Dr Christen Rune Stensvold is a Senior Scientist and Public Health Microbiologist with specialty in parasitology. He has a Bachelor degree in Medical Sciences, an MSc in Parasitology, and a PhD in Health Sciences. He has been based at Statens Serum Institut, Copenhagen, since 2004. Since 2006, he has authored/co-authored more than 80 articles in international, peer-reviewed scientific journals. In 2013, he was awarded the Fritz Kauffmann Prize for his contribution to clinical microbiology in Denmark. For many years, he has been pursuing the role of common intestinal micro-eukaryotes in human health and disease. Follow Rune on Twitter @Eukaryotes.
One of the hot topics in modern-day research is the mapping and understanding of the human intestinal microbiome and its role in health and disease. Studies have suggested that the development of several diseases and conditions depends on how our microbiomes are influenced and shaped, but interpreting the data generated by such studies may not be that simple. Are we holding the key to understanding metabolic, immunological and pathological processes, or do the data produced so far preclude any type of generalization? Are we unraveling the code necessary to develop obesity, irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), or are we looking at a chaos of data, different terminologies and methodologies?
UEG Week 2014 was the first UEG event that I’ve attended in person, and the meeting was so packed with interesting sessions, I felt like cloning myself and deploying my clones to follow the many parallel tracks on offer. But alas, like all my fellow attendees, I had to choose, and rarely have I felt so spoiled for choice! Luckily, accessing the UEG Education Library has allowed me to look up a lot of the material that I was unable to see in person. Of the 52 ‘microbiota’ files available from UEG Week 2014 that can be discovered in the library, 10 are video-recorded presentations. As I take a huge interest in the role of the gut microbiota in health and disease, I've been indulging in these to update myself with some of the most recent advances in the field.
In one of his presentations at UEG Week 2014, Professor Antonio Gasbarrini starts out by asking several questions about the gut microbiota in relation to coeliac disease, an autoimmune enteropahty triggered by gluten proteins. Do patients with coeliac disease have a different gut microbiota to healthy people? Does the microbiota have a role in the pathogenesis of coeliac disease? Can a gluten-free diet (GFD) alter the composition of gut microbiota? He stresses that a GFD does alter the microbiota and that, in healthy individuals, just a few weeks on a GFD may in fact lead to a decrease in beneficial bacteria such as Bifidobacteria/Lactobacilli and an increase in Enterobacteriaceae, thus affecting immune-metabolic responses. Moreover, a decrease in short-chain fatty acids is seen, possibly conferring a decrease in the immunomodulatory role of the microbiota. It appears that an altered microbiota is a characteristic feature of coeliac disease, that Bifidobacteria is decreased, at least in children, along with upregulation of other bacterial species, while any causal link between microbiota composition and disease development remains to be established. At least one HLA genotype is known to select for early microbiota composition, so it is possible that this is in fact one of the mechanisms underlying the genetic component of the disease.
As do so many other scientists nowadays, Professor Gasbarrini stresses that while it may be important to know the structure of the microbiome, it is probably more important to know about the function of the microbiome. He also stresses the importance of sampling by highlighting the fact that identification of microbial communities may differ in the same individual depending on whether analysis of faecal or bioptic samples (mucosal biopsies, for instance) has been performed.
Regarding the function of the microbiome, there are two talks on the microbiota in the context of IBD by Professor Joël Doré, who expands on the existence of Crohn’s disease-specific signature genes that are much less abundant in Crohn’s disease patients than in healthy controls. However, single genes not being very informative, scientists of the MetaHIT Consortium recently took to ‘binning’ genes identified by metagenomic analysis of roughly 400 faecal samples into co-abundance gene groups (CAGs), enabling a comprehensive discovery of new microbial organisms, viruses and co-inherited genetic entities, and facilitating assembly of microbial genomes without the need for reference sequences.1 From these CAGs, a total of 741 metagenomic ‘units’ or ‘species’ could be derived, four of which have been identified as highly discriminatory identifiers of ulcerative colitis when compared with healthy individuals. In our lab, we have also been analysing these data, only with a view to identifying parasitic protist signatures rather than bacterial signatures in these CAGs, and we have just submitted our results for publication. Once the results are out, I’ll be back with more on this; it is safe to say already that we have found some very striking associations, with colonisation by certain parasitic protists being significantly linked to certain microbiota profiles and clinical phenotypes of study individuals. However, just like Professor Doré points out, in most cases we do not know whether such observations reflect causality or mere consequence; this is mostly due to the cross-sectional nature of such studies, but the prognostic/diagnostic value of such findings should, or course, be subject to scrutiny.
Being one of the heavy mantras of recent years, Faecalibacterium prausnitzii has been shown to be a direct predictor of Crohn’s disease relapse following infliximab withdrawal. In one study, Crohn’s disease patients with F. prausnitzii levels above the median were less prone to relapse than those with F. prausnitzii levels below the median, indicating that F. prausnitzii may represent a predictive factor for relapse.2
Professor Doré highlights that this is a trend not only in Crohn’s disease but also in ulcerative colitis. In the second talk by Professor Doré, you can learn more about the anti-inflammatory properties conferred by F. prausnitzii and its potential applicability as a diagnostic/prognostic marker. Professor Doré also gave a presentation on diet as a major modulator of the gut microbiota. He included a very educational slide on the functions of the human intestinal microbiota that are essential to health and wellbeing, and a slide summarising the diseases conferred by low gut species richness/gene count, such as Crohn’s disease, ulcerative colitis, IBS, obesity, Type-1 diabetes, Type-2 diabetes, coeliac disease, allergy and autism, etc., although the situation might not be entirely clear for coeliac disease, for example, as demonstrated by the talk by Professor Gasbarrini. In this talk, you can learn more about the so-called ‘enterotypes’, and you will find a few take-home messages regarding the impact of diet on microbiota development.
