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Wednesday, July 10, 2013

How the microbiome is (slowly) making its way into clinical practice

If you follow my Twitter feed (@bykriscampbell) or read this blog, it will be obvious to you that the microbiome impacts our day-to-day health. The research, granted, is in an early-ish phase where certainties are few and far between (as I mention in this podcast interview). But still, there are myriad studies that say things like "administer probiotics", "avoid prescribing antibiotics to kids", and "consider c-sections only in emergency situations".

What has me puzzled lately is this: if lots of good evidence is already out there, how come it's being incorporated so slowly into clinical practice?

Well, it's Good News Day on this blog. Because here are a few examples where health professionals are taking the information on the microbiome and using it to immediately help patients:

1) Fecal transplants are moving from the realm of weird voodoo cure, into a respectable treatment option. The most likely reason for this is that they work ridiculously well a lot of the time. In a recent NEJM study, for example, fecal transplants were used to treat recurrent C. difficile infection, and were so effective that the study had to be discontinued because it was unethical to withhold the treatment from the control group.

In the US, the FDA recently tried to put up a barrier for doctors wanting to use this treatment with their patients: requiring an Investigational New Drug application for fecal transplants. Recently, though, the requirement was thankfully overturned.

2) I was having another dinner-table conversation about feces the other day (wait, not all families do that??), when I heard from a Winnipeg doctor that the formulary in his hospital carries probiotics, and that he and his colleagues often administer probiotics when antibiotics are given to inpatients. Since then, I've heard that Quebec's Pierre-Le-Gardeur hospital does the same, as do several others in Quebec and Ontario. (And probably more that I haven't heard about.)

3) Should you be fortunate enough to have access to a clinic that does bacterial sequencing, the data can be used to personalize your treatment experience. As explained in the video below (with helpful hand gestures) by Nicholas Chia, Ph.D., at Mayo Clinic, a patient with refractory bacterial vaginosis could get a bacterial swab and have it sequenced. This would help the doctors know what antibiotics she is resistant to, and which bacterial takeovers she'd be susceptible to. Based on that, the doctor could find a treatment that would work better than the repeated rounds of antibiotics she might have had in the past. Here's the video with the full explanation:

Using "the firehose of information that comes down off of sequencers"


Those are three examples that make me happy. But the job is far from done. Anyone can do their part to advance "the cause" by bringing up the microbiome at their next doctor's appointment. Even if the doctor doesn't know much about it, she or he might go home and catch up on the topic by reading a few journal articles.

The microbiome is going to change healthcare, but it'll be one doc and one patient at a time.


Tuesday, May 28, 2013

Two tales of gastric bypass surgery

This story appeared today from The Canadian Press:

Mom's obesity surgery may help her children

It reports on a study that followed kids' risk factors for obesity. Children who were born to an obese mother before she had weight-loss surgery were heavier, and had higher risk factors for heart disease and diabetes, than children born to that same mother after surgery. Researchers say it was because obesity causes differences in the activity of certain genes. Not that obesity affects the genes themselves, but how the genes express themselves.

The story is fine by itself. Rather well written, in fact. (Bonus points for great quotability go to co-author Dr. John Kral, who said fetuses are "differently marinated" depending on the weight of the mother.) And everything would be hunky dory were it not for this item, which was covered by Reuters two months earlier:

After weight-loss surgery, new gut bacteria keep obesity away

This one explains exactly how gastric bypass surgery helps people slim down. Researchers found that it may not have to do with going under the knife, but rather, with how the surgery changes the patient's gut bacteria. (The study was done on mice, and as a result, controlled for nearly everything; control group mice were even given a "sham" surgery.) The study raised an important question: might it be possible to skip surgery, and achieve the same effect by altering gut bugs through diet or another means?

These stories were two separate entities, presented weeks apart. But taken together, here's what I gather:

1) A mother's gastric bypass surgery helps change a baby's gene expression and makes him or her healthier for life

2) Gastric bypass surgery might not be necessary because what matters is the change in bacteria that occurs after the surgery

So if you were a woman of a high body weight who planned to become pregnant, wouldn't you want someone to have raised the connection between these two studies? Maybe you read the news today and have become convinced that gastric bypass surgery is the best way forward, even with the risks it presents. And your appointment to discuss it with your doctor is tomorrow.

