“The MS Microbiome”:  a lot of research on this topic lately, and a lot more research needed.

I don’t think MS can be reversed without addressing the gut health. When it comes to the gut health there are few important factors to consider: gut flora, gut permeability and the gut-brain axis. Of course, there are microbes outside the gut too- in the mouth and all along the GI tract, skin, vagina and other sites. Many more in the environment. 

Let’s focus on gut flora(microbiome) today.

  1. About Gut Microbiome

  2. The Many Functions of The Gut Microbiome

  3. Factors That Alter Gut Microbiome

  4. Conditions Associated with Altered Gut Microbiome

  5. The Normal Gut Microbiome

  6. The MS Gut Microbiome

  7. More Links Between Gut Microbiome and MS

  8. How to Improve Gut Microbiome

1.About Gut Microbiome

Microbes existed on Earth long before humans, thus we (the humans) had to learn over time to cohabitate with them. 

Each of us has around 100 trillion microorganisms in the gut- collectively known as gut flora or gut microbiome. Gut flora weights up to 2 kilograms and 95% of these microbes reside in the large intestine. Your body is made up of more bacterial cells (10 times more) than human cells. There are over 2000 different microbial species, with distinct roles. Besides bacteria, there are other microorganisms that are part of the gut microbiome- including viruses, fungi, archaea, and eukaryotes. The gut microbiome is so complex and influences virtually all aspects of human physiology and biology, through interactions with you(the host)- so that is now classified as an organ. And just like another organ like heart and lungs- when the function of microbiome is impaired, the result can be disease.

2.The Many Functions of The Gut Microbiome

The gut microbiome serves essential functions such as:

  •  plays a key role in the development and function of the immune system (80% of your immune system is in the gut) improves the metabolism of gut and its ability to absorb nutrients

  • is essential to maintain a healthy intestinal barrier (by controlling mucus production and intestinal tight junctions); increased intestinal permeability (aka leaky gut) increases the risk of developing MS and other autoimmune conditions

  • manufacture neurotransmitters (ie serotonin, GABA, dopamine, histamine), enzymes and vitamins. I wrote several blog posts about neurotransmitters- why they are important, the changes that are seen in MS and how their levels can be improved — you can review them here. Technical : gut microbiota can synthesize and secrete essential vitamins that support immune regulation, endothelial growth, and the development of the CNS. Lactic acid bacteria produce B12 (this can’t be synthesized by animals or plants; Bifidobacteria are the main producers for folate- needed for DNA synthesis and repair; other vitamins: vitamin K, B3, B2, B7. B5, B1, B6 can also be synthesized by the human gut microbiota. The beneficial effects of the gut microbiota on host metabolism are often considered to be mediated by short-chain fatty acids (SCFA)MS MICROBIOME_2018.

  • protects you from pathogenic (bad) bacteria by competing with them and inhibit their growth. On the other hand, when the gut microbiome is altered by pathogenic bacteria, it becomes a starting point to developing a chronic condition (for example certain strain of E Coli is involved in the development of Crohn’s disease). These “bad” bacteria learned a few tricks about how to develop resistance and fight the friendly bacteria from the gut. For example, they release toxins and cause intestinal inflammation [1],[2]. Another example: pathogenic bacteria know how to use more efficiently iron, which is needed for bacterial growth. This is why every time I check lab tests and see low levels of iron I consider (among other causes), a hidden infection. I suspect that the gut microbiome also plays a role in the alteration of iron metabolism (which is seen in MS)

  • the gut microbiome metabolize food that you can’t digest on your own and also break down drugs and toxins [3]. Of course, there will be times when the gut flora will be overwhelmed and unable to manage excess toxins. The result : infections and chronic diseases.

In exchange for all these benefits provided by the gut flora, the host (you) will offer the gut microbiome nutrients and environment in which the friendly bacteria can thrive.

3. Factors That Alter Gut Microbiome:

  • Prescription drugs : antibiotics, birth control pills, acid blockers, NSAIDs and more. For a long time, the antibiotics were considered the biggest disruptors of gut flora. Yet, a recent study shows that 1 in 4 non-antibiotic meds do alter gut microbiome) [4] .Another study shows that antibiotics given early in life shift the gut microbiome, increasing the risk of obesity, metabolic syndrome and autoimmune diseases later on in life [5]. Therefore, it shouldn’t be a surprise all these medical problems are so prevalent nowadays. Antibiotics show some short term benefits in decreasing unhealthy levels of gut microbes (and also treat MS), but I see only very short term benefits. Antibiotics create long term (and hard to reverse) damage to the gut flora.

