Research

I have neglected to post very much lately because of (a) work responsibilities (b) illness, and (c) for the past three weeks I’ve been using my spare time and energy to put together an academic grant application which, if successful, will pay for a lot of sequencing. Without the grant the work will still move forward, only sequencing (and, results) will have to wait until I have been able to raise funds to pay for it. I’ve learned from last year that crowdfunding is only mildly successful unless you know a lot of people- I do not know a lot of people, so I’m not giving that another try. I would rather take out a bank loan.

In the course of writing the grant application I’ve had to nail down specifics about what will be done in the labs of my various collaborators, and when. It’s exciting work! Material transfer agreements have been signed between my university, UCLA, and Duke, and two separate small projects will be conducted which, if successful, will shed light on the issue of whether my ideas for helping chemotherapy patients have any merit. They also may shed light on some basic mechanisms by which gut bacteria and their hosts communicate, which is pretty exciting.

In a related note, I’ve spoken with a researcher at Johns Hopkins and he has given me a lead on some exciting new methods that will really help my project, if I can find a way to convince someone to perform the assay for me (I am afraid I do not have enough expertise- and I’ve been away from bench work for more than a year! So I can’t do this myself).

Hello readers: today’s article is about how your lungs and your gut seem to interact: changes in gut microflora can affect lung activity, and vice versa. It is entitled, “Changes in the Bacterial Microbiota in Gut, Blood, and Lungs Following Acute LPS Instillation into Mice Lungs”. LPS is short for lipopolysaccharide, which is a component of the surface of some bacteria.

Here they were looking at total bacterial counts in blood and in the cecum (a region of the gut), as well as the microbiome composition present in lung fluid, blood, and the cecum. They found that adding LPS (it’s not clear what species the LPS is from, or if it is from a mixture of species) changed total bacterial counts in the cecum as well as the blood, and that adding antibiotics could reduce the changes seen in blood.

This evidence supports prior work indicating that, bacteria may translocate from the gut to the blood (where perhaps they interact with lung tissue) and indicates that the lungs- much like the gut- contain a large and diverse population of bacteria. More work is needed to characterize this environment and determine relationships between lung bacteria and lung dysfunction. The link to gut bacteria is also interesting- could this be why there are websites recommending different foods for helping people with asthma? Studies are inconclusive, but that may be expected if people weren’t taking the starting gut community into account when designing studies intended to determine if diet changes help asthma. A link between diet, your gut microbes, your lung microbes, and your breathing suggests all kinds of new ways to help treat asthma, and possibly other lung problems as well.

Hello, readers! Today’s interesting paper, which outlines evidence supporting the hypothesis that the composition of the bacteria in your gut will influence your eating behaviour, comes from Alcock et al. and was published earlier this year. The article is entitled, “Is eating behavior manipulated by the gastrointestinal microbiota? Evolutionary pressures and potential mechanisms” and is found here.

To summarize this article, it’s thought that there may be several ways in which the composition of your gut bacteria might affect eating behaviour, and by doing so, affect phenomena like metabolic disorders, heart disease, or cancer. Some key points are listed below:

1. There is a selective influence of diet on the composition of gut bacteria: different bacteria eat or thrive on different nutrients, so what you eat will affect the composition of bacteria in your gut.

2. Microbes can manipulate host behaviour: This section outlines some studies which indicate that food cravings and mood are associated with differences in gut microflora. For example: a study in which chocolate cravings are associated with a changed gut bacterial composition can be found here. Additional evidence indicating that negative mood, or psychological shifts (e.g. “gut-brain axis”- related changes) can be associated with particular gut bacterial composition is given in this section. This might make sense if feeling anxious or unhappy leads to eating certain foods.  The authors suggest that by changing host psychology, gut microbes affect eating patterns.

3. Microbes modulate host receptor expression: Might gut bacteria alter host eating preferences by changing taste receptors in the host, which would make food taste different?

