Hello, readers! I’ve been ill for some time and focusing on other projects, so unfortunately I’ve been neglecting this blog. I haven’t stopped my work on Project: Cancer-Fighting Gut Bacteria, and an NIH grant is in the works for that project with some collaborators of mine. If I had adjunct professor status at a university, that would make writing such a grant a lot easier, but alas, my funding situation is too precarious for me to get status at my home university, the University of Guelph, and unless funding comes through for my UCLA collaborator, there won’t be a chance for me to get this status at UCLA, either.

My UCLA collaborator, Dr. Robert Schiestl, has shared with me some of his ambitious plans for studying the Lactobacillus johnsonii gut bacterium that he’s already demonstrated has the ability to suppress lymphoma development in mice. I can’t tell you what the plans are, except to say he’d like to examine the possibility of this bacterium helping with a wide variety of diseases and syndromes linked to inflammation (and there are quite a number of these!). I am helping him seek funding for his project, partly because I want to see the trials go ahead, and partly because it would allow Dr. Schiestl to hire me and, if I am hired for long enough, I can get adjunct status at UCLA and take a lead role in the grant I’m trying to coordinate for Project: Cancer-Fighting Gut Bacteria.

Wish us luck! I wish I could tell you what is planned, as it is very exciting indeed, but I have promised not to.

I hope over the Christmas break, in between working on some other projects, to post a few more details of articles I’ve come across which I find interesting, and which you may find interesting, too.

Merry Christmas, if you celebrate, and if you do not, I hope you have a nice day.

Hello readers! I apologize for the lack of posts- I’ve been devoting my spare time to a novel I’ve been writing, as well as a number of grant applications. One of them is for an NIH R21 for Project: Cancer-Fighting Gut Bacteria.

Earlier this week I experienced a bout of food poisoning, and at the same time an intensification of symptoms associated with my bipolar disorder. This made me think of the articles I had been posting on this site and once I recovered, and looked through my notes for Project: Cancer-Fighting Gut Bacteria, I realized that I needed to find more articles on probiotics and whether they establish in the gut, as well as whether they have any beneficial effects on diseases of the gastrointestinal tract, and how they work.

The results of this search, which I conducted over several hours tonight, have been fruitful! I share with you the URLs for three of the most accessible articles I have come across.

First of all, an older article but a good one that’s been cited more than 400 times: Probiotics: determinants of survival and growth in the gut. Essentially, the take home message is that, while probiotics can have beneficial effects on controlling things like diarrhoea, and can survive transit of the stomach into the lower GI tract, there’s no evidence they actually establish in the intestines- they seem to exert their effects while passing on through. This suggests that in order to get a beneficial effect from probiotics, you might have to keep taking them consistently.

Here’s a newer article on the same subject: A Meta-Analysis of Probiotic Efficacy for Gastrointestinal Diseases. This article summarizes research from a lot of other articles, all studies of the effects of probiotics on different diseases. The take-home message is that, for most probiotic bacterial strains and diseases, taking probiotics can help- but there are some diseases that are not as well treated, and some bacterial strains that are less effective. Quoting from the abstract, “Six of the eight diseases: Pouchitis, Infectious diarrhea, Irritable Bowel Syndrome,Helicobacter pylori, Clostridium difficile Disease, and Antibiotic Associated Diarrhea, showed positive significant effects. Traveler’s Diarrhea and Necrotizing Enterocolitis did not show significant effects of probiotcs. Of the 11 species and species mixtures, all showed positive significant effects except for Lactobacillus acidophilus, Lactobacillus plantarum, andBifidobacterium infantis.” The last sentence is important, since L. acidophilus is typically found in yogurts, and if this is the only strain in your probiotic preparation, or the main strain, it might not be as effective as you’d like against a disease. There still may be other health benefits, just not necessarily control of disease.