  • Diet seems to be the most important factor influencing the gut microbiome.  The Western type diet (sugar, processed foods, unhealthy fats, gluten and most grains, soy, corn).  On the other hand, healthy foods contain fibers i.e. food-based resistant starch, soluble fiber and insoluble fiber are essential nutrients that promote fermentation and variety of microbiome (fibers feed friendly bacteria)

  • Genetics. A recent study shows that genetics play a minor role- only 2%, where diet and lifestyle factors have a lot more influence on gut microbiome [6]

  • Living in US and most other Westernized, industrialized populations may not be that beneficial: in these countries, the gut microbiome is less diverse and dominated by different species of microbes compared people from rural, less developed areas. On the other hand, having a dog at home can help increase the diversity of the gut microbiome, and even protect your child from allergies

  • Environmental toxins [7]

  • Chronic infections

  • Chronic stress- it goes both ways (stress has a negative impact on gut flora, and altered flora causes stress — via HPA axis activation and sympathetic nervous system dominance) Technical: Stress seems to be linked with reduced numbers of Lactobacilli and increased the growth of pathogens such as Escherichia coli and Pseudomonas species [7].

  • Mode of delivery: vaginal delivery means associated with healthier gut microbiome compared with C section (less Bifidobacteria species found in babies delivered via C section) [7].

  • Being breastfed promotes healthier gut flora (more Bifidobacteria and Lactobacilli) compared with bottle fed

  • Aging correlates with less diversity and count of friendly bacteria [8].

  • Being lean vs obese (Technical: overall less microbial variety, too much Firmicutes bacteria and less Bacteroidetes bacteria associated with obese subjects while the lean ones had healthier, more variety of bacteria, including more beneficial Bacteriodetes) [7]).

  • Different ethnicities have different microbes, and the human gut microbiota does not remain constant (as it was thought before) but rather changes as we age

  • Gender: men have increased abundance of Bacteroides and Prevotella compared with women

  • Other implicated factors include lifestyle, illness, smoking, drug addiction, place of residence, and the climate MS MICROBIOME_2018

A super smart concept …

Many problems related to altered gut microbiome actually may be manifestations of small intestinal bacterial overgrowth (SIBO)[7]. Very little known, but this is a very interesting concept and  my research leads me to the same conclusion. I agree 100% with this idea. 

4. Conditions Associated with Altered Gut Microbiome

Altered gut microbiome had been associated with over 25 health conditions (from autism, allergies, obesity to cancer and autoimmune diseases) and more recently with nerurodegnerative conditions like Parkinson’s ad Alzheimer’s as well as neuroinflammation seen in MS.

Simply put, when the gut microbiota is altered (aka dysbiosis), several diseases may develop- including  MS.

Technical: How gut microbiome impacts the nervous system: enteric nervous system (ENS) innervates the gut and transmits signals from it to the CNS. The gut microbiome also produces metabolites that go into the bloodstream and some will cross the BBB [7]. . Besides regulating neural pathways (neurotransmitters, ENS, autonomic nervous system, the gut microbiome influences the endocrine pathway-HPA axis, and the immunoregulating pathway (via lymphocyte, cytokines, chemokines, and antigens presenting effect of SCFAs). MS MICROBIOME_2018.

5. The Normal (Healthy) Gut Microbiome

Let’s recap- we have around 100 trillions of microorganisms found in different parts of the body- all along the digestive tract, urogenital,respiratory systems and the skin, forming 4 micro ecosystems. More than 95% of them are located in the large intestine. In the recent years we have learned a lot about the gut microbiome, thanks to the Metagenomics of the Human Intestinal Tract and the Human Microbiome Project. There are 2172 species of microorganisms isolated so far in humans, divided into 12 different phyla. The majority of them (93.5%) belong to the Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes phyla.

Furthermore, a healthy gut microbiome contains large fractions of the Firmicutes and Bacteroidetes, including genera Prevotella, Bacteroides, and Ruminococcus, followed by Verrucomicrobia and Actinobacteria but contains a low number of microbes belonging to Proteobacteria phyla MS MICROBIOME_2018.

A few interesting things about the gut microbiome and its changes with diet : The gut microbiome is dynamic, it changes within a 24 hours period (that’s a very good thing, as adopting a healthier diet can have a positive change right away). The gut flora also changes with the environment and the season. Each person has an unique set of microbes in the body. There is a classification based on 3 types of gut flora (enterotypes), and these types differ by which species dominate the bacterial composition, focusing on 3 types : Bacteroides, Prevotella, or Ruminococcus species. Talking about the importance of diet, researchers found that Prevotella species enterotype is linked with diets high in carbohydrates; while those who follow a high protein diet will have Bacteriodes species as dominant species. (note: these three  enterotypes are independent of environmental components such as age, body-mass index, gender and geographic location and seem to only be dependent on diet and genetics) [10].

6. The MS Gut Microbiome

Based on research studies, this is what we know so far about the changes in gut microbiome in people with MS:

There is an increase of the following microorganisms: Methanobrevibacter smithii  (M. smithii ), Akkermansia, Desulfovibrionaceae, Actinobacteria, Bifidobacterium, Streptococcus, Firmicutes, Euryarchaeota, Ruminococcus, Pseudomonas, Mycoplana, Haemophilus, Blautia, and Dorea.

There is a decrease in Butyricimonas, Lachnospiraceae, Ruminococcaceae, Faecalibacterium, Prevotella, Anaerostipes, Clostridia XIVa and IV Clusters, Fusobacteria, Bacteroidaceae, C. perfringens type A, Parabacteroides, and Adlercreutzia.MS MICROBIOME_2018

I am going to pick on  Methanobrevibacter (Arachea microbes) because I’ve done a lot of research when I looked at the best ways to treat SIBO-C. More details about M. smithii in this article. These microorganisms produce methane (which is responsible for constipation and bloating) and alter the bowel function in several ways.

