Research Decoder: Gut Microbiome

hOur digestive tract contains trillions of bacteria encompassing thousands of different species that collectively make up the gut microbiome. In fact, the number of bacterial cells that have colonized our bodies outnumbers the human cells that make up our bodies by a factor of ten to one, and the majority of those bacteria reside in our gut! These little passengers aren’t just along for the ride, and you could say that we’ve entered into a mutually beneficial contract with them; they enjoy a place to call home and a constant supply of food, while we benefit from their ability to break down our food into vital nutrients.

It turns out, however, that the gut microbiome plays an even larger role than helping us digest our food, and many of our body’s biological functions – from our metabolic processes to our immune system – are exquisitely sensitive to changes in the composition of the bacteria that reside in our gut. Disruption of this delicate balance has been implicated in a host of health conditions such as diabetes, obesity and autoimmune diseases like inflammatory bowel disorder and multiple sclerosis. I will return to the link between the gut microbiome and MS in a moment.

The microbial ecosystem in our guts is shaped by the various exposures that we come across in life, such as the food we eat, the air we breathe, any infections we’ve acquired or drugs we’ve taken, along with a host of other environmental factors. These environmental exposures interact with our body’s own physiological processes, such as metabolism and stress, to further alter the balance of our microbial communities. There’s even evidence to suggest that our genes have a hand in influencing the composition and abundance of the gut microbiome, and that these “heritable” strains of bacteria are associated with health and disease. What this means is that each individual’s gut microbiome is unique, acting as a microbial “fingerprint” that carries the potential in the future to help predict risk of various diseases or offer new therapeutic targets.

Credits: Daniel Mietchen / CC BY 2.0 (Wikimedia Commons

Credits: Daniel Mietchen / CC BY 2.0 (Wikimedia Commons)

Mapping out our gut microbiomes is no trivial task. To realize such a complex endeavour, the Human Microbiome Project (a play on the Human Genome Project from several decades ago) was launched in 2008 by the US National Institutes of Health (NIH) with the aim of cataloguing the diverse species of microbes residing in a sample of healthy individuals. Such a catalogue, in turn, can serve as a reference point for comparing how different disease states can alter the composition of the gut microbiome and suggest new avenues for therapy.

While studying bacteria traditionally has involved “culturing” bacterial colonies on plates of growth medium, modern approaches have shifted to advanced, high-throughput sequencing techniques that are faster, more accurate, and provide a great deal more information. Today, gut microbiome researchers rely on DNA sequencing approaches and complex computational tools to catalogue the genes comprising our complex gut microbial communities. Researchers first purify DNA from samples that are teeming with microbes (to sample the gut microbiome, researchers rely on stool samples), sequence the genetic information using one of several techniques, and compare this sequencing data using complex algorithms to existing databases. One technique, called 16S rDNA sequence analysis, allows researchers to determine which bacterial species are present in the sample (i.e. “who’s there?”), while a second approach called metagenomics analysis determines the function(s) of the microbes, or answer the question “what can they do?” At the end of the day, these powerful approaches are not only able to capture the biological diversity of the gut microbiome, but also their functional interactions with the host’s physiology, leading to valuable insights for health and disease.

Gut microbiome: The link to multiple sclerosis

Earlier, I mentioned that imbalances in the composition of the microbial communities in our guts have been linked to various diseases, including MS. The connection between the gut microbiome and MS is rooted in the interactions between microbes in the gut and the immune system.

Since the gastro-intestinal system is a major point of entry for many foreign substances into the body, including potential pathogens, the immune system employs a complex surveillance system that monitors the composition of the gut microbiome in order to distinguish the “good” bacteria from the “bad” ones. Our gut microbes, in turn, secrete certain compounds – such as cytokines and chemokines – that can regulate the activity of certain immune cells that are implicated in autoimmune disorders like MS. For example, the bacterial species Bacteroides fragilis has been shown to promote uncontrolled activity of T helper-1 cells – which are normally involved in host defense against infection but can lead to attacks on our own tissues in autoimmune disease – through the release of certain molecules. In addition, segmented filamentous bacteria activate another type of immune cell called T helper-17 cell which also contributes to the MS disease process.

