OK, so just for the record I'm not actually saying that NICE (the National Institute for Health and Care Excellence) actually provide faecal microbiota transplants (FMTs) as some sort of in-house service; that's not their job. But as the BBC reported (see here) they have published guidance on the use of FMT specifically with recurrent Clostridium difficile infection in mind (see here for the full guidance). And that guidance is, as was expected, positive on the use of FMTs where and when other treatments have failed.
I'm not surprised that they have come down on the side of FMTs for recurrent C.diff infection in light of the data being presented, some of which has been previously covered on this blog. As I've mentioned before, however you perceive this type of intervention and the thought of receiving the collected bacteria from someone else's deepest, darkest recesses, FMT does seem to reach the parts that other treatments fail to do for some people.
I suppose the next question is: are there other conditions or other instances where FMT might prove to be useful? (hint: possibly... but with more research required).
Showing posts with label gut bacteria. Show all posts
Showing posts with label gut bacteria. Show all posts
Wednesday, 26 March 2014
Thursday, 12 September 2013
A true rise in pediatric coeliac disease
Consider this something of a micro blog post as I offer up your scientific TV dinner today in the form of the paper by White and colleagues* (open-access) on the numbers game when it comes to coeliac disease (even celiac disease if you prefer) in children.
On the understanding that not everyone knows about the currently known hows and whys of coeliac disease (CD) - the premier autoimmune condition linked to the protein gluten - readers might want to check out my CD mega-post over on a sister blog (see here).
Self-promotion over and done with, the paper from White et al looking at the incidence (that's incidence not prevalence) of CD is an important one, because as the authors conclude: "The significant increase in classic cases is strongly suggestive of a true rise in CD incidence". In other words, it's not just about better case ascertainment, at least when it comes to CD in Scotland.
So to the next question: 'why the increase?' We've been given a few areas that might require some further investigation (see here and here and here) but I'm not going to make any sweeping generalisations at this time.
On the understanding that not everyone knows about the currently known hows and whys of coeliac disease (CD) - the premier autoimmune condition linked to the protein gluten - readers might want to check out my CD mega-post over on a sister blog (see here).
Self-promotion over and done with, the paper from White et al looking at the incidence (that's incidence not prevalence) of CD is an important one, because as the authors conclude: "The significant increase in classic cases is strongly suggestive of a true rise in CD incidence". In other words, it's not just about better case ascertainment, at least when it comes to CD in Scotland.
So to the next question: 'why the increase?' We've been given a few areas that might require some further investigation (see here and here and here) but I'm not going to make any sweeping generalisations at this time.
Friday, 12 July 2013
Probiotic mix effective for IBS?
We are already starting to appreciate just how (a) complex and (b) important our gut microbiota are to health and wellbeing outside of the more traditional duties of food digestion and making the odd nutrient or two. Those trillions of beasties which call us home seem to be cropping up everywhere these days in research terms, based on investigations as diverse as obesity (see here) and autoimmunity (see here) even to the point of speculation about involvement in psychological development (see here) (mice, not humans, mice... so far). That and the fact that stability seems to be a good word to describe their bacterial lives* (assuming that you don't swallow a grenade).
That being said, the involvement of gut bacteria whether alone or as part of the triad of gut involvement - gut bacteria, gut permeability and mucosal / systemtic immunity** - in relation to gastrointestinal (GI) illness and/or dysfunction should not get too lost in the dialogue. Indeed, how modification of gut bacteria, whether through diet, medicine or other means (yes, yuck factor 10) remains a real point of interest when it comes to GI conditions.
With that in mind I turn today to the paper by Yoon and colleagues*** who following quite a rigourous trial (double-blind, placebo-controlled) suggested that a mix of probiotics given over 4 weeks might be able to do some positive things to the symptoms of formally diagnosed irritable bowel syndrome (IBS). The "multi-species" mix included various species and strains: Bifidobacterium longum, Bifidobacterium bifidum, Bifidobacterium lactis, Lactobacillus acidophilus, Lactobacillus rhamnosus, and Streptococcus thermophilus. The authors reported that more of those in receipt of the probiotic mix reported greater relief from their IBS symptoms over and above placebo, and when looking at fecal microflora, there were accompanying changes too as a result of the mix. Interestingly even in the placebo group there were some bacterial changes to be had (mind over matter?).
I know that the Yoon paper is not necessarily new news when it comes to probiotics and IBS (see here) but what this paper does add is its suggestion that rather than thinking too narrow about specific bacteria and species affecting specific conditions, we should perhaps be taking a more broad perspective and realising that the whole is greater than the sum of its parts when it comes to the intricate connections between our various passengers residing in the gut.
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* Faith JJ. et al. The long-term stability of the human gut microbiota. Science. 2013 Jul 5;341(6141):1237439. doi: 10.1126/science.1237439.
** Groeger D. et al. Bifidobacterium infantis 35624 modulates host inflammatory processes beyond the gut. Gut Microbes. 2013 Jun 21;4(4).
*** Yoon JS. et al. Effect of multi-species probiotics on irritable bowel syndrome: a randomized, double-blind, placebo-controlled trial. J Gastroenterol Hepatol. 2013 Jul 5. doi: 10.1111/jgh.12322.
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That being said, the involvement of gut bacteria whether alone or as part of the triad of gut involvement - gut bacteria, gut permeability and mucosal / systemtic immunity** - in relation to gastrointestinal (GI) illness and/or dysfunction should not get too lost in the dialogue. Indeed, how modification of gut bacteria, whether through diet, medicine or other means (yes, yuck factor 10) remains a real point of interest when it comes to GI conditions.
With that in mind I turn today to the paper by Yoon and colleagues*** who following quite a rigourous trial (double-blind, placebo-controlled) suggested that a mix of probiotics given over 4 weeks might be able to do some positive things to the symptoms of formally diagnosed irritable bowel syndrome (IBS). The "multi-species" mix included various species and strains: Bifidobacterium longum, Bifidobacterium bifidum, Bifidobacterium lactis, Lactobacillus acidophilus, Lactobacillus rhamnosus, and Streptococcus thermophilus. The authors reported that more of those in receipt of the probiotic mix reported greater relief from their IBS symptoms over and above placebo, and when looking at fecal microflora, there were accompanying changes too as a result of the mix. Interestingly even in the placebo group there were some bacterial changes to be had (mind over matter?).
I know that the Yoon paper is not necessarily new news when it comes to probiotics and IBS (see here) but what this paper does add is its suggestion that rather than thinking too narrow about specific bacteria and species affecting specific conditions, we should perhaps be taking a more broad perspective and realising that the whole is greater than the sum of its parts when it comes to the intricate connections between our various passengers residing in the gut.
----------
* Faith JJ. et al. The long-term stability of the human gut microbiota. Science. 2013 Jul 5;341(6141):1237439. doi: 10.1126/science.1237439.
** Groeger D. et al. Bifidobacterium infantis 35624 modulates host inflammatory processes beyond the gut. Gut Microbes. 2013 Jun 21;4(4).
*** Yoon JS. et al. Effect of multi-species probiotics on irritable bowel syndrome: a randomized, double-blind, placebo-controlled trial. J Gastroenterol Hepatol. 2013 Jul 5. doi: 10.1111/jgh.12322.
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Tuesday, 21 May 2013
Gut bacteria determines social development? Psychobacteriomics?
The paper by Desbonnet and colleagues* (open-access) asks some intriguing questions about how our gut bacteria - those trillions of passengers which we all carry in our deepest, darkest recesses - might have the propensity to affect the behavioural development of a mouse specifically focused on social development.
Whilst to some people this might not sound like a particularly exciting finding, to others such a suggestion might potentially signal the start of a whole new way of looking at how our (human) physiology might actually impact on our psychological development. Move over Piaget et al and make way for something rather more complex. Even possibly a new -omic..... psychobacteriomics (you heard here first folks).
OK let's not get ahead of ourselves here. This was only a small study of germ-free (GF) and conventionally colonised (with bacteria) mice measuring their mouse-like behaviours across various 'sociability tests'. Mice are mice not humans and this finding needs replication.
That being said I'm interested. I'm interested whether these findings could be crossed over to other animals and even humans. I'm interested whether different bacteria might be linked to various aspects of social development. I'm interested whether this means that taking lots of antimicrobials during early infancy could affect social development. Indeed, I'm interested if this might have implications for the arguments: breast vs. bottle, c-section vs. natural birth, even whether supplementation with probiotics during critical stages of development might show some relationship to a person social development bearing in mind I'm not making any recommendations by the way.
And then there's conditions like autism to consider...
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* Desbonnet L. et al. Microbiota is essential for social development in the mouse. Molecular Psychiatry. May 2013.