A very useful article with a lot of really nice figures that explain in detail how probiotic bacteria exert their effects on you (it might be a bit too technical, but it is open access so there’s no harm in taking a look) is this one: Effects of probiotics on gut microbiota: mechanisms of intestinal immunomodulation and neuromodulation. It talks a bit about the gut-brain axis, which is of particular interest to me (especially this week, given my health issue from earlier), and it also talks about how gut bacteria can affect your immune system. There also is a bit of discussion of how dietary compounds (like histidine, glutamate, and dietary fibre) lead to the production of compounds that affect your metabolism (like short-chain fatty acids (important for colon health), gamma-aminobutyric acid (GABA, a neurotransmitter) and histamine (influences inflammation and immune responses).

I apologize for being absent from this blog for so long and I hope you enjoy these articles- all are or should be open access, but if you have problems accessing any of them write to me and I will see if I can help you find a PDF.

Several of my friends suffer from fibromyalgia. I wondered if there was a possible link between the fatigue and muscle pain (myalgia) they suffer, and I found this interesting article from the Journal of the American Medical Association, authored by Henry C. Lin: “Small intestinal bacterial overgrowth: a framework for understanding irritable bowel syndrome“.

Now, bear with me, this article is not just about irritable bowel syndrome (IBS)- in the abstract it mentions, at the very end, how the distinction between small intestinal bacterial overgrowth and IBS may focus on a specific set of symptoms that exclude fatigue and muscle pain, while diagnoses of chronic fatigue and fibromyalgia are focused mainly on these symptoms. The authors of the article suggest that this distinction may be academic- an artefact of medical training- and put forth the idea that maybe all these various symptoms can be traced to a single cause, namely, gut dysbiosis (here specifically focusing on small intestinal bacterial overgrowth).

This is a hugely important and interesting idea, and taken along with the article I have mentioned in my preceding post, a review of the gut-brain axis (where changes in gut microflora can result in psychological changes), gut dysbiosis (unhealthy gut microflora) may contribute not only to symptoms like muscle pain and fatigue, but to mood disorders as well.

The obvious question for people suffering from these symptoms is, how can I fix my gut microbiome, if it might be unhealthy? This is a hugely important question. Right now research is focusing on finding “good guy bacteria” that can help maintain healthy states, but it’s important to remember that it’s not enough to simply take a probiotic- if you take bacteria and add them to an environment where they can’t grow and establish, they will simply pass right on through your intestines without making much of a change. It’s known that factors such as what you eat, how much and when you exercise, how much and when you sleep, and if you’ve become sick (food poisoning, for example) will all affect the composition of your gut microflora. Establishing a healthy microbiome will probably require that you follow a doctor’s advice with all these factors and do so in a steady, long-term fashion- not that you simply take a probiotic supplement or eat fancy bacteria-containing yogurt.

[UPDATE: There are a TON of quack websites out there which claim to have miracle diets or cures for small intestinal bacterial overgrowth (SIBO): if you read anything like that, stop! It’s fake! It won’t help and might harm you. SIBO treatments have to be custom-tailored for each person. Please take the above cited article and this one to a real medical doctor, not a naturopath, and if you look at websites make sure they are from reputable, accredited medical schools.]

In future, I am hoping that work based on ideas I have might help people whose gut microbiomes are unhealthy and, for whatever reason, can’t take probiotics, or in whom probiotics are not effective (probably because the gut environment is hostile to those added bacteria). Right now I am focusing on an interesting strain of Lactobacillus that helps fight lymphoma, but the lessons I learn from this organism may help me study ways to use other gut bacteria with different kinds of effects on human health, to help a lot more people.

Hello readers! I have downloaded the most interesting- and high quality- review I could find on links between gut bacteria and brain functioning/mood, and it is can be found via this link: “Gut-brain axis: how the microbiome influnces anxiety and depression”. The journal is Cell and the review is written by Jane A. Foster and Karen-Anne McVey Neufeld, both of McMaster University.

