Showing posts with label ibd. Show all posts
Showing posts with label ibd. Show all posts

Wednesday, July 1, 2015

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

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 Køge 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.


Wednesday, April 3, 2013

Blastocystis and IBD

We recently published what could be seen as a pilot study on inflammatory bowel disease (IBD) and the two most common intestinal parasites, Blastocystis and Dientamoeba fragilis.

The aim of the study was to identify possible differences in the prevalence of infection with Blastocystis and D. fragilis in patients with active and inactive IBD compared to controls.

We included 100 Danish patients with IBD (42 with Crohn's Disease, 41 with ulcerative colitis and 17 with ileal pouch-anal anastomosis) and 96 controls, used state-of-the-art diagnostics for Blastocystis and D. fragilis (PCR) and we saw striking differences in prevalence. While 19% of all healthy individuals had Blastocystis, only 5% of those with IBD had Blastocystis, and of the 42 patients with Crohn's Disease, only 1 had Blastocystis. In contrast, D. fragilis was not more common in healthy individuals than in IBD patients. Also, in patients with ulcerative colitis, Blastocystis was significantly more common in patients with inactive disease compared to patients with active disease.

Absence of Blastocystis in patients with Crohn's Disease and active ulcerative colitis may be due to unfavourable conditions for colonisation and should be explored further in order to investigate whether these potentially unfavourable conditions reflect differences in the composition of the microbiota in these patients, and/or whether this has something to do with host immunity. We are currently confirming the virtual absence of Blastocystis in Crohn's patients in another study based on metagenomic analysis of faecal DNA, and it will be very interesting to analyse the differences in Blastocystis prevalence in view of potential differences in bacterial communities.

The literature on Blastocystis and IBD is relatively limited, and I plan to return, maybe later this year, with a more elaborate post on the topic.

Reference:

Petersen AM, Stensvold CR, Mirsepasi H, Engberg J, Friis-Møller A, Porsbo LJ, Hammerum AM, Nordgaard-Lassen I, Nielsen HV, & Krogfelt KA (2013). Active ulcerative colitis associated with low prevalence of Blastocystis and Dientamoeba fragilis infection. Scandinavian journal of gastroenterology PMID: 23528075

Monday, January 14, 2013

A Penny For Your Thoughts

So, what should we do about Blastocystis? What do we want to know?

I believe the imminent answer to the latter question is easy: We want to know whether it’s pathogenic, whether we should treat it and how. But I also think that there are many other interesting aspects of Blastocystis which are also of broad interest to the general public, namely: How about the many cases of asymptomatic Blastocystis carriage? What does Blastocystis do in our guts? Could it have any potentially beneficial impact on our health?

Given the fact that Blastocystis has not been implicated in any outbreaks (admittedly: I guess that no one actually ever looked for Blastocystis in outbreak investigations... except for me!), I reckon that the chance of it being involved in acute diarrhoea is small. So, in that respect it's very different from the other intestinal protists such as Giardia, Cryptosporidium, Cyclospora, microsporidia, even Entamoeba histolytica. It's actually more reminiscent of helminth infections, which are are often chronic, and when light hardly give rise to symptoms (depending on species that is!).So I'm more thinking along the lines of co-evolution, adaptation, etc.

Maybe future research will call for a shift in paradigm, but until then I think that we should do what we already can, just at a larger scale and see where it takes us, namely:

Saturday, November 17, 2012

Amelioration of Colitis by Parasites - or "An Elliott & Weinstock Special"

Common parasites such as Blastocystis and Dientamoeba fragilis are often incriminated of causing chronic or intermittent diarrhoea or other intestinal symptoms despite the absence of compelling evidence. What most of us probably fail to realise is that parasites may actually prevent and ameliorate intestinal illness, including inflammatory bowel disease, other types of colitis, and other types of autoimmune diseases.