But maybe you could have had other options.

Source:  http://www.citelighter.com/card/Gastric-Bypass/1352


The fact that no one communicated the connection between these studies is a huge oversight. I'd even argue that it is bad for scientific progress. Science is about converging upon the truth with different studies conducted under different circumstances. So why are we still presenting science studies without context or analysis, as individually-wrapped peppermint candies?

Let's give everyone the benefit of the doubt in this case and say it's because the person assigned to cover the study wasn't aware of any other relevant studies. Sure, the scientists this person interviewed are supposed to have told him or her about the context. But it's not actually a scientist's job to be aware of the news coming out of other labs at any given moment. It's the journalist's job to be informed in real time.

This is a strong argument for assigning health and science stories to those who make it their full-time mission to keep abreast of a certain area of health and science. That is to say, specialist journalists. (Luckily there are several great people, including Rob Steiner at U of T, who are working to create a new generation of specialist journos that will provide content to newsrooms that are operating on a skeleton staff of generalists.)

These two studies are just one example of something I notice all the time. Other specialists could probably cite examples from their own fields. The point is, news is set up for these obvious failures to connect the dots. But we need to work toward changing that. It's only fair to that woman - a future mother - signing the surgery release form at this very moment.

Thursday, May 2, 2013

Autism and gut bacteria: The vax. Er, the facts.

When you do an internet search for "autism" and "vaccine", you open the can of worms that was the claim that MMR vaccines caused autism. That fraudulent research and the conniving scientist behind it, Andrew Wakefield, have now been discredited. (For more on that, see the dedicated chapter in the book "Bad Science" by M.D. and writer Ben Goldacre.)


But lately in the news, we came across the words "autism" and "vaccine" in the same sentence again. As in these headlines:

Vaccine developed at U of G could help in battle against autism

Vaccine developed to fight gut bacteria and autism symptoms

First vaccine against autism-associated bacterium Clostridium bolteae

Just how did those two words end up together again? It piqued my interest.

The word vaccine is particularly suggestive. Because what we do know about the cause of autism is this:

(1) There is definitely a genetic component
(2) There may be an environmental component, but scientists don't agree on what it is

A vaccine would not address genes, of course. It would address one of the environmental components thought to cause the condition. But... hold on, if we're not sure what the environmental causes are, how can we take a vaccine and say it addresses that environmental cause?

With that question in mind, I approached this research, which came from the chemistry lab of Dr. Mario Monteiro at the University of Guelph.

I took the step (as always) of reading through the original research paper in the journal Vaccine (in press as of early May, 2013).  Ahem... that was clearly one more step than most of the reporters who produced articles on the topic (bless their time-strapped hearts). See, anyone who said there was a vaccine obviously didn't read or understand the paper. Because in the article, there is no vaccine.



Here are the facts:

A team of chemists has examined the cell walls of a kind of bacteria (Clostridium bolteae), and have determined that the bacteria can provoke an immune reaction in rabbits.

That is all.

The researchers say their knowledge could be used to develop a vaccine for human use (i.e. they now have a vaccine target), but they did not yet create the vaccine themselves. Contrary to what  pretty well every mainstream news article has reported.

Moreover, the facts in this article are padded with the stuff about autism that, given the context, seems absurdly off topic. They took their discovery of making the immune system of rabbits react to a bacteria, and they said, "Hey, some children with autism also have this bacteria in their guts. Maybe we could develop a vaccine against this bacteria and give it to them. And the bacteria would go away. And maybe so would their autistic behaviours."

Do I need to say it? That is not sound scientific reasoning. It's like saying:

"Hey, some children with blonde hair also have this bacteria in their guts. Maybe we could develop a vaccine against this bacteria and give it to them. And the bacteria would go away. And maybe so would their blonde hair."


To me, the paper is about developing a knowledge about a species of bacteria. At most, the discussion section should have mentioned that this particular bacteria may be found in the digestive tracts of some children with autism.

