rural African gut microbiomes is strongly shaped by parasitism and diet', and can be downloaded here. The backbone in this type of research is the recognition that studies revealing a large contrast between the microbiomes of populations in developing countries and those of populations in urban industrialised areas have shown that geography is an important factor associated with the gut microbiome, but that such studies yet have to disentangle the effects of factors such as climate, diet, host genetics, hygiene and parasitism.

It's very refreshing that for once, 'parasitism' is included in such considerations. As mentioned in one or more of my previous blog posts, we have metagenomics data stongly indicating that Blastocystis colonisation is associated with certain microbial communities. As of yet, we have no idea about cause and effet, but the idea alone is immensely intriguing.

A large and a small cyst of Entamoeba coli. Courtesy of Dr Marianne Lebbad.

Now, Morton et al. have produced data that suggest that the presence of Entamoeba—another gut-associated eukaryotic genus comprising multiple species of varying pathogencitiy—is strongly correlated with microbial composition and diversity. They showed that an individual's liability to being infected by Entamoeba could be predicted with 79% accuracy based on gut microbiome composition.

The authors used 16S PCR and Illumina-based sequencing of 16S amplicons, and I could have wished that molecular assays, e.g., the 18S PCR that we have developed in our lab + associated software, had also been used to test the faecal samples from the 64 individuals enrolled in the study in order to obtain more precise data, not only on Entamoeba but also on other human-associated gut protists, such as Blastocystis.

While alpha (intra-host) diversity of Entamoeba-positive individuals was significantly higher than that of Entamoeba-negative individuals, analysis of the beta (inter-host) diversity revealed that gut communities across Entamoeba-positive individuals were more similar than across Entamoeba-negative individuals, suggesting that, as alpha diversity increases, there are fewer potential stable states for individual gut communities, or that infection by Entamoeba drives changes in the microbiome that are dominant over other factors.

Right—this is Entamoeba, I know, but in principle, the type of analyses that were performed in the present study could be applicable to Blastocystis, Dientamoeba, and other gut parasites, which may help us understand their role in health and disease. Are these parasites able to influence gut microbiota? Can they be used for gut microbiota manipulation? Or do they only infect people with certain microbiota profiles? Time will show... maybe.

For those of you who would like to read more about what is shaping our microbiomes and how the gut microbiota may impact on our gastrointestinal health, I recently did a couple of blog posts for United European Gastroenterology (UEG) Education that might be of some interest:

Are we finally saluting the fungal kingdom as a co-ruler of GI health and disease?

The intestinal microbiome—Rosetta Stone or Tower of Babel?


Reference:

Morton ER, Lynch J, Froment A, Lafosse S, Heyer E, Przeworski M, Blekham R, Segurel L.
Variation in rural African gut microbiomes is strongly shaped by parasitism and diet. bioRxiv doi http://dx.doi.org/10.1101/016949 - accessible here.

UEG Week 2014

The United European Gastroenterology (UEG) Week 2014 in Vienna is just around the corner. The conference kicks off on Saturday the 18th of October and judging from the program it will be a very interesting and inspiring event with so much to choose from that you will hardly be able to make up your mind about what to attend.

The general UEG website has now changed to the UEG Week Live site, which can be accessed here; however, you can still access the regular site here.

The programme for the entire venue can be downloaded here. There is also a very useful conference app (look for 'UEG Week 2014' in iTunes or go here), and a pathways tool, which you can download here.

However, I would like to invite you on a guided tour of some of the #UEGWeek topics for your inspiration. So, if you're interested in the clinical management and research developments in upper GI diseases, particularly in Helicobacter pylori, you may want to visit this blog post.

There's a panoply of interesting presentations and discussions on the menu for those who, like me, take an interest in the role of gut microbiota in health and disease, and to guide you through the jungle of treats, we developed this post. I doubt that there will be a lot on common intestinal microbial eukaryotic communities, but I'll try and see if I can stimulate the debate here and there...!

This Month in Blastocystis Research (AUG 2014)

Some August highlights in Blastocystis research:

1) The PRE-IOPCA Molecular Parasitology Workshop took place from the 7-10 August at CINVESTAV, Mexico City. Top-motivated students from some 10-15 countries worked hard from 7 am to 7 pm in dry+wet lab sessions, and we all had a really great time, thanks to both participants and fantastic organisers. There was a 4 h session on Blastocystis molecular epidemiology, and I was pleased to learn that some of the participants currently work with (or plan to work with) Blastocystis. I look forward to doing something similar in Ankara, Turkey on the 27th of May next year (www.blastomeeting2015.com - did you bookmark it?).

Most of the task force of the Molecular Parasitology Workshop (ICOPA 2014).

2) At the actual ICOPA conference, I chaired a session on Blastocystis in the context of IBS, with talks delivered by Ken Boorom, Pablo Maravilla, Pauline Scanlan and myself. In the audience I was honoured to see and meet Dr Hisao Yoshikawa, who has been a main contributor to Blastocystis research over the past 25 years or so (you can look up the publications by Dr Yoshikawa here). Considering the focus of this post, I guess that Pauline's talk was of particular interest, since she presented the data that we just published in FEMS Microbiology and Ecology:

3) The microbial eukaryote Blastocystis is a prevalent and diverse member of the healthy human gut microbiota. That's the title of the paper appearing in FEMS Microbiology and Ecology. The study, led by Pauline, showed that Blastocystis was present in 56% of 105 healthy adults, which is much higher than previously reported from an industrialised county (Ireland). Moreover, a diversity of different subtypes (species) were detected and Blastocystis was present in a subset of individuals sampled over a period of time between six and ten years, indicating that it is capable of long-term host colonisation. These observations show that Blastocystis is a common and diverse member of the healthy gut microbiota, thereby extending our knowledge of the microbial ecology of the healthy human intestine. And one of the interesting things here is: Why do we see this great divide? Why does half of the population appear colonised while the other half not? What are the factors driving successful Blastocystis colonisation? Would some people be refractory to colonisation or does it really boil down to some sort of enterotype-driven phenomenon as previously indicated?