Four of the video-recorded presentations are from the session “The role of microbiota in non-alcoholic fatty liver disease”. If terms such as ‘microbiota’, ‘microbiome’ and ‘metagenome’, scare you off, you are offered a useful introduction from Dr Alexander Moschen. And in case these conspicuous accomplishments have slipped your attention, in this talk you are also introduced to the famous and heavily cited mouse studies by Bäckhed and colleagues3 and Turnbaugh and colleagues4 on the influence of gut microbiota on energy uptake. For me, Dr Moschen delivers one of the big take-home messages in this series of presentations, which again relates to microbiota structure and function: just because different people have different microbiota, this may not mean that these microbiota do different things. Rather, different species assemblages appear to lead to similar functional profiles (i.e. the metabolic properties of a given microbiota can be more or less identical to those metabolic properties characteristic of a microbiota of a different composition).
Focusing mainly on IBS, Dr Purna Kashyap presents studies showing that the gut microbiota can influence mechanisms characteristic of IBS, including gastrointestinal motility and secretion, visceral hypersensitivity and intestinal permeability, and that the microbiota influences entero-endocrine cells, stimulates the release of neurotransmitters like GABA, and mediates activation of immune cells, all affecting CNS function. Giving a thorough account of some of his own work too, Dr Kashyap shows that the effect of the gut microbiota on intestinal motility may in part be due to the effect on the host serotonergic system and that diet-related changes in microbiota fermentation products may alter host serotonergic pathways and gastrointestinal function.
Finally, I would like to recommend the presentation “Probiotics and antibiotics in IBS: Do they work?”, which was delivered by Dr Viola Andresen. Dr Andresen summarizes data from randomized controlled trials on the effect of rifaximin on non-constipated IBS patients, which includes a significant improvement of particularly (refractory) bloating, but also stool consistency and global symptoms. There may be some uncertainty as to whether the effect of rifaximin in IBS patients is due to alleviation related to unidentified small intestinal bacterial overgrowth (SIBO), and in general, the link between IBS and SIBO remains obscure, primarily due to a paucity of data. However, a study using animal experimental models that appeared in Gastroenterology almost a year ago proposed that rifaximin modulates the ileal bacterial community (leading to a relative abundance of Lactobacillus), reduces subclinical inflammation of the intestinal mucosa and improves gut barrier function to reduce visceral hypersensitivity.5 Although expensive, among its many advantages, rifaximin has few side effects, if any, and more studies on the use of this antibiotic in the management of functional bowel diseases are anticipated.
The language of the intestinal microbiome is being developed. Deciphering its many signs and symbols requires patience, but hopefully, this will eventually provide us with the tools and knowledge necessary to manipulate the gut microbiota to prevent, alleviate and cure a variety of diseases and promote health.
Presentations on the microbiota at UEG Week 2014
Gasbarrini A. Microbiota in coeliac disease. From New challenges in gluten sensitivity: From bench to bedside.
Dore J. Microbiota signatures in IBD. From IBD: What's new in 2014?
Dore J. Microbiota: The key player in IBD? From New insights into the pathophysiology of inflammatory bowel diseases.
Dore J. Diet: Major modulators of gut microbiota. From Diet, immunity and systemic disease.
Moschen AR. Microbiota composition in obesity and related disorders. From The role of microbiota in non-alcoholic fatty liver disease (NAFLD).
Gasbarrini A. Antibiotics, pre- and probiotics in NAFLD. From The role of microbiota in non-alcoholic fatty liver disease (NAFLD).
Tilg H. Innate immunity in NAFLD. From The role of microbiota in non-alcoholic fatty liver disease (NAFLD).
Serino M. Metabolic infection. From The role of microbiota in non-alcoholic fatty liver disease (NAFLD).
Kashyap P. Impact of gut microbiota on gut function and dysfunction. From Normal and abnormal cross-talk at the mucosal border: Relevance for GI function and dysfunction.
Andresen V. Probiotics and antibiotics in IBS: Do they work? From Altered intestinal microbiota composition in IBS: Does it affect clinical practice?
References
- Nielsen HB, Almeida M, Juncker AS, et al. Identification and assembly of genomes and genetic elements in complex metagenomic samples without using reference genomes. Nat Biotechnol 2014; 32: 822–828. http://www.nature.com/nbt/journal/v32/n8/full/nbt.2939.html
- Rajca S, Grondin V, Louis E, et al. Alterations in the intestinal microbiome (dysbiosis) as a predictor of relapse after infliximab withdrawal in Crohn's disease. Inflamm Bowel Dis 2014; 20: 978-986. http://journals.lww.com/ibdjournal/Abstract/2014/06000/Alterations_in_the_Intestinal_Microbiome.2.aspx
- Bäckhed F, Ding H, Wang T, et al. The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci USA 2004; 101: 15718–15723.
- Turnbaugh PJ, Ley RE, Mahowald MA, et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 2006; 444: 1027–1031. http://www.nature.com/nature/journal/v444/n7122/full/nature05414.html
- Xu D, Gao J, Gillilland M 3rd, et al. Rifaximin alters intestinal bacteria and prevents stress-induced gut inflammation and visceral hyperalgesia in rats. Gastroenterology 2014; 146: 484–496. http://www.gastrojournal.org/article/S0016-5085(13)01500-X/abstract
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