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Whilst to some people this might not sound like a particularly exciting finding, to others such a suggestion might potentially signal the start of a whole new way of looking at how our (human) physiology might actually impact on our psychological development. Move over Piaget et al and make way for something rather more complex. Even possibly a new -omic..... psychobacteriomics (you heard here first folks).
OK let's not get ahead of ourselves here. This was only a small study of germ-free (GF) and conventionally colonised (with bacteria) mice measuring their mouse-like behaviours across various 'sociability tests'. Mice are mice not humans and this finding needs replication.
That being said I'm interested. I'm interested whether these findings could be crossed over to other animals and even humans. I'm interested whether different bacteria might be linked to various aspects of social development. I'm interested whether this means that taking lots of antimicrobials during early infancy could affect social development. Indeed, I'm interested if this might have implications for the arguments: breast vs. bottle, c-section vs. natural birth, even whether supplementation with probiotics during critical stages of development might show some relationship to a person social development bearing in mind I'm not making any recommendations by the way.
And then there's conditions like autism to consider...
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* Desbonnet L. et al. Microbiota is essential for social development in the mouse. Molecular Psychiatry. May 2013.
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Tuesday, 14 May 2013
Akkermansia muci... muciniphila and diet induced obesity
It just rolls off the tongue: Akkermansia muciniphila*.
As we speak A.muciniphila is making headlines across the world based on the study by Amandine Everard and colleagues** (open-access) on what happened to mice who had or were lacking in this stalwart of the gut microbiome.
No need for me to go into great detail about the Everard trial because (a) the paper is open-access and (b) it's already received plenty of coverage as per an entry in Nature (see here) and the National Geographic (see here).
The long-and-short of it (I should perhaps rename this blog with those words) was that A.muciniphila is, as it's name suggests, a bacteria with a connection to mucin; in particular it's love of the stuff. The finding: mice who were obese and diabetic (type 2 diabetes) seemed to have lower levels of A.muciniphila, and "that A. muciniphila treatment reversed high-fat diet-induced metabolic disorders, including fat-mass gain, metabolic endotoxemia, adipose tissue inflammation, and insulin resistance". The speculation is whether these mouse findings might, just might turn out to be something truly remarkable for humans presenting with similar symptoms.
But as with everything in life, things are rarely so simple. My first thought when I saw the name A.muciniphila were the intriguing findings reported by Lynne Wang and colleagues*** of lower numbers of A.muciniphila in fecal samples from children diagnosed with an autism spectrum disorder and their siblings. Just in case your interested, I talked about this paper on a post for a sibling blog. So unless we are talking about children with autism subsequently being a greater risk for obesity and type 2 diabetes, I would wager that there is more to A.muciniphila than just weight loss and insulin.
Leaky gut anyone?
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* Derrien M. et al. Akkermansia muciniphila gen. nov., sp. nov., a human intestinal mucin-degrading bacterium. IJSEM. 2004; 54: 1469-1476.
** Everard A. et al. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. PNAS. May 2013.
*** Wang L. et al. Low Relative Abundances of the Mucolytic Bacterium Akkermansia muciniphila and Bifidobacterium spp. in Feces of Children with Autism. Appl Environ Microbiol. 2011; 77: 6718–6721.
----------
As we speak A.muciniphila is making headlines across the world based on the study by Amandine Everard and colleagues** (open-access) on what happened to mice who had or were lacking in this stalwart of the gut microbiome.
No need for me to go into great detail about the Everard trial because (a) the paper is open-access and (b) it's already received plenty of coverage as per an entry in Nature (see here) and the National Geographic (see here).
The long-and-short of it (I should perhaps rename this blog with those words) was that A.muciniphila is, as it's name suggests, a bacteria with a connection to mucin; in particular it's love of the stuff. The finding: mice who were obese and diabetic (type 2 diabetes) seemed to have lower levels of A.muciniphila, and "that A. muciniphila treatment reversed high-fat diet-induced metabolic disorders, including fat-mass gain, metabolic endotoxemia, adipose tissue inflammation, and insulin resistance". The speculation is whether these mouse findings might, just might turn out to be something truly remarkable for humans presenting with similar symptoms.
But as with everything in life, things are rarely so simple. My first thought when I saw the name A.muciniphila were the intriguing findings reported by Lynne Wang and colleagues*** of lower numbers of A.muciniphila in fecal samples from children diagnosed with an autism spectrum disorder and their siblings. Just in case your interested, I talked about this paper on a post for a sibling blog. So unless we are talking about children with autism subsequently being a greater risk for obesity and type 2 diabetes, I would wager that there is more to A.muciniphila than just weight loss and insulin.
Leaky gut anyone?
----------
* Derrien M. et al. Akkermansia muciniphila gen. nov., sp. nov., a human intestinal mucin-degrading bacterium. IJSEM. 2004; 54: 1469-1476.
** Everard A. et al. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. PNAS. May 2013.
*** Wang L. et al. Low Relative Abundances of the Mucolytic Bacterium Akkermansia muciniphila and Bifidobacterium spp. in Feces of Children with Autism. Appl Environ Microbiol. 2011; 77: 6718–6721.
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Thursday, 28 March 2013
Gut bacteria - obesity and coeliac disease - stem cells
Another very quick post to bring to your attention two very interesting papers which caught my attention recently.
The first is by Ciccocioppo and colleagues* and how, quote: "allogeneic HSCT may lead to induction of gluten tolerance in patients with CD [coeliac disease]." HSCT = hematopoietic stem cell transplantation, which is indeed as controversial as it sounds. Two patients, both with CD and β-thalassemia major who at 5 year follow-up after HSCT did not appear to show a reappearance of the some of the serological and histological markers of CD following gluten consumption. I'm not making any recommendations from this (or anything else) aside from stressing the need for quite a bit more research in this area.
The second paper by Liou and colleagues** suggested that based on a mouse model, changes to the gastrointestinal (GI) bacterial population following a gastric bypass might play some role in the weight loss above and beyond the surgery itself. This paper has received gallons of media coverage from places such as the BBC (see here) to Scientific American (see here) to Nature (see here). It's an interesting idea, that our gut bacteria might actually influence our body shape and particularly pertinent to our modern day obsession with weight and its health implications. That's not to say that this is the first time such a suggestion has been made (see this and this post from a sister blog) but at least now it is in the public consciousness and potentially opens the door to lots of possibilities not least the dreaded fecal bacterial transplant...
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* Ciccocioppo R. et al. Allogeneic Hematopoietic Stem Cell Transplantation May Restore Gluten Tolerance in Patients With Celiac Disease. J Pediatr Gastroenterol Nutr. 2013; 56: 422-427.
** Liou AP. et al. Conserved Shifts in the Gut Microbiota Due to Gastric Bypass Reduce Host Weight and Adiposity. Sci Transl Med 2013; 5: 178ra41.
The first is by Ciccocioppo and colleagues* and how, quote: "allogeneic HSCT may lead to induction of gluten tolerance in patients with CD [coeliac disease]." HSCT = hematopoietic stem cell transplantation, which is indeed as controversial as it sounds. Two patients, both with CD and β-thalassemia major who at 5 year follow-up after HSCT did not appear to show a reappearance of the some of the serological and histological markers of CD following gluten consumption. I'm not making any recommendations from this (or anything else) aside from stressing the need for quite a bit more research in this area.
The second paper by Liou and colleagues** suggested that based on a mouse model, changes to the gastrointestinal (GI) bacterial population following a gastric bypass might play some role in the weight loss above and beyond the surgery itself. This paper has received gallons of media coverage from places such as the BBC (see here) to Scientific American (see here) to Nature (see here). It's an interesting idea, that our gut bacteria might actually influence our body shape and particularly pertinent to our modern day obsession with weight and its health implications. That's not to say that this is the first time such a suggestion has been made (see this and this post from a sister blog) but at least now it is in the public consciousness and potentially opens the door to lots of possibilities not least the dreaded fecal bacterial transplant...
----------
* Ciccocioppo R. et al. Allogeneic Hematopoietic Stem Cell Transplantation May Restore Gluten Tolerance in Patients With Celiac Disease. J Pediatr Gastroenterol Nutr. 2013; 56: 422-427.
** Liou AP. et al. Conserved Shifts in the Gut Microbiota Due to Gastric Bypass Reduce Host Weight and Adiposity. Sci Transl Med 2013; 5: 178ra41.
Tuesday, 26 February 2013
The science of microbiomics
A very short post to plug... well, to plug me really, and my very, very small contribution to an article featuring in the Pharmaceutical Journal titled: Microbiomics: its growing significance in the world of medicines testing. The article is only open-access for a short period of time, so if you happen to have stumbled across this post years and years into the future (today is Tuesday 26th February 2013 according to my flux-capacitated DeLorean) sorry.