4. Microbes can influence hosts through hormones and effects on weight: Microbes can produce compounds which are similar in structure to mammalian hormones- and by so doing, can directly affect mood and behaviour, and probably directly affect physiological changes as well. There are studies describing links between metabolic disorders such as obesity with changes in gut bacterial communities, and other studies linking probiotics with changes in weight and weight-related phenomena. 

Further work on links between gut bacteria and eating habits may help us figure out how to make it easier for people to choose and maintain a healthy diet.

Hello readers! Just last month an interesting paper was published on links between the composition of bacteria in the guts of alcoholics seeking treatment, and psychological or physiological symptoms that are associated with relapse. The paper is by Leclercq et al. and comes from a variety of European labs, and is published in the Proceedings of the National Academy of Sciences of the USA (find it here).

Essentially, the authors found that some, but not all, alcohol-dependent subjects developed gut leakiness, which was associated with higher scores of depression, anxiety, and alcohol cravings after a short period (three weeks) of abstinence in a treatment program. These may be important indicators of the potential for relapse. Subjects with gut leakiness had an altered composition of the gut bacterial community, and the bacteria were differently active (this was measured by studying the metabolic compounds that were present in feces).

What does this mean? It means that in some people, changes in gut bacterial community composition (dysbiosis) can lead to physical and psychological changes that affect mood, and possibly behavior. In this particular study, dysbiosis in the guts of some alcoholics resulted in effects that might make it more difficult for them to stay away from alcohol.

It may be possible in future to help people with substance abuse problems manage these problems with changes in diet and exercise! In fact, there’s no reason why a person can’t try to help manage these problems now by eating a healthy diet, getting regular sleep, and getting regular exercise. Probiotics may, in future, assist with problems like these but at the moment no products have been tested for helping with behavioral problems like alcohol abuse.

A while ago, I came across this interesting and very important review in Cell (a very reputable journal), on how gut microbes (part of your microbiome) can affect the aging process. Ten years ago people would have thought this was impossible!

The review, published in January 2014, is by Caroline Heintz and William Mair, both from Harvard. The article can be found here: “You are what you host: microbiome modulation of the aging process.“. To summarize, the microbes living in symbiosis with invertebrates, and possibly other animals (mostly in the gut, but also in other places, like the mouth or on the skin), can affect the rate at which aging occurs. This could occur by the microbial production of compounds that affect the expression of genes, or possibly by the microbes metabolizing compounds into products that have direct effects on host physiology. There is also evidence to suggest that different microbial species may have different effects. It makes sense if you think of how long digestive systems have existed in symbiosis with microbes- maybe we and they have co-evolved.

Most of the work cited in this review has been done with invertebrates, particularly nematodes, which have been intensively studied for many years as model organisms. How exciting if the results from these studies are supported by work done with mammals!  Until we know more about how microbes interact with mammals, the best thing you can do is try to make sure you eat a healthy, balanced diet with lots of fruits and vegetables, get regular sleep (disrupting circadian rhythms can lead to changes in your gut microfloral composition and changes in your body, like a tendency to gain weight), and get regular exercise (in addition to health benefits, most cardio exercise helps your gut move food along by peristalsis- there’s a reason why for many years people would take walks after meals to help with digestion!). If you want to take a probiotic, I can’t recommend a specific product, but you may be able to find more information at sites like probiotics.org.

Have a great day!

Hello readers, I’m very encouraged- I’ve sent a short summary of findings based on sequence data from Project: Cancer-Fighting Gut Bacteria to Dr. Schiestl at UCLA, and he’s agreed that it’s worth publishing! There’s a lot of supporting data from the literature, and I’m planning some in silico (on computer) experiments to bolster the findings as well.

If I can arrange for support I’ll see about including a separate experiment I have planned which would look at systemic (body-wide) effects of bacteria like the Lactobacillus strain used in the project. I need to get permission to do this, since it would involve analysis of blood (my blood! I plan to volunteer as guinea pig) taken before and after ingestion of the Lactobacillus probiotic. It’s admittedly a kind of risky idea, but less so than the researcher who ingested the pathogenic bacterium Helicobacter pylori and photographed his stomach before and after to demonstrate that H. pylori is involved in gastric ulcers. I am not certain that, like the H. pylori study, this work will result in a Nobel prize, but it would certainly be novel and groundbreaking if it works and ties in with the results of Project: Cancer-Fighting Gut Bacteria the way I suspect it could.