I haven’t had time to read all the articles listed in Table 1, which is an outline of different kinds of studies done with mice and the psychological effects of changes in gut microbiota. However, while I plan to discuss these works in more detail in the future, I’d like to direct your attention to Figure 1 in this article: it nicely sums up the different, and interconnected, effects that changes in gut bacterial community composition (or, changes in your gut microbiome) have on your body, including your brain. A change on one partner (your body, or your gut microbiota) will have feedback effects on the other partner, which then leads to additional changes to the first partner.

Figure 1 caption (I’ve added additional notes in italics): Bidirectional (two-way) communication between gut microbiota and components of the gut–brain axis which influence normal homeostasis (the state your body is in when you are healthy, and the systems which maintain that state) and may contribute to risk of disease. Alterations in gastrointestinal (GI), central nervous system (CNS), autonomic nervous system (ANS), and immune systems by microbiota may lead to alterations in (a) fat storage and energy balance (or, you may find yourself prone to changes in weight); (b) GI barrier function (the GI barrier keeps your gut from “leaking” and allowing in antigens that cause inflammatory responses, which if unchecked can lead to disease states like colitis); (c) general low-grade inflammation (GI and systemic, or body-wide); (d) increased stress reactivity (or you are more sensitive to stressors); and (e) increased anxiety and depressive-like behaviors. Each of these mechanisms is implicated in the pathophysiology (disease physiology) of mood and anxiety disorders.

I apologize for not having an explanation of this article ready for consumption today, but please stay tuned for it in coming weeks.

Hello, blog readers! I apologize, for I have sadly neglected you- and I failed to update this blog with summaries of the many interesting articles that have crossed my desk. I have been taking courses in bioinformatics, and travelling- and one of my travels took me to Duke University where I met with one of my collaborators in person for the first time.

While I was there, I received email notification that the small grant I had applied for in June was not going to be funded. I hadn’t expected it to be- only four of those grants are funded out of however many applications they get, and so it is a very competitive program. My co-PI and I still await the reviewers’ commentary on our application.

However, all is not lost- it’s been decided that my Duke collaborator will help me apply for an NIH R21 grant, which would allow everyone (not just the Canadians) to be paid from the grant. My Duke collaborator and I sat down that afternoon and put our heads together, and came up with a marvellously scribble-filled page of notes for the project we think we should do- and it is bigger, better, and if funded will be an amazing piece of science! I am slowly putting all our thoughts into words- slowly because I am still waiting for feedback on our first grant application, which will inform this one, and also slowly because the deadline for this program is in October, though I believe we can apply earlier than that.

So my trip to Duke was not simply an exercise in networking, it was very fruitful and I’m so glad that I was able to do that! Stay tuned for more updates on the R21. Again, these are competitive grants, and it’s possible our application won’t be funded- but it won’t be for lack of our trying, or doing the best job we possibly can.

I hope to post a few more summaries of interesting research articles in the coming weeks- it’s been hard to find the time, as I am responsible for putting together this R21, other personal writing projects have caught my attention and, as always, I still have a full-time job that I have responsibilities toward. Still, every week new and interesting research on the subject of gut bacteria and how they affect their animal hosts is published, much of it not very accessible to the general public. I’d like to share more of these articles with you in hopes that you find the work as interesting and informative as I do.

Hi- I’ve been writing articles for fun for The Conversation, and enjoying the attention those get. I’ve neglected to post much to this blog because of that, but later today or tomorrow I plan to contribute a new post describing a paper from Neuroscience in which links between gut bacterial composition and the functioning of the mouse nervous system are described. It will be a very interesting read!
I’ve also written an article on probiotic bacteria for a website called probiotics.org, but that hasn’t been posted- the website’s maintainer has faced some difficulties recently and hasn’t had time.
Here are the four articles I’ve written so far for The Conversation, and I hope you find them of interest.
How gut bacteria affect your immune system and response to vaccines – https://theconversation.com/what-do-the-bacteria-living-in-your-gut-have-to-do-with-your-immune-system-36732
How soil bacteria and fungi can help plants grow (this one was the first and it was not well edited- it needs a bit of work) – https://theconversation.com/tapping-the-plant-microbiome-to-improve-farming-and-plant-health-36288

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).

