Hello readers: I’ve come across an interesting article from my own home university, the University of Guelph! It’s entitled “Stress and the microbiome: linking glucocorticoids to bacterial community dynamics in wild red squirrels“, and it’s fascinating because (a) wild animals were used, responding naturally to their environments, and (b) it shows a direct link between levels of stress, as measured by faecal glucocorticoid hormones, and the microbiome, which controls so many aspects of one’s health. The paper comes out of the lab of Amy E. M. Newman.

The analysis is a little crude- the authors only looked at diversity of bacteria in faecal samples, not composition of bacteria to find which bacteria changed in abundance with stress- but it’s very clear that the overall diversity of bacteria in the microbiome of the squirrels analyzed in the study (via collection of faecal pellets) dropped when those pellets had higher levels of glucocorticoid hormones (which are an indicator of stress response).

What does this mean for you? Well, it’s clear from many studies that stress negatively impacts your health, and the alteration of the gut microbiome in response to stress probably happens in people as well as squirrels. This may be one more mechanism by which our psyche is connected to our physiological state via the gut-brain axis.

It had to happen sooner or later- I’ve come across the buzzword “psychobiotic” (meaning a probiotic, or live bacterium, which when ingested can help treat symptoms of mental disorders) online, and now in a publication (Psychobiotics and the gut-brain axis: in the pursuit of happiness, by Zhou and Foster, a review in Neuropsychiatric Disease and Treatment).  In the abstract, the authors state that a combination of probiotics, antibiotics, and fecal microbiome transplants (the latter is a drastic step to take indeed!) might be used to treat mental illness.

I think it’s a little early to be jumping on this particular bandwagon. While it’s clear that there are links between brain and central nervous system function and the composition of microbiota in the gut, it is likely that host genetics plays a part, and until we know which specific gut bacteria to remove or enrich for, and have therapies designed for these purposes, really it’s just shooting randomly in the dark. We still don’t know enough. The pace of research in microbiome studies is rapid, though- and I anticipate having real, designed therapies (clinically proven ones- do not forget this criterion, it is important!) in the next decade, if not sooner.

Another good paper to look at, if you are interested in the gut-brain axis, is this one, by Foster and Neufeld, published in Cell: Gut-brain axis: how the microbiome influences anxiety and depression. Most of the work they write about has been conducted in mice. I myself can’t find a single study on bipolar disorder and the human gut microbiome- if anyone wants to use me as a subject in such a study I’d be happy to volunteer! I notice links between what I eat and how I feel, both physically and psychologically. While it is possible that the food directly links these phenomena, it is also possible that food influences gut bacterial composition and activity, and then the changed microbiome has effects on my physiology and brain.

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.

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

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.

What role does your gut microbiome (the sum of bacterial species living in your gut) play in your body’s immune response to vaccines? I address this question here:

https://theconversation.com/what-do-the-bacteria-living-in-your-gut-have-to-do-with-your-immune-system-36732

I don’t go into a lot of detail, but it’s clear that the gut microbiome plays a role, and if I had to speculate about rare, adverse events, I’d speculate that they may be caused in part by your body’s past responses/ current overload or under-stimulation by the specific species of bacteria in your gut. Other factors will play a role too- like genetics- but I really do think your gut microbiome will play a significant part.

Happy reading!