Environment and the Brain 2 Flashcards
Name four countries where malaria is particularly common. (4)
- Nigeria
- Democratic republic of the Congo
- Tanzania
- Niger
***These are all African countries
Give two social consequences of Malaria. (2)
- Costs a lot of money to prevent and treat
- Results in huge economic losses
Describe the general prognosis of malaria. (2)
- Many people still die from it but is not always fatal
- 80% of deaths are children under 5 years old
True or false? Explain your answer if appropriate. (1)
Malaria remains a huge public health challenge, with some countries still experiencing endemic levels of the disease.
True
Name the vector which passes malaria between humans. (1)
Female Anopheles mosquito
Give five types of malaria parasite. (5)
- Plasmodium falciparum
- Plasmodium vivax
- Plasmodium ovale
- Plasmodium malariae
- Plasmodium knowlesi
Which malaria parasite is responsible for the majority of malaria deaths worldwide? (1)
Plasmodium falciparum
The five types of malaria parasite are all which type of parasite? (1)
Protozoa
Describe the malaria illness and its timecourse associated with Plasmodium vivax and Plasmodium ovale parasites. (1)
Lie dormant in liver and cause malaria relapses months or years after initial infection
Which malaria parasite can cause lifelong, chronic infection if it is left untreated? (1)
Plasmodium malariae
State which organisms are mainly affected by Plasmodium knowlesi. (2)
Mainly monkeys in South-East Asia
however can sometimes cause severe/fatal illness in humans
Describe the life-cycle of malaria, as occurs in humans (do not describe the mosquito parts). (8)
- Mosquito transmits motile sporozoite to humans
- Sporozoite travels through blood to liver cells
- Sporozoite reproduces asexually in liver (schizogony)
- This produces thousands of merozoites
- Merozoites infect red blood cells
- And further divide asexually, to develop into ring forms, trophozoites, and schizonts, which burst from blood vessels
- Merozoites can also develop into precursors of gametes
- Gametes taken up by mosquito bite
Describe the life-cycle of malaria, as occurs in mosquitoes (do not describe the human parts). (5)
- Mosquito bites infected human and takes up gametocytes
- Gametocytes mature in mosquito gut
- Male and female gametocytes fuse and form ookinete
- Ookinetes develop into new sporozoites that migrate to salivary glands
- Sporozoites transmitted to humans through bite
Name the definitive host for Malaria. (1)
Mosquito
Name the intermediate host for malaria. (1)
Humans
Describe the small life-cycle of malaria occurring in red blood cells of humans. (4)
- Merozoites infect red blood cells
- Divide asexually to produce ring forms, trophozoites, and schizonts
- RBCs burst and release parasites
- Which can go on to infect more RBCs
Give three general consequences of malaria parasites bursting from and destroying red blood cells in malaria infection. (3)
- Damage to blood vessels
- Damage to organs
- Allows infection to continue proliferating
What is the most common clinical presentation of malaria in humans? (1)
Most infections are asymptomatic
(However a small percentage of individuals develop severe malaria)
Give a life-threatening complication of severe malaria, which occurs in 575,000 children annually in Africa. (1)
What percentage of people with this complication die from it? (1)
What consequence can it cause in survivors? (1)
Cerebral malaria
20% die from it
Survivors can have neurological impairment
Cerebral malaria, a complication of severe malaria, can develop at any age.
Which age group is the most at risk? (1)
Children under 5 years old
Give two groups of people particularly at risk for cerebral malaria. (2)
- Young children who haven’t yet developed immunity
- People from other countries who have not been exposed to malaria
(People with low immunity to the disease)
Describe the typical timecourse of classic malaria. (2)
Lasts 6-10hrs
However can come and go in waves for 12-48hrs as new parasites are released into the bloodstream.
Name the three symptomatic stages of classic malaria. (3)
Cold stage
Hot stage
Sweating stage
Briefly describe the ‘cold stage’ of classic malaria. (1)
Sensation of cold and shivering
Give four symptoms which may be experienced in the ‘hot stage’ of classic malaria. (4)
- Fever
- Headaches
- Vomiting
- Seizures in young children
With classical malaria, it is possible to get relapses years later.
Why is this possible? (1)
Due to dormant parasites in the liver
Give nine signs/symptoms that can be seen in severe malaria. (9)
- Severe anaemia
- Immune responses throughout the body
- Haemoglobin in urine
- Acute kidney injury
- Acute respiratory distress syndrome
- Abnormalities in blood coagulation (DIC)
- Cardiovascular collapse
- Metabolic acidosis
- Cerebral malaria
In severe malaria, immune responses are seen in many areas of the body.
Give two reasons why a large, widespread inflammatory response is seen. (2)
- Due to parasites infecting the body and bloodstream
- Due to destruction of red blood cells
Why is anaemia seen in severe malaria? (1)
Due to destruction of red blood cells
Why is acute respiratory distress syndrome seen in malaria? (1)
Due to inflammatory response in the lungs
Finish the sentence, regarding severe malaria. (1)
Severe malaria may be associated with hyperparasitaemia, which is where ……………………………
malaria parasites infect more than 5% of the total red blood cells
When is cerebral malaria diagnosed? (1)
If the patient is in a coma
Apart from coma, give another symptom/sign of cerebral malaria. (1)
Seizures
Briefly describe three brain pathologies that are seen in cerebral malaria. (3)
- Obstruction of microvasculature
- Neuroinflammation
- Loss of BBB integrity
Describe why the brain microvasculature becomes blocked in cerebral malaria. (2)
Give two consequences of this. (2)
- Adhesion/sequestration of plasmodium-infected RBCs to endothelial cells
- Platelets can then also adhere to contribute to blockage
CONSEQUENCES:
hypoxia
oedema
Compromised integrity of active endothelial cells leads the BBB to become permeable in cerebral malaria.
Give three possible consequences of this. (3)
- Loss of brain homeostasis
- Oedema
- Small haemorrhagic events
Suggest two mechanisms by which BBB integrity may be disrupted in malaria. (2)
- Infected RBCs which stick to endothelial cells may damage them
- Neuroinflammation and pro-inflammatory cytokines damage BBB
Suggest reasons why neuroinflammation may occur in malaria. (3)
- Hypoxia leads to neuronal damage
- Plasmodium parasites activate immune response in blood vessels
- BBB integrity compromised which leads to foreign cells/molecules in brain
True or false? Explain your answer if appropriate. (1)
Brain changes seen in cerebral malaria may also be seen in malaria patients who do not meet the criteria for cerebral malaria, some of which may even have uncomplicated malaria.
True - seen in patients with severe non-cerebral malaria and also uncomplicated malaria
Give a brain change which may be seen in patients with non-cerebral malaria. (1)
Oedema
Give a blood marker indicating brain damage, which may be seen in people with non-cerebral malaria. (1)
What does this marker indicate? (2)
S100B
Glial marker
which may also indicate BBB breakdown
Give five post-malaria neurological sequelae which may affect patients. (5)
- Long-term cognitive deficits
- Epilepsy
- Impaired hearing
- Sensory disorders
- Motor weakness
True or false? Explain your answer if appropriate. (1)
In malaria, the Plasmodium parasite is able to cross the BBB and directly activate the immune response, causing neuroinflammation.
False - the parasite itself does not get into the brain, however damages the brain through the cerebral vasculature and can cause small stroke-like events
Give three general treatment approaches to malaria. (3)
- Prevention
- Anti-malaria drugs (both as prevention and treatment)
- Vaccines
Give four general prevention strategies for malaria. (4)
- Mosquito nets
- Repellents
- Removing stagnant water
- Long-sleeved clothes
Give two malaria vaccines which may be used to treat/prevent malaria. (2)
Give the current status of these vaccines. (2)
RTS,S/AS01 - already rolled out but more demand than supply
R21 - recently approved but not yet rolled out
There are 2 new vaccines being rolled out for malaria.
Which malaria parasite are both of these vaccines effective against? (1)
Plasmodium falciparum
True or false? Explain your answer if appropriate. (1)
New vaccines against malaria have been proven to be safe and effective for adults, but not children in clinical trials.
False - they have proved safe and effective for children in clinical trials
Which is the most common malaria parasite? (1)
Plasmodium falciparum
What is the ‘scientific’ name of the pork tapeworm? (1)
What type of parasite is this? (1)
Taenia solium
Helminth
Describe the lifecycle of Taenia solium. (7)
- Eggs (or gravid proglottids) passed into environment via faeces of infected human
- Cattle and pigs ingest eggs from contaminated soil or vegetation
- Oncospheres (which were contained in eggs) hatch and get into circulation by penetrating the wall of the digestive system
- Oncospheres travel to muscle tissue where they form cysticerci (cysts)
- Humans become infected by eating raw/undercooked meat
- Immature form attaches to human intestine
- Worm matures and becomes an adult within the small intestine
***Tapeworm produces eggs while in the intestine which are released via faeces
Name the definitive hosts for Taenia solium. (1)
Humans
Name the intermediate hosts for Taenia solium. (1)
Pigs
Name the main effect of Taenia solium on the human brain. (1)
Neurocysticercosis
Taenia solium can cause neurocysticercosis in humans.
What is neurocysticercosis? (1)
Give two symptoms. (2)
Cysts in the brain
- Headaches
- Seizures
True or false? Explain your answer if appropriate. (1)
Humans are at risk from neurocysticercosis if they eat undercooked pork which has been infected with Taenia solium.
False - cysts only develop in humans if the eggs are ingested directly from human faeces, not via uncooked meat.
Eating undercooked pork may, however, result in an intestinal tapeworm.
Taenia solium can cause cysts in the brain.
Give two other tissues where cysts may develop due to Taenia solium. (2)
- Muscle
- Eye
Complete the sentence relating to Taenia solium. (2)
Taenia solium can cause a condition called ……………………., which is a major cause of ……………………. worldwide.
neurocysticercosis
seizures
Which parasite is a major cause of seizures worldwide? (1)
Taenia solium
Briefly describe five ways in which climate change may affect infectious and parasitic diseases in the future. (5)
- More places will become suitable for vectors to survive and breed
- Extreme weather events may disrupt health systems, making more people more vulnerable to serious infection
- Migration, urbanisation, and deforestation may impact disease spread
- Warmer climates extend the disease transmission season
- Temperature change can affect the behaviour of vectors
Describe how climate change will result in more place becoming suitable for vectors of infectious diseases to survive and breed. (3)
- Warmer climates
- Increased rainfall and floods
- Droughts may form pools of standing water from previously flowing water
Describe an example of how temperature change may affect the behaviours of vectors carrying infectious diseases, therefore increasing spread of infectious disease. (3)
Increased temperatures change the biting behaviour of mosquitoes
and this reduces the effectiveness of barriers such as bed nets
leading to increased disease transmission.
Describe how climate change has altered the prevalence of tick-borne encephalitis. (3)
- Ticks carrying the virus have moved into northern subarctic regions of Asia and Europe
- Due to climate change and changes in temperature/weather patterns
- Which expands the area in which they can spread the disease
What is the main condition caused by fungi in/around the brain? (1)
Fungal meningitis
Give five types of fungi which can cause fungal meningitis. (5)
- Cryptococcus
- Histoplasma
- Bastomyces
- Coccidioides
- Candida
Anyone can get fungal meningitis.
However, give five groups of people who might be at higher risk. (5)
What do all of these groups have in common? (1)
- People with HIV
- People with cancer
- People taking steroids (such as prednisone)
- People taking immunosuppressants
- People taking anti-TNF for rheumatoid arthritis or other autoimmune conditions
These groups all have a weakened immune system.
True or false? Explain your answer if appropriate. (1)
As well as lurking around the brain and causing fungal meningitis, some fungal infections can actually invade the brain tissue as well.
True - although this is rare
What is the gut microbiota? (1)
The organisms that live in the gastrointestinal tract
What is the gut microbiome? (1)
The genetic material of the organisms that live in the gastrointestinal tract
Fill the gaps regarding the gut microbiome. (5)
…………………….. of microorganisms live in the GI tract, and these organisms can come from >1000 species of …………………….., archaea, ……………………, single-celled eukaryotes, helminths, ………………………., and ……………………
Trillions
bacteria
yeasts
parasites
viruses
True or false? Explain your answer if appropriate. (1)
Each person usually has an individual ‘fingerprint’ of microorganisms in their gut, comprising about 10-20 different species.
False - each person’s individual fingerprint usually comprises about 160 different species of microorganisms.
True or false? Explain your answer if appropriate. (1)
The gut microbiome contains more genes than the whole human genome.
True
True or false? Explain your answer if appropriate. (1)
The large intestine is one of the most densely populated microbial ecosystems on Earth.
True
True or false? Explain your answer if appropriate. (1)
There are approximately 3x more bacterial cells in the body than human cells.
False - there is roughly the same number of bacterial cells and human cells in the body
In an individual weighing 70Kg, the gut microbiota weighs approximately what weight? (1)
200g
95% of the gut microbiota is located in which part of the GI tract? (1)
Large intestine
About 60% of an individual’s gut microbiota comes from what source? (1)
The mother (during birth and/or breastfeeding)
Give three sources that can influence an individual’s gut microbiota prenatally. (3)
Mother’s gut microbiome
Mother’s oral microbiome
Mother’s vaginal microbiome
Give two general ways that an individual’s gut microbiota can be influenced around the time of birth. (2)
Mode of delivery
Gestational age
Briefly describe how the mode of delivery/birth is able to influence the microbiota of a baby. (2)
- Vaginal delivery confers microbiota from vagina and faeces (and possibly from skin)
- C-section confers microbiota from skin
Describe two ways in which breastfeeding can influence the microbiome of an infant. (2)
- Microbiota can be passed from mother through breastmilk itself
- Can also be passed from mother’s skin
At what age does a child’s microbiota become relatively stable and adult-like? (1)
About 3 yrs of age
Give five factors (with examples if necessary) which influence an infant’s gut microbiome in early life (before about 3yrs). (5)
- Antibiotic use
- Diet (eg. breastfeeding, formula, foods used for weaning)
- Geographical location/region
- Genetics (including sex)
- Living environment (eg. pets, siblings, sanitation)
Define ‘gut dysbiosis’. (1)
An imbalance in bacterial composition, changes in bacterial metabolic activities, or changes in bacterial distribution within the gut.
Give three types of gut dysbiosis. (3)
- Loss of beneficial bacteria
- Overgrowth of potentially pathogenic bacteria
- Loss of overall bacterial diversity
One type of gut dysbiosis can be the loss of beneficial bacteria.
Give two examples of beneficial bacteria that may be lost in gut dysbiosis. (2)
Bifidobacteria
Lactobacilli
One type of gut dysbiosis can be the overgrowth of potentially pathogenic bacteria.
Give three examples of bacteria, which may be overgrown in gut dysbiosis. (3)
- Escherichia coli
- Clostridium
- LPS-forming Enterobacteriaceae
One type of gut dysbiosis can be the overgrowth of potentially pathogenic bacteria.
Suggest a way that this could be measured/represented/quantified. (1)
Altered Firmicutes:Bacteroidetes ratio
Name the two most prominent types/phyla of bacteria in the gut. (2)
Firmicutes
Bacteroidetes
Give four indirect pathways which the gut can use to communicate with and influence the brain. (4)
- Neuroactive metabolites
- Immune system
- Endocrine pathways
- Microbiome-derived metabolites
Describe how neuroactive metabolites may allow the gut microbiota to communicate with and influence the brain. (3)
- Bacteria and other microorganisms may synthesise metabolites
- Such as amino acids which can act as NT precursors
- Or NTs themselves
(eg. gut bacteria can produce tryptophan or serotonin)
Describe how the immune system may allow the gut microbiota to communicate with and influence the brain. (3)
Microorganisms in the gut may stimulate an immune response
which leads to the production of cytokines which can affect the brain
This can happen especially if the microbiota is disrupted
Describe how endocrine pathways may allow the gut microbiota to communicate with and influence the brain. (2)
The microbiota may influence (stimulate or dampen) the HPA axis
which then affects the brain via glucocorticoids and noradrenaline.
Describe how microbiome-derived metabolites (not NTs or amino acids) may allow the gut microbiota to communicate with and influence the brain. (2)
Microorganisms can produce metabolites such as short chain fatty acids (SCFAs)
which can affect the brain in many different ways.
Give three direct neural pathways which allow bidirectional communication between the gut and the brain. (3)
- Vagus nerve
- Enteric nerves
- Spinal nerves
Briefly describe the protocol of a study that provides evidence that the gut microbiome does affect the brain, and can cause psychiatric disorders such as depression and anxiety. (3)
- Rats had microbiota depleted with 4 weeks of antibiotics
- Faecal samples from depressed patients transferred to rats
- After one week, carry out behavioural and physiological tests to identify any brain changes seen
A study transferred faecal samples from depressed patients to rats who had their own microbiome depleted.
After one week, they carried out tests to assess depression and anxiety-like behaviours.
Give the four tests used and the results that were seen. (4)
SUCROSE PREFERENCE TEST
- Depressed microbiome rats showed less sucrose preference
FORCED SWIM TEST
- Depressed microbiome rats showed no differences in immobility, swimming, or climbing time compared to controls
ELEVATED PLUS MAZE
- Depressed microbiome rats showed less visits to the open arms
OPEN FIELD TEST
- Depressed microbiome rats showed less time in centre
A study transferred faecal samples from depressed patients to rats who had their own microbiome depleted.
After one week, they carried out tests to assess depression and anxiety-like behaviours, as well as physiological changes.
Describe the overall conclusion that was shown with these tests. (1)
Microbiome from depressed patients transfers depressive-like state (anhedonia and anxiety) to rats.
A study transferred faecal samples from depressed patients to rats who had their own microbiome depleted.
After one week, they carried out tests to assess depression and anxiety-like behaviours, as well as physiological changes.
Give two physiological changes they saw with a depressed microbiome that were significant. (2)
Give another change which showed a trend, but which was not statistically significant. (1)
- Increased kynurenine/tryptophan ratio
- Increased intestinal motility
- CRP was increased but found to not be significant
A study transferred faecal samples from depressed patients to rats who had their own microbiome depleted.
After one week, they carried out tests to assess depression and anxiety-like behaviours, as well as physiological changes.
One of the physiological changes that they saw was an increased kynurenine/tryptophan ratio.
Describe what is meant by the kynurenine/tryptophan ratio, and what it means if this ratio is increased. (2)
Kynurenine is a breakdown product of tryptophan, which is used to make serotonin, so altered ratio may mean altered serotonin synthesis
Increased ratio may be a marker for inflammation
When assessing gut microbiome composition, describe what is meant by ‘richness’ and ‘diversity’. (2)
Richness - the number of different species present
Diversity - takes into account the number of species present, and the relative abundance of these species
A study transferred faecal samples from depressed patients to rats who had their own microbiome depleted.
After one week, they carried out tests to assess depression and anxiety-like behaviours, as well as physiological changes.
They also assessed the composition of the microbiota.
Give three changes that were seen in the microbiota of depressed people. (3)
- Reduced species richness (fewer species present)
- Reduced species diversity (alterations seen in number of species and their relative abundance)
- Reductions in some phylogenic groups and increases in others
True or false? Explain your answer if appropriate. (1)
The core gut microbiota in adulthood is relatively stable, but can be affected by several environmental factors.
True
Give three environmental factors which can alter the composition of the gut microbiota in adulthood. (3)
- Stress
- Diet
- Pharmaceuticals (antibiotics)
Complete the sentence relating to diet and the gut microbiome. (2)
Maternal diet is thought to influence ………………….. development of the offspring, potentially through ………………..-mediated mechanisms, among others.
cognitive
microbiota
As well as a maternal high fat diet (MHFD) altering offspring’s gut microbiome, give three other effects that it has on the offspring, in terms of behaviour and brain function. (3)
Describe a piece of evidence supporting the fact that these alterations are due to microbiome changes. (1)
- Altered social behaviour
- Altered hypothalamic oxytocin levels
- Altered neuronal plasticity
Controlled microbiome alterations normalise MHFD offspring.
Briefly describe a piece of evidence supporting maternal diet influencing cognitive development of the offspring through microbiota-mediated mechanisms. (2)
- Maternal high fat diet alters several cognitive domains in offspring (microbiome, sociability, oxytocin, plasticity) in mice
- And microbiome changes normalise these alterations
Suggest how a healthy diet may alter the gut microbiome throughout life. (1)
A healthy diet may contribute to continued development of the gut-brain axis and gut microbiome.
Give a piece of evidence supporting a healthy diet contributing to continued development of the gut-brain axis and gut microbiome throughout life. (2)
- In adolescent rats, social instability stress has a range of long-term negative consequences (such as altered microbiome, cognitive behaviour, and BDNF)
- Fatty acid supplements reverse negative changes
This question relates to the gut-brain-axis.
In adolescent rats, social instability stress has a range of negative consequences that continue into adulthood.
Give three consequences that are seen due to stress. (3)
Suggest how these consequences may be reversed. (1)
What does this suggest about the gut-brain axis? (1)
- Changes in gut microbiome
- Changes in cognitive behaviour
- Changes in BDNF expression
May be reversed with fatty acid supplements.
Stress negatively affects the gut-brain axis, however a healthy diet can help to overcome the changes.
Briefly describe two possible mechanisms by which diet may affect the gut-brain axis. (2)
- Healthy diet may promote growth of beneficial bacteria that produce neuroactive metabolites
- Unhealthy diet may promote growth of harmful bacteria
Give three components of a healthy diet which may promote growth of beneficial microbes and neuroactive metabolite production in the gut. (3)
- Fibre
- Polyphenols
- Fermented foods
An unhealthy diet (potentially a ‘Western’ diet) can promote growth of harmful bacteria in the gut, and the end result of this may be more inflammatory mediators reaching the brain.
Describe three mechanisms by which these harmful bacteria may alter gut communication with the brain to ‘send’ more inflammatory mediators to the brain. (3)
- Bacteria may be ‘pro-inflammatory’ and activate immune system
- May alter bile acid metabolism
- May alter intestinal permeability
***This means that more inflammatory mediators can reach the brain
Describe the moderation/mediation question of how diet may impact the gut-brain axis. (2)
State a factor that must be taken into account when assessing the effects of diet on the gut-brain axis. (1)
Does diet moderate (strengthen or weaken) existing communication pathways between gut and brain?
Does diet directly mediate a change to the microbiome composition, which will have a knock-on effect of GBA and brain function?
A factor which must be taken into account is that diet may also have direct effects on brain processes which do not involve the gut microbiome.
A preclinical study investigated the effects of 3 week multi-antibiotic treatment to deplete the microbiome of either adolescent or adult mice.
Behavioural testing was carried out 3 weeks after antibiotics.
Describe the general results/difference seen between adolescents and adults after antibiotic treatment. (2)
Adolescents showed lasting increases in anxiety.
Adults showed a trend for increased anxiety but it was not statistically significant.
A preclinical study investigated the effects of 3 week multi-antibiotic treatment to deplete the microbiome of either adolescent or adult mice.
