The joint annual congress of ECTRIMS (European Committee for Treatment and Research in Multiple Sclerosis) and its American counterpart, ACTRIMS, took place virtually from 11-13 September 2020. In our previous article, we presented some congress highlights on remyelination, EBV-specific immunotherapy, and the prodromal phase of MS. In this second article, you will find highlights on the role of microbiome and comorbidities in multiple sclerosis, presented at the joint annual congress.
Bacteria, fungi, and viruses of the intestinal flora, and their genes and products, influence the function of the immune system and are increasingly becoming the focus of research. Numerous studies are now looking at the role of the microbiome in MS susceptibility, disease activity, and response to disease-modifying therapies.
The largest study to date, the 'International MS Microbiome Study' (iMSMS) in the USA, Latin America, and Europe examines MS patients and one non-diseased household member.
Initial results of 576 such matched pairs presented at the congress show moderate but statistically significant differences in the composition of intestinal bacteria between people with MS and healthy individuals.2 Multiple species of bacteria were abundant in people with MS (including the mucin-degrading bacterium Akkermansia muciniphila), while others were significantly depleted (e.g. Faecalibacterium prausnitzii, a major producer of butyrate, the main energy source of healthy intestinal cells).
Therapy with disease-modifying drugs appeared to normalize the microbiome.1 L-tryptophan and L-threonine biosynthesis was slightly elevated in untreated individuals, while AIR synthesis I (5-aminoimidazole ribonucleotide) was increased in treated individuals.
Another presentation also stated that metabolic changes resulting from alterations of the microbiome, e.g. the dysregulation of specific metabolic signaling pathways by over- or undersupply of certain taxa, are a crucial subject of current research. The complexity is increased by the fact that intestinal bacteria are influenced by age, geographical location, nutrition, and medication. Pilot studies are currently underway to investigate whether optimizing the microbiome (e.g. through probiotic supplementation or fecal transplantation) could modify the course of the disease.2,3
This partly overlaps with another important topic addressed at the event: the role of the metabolic syndrome in MS progression. This is because being overweight not only increases the risk of developing MS. The growing evidence suggests that obesity, hypertension, insulin resistance, and dyslipidemia are associated with longer diagnostic delays, higher rates of recurrence, faster disability progression and brain atrophy, and higher mortality. Obesity in particular also appears to influence the effectiveness of disease-modifying therapies.
These findings are highly relevant to disease prevention and management. A small study suggested that the treatment of metabolic syndrome components could reduce disease activity in MRI.2,4
Another study presented, involving 50 people with MS and 55 controls, confirms what we already know: Polypharmacy (defined as taking five or more long-term medications at the same time) can have harmful consequences, especially in older patients. MS patients received more medication and their number correlated with an increase in fatigue, pain, and depression. Antidepressants, anticonvulsants, and stimulants were prescribed more often in MS. The researchers recommend reviewing the list of medications in MS patients who complain of pain, fatigue, and affective symptoms.2
Sleep-related breathing disorders can be dangerous but can be difficult to diagnose in people with MS due to limitations in mobility and cognition. A new study from France highlights the frequency of respiratory disorders and the importance of multidisciplinary care (e.g. respiratory therapy): 70% of 71 advanced MS patients (median 54 years; Expanded Disability Status Scale or EDSS: 7.5) had pathological polysomnographic findings, most often due to diaphragmatic dysfunction (65%). Correlation studies with disability scores and MRI lesion load are ongoing.2,5
References:
1. Poster P0671 - Exploring the gut microbiome in multiple sclerosis via the international MS Microbiome Study (iMSMS). https://msvirtual2020.org/wp-content/uploads/2020/09/P0671.pdf.
2. World’s Largest MS Research Conference Goes Virtual to Share Research Progress. National Multiple Sclerosis Society http://www.nationalmssociety.org/About-the-Society/News/World’s-Largest-MS-Research-Conference-Goes-Virtua.
3. Presentations E. Waubant. https://cslide.ctimeetingtech.com/msdc2020/attendee/person/3137.
4. Presentations R. Marrie. https://cslide.ctimeetingtech.com/msdc2020/attendee/person/3757.
5. Presentations E. Maillart. https://cslide.ctimeetingtech.com/msdc2020/attendee/person/543.