But just so you don't feel to left out, a few article highlights: yoghurt and C.diff infection, the human microbiome project (HMP), gut bacteria and immune function, dysbiosis, the microbiota-gut-brain axis, fecal transplants (yuck factor 10) and pharmacometabonomics.
But just so you don't feel to left out, a few article highlights: yoghurt and C.diff infection, the human microbiome project (HMP), gut bacteria and immune function, dysbiosis, the microbiota-gut-brain axis, fecal transplants (yuck factor 10) and pharmacometabonomics.
Sunday, 24 February 2013
Gluten, guts and glory
Yep, I know. First post for several months - indeed first post for 2013 - and more apologies to readers about not keeping up with this blog. A short post on this occasion focused on an interesting opinion piece by Moises Velasquez-Manoff titled: Who has the guts for gluten?
I'll admit to being pretty entertained by the work of Velasquez-Manoff given his previous articles crossing over into topics like autism spectrum disorders (see here and also covered here). This latest piece is equally thought-provoking and alongside the opinions of people like Alessio Fasano, he of the [General] zonulin (see here), asks some potentially important questions about our relationship with gluten.
One quote in particular caught my attention from Dr Fasano: “Keep the lactobacilli high enough in the guts of these kids, and you prevent autoimmunity.” following some observations based on the onset of type 1 diabetes and coeliac (celiac) disease.
I'm intrigued and am waiting for that confirmatory peer-reviewed evidence.
I'll admit to being pretty entertained by the work of Velasquez-Manoff given his previous articles crossing over into topics like autism spectrum disorders (see here and also covered here). This latest piece is equally thought-provoking and alongside the opinions of people like Alessio Fasano, he of the [General] zonulin (see here), asks some potentially important questions about our relationship with gluten.
One quote in particular caught my attention from Dr Fasano: “Keep the lactobacilli high enough in the guts of these kids, and you prevent autoimmunity.” following some observations based on the onset of type 1 diabetes and coeliac (celiac) disease.
I'm intrigued and am waiting for that confirmatory peer-reviewed evidence.
Friday, 14 September 2012
Gut microbes and health
I'd like to apologise to my Gutness Gracious Me blog. I've neglected you and your subscribers for quite a few months now and I'm sorry. I have no excuse so please accept my humble apology.
Friends again?
OK. There's been quite a bit of new research come out in the intervening months which I need to catch up on. For this entry I'm going to list a couple of interesting papers showing how, if it was ever needed, gut bacteria really are starting to be taken quite seriously in lots of science circles.
Nature is a good starting point (the journal Nature not nature in general). A whole supplement was recently dedicated to gut bacteria which can be viewed here. Unfortunately the papers aren't open-access but I might draw your attention to two of them in particular:
Next up is another Nature journal, Nature Neuroscience, which carried an interesting piece by Cryan & Dinan***** on the potential 'mind-altering' effects of gut bacteria and everyone's favourite term: the gut-brain axis. I've kinda done bacteria potentially influencing behaviour before on a sister blog entry (see here) so don't really want to rehash that again. Suffice to say that as well as being home to quite a lot of bacteria, our gut also houses quite a few neurotransmitters and their receptors more traditionally associated with brain, so why would we expect these not to potentially serve functions other than controlling gut motility and the like. Whether there is interaction between these neurotransmitters and gut bacteria.... well I'd speculate there might very well be.
----------
* Tremaroli V. & Bäckhed F. Functional interactions between the gut microbiota and host metabolism. Nature. 2012; 489: 242-249.
** Semova I. et al. Microbiota regulate intestinal absorption and metabolism of fatty acids in the zebrafish. Cell Host & Microbe. 2012; 12: 277-288.
*** Maynard CL. et al. Reciprocal interactions of the intestinal microbiota and immune system. Nature. 489: 231-241.
**** Cucchiara S. et al. Interactions between intestinal microbiota and innate immune system in pediatric inflammatory bowel disease. Journal of Clinical Gastroenterology. 2012; 46: S64-S66.
***** Cryan JF. & Dinan TG. Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nature Reviews: Neuroscience. September 2012.
Friends again?
OK. There's been quite a bit of new research come out in the intervening months which I need to catch up on. For this entry I'm going to list a couple of interesting papers showing how, if it was ever needed, gut bacteria really are starting to be taken quite seriously in lots of science circles.
Nature is a good starting point (the journal Nature not nature in general). A whole supplement was recently dedicated to gut bacteria which can be viewed here. Unfortunately the papers aren't open-access but I might draw your attention to two of them in particular:
- Valentina Tremaroli & Fredrik Bäckhed* discuss the "functional interactions between the gut microbiota and host metabolism" and how gut bacteria might, just might have the ability to affect how we derive energy from our food. I suppose this crosses quite a few different issues such as 'is a calorie a calorie' and how overweight and obesity might not just be a simple 'energy in - energy out' relationship. Indeed the concept of gut bacteria potentially regulating metabolism and absorption of things like fatty acids as per this paper by Semova and colleagues** (discussed here) may very well also be relevant.
- The paper by Craig Maynard and colleagues*** highlights another important function of our gut bacteria with regards to immune function and how the communication between the two systems may have the ability to influence our health and ill-health. Other authors have similarly speculated on this process as per this study by Cucchiara and colleagues**** using pediatric inflammatory bowel disease as an example.
Next up is another Nature journal, Nature Neuroscience, which carried an interesting piece by Cryan & Dinan***** on the potential 'mind-altering' effects of gut bacteria and everyone's favourite term: the gut-brain axis. I've kinda done bacteria potentially influencing behaviour before on a sister blog entry (see here) so don't really want to rehash that again. Suffice to say that as well as being home to quite a lot of bacteria, our gut also houses quite a few neurotransmitters and their receptors more traditionally associated with brain, so why would we expect these not to potentially serve functions other than controlling gut motility and the like. Whether there is interaction between these neurotransmitters and gut bacteria.... well I'd speculate there might very well be.
----------
* Tremaroli V. & Bäckhed F. Functional interactions between the gut microbiota and host metabolism. Nature. 2012; 489: 242-249.
** Semova I. et al. Microbiota regulate intestinal absorption and metabolism of fatty acids in the zebrafish. Cell Host & Microbe. 2012; 12: 277-288.
*** Maynard CL. et al. Reciprocal interactions of the intestinal microbiota and immune system. Nature. 489: 231-241.
**** Cucchiara S. et al. Interactions between intestinal microbiota and innate immune system in pediatric inflammatory bowel disease. Journal of Clinical Gastroenterology. 2012; 46: S64-S66.
***** Cryan JF. & Dinan TG. Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nature Reviews: Neuroscience. September 2012.
Wednesday, 13 June 2012
The Human Microbiome Project
13th June 2012. The Human Microbiome Project reports first results on the bacterial constitution of 242 healthy adults sampled over 15-18 body parts up to three times. Framework results can be viewed here* (full-text) alongside what they found results here** and represent a bit of a milestone in our beginning to understanding how the trillions of bacteria which inhabit the human body, either in it or on it, play an important role in our lives.
I have to say that I am pretty excited about these papers and the other results published which can all be found at the PLoS Collections site (here). There is a massive of amount of material to go through which I want to talk about in future posts. For now, browse through a moment in scientific history.
* The Human Microbiome Project Consortium. A framework for human microbiome research. Nature. June 2012
DOI: 10.1038/nature11209
** The Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature. June 2012
DOI: 10.1038/nature11234
I have to say that I am pretty excited about these papers and the other results published which can all be found at the PLoS Collections site (here). There is a massive of amount of material to go through which I want to talk about in future posts. For now, browse through a moment in scientific history.
* The Human Microbiome Project Consortium. A framework for human microbiome research. Nature. June 2012
DOI: 10.1038/nature11209
** The Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature. June 2012
DOI: 10.1038/nature11234
Thursday, 17 May 2012
Coeliac disease as a model of autoimmunity
A very short post primarily to link to a recent paper by Kumar and colleagues* (full-text, at least for the moment).
The paper is a sort of 'all you ever wanted to know about coeliac / celiac disease but were afraid to ask' type piece and jolly informative in terms of what we think we know so far about the condition regarding genes, heritability, biochemistry and the like.
Just for good measure, here also are a few other links to some interesting discussions appearing in Nature recently on our gut microbiota and the Barker hypothesis. All I will say is 'all hail our gut bacteria' and onwards with the epigenetic revolution.
Happy reading!
P.S. I know I have been neglecting this blog for a few weeks and apologise. I will hopefully devote more time to it as the year goes on. In the meantime, a link to a peculiar song which has been running through my mind for a few week now.. Gotye and 'Somebody that I used to know' (UK readers might have heard this as an advert for 2Day 2012 from BBC Radio 2).