Some personal thoughts on Methanobrevibacter :

The overgrowth of methane producing bacteria is currently recognized as a problem- and treated only in SIBO. However, I found some evidence and now suspect an overgrowth of these microbes in any case of chronic constipation, IBS-C  (not just in SIBO-C). For more details read this article. I also  know all that constipation, SIBO-C and IBS-C are more frequently seen in MS compared with healthy population. What they all have in common is an altered gut flora and abnormally high levels of methane producing microbes.  (IBS-C=irritable bowel syndrome with constipation and  SIBO-C= small intestinal bacterial overgrowth with constipation). 

I highly suspect (no study I’m aware of) that optimizing Methanobrevibacter levels can lead to an improvement in all other microbes/the overall gut flora because the methane produced by these microbes has a huge impact on the gut health. Basically, methane paralyzes the gut causing constipation and bloating, and also creates a toxic, unhealthy environment for the friendly bacteria. I also connect gut microbiome with oral microbiome and in women -with vaginal microbiome- as all these sites contain certain species of methane producing microbes.

One more thing: I believe that the number of Methanobrevibacter microbes may be higher than is currently thought. That’s because researchers are counting these microorganisms in the large intestine (where they suppose to live), when in fact they can populate small intestine as well (as seen in SIBO). We certainly need more research on this topic. 

7. More Links Between Gut Microbiome and MS

Research conducted in EAE (animal models of MS) confirm the influence of gut microbiome- like increasing the blood brain barrier (BBB) permeability, activate immune cells in the brain and express certain myelin genes. Other studies found that the gut bacteria from MS modulate the T cells and aggravate the symptoms. Scientists believe now that future MS treatments will specifically target gut bacteria [9]. 

To read more about the links between MS and gut microbiome simply read the “latest research” section of this blog- new studies confirming this connection are published every month. 

Probiotics such as Bifidobacterium, Lactobacillus spp and other lactic producing probiotics, Prevotella histicola, Salmonella typhimurium Bacteroides fragilis and Clostridia clusters XIVa and IV, Candida kefyr seem to be particularly helpful to decrease inflammation and the severity of MS symptoms MS MICROBIOME_2018.

8. How to Improve Gut Microbiome

  • Diet is the most important. Variety is the key. Consuming greens and vegetables rich in vitamins, minerals, fibers and healthy fats equally important. Processed foods, grains, excess sugar and salt should be avoided. The more variety of healthy foods the healthier your gut (if there are food sensitivities, SIBO, IBS — the diet may be restricted short term to address these issues first).It is important to correct vitamin D, serotonin and SCFA (short chain fatty acids), stomach acid deficiencies.

  • Improving digestion (with supplements) is a key element to actually absorb all those healthy nutrients from diet. Treating chronic constipation/IBS-C/SIBO-C should also be a top priority- I will cover this topic in another article. Note: digestive tract starts in the mouth, thus oral hygiene is important. I mentioned Methanobrevibacter earlier, but there are other microbes that influence your health — ie the periodontal Porphyromonas gingivali promotes inflammation and causes symptom severity in animal models of MS). Triphala can be very helpful to restore healthy gut microbiome.

  • Review all the prescription drugs with your doctors, see if you can cut down on some. Use nutrition and supplements to correct drug induced nutrient deficiencies. A less known, but otherwise a very big problem- prescription drugs induce multiple nutrient deficiencies [10]. For healthcare professionals- there is an excellent book on this topic : Drug-Induced Nutrient Depletion Handbook (Pelton et al, 2001).

  • Cut down on stress — start with meditation and yoga and find a stress reduction plan that you can use long term.

  • Look for chronic infections — and treat them (H pylori, B hominis, Candida) . Note: these infections can be often treated with natural antibiotics as you can read in my article .

  • Probiotics are helpful. My first choice would be probiotic rich foods such as home made fermented foods,beet kvass, kimchi, kefir, kombucha etc. Probiotic supplements seem to help to a certain degree, but really depends on the strains, the quality of supplement and how your gut microbiome is altered. You may need to try a few different supplement before finding the one that works for you. For women, I also recommend a special probiotic blend to improve vaginal microbiome. I do see a strong connection between gut and vaginal health. I also consider important the gut mycobiome (the fungi of the gut microbiome), thus I often recommend S. boulardii and anti Candida supplements.

  • Fibers, fermented foods and soil based organisms (SBO) can be even more helpful and better tolerated than probiotics in some cases.

  • Fecal transplantation and therapy with parasites (particularly helminths) show a lot of promise.

 

Do you want to learn more about your gut microbiome?

For $99 (a bit extra if don’t live in US), you can participate in the American Gut Project and have your gut microbiome analyzed. Click here for details. To get more details of your microbiome and some dietary recommendations you can try Viome. 

More info on this topic on The International MS Microbiome Study site- click here. 

Do you have chronic constipation or had been diagnosed with SIBO-C or IBS- C? Read more details here and here .