4) I would like to reiterate the paper by Klimes et al. published a study in Genome Biology and Evolution (GBE) on a striking finding in the Blastocystis nuclear genome. Stop codons created by mRNA polyadenylation have been seen so far in mitochondrial genomes only and not in nuclear genomes; however, the authors observered this feature in Blastocystis's nuclear genome. Partly due to limitations of currently available annotation software, this finding ostensibly calls for reannotation of the genome currently available in GenBank (ST7). The paper was highlighted in a separate article in GBE that can be accessed from here.

5) Speaking of Blastocystis genomes: The genome of Blastocystis ST4 (WR1 strain) is now available on-line and can be accessed here.

6) Wang and colleagues studied the location and pathogenic potential of Blastocystis in the porcine intestine. They studied a total of 28 pigs from a commercial piggery, a small animal farm, and a research facility, and all pigs were positive (for ST5, and mixed subtypes were also seen in some). Post-mortem analyses showed that all pigs were consistently found to harbour Blastocystis in the colon, and approximately 90% of the caeca and rectums examined were positive. Some of the pigs were immunosuppresed (Dexamethasone), and interestingly, Blastocystis was occasionally detected in the small intestine, notably in immunosuppressed pigs, suggesting that immunosuprression may alter host-agent relations and predispose to small intestinal colonisation. Histopathological analysis saw the presence of vacuolar and granular forms of Blastocystis, but there was no evidence of attachment or invasion of the intestinal epithelium. The lack of pathology, including inflammation, epithelial damage, mucosal sloughing, and lamina propria oedema, confirmed the trend from a previous study carried out by Ron Fayer's group (see reference below). The study adds to the string of papers finding no evidence in support for Blastocystis causing primary intestinal damage.

6) Lastly, I want to extend a cordial thank you to Shashiraja Padukone and Subhash Chandra Parija, Department of Microbiology, Jipmer, Puducherry, India, for writing up a review of my 'Thoughts on Blastocystis' available on Amazon for the price of only one US$ or so. The review was published recently in Tropical Parasitology and can be accessed here.

And, for those who are worried about researchers 'overselling' microbiome research, there is a small comment in Nature calling for sound scepticism to be applied to research dealing with the relationship between the microbiome and different types of diseases. There is much to be agreed upon, and what I find particularly important, is to take the reductionist approach where possible - in terms of Blastocystis there are lots of ways to study the impact of Blastocystis on bacteria in vitro, and also host microbiota, physiology and immunology in vivo; ways that can be controlled quite diligently. Also, I think that simple validation of methods applied to map e.g. intestinal microbiota is key. This is for some reason something that is generally being utterly and completely ignored. Why?

References 

Fayer R, Elsasser T, Gould R, Solano G, Urban J Jr, & Santin M (2014). Blastocystis tropism in the pig intestine. Parasitology Research, 113 (4), 1465-72 PMID: 24535732

Hanage, W. (2014). Microbiology: Microbiome science needs a healthy dose of scepticism Nature, 512 (7514), 247-248 DOI: 10.1038/512247a

Klimeš V, Gentekaki E, Roger AJ, & Eliáš M (2014). A large number of nuclear genes in the human parasite blastocystis require mRNA polyadenylation to create functional termination codons. Genome Biology and Evolution, 6 (8), 1956-61 PMID: 25015079

Scanlan PD, Stensvold CR, Rajilić-Stojanović M, Heilig HG, De Vos WM, O'Toole PW, & Cotter PD (2014). The microbial eukaryote Blastocystis is a prevalent and diverse member of the healthy human gut microbiota. FEMS Microbiology Ecology PMID: 25077936 

Venton, D. (2014). Highlight: Not Like a Textbook--Nuclear Genes in Blastocystis Use mRNA Polyadenylation for Stop Codons Genome Biology and Evolution, 6 (8), 1962-1963 DOI: 10.1093/gbe/evu167

Wang W, Bielefeldt-Ohmann H, Traub RJ, Cuttell L, & Owen H (2014). Location and pathogenic potential of Blastocystis in the porcine intestine. PloS One, 9 (8) PMID: 25093578 

Happy World Digestive Health Day!

Today is World Digestive Health Day!

The theme is 'Gut Microbes -  Importance in Health and Disease'.

United European Gastroenterology (UEG), a professional non-profit organisation combining all the leading European societies concerned with digestive diseases, has launched a short video to raise awareness of such diseases:

In 2000, 600 million patients suffered from a gastrointestinal disease. By 2025, this is predicted to double to 1.2 billion (source).

For those interested (and with access!), there is a special issue on 'The Gut Microbiome in Health and Disease' in the journal Gastroenterology, one of the most renown and established journals in the field.

I would also like to bring your attention to the 5th ASM Conference on Beneficial Microbes, September 27-30 in Washington DC. Deadline for submission of abstracts is July 14.

Wishing everyone a nice World Digestive Health Day!

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