* Kumar V. et al. From genome-wide association studies to disease mechanisms: celiac disease as a model for autoimmune diseases. Seminars in Immunopathology. May 2012
DOI: 10.1007/s00281-012-0312-1
The paper is a sort of 'all you ever wanted to know about coeliac / celiac disease but were afraid to ask' type piece and jolly informative in terms of what we think we know so far about the condition regarding genes, heritability, biochemistry and the like.
Just for good measure, here also are a few other links to some interesting discussions appearing in Nature recently on our gut microbiota and the Barker hypothesis. All I will say is 'all hail our gut bacteria' and onwards with the epigenetic revolution.
Happy reading!
P.S. I know I have been neglecting this blog for a few weeks and apologise. I will hopefully devote more time to it as the year goes on. In the meantime, a link to a peculiar song which has been running through my mind for a few week now.. Gotye and 'Somebody that I used to know' (UK readers might have heard this as an advert for 2Day 2012 from BBC Radio 2).
* Kumar V. et al. From genome-wide association studies to disease mechanisms: celiac disease as a model for autoimmune diseases. Seminars in Immunopathology. May 2012
DOI: 10.1007/s00281-012-0312-1
Friday, 13 January 2012
Gut bacteria and heart health?
Happy (belated) New Year! Welcome back to Gutness Gracious Me in 2012. I start this year with a post on something pretty central to the ethos of this blog: gut bacteria.
I should perhaps first apologise to Alex Gazzola (#HealthJourno) who very kindly asked if I would be discussing the new Codex standards for labelling foods and gluten-free and the 20 parts per million threshold introduced. I did say I would have a look at this and I am still looking. I do however think that Alex has done a wonderful job of covering this topic on his own blog (see here) as per the reader response he has received.
Back to task. Despite being only 13 days into the New Year (Friday 13th...mmm?), already the research is coming thick and fast. Over at my Questioning Answers blog, the big news recently has been on the bacteria Sutterella and its detection via various methods in quite a few biopsy samples from children with autism and gastrointestinal (GI) issues. I say big news but in among the very detailed explanation of how that team came to find Sutterella, the main story for me is the suggestion that gut hyperpermeability in some cases of autism might be a route through which the immune system meets gut bacteria in places it really shouldn't and onwards formulates an antibody response. The template for this is Crohn's disease and leads into some interesting suggestions about whether gut bacteria itself might not necessarily be the bad guy but rather what happens when it is allowed to roam.
The other quite interesting news is from this paper by Vy Lam and colleagues* suggesting that different amounts and varieties of gut bacteria might influence the severity of and recovery from heart attacks in rats. I am well used to seeing papers talk about gut bacteria in relation to GI issues and conditions, even conditions like autism where functional and more systemic bowel disorders have been noted in some cases. This is however one of the first times that I have come across gut bacteria potentially so directly influencing the physical health of an organ like the heart.
So what did the researchers do?
Whilst the authors describe this as a 'proof-of-concept' study, there are potentially many implications from this work not least that our gut bacteria might do far more than call us home and help digest our food. I have previously (jokingly) referred to gut bacteria as being our 'masters'. Assuming the results from this study are pertinent to humans as well as rats, I might well be offering a sacrifice to 'those who must be obeyed' in the near future.
Should we be surprised that the human body is interconnected? No probably not, although it might take a while and a few more bits of evidence of effect before cardio health care professionals start giving probiotics to help treat (prevent?) myocardial infarction (please note I am not giving any medical advice about this). Going back to the Sutterella post and the proposed link between bacterial translocation and gut permeability, I do wonder whether research should also be looking more closely at gut permeability and lots of other conditions just to see if findings such as these might provide a few more clues about health and illness.
*Lam V. et al. Intestinal microbiota determine severity of myocardial infarction in rats. The FASEB Journal. January 2012
I should perhaps first apologise to Alex Gazzola (#HealthJourno) who very kindly asked if I would be discussing the new Codex standards for labelling foods and gluten-free and the 20 parts per million threshold introduced. I did say I would have a look at this and I am still looking. I do however think that Alex has done a wonderful job of covering this topic on his own blog (see here) as per the reader response he has received.
Back to task. Despite being only 13 days into the New Year (Friday 13th...mmm?), already the research is coming thick and fast. Over at my Questioning Answers blog, the big news recently has been on the bacteria Sutterella and its detection via various methods in quite a few biopsy samples from children with autism and gastrointestinal (GI) issues. I say big news but in among the very detailed explanation of how that team came to find Sutterella, the main story for me is the suggestion that gut hyperpermeability in some cases of autism might be a route through which the immune system meets gut bacteria in places it really shouldn't and onwards formulates an antibody response. The template for this is Crohn's disease and leads into some interesting suggestions about whether gut bacteria itself might not necessarily be the bad guy but rather what happens when it is allowed to roam.
The other quite interesting news is from this paper by Vy Lam and colleagues* suggesting that different amounts and varieties of gut bacteria might influence the severity of and recovery from heart attacks in rats. I am well used to seeing papers talk about gut bacteria in relation to GI issues and conditions, even conditions like autism where functional and more systemic bowel disorders have been noted in some cases. This is however one of the first times that I have come across gut bacteria potentially so directly influencing the physical health of an organ like the heart.
So what did the researchers do?
- Three groups of rats were fed three different types of diet: a standard diet, a standard diet plus quite a powerful antimicrobial (vancomycin) and a standard diet plus a probiotic very aptly named GoodBelly.
- The primary probiotic constituent of GoodBelly is Lactobacillus plantarum 299v quite commonly found in fermented foods like sauerkraut and subject to a few claims. One of those claims is that the bacteria might be able to reduce the production of leptin among other things.
- Both the vancomycin and GoodBelly supplemented groups showed a decrease in circulating leptin levels (38% and 41% respectively) alongside some changes to gut bacteria as one might expect.
- The vancomycin and GoodBelly supplemented groups also showed evidence of smaller heart attacks and improved recovery after heart attack compared with the standard diet group.
Whilst the authors describe this as a 'proof-of-concept' study, there are potentially many implications from this work not least that our gut bacteria might do far more than call us home and help digest our food. I have previously (jokingly) referred to gut bacteria as being our 'masters'. Assuming the results from this study are pertinent to humans as well as rats, I might well be offering a sacrifice to 'those who must be obeyed' in the near future.
Should we be surprised that the human body is interconnected? No probably not, although it might take a while and a few more bits of evidence of effect before cardio health care professionals start giving probiotics to help treat (prevent?) myocardial infarction (please note I am not giving any medical advice about this). Going back to the Sutterella post and the proposed link between bacterial translocation and gut permeability, I do wonder whether research should also be looking more closely at gut permeability and lots of other conditions just to see if findings such as these might provide a few more clues about health and illness.
*Lam V. et al. Intestinal microbiota determine severity of myocardial infarction in rats. The FASEB Journal. January 2012
Tuesday, 20 December 2011
Diagnosis by gut bacteria?
Please don't take the title of this post too literally. Sciences is only just beginning to unravel the first strands of the complicated universe that is our gut microbiota but two recent papers certainly do make for some interesting reading.
The first paper by Iebba and colleagues* provides quite a nice summary of where we stand (research-wise) with regards to different bacterial species seemingly predominating in different childhood conditions. The second paper by Jeffery and colleagues** details the intriguing possibility that irritable bowel syndrome (IBS), or some phenotypes of IBS based on the presence of functional bowel disturbances, might be classifiable by the predominating types of gut bacteria.
The Iebba paper was of double (triple) interest to me because it mentioned autism, coeliac disease (CD) and inflammatory bowel disease (IBD) in the same sentence. In particular, the prevalence of Bacteroidetes alongside a parallel decrease of Firmicutes was a commonality between these three conditions; the first time I've seen a research group looking (bacterially) at these conditions together. I have to point out that autism is an extremely heterogeneous condition with quite a lot of scope for comorbidity; hence I am careful with any generalisations.
By contrast the Jeffery paper, although based on quite a small participant group, suggested quite a few things including that cluster analysis might be able to 'pick out' those cases of IBS associated with diarrhoea compared with those where constipation or alternating bowel habits were more common. Interestingly, their analysis also reported the opposite trend in terms of an increase of Firmicutes-associated taxa and a depletion of Bacteroidetes-related taxa in some of their participant cases. This alongside other related findings which perhaps indicate that the so-called 'leaky gut' (gut hyperpermeability) might also show some differences in terms of site when sub-categorising IBS on the basis of predominant functional bowel patterns.
Aside from factors such as different ages, different populations, different genders, et al, all of this makes me wonder about things like the immune system differences between conditions like IBD and CD compared with IBS. Indeed a few open questions: do the gut bacteria findings in autism perhaps reflect similar immune features to CD and IBD or is it all merely a coincidence? Is IBS an immune-mediated condition the same way as CD or IBD are or are other forces at work?
