Health and Disease

Question 1

Adaptation to starch

Answer 1

• multiple copies of AMY1 have been selected in Homo sapiens
• amylase gene copy number bursts associated with salivary amylase
• lower AMY1 copy number associated with obesity in humans

Question 2

Adaptation to milk

Answer 2

• lactose tolerance is gene-culture co-evolution
• convergent evolution
• organism creates a niche (dairy farming) and then adapts to it (lactase persistence)

Question 3

Modern Western diet

Answer 3

• industrial revolution
• changes to diet = increased glycaemic load, reduced micronutrients and fibre etc
• rising obesity and diabetes levels

Question 4

Fetal programming

Answer 4

• mothers pregnant during Dutch hunger winter bore children programmed for famine
• increased risk of developing T2D, heart attacks etc.
• maternal obesity can cause abnormal glucose metabolism in fetus = increased risk of metabolic diseases

Question 5

Epigenetics and fetal programming

Answer 5

• Dutch famine = differences in IGF2 methylation between individuals prenatally exposed to famine and same-sex siblings
• T2D can be transgenerationally transmitted from fathers to F2 males

Question 6

Microbiome

Answer 6

• genetic reservoir
• variation between individuals
• there is an optimum

Question 7

Microbiota acquisition

Answer 7

• vertical transition mother to child
• social relationships allow vertical and horizontal transmission
• fermenting foods can support a healthy gut microbiome

Question 8

Microbiome metabolism

Answer 8

diet alters balance of microbiota and molecular products
healthy gut
- butyrate used for energy via beta-oxidation
- uses oxygen = makes gut anaerobic
- favours anaerobic bacteria = butyrate and SCFA

low butyrate
- glucose for glycolysis
- higher oxygen = favours pathogenic bacteria

Question 9

Co-evolution of microbiome

Answer 9

• early exposure to H. pylori protects against immune-mediated diseases such as ulcerative colitis
• co-evolutionary relationship between humans and H. pylori
• preserved by vertical transmission and disrupted by horizontal transmission via migration as different strains in different populations

Question 10

Evolution of immune response

Answer 10

• reciprocity during host-pathogen co-evolution means changes in allele frequencies due to selection in one species leads to changes in allele frequencies in the other
• a pathogen that wipes out 100% of the host is an evolutionarily dead end for both species

Question 11

Old friends hypothesis

Answer 11

• co-dependence of key microbes and worms
• now a mismatch as modern hygiene removes old friends
• prenatal and early childhood period important for acquiring microbes
• microbes trigger pattern recognition receptors and activate innate and adaptive immune responses
• expect to be exposed early to old friends
• no old friends = immune system overshoots = increased incidence of autoimmune diseases

Question 12

Karelia

Answer 12

• Finland developed
• Russia = no development = more microbes and dust = protection against allergy and autoimmune

Question 13

Chronic inflammatory diseases

Answer 13

• persist as in an evolutionary shadow, during post-reproductive life
• genetic predisposition + exposome risk factors
• old friends teach the immune system when to attack and when to turn off
• no old friends = overshoots = increased CIDs
• worms produce anti-inflammatory molecules that offset pro-inflammatory cytokines
• no worms = more cytokines = increased risk of CIDs

Question 14

Developmental Origins of Health and Disease

Answer 14

• adversity during sensitive periods increase risk of impaired immune system and cognition
• stress = HPA axis = cortisol release = acts on glucocorticoid receptor
• more GCR = reduced cortisol = reduced stress response
• prenatal stress = highly methylated GCR = increased stress response = hypervigilant as expect to be in a stressful response
• corrected by maternal care - more grooming by rat mother = increased GCR = reduced stress response

Question 15

3 hit model of early life history

Answer 15

• 1st and 2nd hit = genetic predisposition and early life environment
• latent period = programmed phenotypes
• 3rd hit = later life environment
• development of disease after 3rd hit depends on how the phenotype was programmed after the first 2 hits

Question 16

Gut-brain axis

Answer 16

bidirectional communication between gut and brain

Question 17

Microbes and the gut-brain axis

Answer 17

• gut microbial metabolites regulate epigenetic mechanisms
• butyrate is an HDAC inhibitor, prevents deacetylation so genes are more expressed
• gut microbes can produce NT precursors
• can alter reward system through hormonal, immune or vagal pathways

Question 18

Anxiety and microbes

Answer 18

gut microbiota metabolite 4EPS can alter brain activity and increased anxiety behaviour in mice

Question 19

Poverty

Answer 19

• exacerbates all stressors
• better hygiene to clear infectious disease
• but this will reduce old friends and increase CIDs

Question 20

Socioeconomic status

Answer 20

• poor nutrition as proxy for low SES
• DNA methylation dependent on folate, vitamin B12 and B6
• lack of these nutrients = reduced methylation
• Dutch winter = starving fetuses had increased likelihood of obesity later in life as expect to be malnourished
• those exposed to the Holocaust = epigenetic imprinting on stress genes detectable in offspring conceived post-Holocaust
• can be reversed by good nutrition and maternal care

Question 21

Poverty interventions

Answer 21

• WaSH programmes to improve water, sanitation and hygiene
• reduced stressors, burden of infectious disease and violence against women
• Barnsley council fruit and veg scheme