To date, the bulk of the research examining the link between the gut microbiome and MS has taken place in animal models. Interestingly, one of the first studies to look at this question came to a sobering conclusion: the gut microbiome is essential for the development of MS-like disease in mice. The Nature paper, published by Kerstein Berer (Max Planck Institute of Neurobiology, Germany) and colleagues, described an experiment where mice that were experimentally induced to develop an MS-like disease were bred under two different conditions: a sterile, germ-free environment or a conventional, pathogen-free (but not sterile) environment. They found that mice raised in the sterile environment did not harbour microbes in their guts and, importantly, did not develop the MS-like disease. On the other hand, most non-sterile mice did go on to develop the disease. When sterile mice were recolonized with the gut microbiomes transplanted from the non-sterile ones, they rapidly went on to develop the MS-like disease. These observations followed in the wake of an earlier study from a group in Dartmouth Medical School (Hanover, NH), who treated mice induced to develop MS-like disease with a cocktail of various antibiotics. They found that antibiotics appeared to protect against development of MS-like disease, presumably through a reduction in proinflammatory cytokines.

At first glance, this broad-brush approach would seem to suggest that the microbes inhabiting our gut are detrimental and can increase the risk of developing MS, but it’s not necessarily quite so simple. On the contrary, more recent research has put the spotlight on certain gut bacterial strains as playing a potentially beneficial and even therapeutic role for combating autoimmunity. A study by Shahram Lavasani and colleagues (Lund University, Sweden) found that a probiotic mixture of three Lactobacillus strains suppressed the progression of MS-like disease and reversed both clinical signs of the disease and inflammatory lesions. Of course, these findings showing a gut microbiome-driven therapeutic strategy in an animal model, while exciting, are still in their infancy and a great deal more work needs to be done to draw conclusions about the therapeutic potential of using probiotic substances in humans.

More recently, researchers have begun to investigate the role of the gut microbiome in humans in order to ask the question “is there something about the gut microbiome in people living with MS that’s unique compared to people without MS?” Dr. Sushrut Jangi, who works in the laboratory of Dr. Howard Weiner (Brigham and Women’s Hospital, Boston MA), has been determined to answer just that question. Dr. Jangi and colleagues collected stool samples from a cohort of people living with relapsing remitting MS as well as healthy controls and subjected the samples to high-throughput sequencing to determine the functional composition of the gut microbiome. They found that the proinflammatory bacterium Methanobrevibacteriaceae was found in a higher proportion in the gut of people living with MS, whereas the Butyricimonas bacteria, which produce a compound that generally suppresses the immune system, was found to be relatively lower compared to healthy individuals.

With a great deal of research attention now turned towards determining how and why MS can develop in children and adolescents, the inquiry into the role of the gut microbiome in MS has followed suit. Since the gut microbiome is thought to play a pivotal role in how the immune system develops during childhood, it only stands to reason that researchers will seize on this “critical window” of immune development to ask whether the gut microbiome differs in youth living with MS compared to their healthy counterparts and, if so, whether this difference is a cause or consequence of the disease. Just today, we announced the launch of a new study called “From bugs to brains: the gut microbiome in paediatric multiple sclerosis” that is asking that exact question. The study, led by Dr. Helen Tremlett (University of British Columbia) and funded by the Multiple Sclerosis Scientific Research Foundation, is being carried out in collaboration with Dr. Brenda Banwell’s pediatric MS study as part of the Canadian Pediatric Demyelinating Disease Network at pediatric MS centres across Canada and The Children’s Hospital of Philadelphia. Although the study is just starting to get underway, the MS community will be keeping an eager eye on this pivotal study in the coming years, since the results will reveal important information about the triggers and drivers of MS for people of all ages. Read our news update for more information about this exciting collaboration.

Any thoughts or questions about the gut microbiome? Leave them here.