Just a short blurb regarding this new Nature Communications article regarding differences in the gut bacterial communities (microbiomes) of people living different lifestyles. In this study, microbiomes of people living in different ways, from the following groups: (1) the Matses, a remote hunter-gatherer population from the Peruvian Amazon; (2) Tunapuco, a traditional agricultural community from the Andean highlands; and (3) residents of Norman, Oklahoma, a typical US university community that serves as a comparative population following an urban-industrialized lifestyle.

What was found that, in support of prior work, the rural community microbiomes had greater richness (number of different organisms) than the microbiomes of people in the urban population sample. There were a variety of differences in the compositions of the microbiomes that meant it was possible to predict what group a person came from based solely on their gut microbiome. Perhaps even more interesting, though, is that the Matses people had strong signatures of variants of the bacterial genus Treponema that were present to a lesser extent in the Tunapuco people, and largely absent from the urban sample.

If you’ve heard of Treponema, you’ve probably heard of it in its context as a pathogen: species of this genus can cause different diseases, including syphilis. However, the Matses people sampled were perfectly healthy, and the signatures of Treponema found in them are more closely related to symbiotic gut bacteria in creatures such as termites than they are to the pathogenic species.

What are these newly discovered varieties of Treponema doing? Functional gene analysis between the microbiomes of the three groups of people showed differences in the abundances of some gut bacterial genes, associated with things like metabolism of carbohydrates.  Might these bacteria belong to a long-lost group of “good” gut bacteria that a typical Western lifestyle has eradicated? It will be interesting to see if there is work following up this study to learn more about these bacteria.

 

I spent some time putting together drafts of two articles that may be of interest:

1. How CRISPR-Cas systems (combinations of RNA and proteins) can be used as very precise tools to target and kill specific bacteria of interest in a mixed community, leaving non-targeted neutral or “good” bacteria alone. These tools require further development before they can be used in medicine, but hold so much promise! This article was written for the website The Conversation.

2. How some isolates of probiotic bacterial strains originating in the human gut can affect the lining of your intestine- in the study I reference, some of the isolates (notably Bifidobacterium bifidus) that were found were able to actually repair damage done to the gut lining by a molecule known as tumour necrosis factor alpha. This is exciting news! This article was written for the website probiotics.org.

I will post a link to each article as they become publicly available.

So, getting the materials I need to conduct the follow-up tests I have planned for study of the Lactobacillus johnsonii lymphoma-fighting strain is proving to be more challenging than I had anticipated. I think this could be smoothed out by liberal doses of cash, but of course, everyone’s research project could use more cash. I will try again to try and find funding sources for this sort of work- all the ones I had looked into before now ruled me out, because I am Canadian or not a faculty member, or ruled out my being able to work with UCLA, because it is a US institution. You’d think with NAFTA this sort of thing would be easier! Business grants care less but need a marketable product, and this is for basic research. Still, perhaps there will be a funding source I haven’t come across yet, or perhaps I will find a collaborator that can help me.

People wonder why scientific research is so slow- half the time we have is spent chasing money sources to do the actual work, a quarter of what is left is spent trying to train other people how to do the work properly, and then half of what’s left after that is spent trying to solve lab problems, like malfunctioning equipment or why Josie’s PCR experiment didn’t work. Add in teaching and administrative duties, and it’s a wonder that any science gets conducted at universities at all.

I consider this project still in progress- I will look into how much it will cost to get the equipment needed to do the work I have in mind and buy it out of my own pocket, and fly back to LA to do the work myself, if this is what’s needed.