Inflammatory bowel disease (IBD) includes the two most common manifestations ulcerative colitis and Crohn’s Disease and affects more than 2 million people in North America and Europe. They are chronic inflammatory conditions of the gut that usually begin when people are in the second to third decade of life. Although the causes of these inflammatory diseases remain unknown, they are assumed to result from inappropriately aggressive mucosal (i.e. related to our intestinal lining) immune responses to elements or substances in our intestine. IBD is treated with immuno-suppresive drugs.

IBD has emerged primarily in the Western world along with a significant reduction in cases of intestinal helminthiasis due to clean food and water, improved hygiene and sanitation, and the development and use of antibiotics. In Denmark, helminthic infections due to previously common parasitic worms such as Ascaris (roundworm) are now at the point of being almost extinct in the indigenous population.

The hygiene hypothesis proposes that a causal link exists between the adoption of modern hygiene and the increase in the prevalence of immune dysfunctions. The extent of perinatal maturation of the immune system may play a crucial role in terms of our likelihood of developing allergic and autoimmune diseases later in life. The maturation process includes establishment of tolerance to food and harmless microorganisms, but also defence mechanisms against pathogens. If our environment is "too clean", we may fail to give our immune system the best possible opportunity to mature and differentiate appropriately. A robust immune response will protect us from recurrent infections, but if misdirected, it can cause disease.

Part of our immune system is the "adaptive immune system" -  or our "immunologic memory" - made up by cells such as lymphocytes (T- and B-cells), macrophages, dendritic cells, etc. plus antibodies and hormone-like substances (eg. cytokines) that are secreted to activate/inactivate or up- and down-regulate these cells. Our immune systems has to be able to recognise a plethora of foreign material such as bacteria, viruses and parasites, and to distinguish "self" from "non-self". IBD may be caused by mal-functions in our own immune system, and so may a lot of other diseases, diseases that we call "autoimmune diseases", and which include coeliac disease, multiple sclerosis, type 1 diabetes, and rheumatoid arthritis.

10,000 years ago, humans were infected by a variety of species of worms that are common in some parts of the world even today and hence humans and parasites have co-evolved over thousands of years. Importantly, most wild animals in their natural habitat are carriers of many types of parasites. A "clever" parasite does little harm to its host. Parasites have developed mechanisms that enable them to survive in their hosts, and also, the human immune system has developed a way to adapt to these common intruders.

Egg of Trichuris trichiura. Courtesy of Dr Marianne Lebbad.
How can one explain the amelioration of symptoms due to colitis by the presence of intestinal nematodes? Helminths appear to induce immune host regulatory cells that suppress inflammation, and helminth infections are strong inducers of immune regulatory circuits. The immune system changes in response to helminth colonisation and factors secreted by helminths that can influence immune cell function. It is likely that several immune-regulatory mechanisms are exploited by individual helminths. Otherwise, a helminth could not reliably evade our immune system to reproduce.

A new study has produced data that suggest that treatment of macaques suffering from chronic diarrhoea with eggs of the whipworm Trichuris suis can alleviate symptoms and modulate both the intestinal microbiota and immunoregulatory pathways. Trichuris suis is the whipworm of the pig, and contrary to Trichuris trichiura (image), T. suis appears not to be able to produce disease in primate hosts (including humans). When T. suis ova (TSO) are administered to humans, transient shedding of ova in faeces may be seen after a few weeks, but the individual remains asymptomatic.
Gene expression profiling of colonic biopsies from the macaques treated with TSO revealed up-regulation of genes typically involved in the so-called Th1-type immuno-response prior to TSO challenge, while induction of the Th2-type response followed after the TSO challenge; the Th2-type response resulted in mucosal repair, probably by increasing mucus production and turnover of epithelial cells, which again led to a reduction of bacterial attachment to the gut lining and a restoration of microbial diversity.