I'm not really sure why they picked on this species of bacteria, in fact. There is no scientific consensus that C. bolteae is special to the guts of children with autism. Some studies have been done comparing the bacteria in the guts of children with autism to that in non-autistic children, and even though some patterns are emerging, there are no bacteria that reliably distinguish one group from the other. This species of bacteria alone is surely not the "environmental cause of autism" that has been eluding scientists for decades. The researchers do make a case for why they chose C. bolteae, but to me their choice seems questionable, given the conclusions of the papers they cite.

Now, I do think that the connection between autism and gut bacteria warrants more research. (See this episode of David Suzuki's TV show, The Nature of Things.) I'm not dismissing it wholesale. It's just that this paper goes beyond what the empirical evidence shows - both in the peer-reviewed journal and in the media.

The upshot (yep, pun intended): the word "autism" should not be appearing with the word "vaccine" here at all. That's because the word "autism" should not appear at all, and the vaccine is still a dream. The headlines should read something like:

"Scientists may develop vaccine against species of bacteria with unknown importance".

Only, then they wouldn't be headlines. Hmm, see??


  ResearchBlogging.org Pequegnat, B., Sagermann, M., Valliani, M., Toh, M., Chow, H., Allen-Vercoe, E., & Monteiro, M. (2013). A vaccine and diagnostic target for Clostridium bolteae, an autism-associated bacterium Vaccine DOI: 10.1016/j.vaccine.2013.04.018

Tuesday, April 30, 2013

The Intestinal Gardener's Digestive Disease Awareness Month challenge: 100 stories about digestion

Happy May! It's Digestive Disease Awareness Month, an occasion to remember the complexity and general awesomeness of your gut... and how easily things can go awry.

May also happens to be my birthday month.

So I've been thinking about something exciting and birthday-related, in that it involves gifts. For me. But wait, it won't cost you anything.

Gabe-birthday-part.jpg by Twice25

Here's the deal: This month, I want to collect 100 stories about digestion.

The stories can be about anything. Anything at all, as long as it's related to your gut.

Some examples include:

(1) how you got the news of your celiac diagnosis while eating a bagel on vacation in the Bahamas
(2) how your Ukrainian family get-togethers have changed now that several of your family members have dietary restrictions
(3) the "Montezuma's Revenge" story you haven't told a single soul

Email your stories to me at bykriscampbell@gmail.com
Please write DIGESTION STORY in the subject header.

Or just tweet your story to me: @bykriscampbell.

When your story is received, I'll let you know what number you are, from 1 to 100.

And...

Two storytellers, lucky numbers 10 and 100, will receive a *prize*: a digestive health book of your choice from Amazon.

I'm going to learn from the stories and share some of them here on the blog. Eventually I will contact the authors of the most compelling stories, in order to consider including them in the book I'm now writing on digestive health.

The deadline is May 31st or whenever I reach 100 stories, whichever is first.

And finally, remember to give your guts a big, squishy hug today. Disease or no disease, they do a really fantastic job for you.

Monday, April 8, 2013

Red meat and gut bacteria: partners in heart crime

We're used to thinking of nutrition the way we think about computers - input and output. For example, you eat carrots, you get lots of vitamin A. You eat strawberries, you get vitamin C. If you're deficient in a vitamin, take a supplement... or eat more foods containing that vitamin.

So far so good. Only, now science is teaching us it's more complicated.

For one thing, the exact nutrients you need may depend on your genes: see this article, "The nutrigenomics frontier". Which makes the ubiquitous "recommended daily intake" (RDI) nothing more than a ballpark estimate.

But there's another emerging facet of nutrition. There's increasing evidence that if we're going to make use of the nutrients we ingest through asparagus or chick peas or any other food, the body has to act on those nutrients. Sometimes the body's actions make things better for us, and sometimes they produce a bad result.

Hamburger (source: Wikimedia Commons, PDphoto.org)

Let's take red meat. Recently in Nature Medicine, a study found that omnivores who took a compound (found in red meat) called L-carnitine had higher markers of arterial plaque buildup than vegans or vegetarians who also took the compound. It also happened that the omnivores had very different gut bacteria, as measured through fecal samples, than the vegans/vegetarians. That would be correlation, not causation.

