Microbiome Influences on Behaviour

Question 1

microbiome

Answer 1

• “The ecological community of commensal, symbiotic, and pathogenic microorganisms that share our body space” -> bacteria that live in us or on us
• Large intestine colonized by ~39 trillion micro-organisms, many of them bacteria
• Diffuse and complex -> more research needed

Question 2

why could microbiome be considered an organ?

Answer 2

• Microbiome is inherited (passed on)
• Microbiome has physiology and pathology
• Health is impacted when population of microbes is altered

Question 3

what does microbiome play a role in?

Answer 3

• pathogen protection
• nutrition
• metabolism
• immune modulation
• disease
• disorders

Question 4

microbiome and pathogen protection

Answer 4

gut microbiome provides the host with physical barrier (occupation of attachment sites) and chemical barrier (antimicrobial products) against pathogens

Question 5

microbiome and nutrition

Answer 5

allows for extraction of additional calories from foods and digestion of otherwise undigestiable foods, promotes nutrient uptake and utilization

Question 6

microbiome and metabolism

Answer 6

promotes metabolism of dietary fiber

Question 7

microbiome and immune modulation

Answer 7

important for the development of the intestinal mucosa and systemic immune system

Question 8

microbiome and disease

Answer 8

• May be a critical factor in disease:
• • GI associated disease
• • Diseases outside of GI tract

Question 9

microbiome and disorders

Answer 9

Large percentage of disorders can be tracked back to changes in gut microbiome

Question 10

variability in microbiomes

Answer 10

Humans: genomes 99.9% identical; microbiome 80-90% different

Question 11

how does microbiome change over time?

Answer 11

• Aging: At birth, microbiome not diverse, not much bacteria present -> as child grows, diversity and amount of bacteria increase
• Travel can influence microbiome (through food, environment, etc.)
• Infection changes microbiome (ex. Through use of antibiotics to change levels of bacteria in one specific part of the body, which then influences bacteria in other parts of the body)
• Geography: people who live in microbiomes have different microbiomes

Question 12

when is microbiome acquired?

Answer 12

once infant is born

Question 13

early microbiome differences: vaginal delivery vs. c-section babies

Answer 13

• Vaginal delivery: infant colonized by bacteria quicker, resembles vaginal flora
• • Higher concentration of two important bacterial species
• C-section delivery: colonization delayed, resembles skin flora
• • Alterations detected in C-section group, lasting >6 months (Sustained microbiome differences, increased allergies, rapid weight gain)

Question 14

c-sections

Answer 14

• 10-15% of births medically need C-sections; elective C-section rates increasing (~30% of births)
• Elective C-sections potentially less painful, more convenient, less “traumatic” for baby
• There may be a link between the rise of autoimmune diseases and C-sections due to its influence on microbiome

Question 15

influences on early microbiome

Answer 15

• vaginal or c-section delivery
• when solid food introduced
• whether baby has exposure to antibiotics
• exposure to animals

Question 16

vaginal/c-section microbiome study: Dominguez-Bello et al.

Answer 16

• Put gauze in mother’s vagina before C-section; after C-section swabbed baby with gauze in order to expose newborn to microbial environment to birth canal
• Result: microbiome resembled vaginally-born newborns (increase of those 2 key bacteria)
• Potential issues: long-term impact on microbiome; confounds – antibiotics before C-section, maternal differences

Question 17

microbiome impact on behaviour

Answer 17

• Gastrointestinal tract is connected to the brain -> more serotonin in gut than brain
• gut microbiota communicates with brain
• • HPA axis: cortisol alters gut microbiota
• • Microbiota can alter cytokine levels
• • vagus nerve: mode of communication

Question 18

possible mechanisms for gut microbiota -> brain communcation

Answer 18

• Neural connections
• Endocrine communication
• Immune pathways

Question 19

experimental design: removing microbiome -> GF mice

Answer 19

• Germ-free (GF) mice born through C-section and live in a sterilized bubble environment -> No microbiota
• Immune system deficits: abnormal numbers of immune cells, changes in immune organs (spleens and lymph nodes are poorly formed)
• • Require higher caloric intake to maintain same body weight
• • Worse outcomes in disease models
• Important to consider limitations of using germ-free mice and how to re-populate microbiome

Question 20

fecal transplants

Answer 20

• Many C. Difficile patients don’t respond to typical antibiotics, so fecal transplants are used instead
• Cleanse colon and re-constitute gut with healthy bacteria
• Could possibly be used for other GI/mood disorders in the future

Question 21

link between microbiome and depression/anxiety

Answer 21

• Depression/depressive episodes are commonly associated with dysregulation of HPA axis
• GF mice: hyper-respond to stress (increased corticosterone and ACTH response to stress)
• Microbiome has an effect on anxiety behaviour

Question 22

effect of microbiome on anxiety behaviour

Answer 22

• Demonstrated in GF mice:
• • Reduced anxiety-like behaviour in elevated plus maze, light/dark test, and open field
• • Reconstituting microbiome can rescue many of these effects

Question 23

study about microbiome and depression (Kelly et al)

Answer 23

• Experimental group had clinical depression; control was matched subjects without depression
• Analyzed microbiome composition -> experimental group had decreased gut microbiome richness and diversity
• Fecal samples collected from experimental and control groups, and fecal transplants were given to rats, rats with fecal samples from depressed people showed anxiety and depressive-like behaviours in almost all tasks

Question 24

rat behaviours in fecal transplant study

Answer 24

• rats with fecal samples from depressed people showed:
• • Sucrose-preference test: decreased sucrose intake (tied to anx/dep)
• • Open field: decreased time in centre (tied to anx/dep)
• • Elevated plus: decrease visits to open arms (tied to anx/dep)
• • Forced swim test: no differences

Question 25

probiotics

Answer 25

• live microorganisms that can benefit the host; must be live when administered, but many are neutralized by stomach acid
• Animal models show that probiotics can modulate anxiety and depressive-like behaviours

Question 26

probiotics: human studies

Answer 26

• Experimental group got probiotics, control group got placebo
• Test: questionnaires to evaluate anxiety, depression, stress
• Results: less “psychological distress” in experimental group

Question 27

chronic fatigue syndrome

Answer 27

• long-term fatigue, difficulties carrying out ordinary activities
• disease mechanisms unclear
• Mood disturbances (anxiety) and GI problems common

Question 28

chronic fatigue syndrome: human studies

Answer 28

• Experimental group got probiotics for 2 months, control got placebo
• Results: experimental group showed mood improvements

Question 29

remaining questions about the microbiome

Answer 29

• We still don’t know what a microbiome is
• Cultural/geographical differences may exist
• Studies involving GF organism may not be generalizable
• Fecal transplants may have risks
• Probiotics may be possible solution, but unsure of lasting effects