Briefly, a Th1-type response is generally a pro-inflammatory response that, among many other things, is responsible for microbicidal actions and perpetuating autoimmune responses. Excessive pro-inflammatory responses can lead to uncontrolled tissue damage, so there needs to be a mechanism to counteract this. The Th2­-type response includes the secretion of the anti-inflammatory cytokines, co-responsible for a general anti­-inflammatory response. In excess, Th2-type responses will counteract the Th1-mediated microbicidal action. The optimal scenario would therefore seem to be that humans should produce a well balanced Th1- and Th2-type response, suited to the immune challenge.
On top of the immunoregulatory impact, there is emerging evidence that helminths promote the growth and expansion of groups of bacteria that are beneficial or "probiotic" to the host. In the study of the macaques, the TSO induced a change in the intestinal microbiota.

While variation in160 genes in the human genome or more have been associated with increased risk of developing IBD, no specific gene variant that is sufficient or required for dysregulated mucosal inflammation as occurs in Crohn's disease or ulcerative colitis has been identified so far. There is a field of thought now saying that - over thousands of years - the human gut flora, including helminths, drove the development of variations in genes orchestrating various immune response pathways, and such genetic variations selected to operate under the influence of helminth infection could cause disease when operating without that influence.

So, the take home message here is that infestation by intestinal parasites may be a double-edged sword: While on one hand they may cause symptoms, they may on the other hand prevent us from developing inflammatory bowel disease and other autoimmune or allergic manifestations. Hence, helminths, although parasites, may contribute something in return to their hosts, and the loss of helminths removes a natural governor that helped to prevent disease due to immune regulation. Of course, more trials are needed before "helminth therapy" can actually be standardised, commercialised and used in the prophylaxis and treatment of IBD and gut allergic conditions. Once a good mechanistic understanding of how helminths alter immunity is available, it may even be possible to apply identified factors individually or in combination to treat disease.

As always, things are much more complex than presented here, but this post gives an impression of some of the fields of thought. Not all autoimmune diseases are driven by excessive Th1-type responses; some types of asthma may be driven by Th2-type response, but even here, helminths may favourably modulate immunoregulatory pathways.

Obviously, it would be interesting to explore how other parasitic infections impact on our immune system and gut flora. Interestingly, one helminth species appears to have "survived" in our "sterile" environment, - the pinworm (Enterobius)... and as pointed out in one of my recent blog posts (go here), many of us are definitely exposed to parasites that persist in our intestines for months, maybe years. What's their role in all of this?


Further reading:

Dirtying Up Our Diets - go here

Parasitic Worm Eggs Ease Intestinal Ills By Changing Gut Microbiota - go here.

Jostins L, et al. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature, 491 (7422), 119-24 PMID: 23128233

Berger, A. (2000). Science commentary: Th1 and Th2 responses: what are they? BMJ, 321 (7258), 424-424 DOI: 10.1136/bmj.321.7258.424
 
Elliott, D., & Weinstock, J. (2012). Where are we on worms? Current Opinion in Gastroenterology, 28 (6), 551-556 DOI: 10.1097/MOG.0b013e3283572f73
 
Elliott, D., & Weinstock, J. (2012). Helminth-host immunological interactions: prevention and control of immune-mediated diseases Annals of the New York Academy of Sciences, 1247 (1), 83-96 DOI: 10.1111/j.1749-6632.2011.06292.x
 
Weinstock, J. (2012). Autoimmunity: The worm returns Nature, 491 (7423), 183-185 DOI: 10.1038/491183a

Elliott DE, Summers RW, & Weinstock JV (2007). Helminths as governors of immune-mediated inflammation. International journal for parasitology, 37 (5), 457-64 PMID: 17313951

Broadhurst, MJ., et al.Therapeutic helminth infection of macaques with idiopathic chronic diarrhoea alters the inflammatory signature and mucosal microbiota of the colon PLoS Pathogens (PLoS Pathog 8(11): e1003000. doi:10.1371/journal.ppat.1003000).
 

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