Enter the mouse part of the study. Here, the researchers found that arterial plaques increased in mice with normal gut bacteria when they were given L-carnitine. The red meat compound and the gut bacteria appeared to be partners in contributing to heart disease.

As a point of comparison, other L-carnitine-eating mice were given antibiotics that cleared their gut bacteria. Arterial plaques did not increase in these mice.

What are we left with? Certainly NOT that we should pop antibiotics alongside our red meat in order to prevent heart disease. Yikes. (For reasons why antibiotics are not the answer, check out this article by the excellent science writer, Carl Zimmer.)

We're left with a caution against red meat, I guess. An explanation of why vegans and vegetarians might have a lower risk of heart disease. But the research is preliminary, so personally I'm not going to swear off burgers forever. 

Most importantly, I think we're left with a picture of nutrition that's about more than just input. It's a picture of an ecosystem, where each thing interacts with other things to produce an output - in this case, heart disease. Gut bacteria seems to be a big player in these actions. In this article, Stanley Hazen, head of cardiovascular medicine at the Cleveland Clinic, says: "Bacteria make a whole slew of molecules from food... and those molecules can have a huge effect on our metabolic processes."

One more thing: after reading this study, I wouldn't be too quick to take L-carnitine supplements. Certain gut flora might love them... but it's possible that could have dangerous results.
ResearchBlogging.org Koeth, R., Wang, Z., Levison, B., Buffa, J., Org, E., Sheehy, B., Britt, E., Fu, X., Wu, Y., Li, L., Smith, J., DiDonato, J., Chen, J., Li, H., Wu, G., Lewis, J., Warrier, M., Brown, J., Krauss, R., Tang, W., Bushman, F., Lusis, A., & Hazen, S. (2013). Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis Nature Medicine DOI: 10.1038/nm.3145

Tuesday, March 5, 2013

Flora helpers: What expectant parents need to know about baby's gut bacteria

Expectant parents, tell me this:

If there was a thing you could do for your child that would decrease his or her chances of being obese, suffering from asthma, or developing type 1 diabetes later in life - and that's just a start - how hard would you try to do it?

Well, there is a thing. And that thing is protecting the little one's gut bacteria, right from day one. 

When I was expecting my daughter, I was already a full-on gut bacteria geek. Instead of reading What to Expect before bed, I was downloading pdfs of studies on the gut bacteria of newborns. Oddly, the topic was nowhere to be found (outside the scientific literature) in my pre-baby immersion experience. I don't remember a single mention in the parenting books, blogs, prenatal groups, or even my medical professionals.

Luckily for all the babies yet to be born, that silence around gut bacteria will definitely change over the next couple of years.

How do I know? Because the science that's already out there says that gut bacteria is highly relevant to both labour and newborn care. Health outcomes later in life may have everything to do with those couple of days leading up to birth, and with the birthing process itself. It's not just an exercise in getting the baby out. It's the challenge of getting the baby out with good gut microbiota intact. This microbial garden is so important that microbiologists are starting to think of it as the baby's "forgotten organ". Not sure about you, but I would certainly want my baby delivered with all of its organs included.

Photo source: http://www.andrews.af.mil/news/story.asp?id=123117961


In a nutshell, these are the things that can have an impact on baby's gut microbiota:

1) Mom receiving antibiotics before and during labour
2) Baby born by caesarean section
3) Baby breastfeeding
4) Baby receiving antibiotics early in life

What's exciting to me is that, even in the past year, researchers have started to put more empirical data behind these. A few of the above started out as mere theories, but now there is evidence for each one of the four factors.

One recent Canadian study that investigated factors 2 and 3 above was called Gut microbiota of healthy canadian infants: profiles by mode of delivery and infant diet at 4 months, published in the Canadian Medical Association Journal. With 24 subjects, the study is big enough to be interesting, though small enough to warrant continued research.

The study was basically a snapshot of gut bacteria at a single point in time - 4 months - along with information on the infants' birth and health histories. Researchers found that all kids had certain bacteria in common (e.g. Bifidobacteria), but there were some important differences:

Vaginal birth vs. Caesarean section

Certain bacteria were "underrepresented" in all infants born by c-section, as compared to those with a vaginal birth: those of the genus Escherichia–Shigella. And one entire phylum of bacteria (Bacteroidetes) was absent from the c-section babies.

