Following on from the recent episode of our OMS Podcast, 'Gut Health – Your microbiome and you', a research paper has just been published that adds another important piece to this gigantic bacterial jigsaw puzzle.
But before getting to that, it might be worth having a quick refresh on the microbiome:
In a nutshell, our microbiome (or microbiota technically, but the two terms are used almost interchangeably!) is the sum total of all the genes contained within the micro-organisms living in or on our body. It is thought to number between 10 and 100 trillion cells (much greater than the total of human cells), and includes bacteria, viruses, fungi and other microbes. It is thought that we become populated by our tiny guests in the first few years of life, and that factors such as environment, long-term diet, stress and medications continue to influence and alter our microbiome throughout life.
Previous papers have described the differences in the microbiomes of people with MS compared to the general population, in terms of the reduced numbers of certain “beneficial” bacteria, and increased levels of other, potentially harmful bacteria. If this bacterial balance is not correct, then the enormous network of immune system cells surrounding the gut (known as gut associated lymphatic tissue or GALT) produce potent signals that increase levels of inflammation throughout the body, including the brain. This is known as the 'Gut Brain Axis' and is an area of intense scrutiny within the scientific community, in conditions ranging from Alzheimer’s and Parkinson’s diseases, to depression and other mental health disorders, and of course, MS.
It has also been shown that supplementing with courses of probiotics can alter the microbiome and restore the balance of 'good' and 'bad' bacteria, to a more favourable, anti-inflammatory profile. The resultant change in the levels of certain inflammatory immune messengers in the bloodstream, known to be involved in the autoimmune response of MS, has led to further ongoing prospective studies, assessing if probiotic supplements can have an effect on relapse rates and disability progression.
A problem up until now has been that there are too many actors in this piece for scientists to work out the real stars of the show. When you are dealing with so many different types of bacteria, it can be difficult to determine which “bug” or combination of them is providing the beneficial effects. Perhaps it isn’t even the bacteria themselves, but rather something that fuels them, or is produced as they breakdown the various compounds in our diet? In which case it may be more important to feed the good bacteria (prebiotics), rather than simply increasing their numbers in the gut (probiotics) – the age old “chicken or the egg” argument?
A new study into MS and propionic acid
In this latest study, a team of researchers from Germany investigated not the bacteria themselves, but rather a compound called Propionic Acid (PA), that the bacteria produce (postbiotics) as they break down indigestible fibers such as complex carbohydrates, from our diet. PA is a short chain fatty acid (SCFA), a family that also includes acetic acid (household vinegar) and is being increasingly investigated for its role in controlling the immune system.
It is already known that SCFAs increase the population of regulatory immune cells (T-reg cells) within the gut. T-reg cells are responsible for “fine-tuning” our immune response, ensuring that the system only acts on the appropriate target. As we know, in MS, the immune system is inappropriately primed to attack the myelin sheath in the body, rather than a foreign invader; a process known as auto-immunity. The current MS disease modifying drugs (DMDs) aim to suppress pro-inflammatory immune responses, often in a way that is akin to killing a fly with a sledgehammer. But there is a real need to find new treatments that precisely regulate immune cell function and prevent neurodegeneration.
In a large cohort of people with MS (pwMS), investigators found significantly reduced levels of Propionic Acid in blood and stool samples, compared to healthy control (HC) subjects. There was an associated reduction in those bacteria known to produce SCFA in the MS cohort. Interestingly these results were the same in both relapsing remitting and progressive MS sub-types, and did not appear to be influenced by the length of disease duration or by the use of DMDs. This demonstrates a clear association between PA and MS, but is only really useful if it is shown that giving additional PA leads to reduced relapse rates, slowing or stabilisation of disability progression, brain atrophy rates; the things that really matter to people living MS.
Well, this is where it gets interesting. The team then took 91 pwMS, and 24 healthy controls, and gave them 1000mg of Propionic Acid daily in tablet form. Baseline testing showed significantly lower levels of T-reg cells in the MS group compared with the HC group, but after 14 days of PA supplementation T-reg levels had increased by 30% in the MS group (25% increase in HC group).
