How does the gut–brain axis influence neuro-inflammation and the disease course of MS? Although we know that gut homeostasis and gut functions are closely related to food intake, we want to know what advice we can give to MS patients to help reduce the frequency of their relapses. Who better to answer our questions than Professor Caroline Pot, our neighbor to the south, located on the beautiful Lake Geneva.
Professor Pot is a neurologist and prominent researcher from Lausanne University Hospital in Switzerland. Professor Pot specialises in neuro-inflammatory diseases and heads a research group with the goal of understanding the relationships between the gut and brain, and the impact of lipid metabolism, diet and microbiome on neuro-inflammatory diseases such as MS. Hence, she is the perfect interviewee for this subject.
Brainwork: What was the first indication that lipid metabolism might influence neuro-inflammation?
Professor Pot: The first hint towards this link was that statins, which are cholesterol-lowering drugs, reduce neuro-inflammation and disease severity in animal models of MS. However, these findings remain controversial in humans. Although recent findings suggest that statins may be beneficial in the secondary progressive phase of MS, a clear impact of statin treatment on MS disease course has been difficult to establish and the underlying mechanisms are largely yet to be unravelled.
Considering that these cholesterol-lowering drugs also have some cumbersome side effects, our idea was to look downstream of cholesterol to find other drug targets. Oxysterols (oxidised cholesterol) are downstream metabolites of cholesterol which have pleiotropic effects on the immune system. Indeed, in animal models of MS, we showed that removing oxysterols resulted in reduced neuro-inflammation and disease severity. We also discovered that this was associated with reduced trafficking of lymphocytes to the central nervous system (CNS) – an effect that is reminiscent of the target pathways of some MS disease-modifying drugs, such as natalizumab and fingolimod.
Brainwork: How does oxysterol affect MS disease course in human patients? Is there a link between oxysterol and the gut–brain axis?
Professor Pot: This is very much a current research topic of ours. We recently published a study showing that human lymphocytes express the receptor for oxysterols (Epstein–Barr virus induced gene 2; EBI2), and migrate in response to it. While we did not find a difference in receptor expression levels between MS patients and healthy controls, we found increased expression of this receptor in MS patients treated with natalizumab. This was the first indication that MS treatment can influence cholesterol-associated pathways.
Where oxysterols are secreted remains an open question – they could be secreted by immune cells or stromal cells either directly in the CNS or in peripheral organs such as lymph nodes or the gut, which is a large reservoir of immune cells. We are looking into how oxysterol may play a role in periphery-to-brain communication, and how this could be impacted by dietary consumption of fats.
Brainwork: What advice do you give MS patients regarding diet and lifestyle?
Professor Pot: The scientific evidence is not yet strong enough to allow for detailed recommendations specific to MS patients. However, there is evidence that increasing the consumption of vegetables, and decreasing the consumption of fats, may be beneficial in terms of relapse rates.
Given the lack of specific guidelines, I advise MS patients to follow the general nutritional guidelines: consume a minimum of five servings of vegetables/fruits per day, reduce the consumption of meat to twice weekly, and avoid the consumption of red meat in particular. In addition, I advise my patients to cook rather than consume pre-packaged meals.
It is important to note that there is no scientific evidence yet that proves that restricted diets such as complete avoidance of gluten or lactose are beneficial in neuro-inflammatory diseases such as MS. I thus do not advise MS patients to follow these diets, which may eventually lead to vitamin deficiencies, for example.
Finally, I strongly advise MS patients to quit smoking, as there is evidence that smoking promotes the progression of the disease.
Brainwork: How can we gain more information about the relationship between diet and MS progression, so that we can eventually give more specific guidance to patients?
Professor Pot: Firstly, prospective studies should be conducted where the patients’ eating habits are recorded and correlated with disease progression and relapse rates. We are currently setting up a study addressing this question in our centre in Lausanne, Switzerland.
The second avenue would be to include data on intestinal dysbiosis and analyse the gut microbiome of large cohorts of patients. It is known that MS patients have an altered gut microbiome, but further studies are needed to firmly establish the link between diet, intestinal health and MS disease progression.
Finally, in Switzerland, we have the MS cohort and MS registry, which are large, patient-centred studies encompassing nutritional questionnaires and detailed clinical data. It is hoped that studies such as these will shed some light on the relationships between diet, lifestyle and MS.
My personal approach to tackling these questions is through translational, inter-disciplinary research – working with mouse models, then bringing the research into human patients, and back to mouse models again. In a research hospital environment, we are fortunate to have the support of gastroenterologists, endocrinologists and other specialists, as this type of research requires such collaborations.
We hope that all of these initiatives together will help bring answers to patients on what they can do to lower relapse rates and slow down disease progression.
A special thank you to Professor Pot for giving us some of her time. We find her inspirational and a great representation of Swiss research.
Who should we interview next? Comment down below or use this form to make a recommendation.