Without getting too Arthur C. Clarke, there are lots of potential possibilities to these collected works based on our individual and collected patterns of gut microbiota. Unlike fingerprints or retinal scans, gut bacteria is perhaps slightly more dynamic as a function of diet, environment, etc. and so is probably not going to be biometrically encoded onto your passport any time soon. Having said that, if the subtle differences between our gut bacteria might also be reflective of our condition or disease, this could potentially offer some quite startling insights into the way medicine diagnoses and also manages a wide variety of conditions.
Finally, this is probably my last post on this blog until the New Year. I would like to wish readers Merry Christmas and a Happy New Year. I raise a glass of water to your good digestive health over the holiday period!
* Iebba V. et al. Gut microbiota and pediatric disease. Digestive Diseases. December 2011.
** Jeffery IB. et al. An irritable bowel syndrome subtype defined by species-specific alterations in faecal microbiota. Gut. December 2011.
The first paper by Iebba and colleagues* provides quite a nice summary of where we stand (research-wise) with regards to different bacterial species seemingly predominating in different childhood conditions. The second paper by Jeffery and colleagues** details the intriguing possibility that irritable bowel syndrome (IBS), or some phenotypes of IBS based on the presence of functional bowel disturbances, might be classifiable by the predominating types of gut bacteria.
The Iebba paper was of double (triple) interest to me because it mentioned autism, coeliac disease (CD) and inflammatory bowel disease (IBD) in the same sentence. In particular, the prevalence of Bacteroidetes alongside a parallel decrease of Firmicutes was a commonality between these three conditions; the first time I've seen a research group looking (bacterially) at these conditions together. I have to point out that autism is an extremely heterogeneous condition with quite a lot of scope for comorbidity; hence I am careful with any generalisations.
By contrast the Jeffery paper, although based on quite a small participant group, suggested quite a few things including that cluster analysis might be able to 'pick out' those cases of IBS associated with diarrhoea compared with those where constipation or alternating bowel habits were more common. Interestingly, their analysis also reported the opposite trend in terms of an increase of Firmicutes-associated taxa and a depletion of Bacteroidetes-related taxa in some of their participant cases. This alongside other related findings which perhaps indicate that the so-called 'leaky gut' (gut hyperpermeability) might also show some differences in terms of site when sub-categorising IBS on the basis of predominant functional bowel patterns.
Aside from factors such as different ages, different populations, different genders, et al, all of this makes me wonder about things like the immune system differences between conditions like IBD and CD compared with IBS. Indeed a few open questions: do the gut bacteria findings in autism perhaps reflect similar immune features to CD and IBD or is it all merely a coincidence? Is IBS an immune-mediated condition the same way as CD or IBD are or are other forces at work?
Without getting too Arthur C. Clarke, there are lots of potential possibilities to these collected works based on our individual and collected patterns of gut microbiota. Unlike fingerprints or retinal scans, gut bacteria is perhaps slightly more dynamic as a function of diet, environment, etc. and so is probably not going to be biometrically encoded onto your passport any time soon. Having said that, if the subtle differences between our gut bacteria might also be reflective of our condition or disease, this could potentially offer some quite startling insights into the way medicine diagnoses and also manages a wide variety of conditions.
Finally, this is probably my last post on this blog until the New Year. I would like to wish readers Merry Christmas and a Happy New Year. I raise a glass of water to your good digestive health over the holiday period!
* Iebba V. et al. Gut microbiota and pediatric disease. Digestive Diseases. December 2011.
** Jeffery IB. et al. An irritable bowel syndrome subtype defined by species-specific alterations in faecal microbiota. Gut. December 2011.
Friday, 2 December 2011
Probiotics, probiotics, probiotics
Do you ever have one of those days where a certain word seems to keep cropping up again and again no matter where you turn? Well, today is one of those days for me, and today's word is probiotics. Like a good dose of influenza (if there is such a thing as a good dose), I just can't seem to shake that word today.
So here are the papers with that word:
Delzenne and colleagues* (open-access) report on an interesting relationship between gut bacteria and obesity with a specific focus on studies looking to 'alter' the gut microbiota via pre- and probiotics and the various reported outcomes based on anthropometric and biochemical parameters linked to obesity. I talked about something similar a few months back on a sister blog.
Min Tan and colleagues** (open-access) report on the quite positive effects to patients recovering from traumatic brain injury in intensive care following administration of probiotics. Based on a relatively small patient group, patients (n=52) were randomised into either a nutrition + probiotics group or a nutrition alone group. Feeds were administered via a nasogastric tube initially which then progressed to the 'by mouth' route when patients were well enough. Various serum cytokines and related immune markers were analysed over the course of the study which lasted for 21 days.
Unfortunately some of the patients did not make it following their group allocation as sadly might be expected following a serious brain trauma. Other patients developed complications following their accident which did not seem to differ in quantity statistically between the groups aside from the number of pathogens potentially related to infections: fewer pathogens in the probiotic group. The probiotic group (the probiotic including Bifidobacterium longum, Lactobacillus bulgaricus, and Streptococcus thermophilus) did however show an altered immune profile to the control group in terms of indications of the Th1-Th2 slant to the immune system. Although perhaps a little simplistic, Th1 represents the fighting infection side of the immune system and Th2 is the production of antibodies side of things. The probiotic group showed an immune profile more representative of the Th1 response, speculated to be important for their speedier recovery and their less frequent use of antibiotics.
Although the results were not totally astounding in this study, there is an important clinical lesson from this trial in that patients spent statistically less time in intensive care and relied on fewer antibiotics during their recovery as a result of probiotic administration. For patients and physicians alike, this has got to be a good thing.
Finally, ScienceDaily carries an interesting statement from the Annual Scientific Meeting of the American College of Gastroenterology (ACG) regarding probiotics and the potential anti-inflammatory properties of certain types of probiotic. I like to sound of the collected press conference for the studies listed in this release: "Good, bad and ugly bugs: Mother Nature as a treatment for better health in the GI tract". As per the release there are a few headlines including:
What then can we assume from these collected studies. Well, at least in the short-term under various controlled conditions, probiotics, various probiotics, might just be able to influence our health and ill-health particularly in certain conditions/states. As per my previous post, our collected gut bacteria is a complicated organism which talks to our immune system in ways we are only starting to understand. Like every married couple, sometime the talk is positive and healthy; other times the talk is slightly less healthy... (not in front of the kids!).
Whether in the longer-term, supplementing with probiotics offers any added benefit, I don't know. Speculation (and it is only that) would perhaps suggest that the way probiotics are delivered (those all important enteric coatings), how our immune system recognise bacteria as 'self' or 'not-self' and good old homeostasis (the body's drive to keep harmony) are all factors potentially affecting the ability to make a more permanent shift in our not-so-good bacterial species to those preferred choices. Indeed this last point on what is good and bad gut bacteria perhaps needs a little more research in terms of the effects of individual species, etc on health and wellbeing.
* Delzeene NM. et al. Targeting gut microbiota in obesity: effects of prebiotics and probiotics. Nature Revs. November 2011.
** Min Tan. et al. Effects of probiotics on serum levels of Th1/Th2-cytokine and clinical outcomes in severe traumatic brain-injured patients: a prospective randomized pilot study. Critical Care. December 2011.
So here are the papers with that word:
Delzenne and colleagues* (open-access) report on an interesting relationship between gut bacteria and obesity with a specific focus on studies looking to 'alter' the gut microbiota via pre- and probiotics and the various reported outcomes based on anthropometric and biochemical parameters linked to obesity. I talked about something similar a few months back on a sister blog.
Min Tan and colleagues** (open-access) report on the quite positive effects to patients recovering from traumatic brain injury in intensive care following administration of probiotics. Based on a relatively small patient group, patients (n=52) were randomised into either a nutrition + probiotics group or a nutrition alone group. Feeds were administered via a nasogastric tube initially which then progressed to the 'by mouth' route when patients were well enough. Various serum cytokines and related immune markers were analysed over the course of the study which lasted for 21 days.
Unfortunately some of the patients did not make it following their group allocation as sadly might be expected following a serious brain trauma. Other patients developed complications following their accident which did not seem to differ in quantity statistically between the groups aside from the number of pathogens potentially related to infections: fewer pathogens in the probiotic group. The probiotic group (the probiotic including Bifidobacterium longum, Lactobacillus bulgaricus, and Streptococcus thermophilus) did however show an altered immune profile to the control group in terms of indications of the Th1-Th2 slant to the immune system. Although perhaps a little simplistic, Th1 represents the fighting infection side of the immune system and Th2 is the production of antibodies side of things. The probiotic group showed an immune profile more representative of the Th1 response, speculated to be important for their speedier recovery and their less frequent use of antibiotics.
Although the results were not totally astounding in this study, there is an important clinical lesson from this trial in that patients spent statistically less time in intensive care and relied on fewer antibiotics during their recovery as a result of probiotic administration. For patients and physicians alike, this has got to be a good thing.
