Peter Connick, University of Edinburgh

1. Advancing science, building hope
MS Trust Meeting 2019
Peter Connick, University of Edinburgh

2. Gut microbiomes
and their impact
on MS
…really?!

4. Pedant’s corner
Microbiome: the collection of
microbiota in the environment
Gut microbiota: the microbiota
in the gastrointestinal tract
Definitions

5. Gut microbiome
• 2 trillion microbiota
• Outnumber human cells 10:1
• 2kg weight
• About 5000 species
• ‘the lost organ’
Scale

6. Gut microbiome
• Bacteria
• Fungi
• Arachea
• Viruses
Components

7. Determinants of the gut
microbiome
Influences on the gut microbiome

8. Current Biology 2015;
25: R600–R620
The effects of Westernisation

9. Techniques to evaluate the gut microbiome

10. Gut microbiome effects
• Immune system
• Neuronal function
• Endocrine system
Links between gut microbiome and other human organ systems

11. Gut microbiome and biological effects potentially relevant to MS
Metabolite Related microorganisms Effects
α-Galactosylceramide Bacteroides fragilis Essential for myelin synthesis, stimulate host
immune systems
Short-chain fatty acids:propionic
acid, acetate, butyrate,
indolepropionic acid
Bacteroides spp., Clostridium spp.,
Eubacterium spp., Butyrivibrio,
Faecalibacterium spp., Clostridium
sporogenes
Modulate host immune system, energy to
epithelial cells
Vitamins: Vitamin K, vitamin B12,
biotin, folate, riboflavin, etc.
Bifidobacterium spp.,
Propionibacterium freudenreichii,
Salmonella enterica, Listeria innocua,
Enterobacter spp.
Sources of vitamins, stimulate immune system,
exert epigenetic effects
Lipids: LPS, peptidoglycan,
acylglycerols, triglycerides,
Polysaccharide A
Bifidobacterium spp. Roseburia,
Lactobacillus, Clostridium spp.,
Bacillus fragilis
Induce inflammation, enhance immune system,
influence gut permeability
Polyamines: Putrescine, cadaverine,
spermine
Campylobacter jejuni, Clostridium
saccharolyticum
Modulate immune system, anti-inflammatory
and antitumoral effects
Bile acids: Cholate, muricholate, etc. Lactobacillus spp.,
Bifidobacterium spp.,
Clostridium spp., Bacteroides
Influence intestinal permeability

12. Gut microbiome and biological effects potentially relevant to MS
Susceptibility?
Phenotype and course?

13. PNAS 2017; 114: 10719–10724.
• Spontaneous RR-EAE mouse model. Transgenic MOG-specific T cell receptor in >70% of their CD4+ T-
cells. From 2 months 80% develop RR-EAE
• Mice raised in germ-free environment
• Faecal transplant at 2-weeks from monozygotic twins discordant for MS

14. WHY DO PEOPLE GET MS?
RISK
FACTORS
TRIGGER AMPLIFIER
• Genetics
Environment
 Vitamin D
 Smoking
 EBV
 Obesity
?
 Microbial
 Other?
?

15. The International MS Microbiome Study (iMSMS)
n = 2000 case-control pairs globally
• Two people who live together (≥ 6 months)
• One with MS one without
• No other autoimmune diseases
SINGLE VISIT (c. 3 hours)
Edinburgh, Glasgow, Inverness
Bloods in clinic
Stool sample collect at home & mail back
OPEN TO RECRUITMENT

16. Intermittent fasting and disease course
Highlights
• IF ameliorates the clinical course and pathology of the MS
mouse model (EAE)
• IF increases gut microbial diversity, alters their composition and
metabolic pathways
• Gut microbiota transfer from mice on IF led to protection from
EAE in recipient mice
• Findings with IER in MS patients partially recapitulates what is
observed with IF in EAE
In Brief
Intermittent fasting confers protection in the multiple sclerosis
animal model through effects on the gut microbiota;
similar changes to the gut microbiota were observed in
relapsing multiple sclerosis patients undergoing intermittent
energy restriction.
Cell Metabolism. 2018; 27: 1222–1235.

17. The Future
• Site specific microbiome
• Metabolomics, Metatranscriptomics, Metaproteomics
• Exploration of effects on phenotype and course
• Exploration of interactions with MS treatments