Elective caesarean section vs. Emergency caesarean section

Here is an interesting one - the researchers found that the gut bacteria of those born by elective c-section had the least richness and diversity of all groups. Leaving aside the question of whether low richness and diversity is a bad thing, it could be that elective c-sections result in different intestinal bacteria than emergency c-sections, which happen after a woman's body has initiated labour. Researchers are intrigued, but not yet sure why this could be the case.

Breastfeeding vs. Formula

A difference here should be no surprise, since breastmilk is full of great bacteria. Even the fancy probiotic formulas can't do exactly the same job. The breastfed babies had significantly higher numbers of 2 families of bacteria (the eloquently-named Peptostreptococcaceae and Verrucomicrobiaceae). Formula-fed babies had more richness and diversity, meaning that the breastfed babies had fewer overall species present and that certain species tended to dominate in the gut. Notably, babies on formula harboured more C. difficile.

The data in this study is descriptive, and the researchers left out the weighty question of what kind of intestinal garden is better and what's worse. See, we don't yet know what the ideal gut should look like at 4 months, so we don't yet know what a poor gut looks like, either. All 24 infants were healthy, so in some sense the data all describe the range of normal. But judging by other research on health outcomes, it's fair to say that whatever the vaginal birth and breastfeeding do to the babies' gut bacteria, it's a good thing.

I was happy to see this study reported so widely in the media when it was published in February. There were several great articles on it, including one by Paul Taylor in The Globe and Mail.

I did shake my head, however, at one misleading line that was meant as a caution:

"Canadians seem to be opting for c-sections in increasing numbers. "

As I outlined in a series of tweets, the (limited) data show that women are not at all "opting" for c-sections.

The increasing c-section rate is likely because of more emergency c-sections - which has to do more with the decision-making of surgeons rather than mothers. A study right here in British Columbia, a place with one of the highest c-section rates in Canada, found fewer than 2% of those surgeries were a result of maternal request. (Incidentally, collaborative maternity care in B.C. has been shown to reduce the number of c-sections.) 

There's one other thing I have to address with this study. That's the anxiety of parents who have already birthed their bundle of joy in a situation where things weren't exactly optimized for great gut bacteria. I know more than a few people in that boat.

Well, not to worry. There are things you can do later in life to keep your little one's garden growing well. Some of my other "Flora Helpers" blog entries explain what these are (here and here, for example).

And if you are a parent-to-be who really really hopes you can protect that baby's gut bacteria on the important day that it decides to enter the world, I want to share the best piece of wisdom I got before the birth of our little girl: "Labour is like a box of chocolates. You never know..."

Which means, you can't control everything all the time. Least of all a brand new, squirmy human, a mother's wonderful and wise body, and teams of midwives and doctors and nurses. You may indeed end up having a c-section and unable to breastfeed. But simply by being aware of the factors that affect baby's gut bacteria, you can take steps to protect it whenever you can.
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Saturday, December 29, 2012

Metaflora: Wheat Belly book review

If a doctor writes a book in the forest...
Wait a minute, that's not right.

If a doctor writes a book about health... is it science?



This is the question I had in mind while reading Wheat Belly. When a physician like William Davis, MD, takes time out of his (no doubt) busy schedule to write a health-related book, ideally he has taken the time to  get familiar with all the scientific literature on the topic. This may be easier for doctors than for some other writers, as Davis may have had the benefit of hearing research summaries at conferences, or having literature reviews arrive on his desk with the daily mail. Add that to years of clinical experience, and you have the potential for a pretty compelling argument on a health issue.

But what if, instead, a doctor seems to have spent years giving a certain piece of unusual clinical advice about a dietary change. And he has had such great success with patients who follow that advice that he goes looking for science to explain why it works. He scraps together a few studies that he thinks are relevant, connects some dots, and writes a book. What then?

Interesting, but not necessarily science.