References

  1. Ivanov II, Atarashi K, Manel N, Brodie EL, Shima T, Karaoz U, Wei D, Goldfarb KC, Santee CA, Lynch SV, Tanoue T, Imaoka A, Itoh K, Takeda K, Umesaki Y, Honda K, Littman DR. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell. 2009 Oct 30; 139(3): 485–498.
  2. Lavasani S, Dzhambazov B, Nouri M, Fåk F, Buske S, Molin G, Thorlacius H, Alenfall J, Jeppsson B, Weström B A novel probiotic mixture exerts a therapeutic effect on experimental autoimmune encephalomyelitis mediated by IL-10 producing regulatory T cells. PLoS One. 2010 Feb 2; 5(2):e9009.
  3. Mazmanian SK, Liu CH, Tzianabos AO, Kasper DL. An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell. 2005 Jul 15; 122(1):107-18.

10 thoughts on “Research Decoder: Gut Microbiome

  1. Rhea

    I have been followinf Dr Wahls protocol for MS and Autoimmune disorders. My neurologist keeps telling me I don’t match my MRIs. He says they are “intense” and he is happy that I am doing so incredibly well. I thank the diet and Dr Wahls! 😉

    Reply
  2. Andrea

    Thank you for your blogs! They are very informative! I was wondering if there is work being done on the link between MS and digestive issues, is this partially due to the gut microbe? I’ve heard there is a high incidence of digestive conditions with people with MS (Crohn’s, Colitis, IBS) and was wondering if this is tied to the gut microbe or if further research is being done on this?

    Reply
    1. drkarenlee Post author

      Hi Andrea,

      Thanks for your question. Imbalances in the gut microbiome composition have been linked to various gastrointestinal disorders, and it’s certainly possible that the higher prevalence of digestive problems in people living with MS are linked to the gut microbiome. Several other (although not mutually exclusive) hypotheses are that MS and autoimmune disorders like irritable bowel syndrome share the same genetic and/or environmental risk factors, or that the neurological symptoms of MS might manifest as gastrointestinal discomfort and be misdiagnosed as irritable bowel syndrome. Hopefully further research will shed more light into the connection between MS and gastrointestinal disorders.

      Dr. K

      Reply
  3. Terra

    This is all so very interesting. One thing I would be interested in seeing the researchers look at is breastfed versus non breastfed babies. Research already shows a difference in the mirceobacteria in guts of breastfed babies versus non breastfed babies. Breastfeeding also plays a big part in the autoimmune system. I would love to see this also looked at as part of this project and see if there are any correlations between the two.

    Reply
    1. drkarenlee Post author

      Hi Terra,

      That is an excellent observation. In fact, a case-control study conducted by a German research group in 2013 and published in the journal Multiple Sclerosis showed that in their group of 245 people living with MS and 296 non-MS controls, breastfeeding appeared to confer a lower risk of developing MS. On the other hand, a recent study by Dr. Jennifer Graves (UC San Francisco) presented at the American Academy of Neurology meeting demonstrated no association between breastfeeding and MS risk. Whether a potential protective effect is linked to changes in the infant gut microbiome is still unknown and we’ll be keeping an eye on future studies looking at these relationships.

      Dr. K

      Reply
  4. Joyce Ann Theresa MacDonald

    I firmly believe that I have a gut problem and I think so for all of my life . I eat healthy but not following any particular diet. Any advice would be helpful thank you for the update

    Reply
    1. drkarenlee Post author

      Hi Nancy,

      Thanks for the question. At this point in time, it’s too early to say if probiotics are beneficial for people living with or at risk of developing MS. The only study to to date that tackled this question was conducted in animals with an MS-like disease, published in the journal PLOS ONE in 2010. The researchers tested the effects of five different Lactobacillus strains on MS-like symptoms and immune responses in mice, and found that a mixture of three specific strains showed potentially therapeutic effects (reduced inflammation, suppressed symptoms of disability and reduced brain lesions). To my knowledge, these studies haven’t yet been reproduced in people living with MS – we will keep an eye on research in this area and post any updates as they emerge.

      Dr. K

      Reply
  5. Mike Hill

    Dr Lee
    Is there any ongoing clinical trials for MS using Probiotics?
    Is there anyway to naturally reduce Methanobrevibacteriacea?

    Thank you Dr!

    Reply
    1. drkarenlee Post author

      Hi Mike,

      Thanks for the question. Please see my reply to Nancy above regarding research into MS and probiotics.

      Dr. K

      Reply

Leave a Reply

Your email address will not be published. Required fields are marked *