When they tested samples after 90 days of PA supplementation, this effect persisted, regardless of MS sub-type. Other markers of inflammation also significantly improved (reduced Th1 and increased Th17 cell levels). They also tested how effectively these increased levels of T-reg cells actually did their job, and guess what, the cells taken at day 90 had a significantly improved regulatory effect than those taken before commencing PA.
Now the really important bit. 97 patients were given PA for at least 12 months and results compared to past data on previous relapse rates and their levels of disability for up to 6 years prior. The researchers found significantly lower annualised relapse rates following PA supplementation (41.1% of patients had reduced relapse rates, 47.4% remained stable and 11.3% exhibited an increased relapse rate). There was a reduced risk of disability progression in the PA group versus a matched control group over the same time period, and stabilisation of disability in the PA group. Side effects were mild and reported in less than 5% of patients, involving abdominal distension, nausea and flatulence.
22 of those treated with PA underwent baseline MRI scans and a follow-up scan at an average of 1.5 years, and compared with 22 pwMS that had not been taking PA.
Whilst both groups showed equal rates of atrophy in certain areas of the brain, as is typical of MS, the PA group had significant increases in volume of an area of the brain called the striatum, responsible for control of movement.
Another fascinating result was seen in the mitochondria of those pwMS. These tiny little structures live within our cells, and are the power houses that produce energy to fuel key cellular functions. Given that fatigue is such a common and often debilitating symptom of MS, there is much interest in their role in MS. Following 90 days of PA supplementation, there was a significant improvement in the functioning of the mitochondria in the T-reg cells of pwMS, such that it was equal to that of the healthy controls.
There are always limitations in such studies that should be noted, and in this instance include the relatively small sample size, and the fact that the data was collected retrospectively rather than prospectively, which would be preferable when attempting to prove the effects of a particular intervention. With that being said however, this work provides crucial early evidence that a readily available naturally occurring substance can generally be taken without risk or side effects, can significantly reduce relapse rates and stabilise disability progression
So where do I get this stuff I hear you cry?
Well, at present it appears to be rather difficult to get PA in tablet form, and of course it must be reiterated that this is only early data from a small scale study. But we know that bacteria in our guts produce PA and other SCFAs as they ferment the complex carbohydrates that we eat. Studies have shown that people eating wholefood, plant based and Mediterranean diets have higher levels of PA than omnivores, and of course the OMS recovery program has us covered here.
Fermented foods (such as kimchi, sauerkraut and kombucha) are excellent sources of SCFAs, and their consumption should be encouraged, not least because they are delicious! Unfortunately though, in scientific research the puzzle rarely fits neatly together; and dairy fermented foods appear to produce significantly higher levels of PA than plant fermented foods, but we are definitely not advocating dairy consumption at OMS!
Nevertheless, this is really interesting and exciting research. It provides valuable information on the mechanisms underpinning the connections between the gut and immune system, but more than that, it gives us early evidence that the use of supplementary naturally occurring SCFAs can provide meaningful benefits to people living with MS, and gives us yet more reassurance that the OMS Recovery Program has us on the right path.
Thank you to Linda and Ann
One final thought. We often talk about the importance of the OMS community, supporting and encouraging each other to live as well as possible with MS, whilst sharing the latest news and research.
I believe that this blog is a prime example; the original paper was sent to me by Linda Boueke, our OMS Circles Ambassador in Hamburg. She gently 'encouraged' me to look into the topic, as her Circle are extremely interested in it, and had heard the lead author of the paper speak about his research. I read the paper with great interest, and knew that it should be shared, but this particular area is well outside of my comfort zone! So I am very grateful for the guidance of another OMSer, Ann McConnell, the Ambassador of the Belfast OMS Circle. Her knowledge of complex chemistry and all things fermentation really helped to navigate through the murky waters of the microbiome and SCFA. Thank you both.
1) Duscha et al., 2020; Cell; 180; 1067–1080 https://doi.org/10.1016/j.cell.2020.02.035 2) http://imsms.org/?page_id=30
4) https://doi: 10.1111/ane.13045 5) https://doi.org/10.1007/s13311-017-0588-x 6) https://dx.doi.org/10.1111%2Fj.1753-4887.2012.00493.x 7) https://www.theguardian.com/news/2018/mar/26/the-human-microbiome-why-our-microbes-could-be-key-to-our-health
8) doi: 10.3389/fnut.2019.00047