So here's the heads up: Wheat Belly is an example of the latter. Though Davis, a cardiologist, has written a very interesting book with a timely message, you should know that it is not strictly based on science. Meaning: there is no thorough review of the evidence for his claims about the ill health effects of wheat. Case in point: the glycemic index stats he cites are from an article published in 1981 - and he repeats again and again that the study found a greater blood sugar rise with "whole-meal" bread than with white bread, even though - ahem - a fair amount of glycemic index research has been done since, and a quick visit to almost any diabetes association website will confirm that whole wheat breads (for the most part) have lower glycemic indices than white breads. Davis gives a few nods to how his claims fit in, or don't fit in, with the advice of professional bodies. But he doesn't present a complete picture of why and how science shows that eliminating wheat from one's diet is a good idea.

One other reason I know he hasn't done a thorough review? I know about another body of science relevant to the topic, which gets little to no mention in Davis's book. That's the science to do with gut bacteria. But more on that after I summarize the book.

The point of the book is that it's bad to eat things that spike your blood sugar - i.e. things with a high glycemic index (GI). Apparently wheat spikes the blood sugar more than you'd expect - the oft-cited study found whole grain bread had a GI of 72, while a Mars bar had a GI of only 68 - and therefore we should eliminate wheat.

It follows that we should eliminate all things that spike blood sugar. Davis advocates this. So properly, the book should be called "Carb Belly". (Of course, the arguments against carbs have been well-explored in books that promote the Atkins diet, Paleo diet, Specific Carbohydrate diet, etc.) But Davis says the one carbohydrate that people have the most trouble eliminating is wheat. Hence, the name Wheat Belly.

Here's what's in the book:

Part 1:
Davis explains how wheat strains have changed with hybridization and how modern types of wheat affect us in unprecedented ways.

Part 2:
Davis describes wheat's "head-to-toe destruction of health": (1) the addictive properties of wheat that can influence behaviour and mood, (2) the way wheat triggers blood sugar and insulin extremes, which lead to visceral fat accumulation, (3) how intestinal permeability triggered by a protein in gluten may be responsible for the rise of autoimmune disorders and digestive disorders, (4) an argument that wheat may cause type 2 diabetes, (5) an explanation of how wheat affects the body's pH, resulting in an "acid-rich situation" and that promotes osteoporosis, (6) wheat's promotion of AGEs, which signal aging, (7) how wheat leads to heart disease by increasing triglycerides that turn into atherosclerotic plaque, (8) how the immune system's attack on nerve cells results in cerebellar ataxia and brain fog, and (9) how increased levels of insulin, and an immune reaction to gluten, can show up as acne or skin rash.

Note that for most of these claims, Davis's evidence is in the realm of the "theoretically possible." As far as I can tell, the science actually addressing these claims is weak. The studies conducted on humans where all else is equal, except the inclusion of wheat in the diet, are rare. Making his claims premature at best.

Part 3:
He talks about the "how to" of eliminating wheat and other carbohydrates. The book includes menus and recipes for low-carb eating.

I have to jump in here and wave my hands, saying, "What about the gut bacteria? Don't they get any consideration?" Because here are just some of the studies that may be relevant to the issue of eliminating wheat and/or all carbs:

- Evidence on how gut bacteria influences carbohydrate digestion throughout the lifespan
- Evidence on how bacterially-pre-digested white bread (a.k.a. sourdough) is metabolized differently from other breads
- Evidence on how fibre (prebiotics - known for their promotion of good gut bacteria) stimulate the immune system and increases the bioavailability of nutrients

He missed a few things. But can we really knock Dr. Davis for proposing a low-risk treatment that seems to work like magic for a host of health problems? Can we truly fault a compelling book that's convinced a lot of people to do something that clearly helps their health?

Well, not really. I think it's a good thing that he's written this book and that it's sold so widely. I'm biased of course, having been on a gluten-free diet for five years or so. It also doesn't escape me that it took a lot of bravery for him to so emphatically convey this message in a world that is very wheat-centred.

So yes, Davis has perhaps inspired many people to initiate a positive change for their health by penning a bestselling book with lots of media coverage. But by putting together a misleading scientific grab-bag of reasons for convincing people to make this change, he is assuring that they never fully understand what caused their health problems in the first place. They put on a bandaid without understanding what might have caused the wound.

**
These:



...pretty well tell the same story as these: