Microbiome Influences on Behaviour Flashcards
microbiome
- “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
why could microbiome be considered an organ?
- Microbiome is inherited (passed on)
- Microbiome has physiology and pathology
- Health is impacted when population of microbes is altered
what does microbiome play a role in?
- pathogen protection
- nutrition
- metabolism
- immune modulation
- disease
- disorders
microbiome and pathogen protection
gut microbiome provides the host with physical barrier (occupation of attachment sites) and chemical barrier (antimicrobial products) against pathogens
microbiome and nutrition
allows for extraction of additional calories from foods and digestion of otherwise undigestiable foods, promotes nutrient uptake and utilization
microbiome and metabolism
promotes metabolism of dietary fiber
microbiome and immune modulation
important for the development of the intestinal mucosa and systemic immune system
microbiome and disease
- May be a critical factor in disease:
- GI associated disease
- Diseases outside of GI tract
microbiome and disorders
Large percentage of disorders can be tracked back to changes in gut microbiome
variability in microbiomes
Humans: genomes 99.9% identical; microbiome 80-90% different
how does microbiome change over time?
- 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
when is microbiome acquired?
once infant is born
early microbiome differences: vaginal delivery vs. c-section babies
- 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)
c-sections
- 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
influences on early microbiome
- vaginal or c-section delivery
- when solid food introduced
- whether baby has exposure to antibiotics
- exposure to animals
vaginal/c-section microbiome study: Dominguez-Bello et al.
- 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
microbiome impact on behaviour
- 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
possible mechanisms for gut microbiota -> brain communcation
- Neural connections
- Endocrine communication
- Immune pathways
experimental design: removing microbiome -> GF mice
- 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
fecal transplants
- 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
link between microbiome and depression/anxiety
- 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
effect of microbiome on anxiety behaviour
- 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
study about microbiome and depression (Kelly et al)
- 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
rat behaviours in fecal transplant study
- 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