My work is publishable whether or not this additional work is included, though, so stay tuned for updates!

[October 22, 2014: Dr. S. says I can use blood from a clinical trial planned in 2015- so I may not need to be a guinea pig after all! This will require serious funding to analyze samples from as many as 40 people, though, so I will have to figure out if I can write a small grant. Given the difficulty in getting funding for joint US-Canadian projects, it may be more difficult to find funding than to actually do the project! While I try to figure out this issue I’ll go ahead and write up what I have so far, since I don’t want the work to just sit around, and it will be a very nice paper.]

Hello readers! This past week was very busy for me, and I’m currently in the middle of writing a small grant for metatranscriptomics work on a project related to my paying job with the University of Guelph. However, I thought I would share this milestone with you: I received the results of my second major experiment, conducted at UCLA in the Schiestl laboratory! I’ve sent the raw data to others at the Schiestl lab as well, and plan to start the analysis as soon as I am able. This may take a bit of time as I am both trying to submit my grant proposal, and write up an important paper that’s rather overdue for submission. Once that paper is submitted I’ll have a bit more energy to spend time at home during evenings annotating the new data, and determining what it means.

I’m very pleased, though: a preliminary look at the summarized results tells me that at least two of my hypotheses, which I’ve shared with Dr. Schiestl and which I can’t disclose since I’ve signed a confidentiality agreement, are correct! Note: I have to get my interpretation reviewed by others, and I’ll try to publish if Dr. Schiestl agrees, so the work is peer-reviewed.

Project: Cancer-Fighting Gut Bacteria is, in my opinion, a success! There are additional experiments I would like to do and I am evaluating what options I have for funding them, as crowdfunding does not seem to work well for me- I simply don’t have a big enough platform to reach enough interested people in a short enough time frame.

Thanks to all who have donated so far, and I hope to continue with both reading, which helps me evaluate my hypotheses and form new ones, and the actual experiments in the Schiestl lab at UCLA on the cancer-fighting Lactobacillus strain isolated there. I’m optimistic that, for a few thousand more dollars, samples I’ve left behind at UCLA could be analyzed. This could yield enough data so that Dr. Schiestl and I can write an NIH R21 grant and get enough funding to include clinical studies. Please wish us luck! If my hunches continue to be correct, we may discover a new and potentially less toxic way to improve cancer therapies.

 

I just came across this fascinating study today on how adding a particular bacterium (a species of Clostridium) back into the gut microflora of mice rescued the mice from a nut allergy.

Here’s the article summarized from the Science website.

And here is a link to the original article.

Speaking purely anecdotally, my own troubles with negative reactions to food (gluten and dairy proteins) started after a period of time where I was taking a lot of antibiotics. Of course, this may be coincidence, but it would be really interesting to me to find out if there are “healthy” bacteria that are missing from my own gut microbial community. Ideally I could go back in time and sample myself from before I took all those antibiotics! Where’s a time machine when you need one?

I don’t think anyone really knows yet what a truly “healthy” community looks like (though researchers like Dr. Emma Allen-Vercoe at the University of Guelph are working on this subject), and of course research like this is just starting to point in the direction of the different roles particular gut bacteria may play in interacting with our gut and immune systems, and maybe other organs of our bodies as well.

Who knows, in twenty years the knowledge that is just coming forward now might revolutionize medicine!

PS: I realized I promised a blog post on how my cancer-related research relates to the tumour-shrinking bacterium reported recently in news outlets, but quite honestly I have been very busy- in part learning more about new research to do with bacteria that are involved in cancer. Some bacteria seem to promote cancer, others fight it- it’s so interesting to me as a microbiologist to try to think of what molecules these bacteria may be producing that result in their differential effects. More on this subject as soon as I get a chance to digest it all.