Showing posts with label inflammatory bowel disease. Show all posts
Showing posts with label inflammatory bowel disease. Show all posts

Saturday, February 28, 2015

This Month in Blastocystis Research (FEB 2015)

Before heading off to visit dear colleagues at the Public Health Agency of Sweden tomorrow morning, I thought I'd do a quick 'This Month...' post.

Tropical Parasitology has published a paper by Elghareeb and colleagues on  'Laboratory Diagnosis of Blastocystis in Diarrheic Patients'. I was asked to do a Guest Commentary on their paper, and if your're interested you can download my comments here for free (html version). The paper by Elghareeb et al. should also be free for download at the website.

I have been very lucky to work together with Dr Prashant K Pandey and his colleauges in Pune, India. Together we just published the first data on Blastocystis subtypes ever to appear in India for what I know. We subtyped Blastocystis in a cohort of healthy Indian individuals, and found ST1 and ST3 in 27/100 adult individuals tested, while other common subtypes, ST2 and ST4, were absent. Remarkably, ST3 was seen in all positive individuals, while ST1 was seen only in mixed infections. The strains (alleles) found in India were no different to those found in for instance Europe.

There is a paper out by Rossen and colleagues from The Netherlands showing that Blastocystis is relatively uncommon in patients with active ulcerative colitis (UC) and significantly less common in UC patients (13.3%) than in healthy individuals (32.5%). This is completely in line with data that we generated in Denmark a couple of years ago. In fact, at two separate occasions we have been able to look into patients with inflammatory bowel disease. In both cases (one study has been submitted for publication), hardly any Blastocystis was found in patients with Crohn's disease, while a few patients with UC were positive; however, mostly patients with inactive disease appeared to have Blastocystis, while those with flare-ups were negative. Therefore, the influence of dysbiosis on Blastocystis colonisation should be subject to further scrutiny.

A lot of action goes on at the official website for the 1st International Blastocystis Symposium in Ankara in May, with exactly three months to go! Why not take a minute to browse the programme for the Pre-Symposium Course and the Scientific Programme for the actual Symposium? Please go here to familiarise yourself with the new content. 
Also, conference abstracts are pouring in, - did you submit yours yet?

References

Elghareeb AS, Younis MS, El Fakahany AF, Nagaty IM, & Nagib MM (2015). Laboratory diagnosis of Blastocystis spp. in diarrheic patients. Tropical Parasitology, 5 (1), 36-41 PMID: 25709951

Stensvold, C. (2015). Laboratory diagnosis of Blastocystis spp Tropical Parasitology, 5 (1) DOI: 10.4103/2229-5070.149885  

Pandey PK, Verma P, Marathe N, Shetty S, Bavdekar A, Patole MS, Stensvold CR, & Shouche YS (2015). Prevalence and subtype analysis of Blastocystis in healthy Indian individuals. Infection, Genetics and Evolution: Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases PMID: 25701123

Rossen NG, Bart A, Verhaar N, van Nood E, Kootte R, de Groot PF, D'Haens GR, Ponsioen CY, & van Gool T (2015). Low prevalence of Blastocystis sp. in active ulcerative colitis patients. European Journal of Clinical Microbiology & Infectious Diseases: Official Publication of the European Society of Clinical Microbiology PMID: 25680316

Friday, November 22, 2013

Do IBS Patients Lack Blastocystis and Dientamoeba??

I feel like sharing data from a poster created by one of my colleagues, Dr Laura Rindom Krogsgaard who works at K√łge Sygehus, Denmark. She presented the poster last month at the United European Gastrointestinal (UEG) Week in Berlin.

Laura is currently doing a very interesting survey on IBS and IBS-like symptoms in Danish individuals. Her first publication was on the epidemiology of IBS in Denmark (see literature list below). She performed a web-based survey, using YouGov Zapera, and questionnaires were emailed to a web panel (n = 19,567) representative of the general Danish population aged 18-50 years containing info on gender, age, geography and type of intestinal symptoms (if any). IBS and subtypes were estimated by the Rome III criteria. Of 6,112 responders, 979 (16%) fulfilled the Rome III criteria for IBS and had no organic diagnosis likely to explain their symptoms. IBS subtypes detected included  mixed IBS (36%), IBS with diarrhea (33%), IBS with constipation (18%), and unsubtyped IBS (11%).

At the Laboratory of Parasitology, we helped Laura analyse stool samples from survey participants for parasites. Not surprisingly, Blastocystis and Dientamoeba were by far the most common parasites detected; however, it appeared that individuals with IBS symptoms were less likely to be colonised by these parasites than their controls! Which means that we have a situation reminiscent of that seen in IBD patients, only less pronounced. 

Laura was able to survey symptom developement over 1 year and compare this to the incidence of Blastocystis and Dientamoeba, and none of the parasites (indvidually or in co-infection) were linked to symptom development.

Indeed, Laura's data are in line with the general tendency that we see for Blastocystis (see figure below). Blastocystis appears to be rare in individuals with perturbation of the intestinal microbiota (due to antibiotic treatment, inflammation, infection, diet, etc.), while common in healthy individuals, most of whom are probably characterised by high gut microbial diversity and thereby - apparently - the right substrate/growth conditions for Blastocystis.


Literature:

Krogsgaard LR, Engsbro AL, & Bytzer P (2013). The epidemiology of irritable bowel syndrome in Denmark. A population-based survey in adults ≤50 years of age. Scandinavian Journal of Gastroenterology, 48 (5), 523-9 PMID: 23506174

The entire poster "Dientamoeba fragilis and Blastocystis: Two parasites the irritable bowel might be missing" presented at the UEGweek can be viewed here via SlideShare.


Friday, June 22, 2012

More Bits And Pieces On The Microbiome... Or Maybe Mycobiome...

I promised to include some more stuff from some of the many recent publications in Science and Science Translational Medicine on the intestinal microbiome and its potential role in health and disease, and I've chosen two papers that could have broad public interest; for those who need an introduction to the microbiome, please go here (Wikipedia entry).

Because the microbiome has been more or less exclusively synonymous with the "bacteriome" it's very refreshing to discover a paper on fungal diversity in the gut. Like Blastocystis, and other single-celled parasites, intestinal fungi are also micro-eukaryotes, and we are continuously searching for the role of micro-eukaryotes in health and disease.

In general, very little is known about fungi in the intestine, and most clinicians, even mycologists, hardly bother about the fungi that may be present in our intestine, - I think I can say that without offending anyone! Maybe one of the most interesting things in a clinical respect is the fact that antibodies against the yeast Saccharomyces cerevisiae (see below) is a common finding in patients with Crohn's Disease, but relatively uncommon in patients with ulcerative colitis and healthy individuals.

Now, Iliev et al. (2012) start out by confirming the fact that fungi are indeed common commensals and thus a part of our normal intestinal flora. They then showed that colitis chemically induced in mice led to circulating antibodies against S. cerevisiae, which suggested that fungal antigens commonly found in the gut might be responsible for the induction of these antifungal antibodies during colitis.
The innate immune receptor Dectin-1 appears to have a key role in fungal recognition and combating. Therefore the authors wanted to further explore the role of this receptor by studying mice with and without Dectin-1. They found that Dectin-1 deficiency led to increased susceptibility to chemically induced colitis, including weight loss, tissue destruction and cell infiltration by inflammatory cells, etc. Moreoever, evidence was found of fungal invasion of inflamed tissue in the Dectin-1 knockout mice and taken together, their data suggest that Dectin-1 deficiency leads to altered immunity to commensal gut fungi.
To cut a long story short, results from these experiments in mice led the investigators to search for mutations in CLEC1A (the human Dectin-1 gene) in patients with ulcerative colitis, and they found that mutations were significantly more common in patients with severe ulcerative colitis (patients requiring colectomy) than in those with a less aggressive disease progression. This suggests that not only bacteria but also intestinal fungi interact with the intestinal immune system and may thereby influence health and disease. If this can be confirmed by others, this is an example of how biomarkers can predict the disposition towards/progression of disease and the results may have profound consequences for diagnostic strategies (e.g. screening for mutations in the Dectin-1 gene) and therapeutic management of patients with severe ulcerative colitis. Maybe it would have been interesting to know about such mutations in patients with Crohn's Disease as well...

Next, the investigators took to identifying what types of fungi were actually present in the colon of these mice. What may be a little bit controversial is the fact that the authors - by amplification and deep sequencing of  ITS1-2 (genetic marker commonly used to identify and taxonomically group fungi) - appear to have found not only species representing a staggering 50 well-annotated fungal genera in the mouse microbiome, but an additional 100 "novel and/or un-annotated fungi" as well - this does sound like a lot, but somehow the reader is calmed down a bit, when the authors later tell us that 97.3% of all fungi detected in the mouse faeces belonged to only 10 species, with 65.2% of the fungal sequences belonging to Candida tropicalis. So, whether the 100 novel fungi are indeed fungi colonising the intestinal tract is unknown, but they may very well represent fungi "on transit", so to say, acquired from food, drink or environment maybe... we know that fungi are ubiquitous - we inhale fungi every day for instance, and when deep sequencing is applied, it may be possible to trace even fungi only present in very small quantities; also ITS-2 analysis does not tell us whether the sequences are from "intact/live" (i.e. colonising) fungi or from degraded fungi (i.e. ingested); a classic example is Saccharomyces cerevisiae (Brewer's or Baker's yeast), which we may often acquire from food and drink, but which may also colonise (settle and proliferate) our intestines. Contamination of the faecal samples from fungi present in the environment and during processing is also a possibility (one of the reasons why PCR-based diagnostics for fungal infections is a tricky task...). Well so, all of these new species/genera may not necessarily represent the "mouse mycobiome". However, the authors found only few of the fungi in the food that was fed to the mice, so this still may remain a bit of a mystery... it would have been interesting to know whether the fungi detected were yeasts or molds, for instance, and very little information can be extracted from the supplementary material (phylogenetic analysis) accompanying the paper. Anyway, it's all very stimulating and further studies will assist in exploring fungal diversity and, hopefully, the diversity of micro-eukaryotes in general.

Saccharomyces cerevisiae is used in food and drink, but may also colonise our guts.

The next paper is one of many recent papers heralding the implementation of microbiome-based therapies in future personalised and precision medicine, possibly relevant to diseases such as inflammatory bowel disease, obesity and diabetes. Microbiome manipulation, so to say, is key to this concept and includes controlled diet, pre- and probiotic interventions, bariatric surgery (e.g. gastric bypass), faecal transplants (see my recent blog post on feacal bacteriotherapy), helminth therapy (yes!) or ecological engineering. Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host, and these may be known to many as lactobacilli or bifidobacteria (or simply "yoghurt"!) that protect us against harmful bacteria by inhibiting their growth and by helping reduce cholesterol levels, synthesise vitamins and sustain immune responses. Prebiotics are non-digestible dietary sugar molecules (oligosaccharides) that can enhance the activity of for instance lactobacilli and bifidobacteria. While the potential benefits of pre- and probitics have been known for many years, it is only with current available technology that we are starting to get a mechanistic understanding of their impact on our bodies.

The article picks up on host-gut microbiota metabolic interactions and the so-called "host-microbe metabolic axes", which include pathways and interactions responsible for gut permeability, formation of blood vessels (angiogenesis) in the gut mucosa, ion transports, sulfation ability of xenobiotics, and many other things; sulfation ability is a key component in metabolising of drugs, for instance. Differences in our individual abilities to sulfate certain compounds give us at least one explanation as to why different people may respond differently two drugs treatment (see previous posts), and our ability to metabolise a common drug such as acetaminophen (paracetamol) can apparently be predicted form our preinterventional excretion of the microbial co-metabolite 4-cresyl sulfate; other gut microbial contributions that can alter the absorption, metabolism, and safety of drugs have been demonstrated recently.

Gastric bypass (Roux-en-Y) is a surgical procedure carried out to delay and reduce the absorption of calories and includes bypassing a large part of the stomach and a part of the small intestine by a procedure known as "stapling". Roux-en-Y appears to be associated with major and stable changes in the microbiota and in many microbially generated compounds, all of which are key components in the host-microbe metabolic axes. "This suggests that the microbiota is an essential part of the "gearbox" that connects the physical effects of bariatric surgery to the resulting beneficial effects."

Gut ecology changes with age, and current investigations seek to define the rationale of and potential for manipulating the microbiome of older people, for instance with pre- and probiotics, to secure higher microbiome diversity (high microbiome diversity appears to be beneficial) and resilience to antibiotics-induced changes in gut flora.

For those of you who nearly choked on "helminth therapy" - I may put up a post in the future on how helminths (and maybe other intestinal eukaryotes such as amoebae?) apparently play a role in the presentation and regulation of diseases such as asthma and inflammatory bowel diseases...

The cells of our intestinal microbiome outnumber our own body cells by 10 to 1. Within the next decade or so we will be able to extract a lot of information about how the bacteria and other "bugs" in our guts influence and contribute to health and disease. Importantly, we may have to realise now more than ever that "germs and bugs" and their actions and interactions can hold the key to a healthy life in ways that we wouldn't think were possible only a few years ago. This means that we should acknowledge that some bacteria and parasites may be a sign of a healthy intestinal environment / a healthy gut function, and that consumption of drugs such as antibiotics may produce shifts in our microbiota that may not necessarily be beneficial.

References:

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
 
Holmes E, Kinross J, Gibson GR, Burcelin R, Jia W, Pettersson S, & Nicholson JK (2012). Therapeutic modulation of microbiota-host metabolic interactions. Science translational medicine, 4 (137) PMID: 22674556