Finally, ScienceDaily carries an interesting statement from the Annual Scientific Meeting of the American College of Gastroenterology (ACG) regarding probiotics and the potential anti-inflammatory properties of certain types of probiotic. I like to sound of the collected press conference for the studies listed in this release: "Good, bad and ugly bugs: Mother Nature as a treatment for better health in the GI tract". As per the release there are a few headlines including:
- A meta-analysis of studies looking at the use of probiotics used to reduce cases of antibiotic-associated diarrhoea (diarrhea) concluded that yep, probiotics, and particularly that most lovable to yeasts Saccharomyces boulardii, do a pretty good job at curbing your risk of this quite unpleasant condition.
- The use of Bifidobacterium infantis 35624 for those suffering from recurrent abdominal bloating and discomfort did not fare too well in a new randomised-controlled trial. B.infantis 35624 had previously shown some interesting positive results for those with irritable bowel syndrome (IBS).
- Having said that, it was not all bad news for B.infantis 35624 as per another trial which suggested that the probiotic might have some pretty good anti-inflammatory properties when it comes to those dastardly pro-inflammatory cytokines. Indeed that most common of inflammatory markers, C-reactive protein seemed also to be reduced in cases of psoriasis, ulcerative colitis and even in chronic fatigue patients following probiotic administration.
What then can we assume from these collected studies. Well, at least in the short-term under various controlled conditions, probiotics, various probiotics, might just be able to influence our health and ill-health particularly in certain conditions/states. As per my previous post, our collected gut bacteria is a complicated organism which talks to our immune system in ways we are only starting to understand. Like every married couple, sometime the talk is positive and healthy; other times the talk is slightly less healthy... (not in front of the kids!).
Whether in the longer-term, supplementing with probiotics offers any added benefit, I don't know. Speculation (and it is only that) would perhaps suggest that the way probiotics are delivered (those all important enteric coatings), how our immune system recognise bacteria as 'self' or 'not-self' and good old homeostasis (the body's drive to keep harmony) are all factors potentially affecting the ability to make a more permanent shift in our not-so-good bacterial species to those preferred choices. Indeed this last point on what is good and bad gut bacteria perhaps needs a little more research in terms of the effects of individual species, etc on health and wellbeing.
* Delzeene NM. et al. Targeting gut microbiota in obesity: effects of prebiotics and probiotics. Nature Revs. November 2011.
** Min Tan. et al. Effects of probiotics on serum levels of Th1/Th2-cytokine and clinical outcomes in severe traumatic brain-injured patients: a prospective randomized pilot study. Critical Care. December 2011.
Tuesday, 29 November 2011
Innate immunity and the gut microbial ecosystem
A quick-ish post following the publication of a real fact-finding paper by Larsson and colleagues* (full-text). The aim of the paper was to map out how innate immunity intersects with microbial composition along the length of the gastrointestinal tract in a mouse model.
If you are slightly adverse to mouse research I'm afraid that you won't like this study much, which basically looked at bacterial composition in twelve segments of the mouse gut corresponding to the small intestine, cecum and large intestine correlated with several hundred/thousand genes regulated by the gut microbiota.
I won't lie to you in that this is quite a complicated study to follow. My Mr Men take on it suggested a few important findings were presented:
I can't possibly do justice to the amount of data presented in this paper. Extrapolating from the mouse model to humans, this data suggests that we have an extremely important symbiotic relationship going on in our deepest, darkest recesses. A relationship between self and bacteria; where genes and environment seem to play key roles in how we metabolise our food, how we regulate our ability to take on bacteria and viruses, and ultimately how our health in other organs might just want to make reference to the gut also.
* Larsson E. et al. Analysis of gut microbial regulation of host gene expression along the length of the gut and regulation of gut microbial ecology through MyD88. Gut. November 2011
If you are slightly adverse to mouse research I'm afraid that you won't like this study much, which basically looked at bacterial composition in twelve segments of the mouse gut corresponding to the small intestine, cecum and large intestine correlated with several hundred/thousand genes regulated by the gut microbiota.
I won't lie to you in that this is quite a complicated study to follow. My Mr Men take on it suggested a few important findings were presented:
- In the small intestine, several thousand genes were regulated by bacterial microbiota. By comparison, fewer genes were regulated in the colon than other areas thought to be due to some shielding in that part of the gut from bacterial exposure.
- Depending on whether the authors looked at wild or germ-free mice, there were some interesting differences in different parts of the gut for genes related to lipid and fatty acid metabolism and nutrient absorption and metabolism. Genes governing cholesterol biosynthesis seemed to be top of the pile when it comes to being affected by microbiota as a function of whether or not there was a loss of innate immune signalling (Myd88-deficient).
- When it came to gut barrier function along various stretches, gut bacteria had some ability to alter the expression of some important genes according to comparisons between germ-free and wide mice.
- Myd88-deficient mice showed alterations in the types of bacteria present, some signs of disordered antimicrobial resistance as well as being potentially more susceptible to viral infections such as norovirus.
I can't possibly do justice to the amount of data presented in this paper. Extrapolating from the mouse model to humans, this data suggests that we have an extremely important symbiotic relationship going on in our deepest, darkest recesses. A relationship between self and bacteria; where genes and environment seem to play key roles in how we metabolise our food, how we regulate our ability to take on bacteria and viruses, and ultimately how our health in other organs might just want to make reference to the gut also.
* Larsson E. et al. Analysis of gut microbial regulation of host gene expression along the length of the gut and regulation of gut microbial ecology through MyD88. Gut. November 2011
Friday, 25 November 2011
Gut bacteria and the immune system
Quite an interesting article by Lamousé-Smith and colleagues* has appeared on the potential gut bacterial requirements of the immune system. The paper is open-access so readers are invited to read it at their leisure.
The basic conclusion reached from this research is that the ability of a mouse (and by proxy a human being) to mount an immune response to a specific pathogen (bacterial or viral) might be to some degree affected by the presence/absence of certain gut bacteria.
In the case of this paper, researchers undertook investigations based on two different scenarios: (a) a mouse model where antibiotics were used to disrupt the normal gastrointestinal (GI) flora and (b) a germ-free mouse model who were subsequently colonised. Under such models, mice were injected with a suspension of ovalbumin (the main protein in egg white) and an immunity stimulator, Freund's complete adjuvant. The authors then looked at the mice ability to mount an immune response to the egg white protein (ova).
They noted a few interesting observations:
Appreciating that these experiments were carried out on mice and quite a small group of mice, there are some interesting things to take from this research. Already on this blog discussions have ranged from gut bacteria and a possible link to coeliac disease to the potential usefulness of bacterial transplantation for certain bowel conditions. Within these pretty diverse areas, a common theme is a potential role for the immune system in terms of clinical outcomes. What this research adds quite nicely, is that our ability to fight infection, develop immunity might be quite a bit more complex than previously thought. Our gut bacteria potentially being a mediator of immunity.
Thinking back to some findings in that other field of interest to me, autism, I do wonder about the implications of this research. On a sister blog, I recently discussed a paper looking at carbohydrate metabolism and dysbiosis in cases of autism. One of the findings from that small-ish study was that levels of Bacteroidetes were in shorter supply. Coincidence or perhaps tied into some interesting data on antibiotic use? Given the various studies suggestive of problems with immunity at least in some people with autism, I wonder if we should be looking at the gut bacteria/immune system relationship a little more closely?
Of course it easy for me to sit here and speculate, compare and contrast. Precisely how our bodies make and utilise immunity is still a source of much research and investigation.
* Lamousé-Smith ES. et al. The intestinal flora is required to support antibody responses to systemic immunization in infant and germ free mice. PLoS ONE. NOvember 2011
The basic conclusion reached from this research is that the ability of a mouse (and by proxy a human being) to mount an immune response to a specific pathogen (bacterial or viral) might be to some degree affected by the presence/absence of certain gut bacteria.
In the case of this paper, researchers undertook investigations based on two different scenarios: (a) a mouse model where antibiotics were used to disrupt the normal gastrointestinal (GI) flora and (b) a germ-free mouse model who were subsequently colonised. Under such models, mice were injected with a suspension of ovalbumin (the main protein in egg white) and an immunity stimulator, Freund's complete adjuvant. The authors then looked at the mice ability to mount an immune response to the egg white protein (ova).
They noted a few interesting observations:
- Administration of antibiotics lead to some interesting changes in the gut microbiota. I should perhaps mention that pregnant mice were given antibiotics in their feed so the changes were noted in both mother and baby mice when born. The specific combination of antibiotics given to pregnant dams - ampicillin, streptomycin and clindamycin - seemed to particularly deplete Firmicutes and Bacteroidetes bacterial species leaving Enterobacteriaceae to dominate. I don't like the idea of labelling bacterial species as good guys or bad guys because that is a little generalised and unfair. Having said that the Enterobacteriaceae includes things like Salmonella, E.coli, Klebsiella and few more 'pathogenic' species among their lot; if they were people, these would be the ones not to hang around with.
- Those offspring mice born to mothers on antibiotics seemed to show similar changes to gut flora. Additionally, antibody titer levels to ovalbumin were lower in this group when compared to a non-antibiotic exposed group when immunised at 7 days. These findings were not replicated when injected at 14 days.
- Looking at the second mouse model where gut flora was absent, the authors reported consistently lower titer levels across age and when injections were given. This finding was kinda confirmed when germ-free mice (those with no bacterial flora) were colonised via bacteria derived from normal gut flora mice (I guess a sort of bacterial transplant!) thereafter more appropriate antibody titer levels were noted .
Appreciating that these experiments were carried out on mice and quite a small group of mice, there are some interesting things to take from this research. Already on this blog discussions have ranged from gut bacteria and a possible link to coeliac disease to the potential usefulness of bacterial transplantation for certain bowel conditions. Within these pretty diverse areas, a common theme is a potential role for the immune system in terms of clinical outcomes. What this research adds quite nicely, is that our ability to fight infection, develop immunity might be quite a bit more complex than previously thought. Our gut bacteria potentially being a mediator of immunity.
Thinking back to some findings in that other field of interest to me, autism, I do wonder about the implications of this research. On a sister blog, I recently discussed a paper looking at carbohydrate metabolism and dysbiosis in cases of autism. One of the findings from that small-ish study was that levels of Bacteroidetes were in shorter supply. Coincidence or perhaps tied into some interesting data on antibiotic use? Given the various studies suggestive of problems with immunity at least in some people with autism, I wonder if we should be looking at the gut bacteria/immune system relationship a little more closely?
Of course it easy for me to sit here and speculate, compare and contrast. Precisely how our bodies make and utilise immunity is still a source of much research and investigation.
* Lamousé-Smith ES. et al. The intestinal flora is required to support antibody responses to systemic immunization in infant and germ free mice. PLoS ONE. NOvember 2011
Gut bacteria, pesticides and obesity
Although my interest in this blog centres on all things gut-related, within this huge area of research I am particularly interested in how our genetic makeup interacts with our environment and vice-versa. I suppose gastrointestinal (GI) conditions are ideally suited to this complex 'nature-nutrure' relationship as evidenced by conditions like coeliac (celiac) disease, the archetypal gene-environment condition.
An interesting paper has appeared by Hae-Sook Lee and colleagues* suggestive of an interesting 'threesome' between a species of methane gas producing microbe, organochlorine pesticides and obesity. The paper is open-access. A summary of the details:
We do need to take a step back from these findings before making too many associations. The sample population is quite small and the numbers of people included for analysis of OCPs for example is even smaller. Bear in mind that just looking at three primary variables is not necessarily grounds for a relationship.
I am however struck by the 'suggestion' that gut bacterial content and obesity might either increase the risk of greater take-up of compounds such as OCPs or that gut bacteria might interact with our chemical environment to potentially predispose to conditions such as obesity. This latter hypothesis: OCP levels determining Methanobacteriales levels which in turn leads to increases in anthropometric measures is the author's preferred interpretation.
The authors discuss the properties of OCPs as being central to the finding i.e. lipophilic (fat or oil loving) and also note that Methanobacteriales are quite often used to biodegrade hydrocarbons such as petroleum. I have to say I have never really thought about industrial waste management being applied to the human model but perhaps should not be so surprised given the current interest in things like industrial biodigestion.
What this study does more than anything is to reaffirm the complexity of conditions such as obesity as well as providing some new targets, environmental and biochemical, which we should perhaps be exploring with a little more assiduity.
* Hae-Sook Lee et al. Associations among organochlorine pesticides, Methanobacteriales, and obesity in Korean women. PLoS ONE. November 2011.
An interesting paper has appeared by Hae-Sook Lee and colleagues* suggestive of an interesting 'threesome' between a species of methane gas producing microbe, organochlorine pesticides and obesity. The paper is open-access. A summary of the details:
- Fecal and blood samples from 83 Korean women were analysed alongside anthropometric (body mass index) measurements.
- Fecal levels of Methanobacteriales were quantified via qPCR and serum / fecal levels of various organochlorine pesticides (OCPs) were assayed via GC-MS among a selection of participants with detected or non-detected levels of Methanobacteriales.
- The results: Methanobacteriales were present in about a third of patient stool samples (27/83). Higher Methanobacteriales levels were present in women with a waist circumference above 83cm than below and showed some connection with elevated BMI also. Higher fecal levels of Methanobacteriales were also associated with higher serum levels of the OCPs.
We do need to take a step back from these findings before making too many associations. The sample population is quite small and the numbers of people included for analysis of OCPs for example is even smaller. Bear in mind that just looking at three primary variables is not necessarily grounds for a relationship.
I am however struck by the 'suggestion' that gut bacterial content and obesity might either increase the risk of greater take-up of compounds such as OCPs or that gut bacteria might interact with our chemical environment to potentially predispose to conditions such as obesity. This latter hypothesis: OCP levels determining Methanobacteriales levels which in turn leads to increases in anthropometric measures is the author's preferred interpretation.
The authors discuss the properties of OCPs as being central to the finding i.e. lipophilic (fat or oil loving) and also note that Methanobacteriales are quite often used to biodegrade hydrocarbons such as petroleum. I have to say I have never really thought about industrial waste management being applied to the human model but perhaps should not be so surprised given the current interest in things like industrial biodigestion.
What this study does more than anything is to reaffirm the complexity of conditions such as obesity as well as providing some new targets, environmental and biochemical, which we should perhaps be exploring with a little more assiduity.
* Hae-Sook Lee et al. Associations among organochlorine pesticides, Methanobacteriales, and obesity in Korean women. PLoS ONE. November 2011.
Tuesday, 25 October 2011
Bacterial transplantation: undesirable but effective
We have a term common to certain parts of the UK: 'where there's muck, there's brass'. The more usual interpretation of this phrase is that where there is a dirty job to be done, so there is money to be made. In the case of this post on probably the most undesirable therapy ever, bacterial transplantation, money might be replaced with health.
The paper in question is this review by Ethan Gough and colleagues* (available full-text not anymore). I'm not going to go through the whole paper because it is was free to view to everyone. The bottom line is that following the identification of various literature on other-person derived stool infusions, 27 reports fulfilled author criteria for review, of which over 90% of patients reported on showed 'resolution' of their problems of Clostridia difficile infection or pseudomembranous colitis following a bacterial transplant. Perhaps more importantly, the reported rate of side-effects including the ultimate side-effect of death, whilst present, could not be directly attributed to the transplant but rather the disease transplant was attempting to treat.
I note the authors also discuss the likelihood that bacterial transplantation might also be useful for other bowel-related conditions including inflammatory bowel disease and irritable bowel syndrome (although I offer no endorsement for anything on this blog).
Despite the subject matter, I have to say that I am interested in the combined results of bacterial therapy. There are lots of questions to answer about the hows and whys of this method and importantly, what are we transplanting aside from bacteria, the gut virome for example? Assuming that gut bacteria or pathogens affecting gut health are non-responsive to more traditional anti-microbial forms of treatment, and looking at the success rates included in this review, I wonder also how many GI-related conditions might benefit from such an intervention. Extending GI disease to cover other conditions as a comorbidity also, such as autism and the bacterial work being done there or even Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME), does this mean we should be looking at this measure a little more closely rather than just squinting our eyes in disgust?
* Gough E. et al. Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficile infection. Clin Infect Dis. August 2011.
The paper in question is this review by Ethan Gough and colleagues* (
I note the authors also discuss the likelihood that bacterial transplantation might also be useful for other bowel-related conditions including inflammatory bowel disease and irritable bowel syndrome (although I offer no endorsement for anything on this blog).
Despite the subject matter, I have to say that I am interested in the combined results of bacterial therapy. There are lots of questions to answer about the hows and whys of this method and importantly, what are we transplanting aside from bacteria, the gut virome for example? Assuming that gut bacteria or pathogens affecting gut health are non-responsive to more traditional anti-microbial forms of treatment, and looking at the success rates included in this review, I wonder also how many GI-related conditions might benefit from such an intervention. Extending GI disease to cover other conditions as a comorbidity also, such as autism and the bacterial work being done there or even Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME), does this mean we should be looking at this measure a little more closely rather than just squinting our eyes in disgust?
* Gough E. et al. Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficile infection. Clin Infect Dis. August 2011.
Saturday, 15 October 2011
The emergency exits are here and here
The title of this post has very little to do with steward / stewardess instructions delivered just before take-off, despite my recently watching the very funny Walliams/Lucas series 'Come Fly With Me'. Rather, with a straight face, I refer to your route into the world and whether Mother Nature required a helping hand in bringing you from the comfort of your watery cocoon into the real world. Could your route of entry alter your risk of developing certain things in later life... say coeliac (celiac) disease?
I am going to keep this post brief because this is a question that I have tackled before on a sister blog post: caesarean section and coeliac disease? The crux of that entry was the emerging suggestion that people born via caesarean section (c-section) were at greater risk of coeliac disease than those who were pushed through the bacteria-filled birth canal.
Further evidence has now emerged concerning a possible relationship in this paper by Marild and colleagues*. The details summarised:
I quote from the author's final sentence of their abstract: ".. consistent with the hypothesis that the bacterial flora of the newborn plays a role in the development of celiac disease".
I must point out that whilst bacterial colonisation of the infant gut may be a variable in determining your risk of CD, it is most probably not the only important variable. I don't want anyone reading this entry and taking it to their healthcare provider as 'proof' of anything; it is not. Likewise I am not trying to overturn any 'too posh to push' arguments.
What however can be inferred from this paper is that there may consequences to every action; some consequence might be positive (such as getting a breech presenting infant out of mum and avoiding any very serious complications), some of them might be not-so positive. The trick is to see where this research leads and, just a suggestion, whether an early bacterial 'transplant' from mum to baby one day becomes the norm for those babies who don't end up traversing the birth canal. Just a suggestion.
* Marild K. et al. Pregnancy outcome and risk of celiac disease in offspring: a nationwide case-control study. Gastroenterology. October 2011.
I am going to keep this post brief because this is a question that I have tackled before on a sister blog post: caesarean section and coeliac disease? The crux of that entry was the emerging suggestion that people born via caesarean section (c-section) were at greater risk of coeliac disease than those who were pushed through the bacteria-filled birth canal.
Further evidence has now emerged concerning a possible relationship in this paper by Marild and colleagues*. The details summarised:
- A case-control study where recorded pregnancy information was collected via a central database between 1973 and 2008.
- Biopsy-verified coeliac disease (CD) was determined for 11,749 participants compared with 53,887 age- and gender-matched non-CD general population controls.
- There was a positive significant association between elective c-section delivery and later CD diagnosis (p=0.005) but none for emergency c-sections.
- Small for dates babies were over 20% more likely to develop CD also.
- No other pregnancy variables showed an association with CD.
I quote from the author's final sentence of their abstract: ".. consistent with the hypothesis that the bacterial flora of the newborn plays a role in the development of celiac disease".
I must point out that whilst bacterial colonisation of the infant gut may be a variable in determining your risk of CD, it is most probably not the only important variable. I don't want anyone reading this entry and taking it to their healthcare provider as 'proof' of anything; it is not. Likewise I am not trying to overturn any 'too posh to push' arguments.
What however can be inferred from this paper is that there may consequences to every action; some consequence might be positive (such as getting a breech presenting infant out of mum and avoiding any very serious complications), some of them might be not-so positive. The trick is to see where this research leads and, just a suggestion, whether an early bacterial 'transplant' from mum to baby one day becomes the norm for those babies who don't end up traversing the birth canal. Just a suggestion.
* Marild K. et al. Pregnancy outcome and risk of celiac disease in offspring: a nationwide case-control study. Gastroenterology. October 2011.
Tuesday, 4 October 2011
Gluten, bacteria and mouthwash
Peptides. Those short-ish chains of amino acids, are interesting characters. Therapeutically, certain peptides have the propensity to do great things as exemplified by compounds such as the glucagon-like peptides and speculation on a therapeutic role in conditions like diabetes and intestinal disease.
In terms of 'disease' and ill-health, other peptides have a slightly less desirable side; something which I have been interested in for a few years speculatively in relation to conditions such as autism and schizophrenia. Peptides, such as those immunogenic epitopes derived from gluten, in relation to coeliac (celiac) disease (CD) also perhaps show a less speculative negative side in terms of effect.
What can be done about these immune-stimulating gluten peptides? Well, you could try and break them down via enzymes such as endopeptidases. There are also lots of products on the market which claim to do similar things (bearing in mind that I offer no endorsement). A recent paper by Zamakchari and colleagues* also offers another potential solution: certain enzymes produced by bacteria with the propensity to degrade gluten.
Before you go scouring the Internet for some commercial bacterial supplement, know that the authors suggested that we might already have such bacteria in our 'oral cavity' (mouth in plain speak); in our saliva and dental plaque.
The paper summary:
There are a few important points to be taken from this research. First is the suggestion that digestion starts in the mouth and that all important motherly advice 'chew your food properly'. Masticating (or chewing to us mere mortals) is an important first step in presenting the food we eat to the rest of our hard-working gastrointestinal (GI) tract. Second is the suggestion that dental plaque (alongside saliva) might actually serve some purpose rather than just being something associated with poor oral hygiene and bad breath. I am not for one minute suggesting that we should all stop our regular tooth cleaning routine; but perhaps just step back and think about when you clean your teeth and what products you might use in your dental hygiene routine. Finally (finally!) I am already a big fan of the idea that our relationship with bacteria, some strains of bacteria, is an important one. A primary implication from this work is that 'addition' of bacteria to food or whilst eating certain foods (bearing in mind the effect of pH on these bacteria) might actually serve as another tool in the arsenal against conditions like coeliac disease, and even gluten sensitivity when it comes to degrading those very difficult gluten peptides. Please note that I am not recommending anything from this point given the slightly more negative press from these strains; just speculating.
* Zamakhchari M. et al. Identification of Rothia bacteria as gluten-degrading natural colonizers of the upper gastro-intestinal tract. PLoS ONE. September 2011.
In terms of 'disease' and ill-health, other peptides have a slightly less desirable side; something which I have been interested in for a few years speculatively in relation to conditions such as autism and schizophrenia. Peptides, such as those immunogenic epitopes derived from gluten, in relation to coeliac (celiac) disease (CD) also perhaps show a less speculative negative side in terms of effect.
What can be done about these immune-stimulating gluten peptides? Well, you could try and break them down via enzymes such as endopeptidases. There are also lots of products on the market which claim to do similar things (bearing in mind that I offer no endorsement). A recent paper by Zamakchari and colleagues* also offers another potential solution: certain enzymes produced by bacteria with the propensity to degrade gluten.
Before you go scouring the Internet for some commercial bacterial supplement, know that the authors suggested that we might already have such bacteria in our 'oral cavity' (mouth in plain speak); in our saliva and dental plaque.
The paper summary:
- Human dental plaque and saliva were collected from willing volunteers and the various oral micro-organisms cultured. Those bacteria with gliadin-degrading activity were identified by 16S rDNA analysis, a sort of molecular fingerprinting service.
- Various bacterial strains were added to synthetic immunogenic peptide sequences from gliadin and the subsequent effects separated and characterised by a combination of reversed-phase HPLC and mass spectrometric detection (MS/MS).
- The results: 27 aerobic and 30 anaerobic bacterial strains capable of metabolising gluten were found. All the final anaerobic strains cultured (n=10 fastest growing) were of the Bifidobacterium genus. The final aerobic strains (n=5 fastest growing) included bacteria of the Rothia genus.
- Several tri-peptide combinations appearing in the greatest frequency within the larger gluten peptides were broken down by individual bacterial strains. Rothia mucilaginosa and Rothia aeria seemed to come out top in terms of their hydrolysing abilities in terms of amounts and time taken. This effect was also noted when the larger immunogenic epitopes were exposed to the Rothia strains.
There are a few important points to be taken from this research. First is the suggestion that digestion starts in the mouth and that all important motherly advice 'chew your food properly'. Masticating (or chewing to us mere mortals) is an important first step in presenting the food we eat to the rest of our hard-working gastrointestinal (GI) tract. Second is the suggestion that dental plaque (alongside saliva) might actually serve some purpose rather than just being something associated with poor oral hygiene and bad breath. I am not for one minute suggesting that we should all stop our regular tooth cleaning routine; but perhaps just step back and think about when you clean your teeth and what products you might use in your dental hygiene routine. Finally (finally!) I am already a big fan of the idea that our relationship with bacteria, some strains of bacteria, is an important one. A primary implication from this work is that 'addition' of bacteria to food or whilst eating certain foods (bearing in mind the effect of pH on these bacteria) might actually serve as another tool in the arsenal against conditions like coeliac disease, and even gluten sensitivity when it comes to degrading those very difficult gluten peptides. Please note that I am not recommending anything from this point given the slightly more negative press from these strains; just speculating.
* Zamakhchari M. et al. Identification of Rothia bacteria as gluten-degrading natural colonizers of the upper gastro-intestinal tract. PLoS ONE. September 2011.
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