Behavioural testing was carried out 3 weeks after antibiotics.
Describe the results for adolescent mice in terms of the following tests. (3)
a) elevated plus maze for anxiety
b) memory
c) sociability
a) reduced OA time and head dips, showing increased anxiety
b) memory was unaffected
c) sociability was unaffected
A preclinical study investigated the effects of 3 week multi-antibiotic treatment to deplete the microbiome of either adolescent or adult mice.
Behavioural testing was carried out 3 weeks after antibiotics.
Describe the results for adult mice in terms of the following tests. (3)
a) elevated plus maze for anxiety
b) memory
c) sociability
a) a trend for decreased open arm time and head dips, but was not significant
b) no change
c) no change
A preclinical study investigated the effects of 3 week multi-antibiotic treatment to deplete the microbiome of either adolescent or adult mice.
Behavioural testing was carried out 3 weeks after antibiotics, and gut microbiota composition was also assessed.
Describe the changes seen in the adolescent gut microbiota. (1)
Lasting reduction in microbiota abundance and diversity
One clinical study investigating the effects of antibiotics on gut microbiome and the brain was a case-control study using the UK medical records database.
How did a single antibiotic course in the past year affect brain function and mental health? (1)
How did this change with multiple courses of antibiotics? (1)
Increased risk for depression or anxiety by 20% in people with no prior history of mental illness.
Multiple antibiotic courses increased risk by 50%.
One clinical study investigating the effects of antibiotics on gut microbiome and the brain was a case-control study using the UK medical records database.
How did antibiotic use affect the risk of someone developing psychosis? (1)
Risk for psychosis was unaffected
One clinical study investigating the effects of antibiotics on gut microbiome and the brain was a review of 9 observational studies in different countries.
Give the conclusion of this review on how antibiotic treatment affects risk of depression. (1)
Increased risk of depression following antibiotic treatment.
One clinical study investigating the effects of antibiotics on gut microbiome and the brain was a review of 9 observational studies in different countries.
They concluded that there was an increased risk of depression following antibiotic treatment.
Give two drawbacks of this review which may affect the validity of this conclusion. (2)
- Some of the largest studies didn’t collect data on potential confounding factors such as life stress or other medication
- Some studies were in cancer patients where diagnosis of cancer is also a risk factor for depression
There are a number of potential mechanisms by which antibiotics may impact on the gut brain axis to alter brain function and mental health, and it is most likely a combined effect of multiple different mechanisms.
Give eight suggestions of mechanisms by which antibiotics can affect the gut-brain axis and therefore alter brain function and mental health. (8)
- Reduced neurotransmitter synthesis
- Increased HPA activation
- Altered BDNF expression
- Reduced oxytocin levels
- Altered vagal tone
- Reduced levels of neuroactive short chain fatty acid metabolites
- Reduced intestinal barrier integrity
- Interaction with gut hormones leptin and ghrelin
Two antibiotics in particular, isoniazid and minocycline, are known to have effects on the brain that do not occur via the gut.
Describe the direct effect that isoniazid has on the brain. (1)
How has this led to the development of other drugs to alter brain function? (3)
- Antidepressant activity
Isoniazid was first developed to treat tuberculosis
However was found to be an antidepressant and mildly inhibit monoamine oxidase
Which led to the development of the first MAOI antidepressants in the 1950s
Two antibiotics in particular, isoniazid and minocycline, are known to have effects on the brain that do not occur via the gut.
Describe the direct effect that minocycline has on the brain. (1)
For what condition (other than infections) can minocycline be useful and how would it be used? (1)
Anti-inflammatory effects on microglia
Can be beneficial when administered as adjunctive therapy alongside antidepressants
Give four things, some of which could potentially be confounding factors, that should be considered when looking at the effects of antibiotics on the gut-brain axis and mental health. (4)
- Most people prescribed antibiotics do not develop mental illness
- It is not yet clear why some patients are at higher risk of mental illness after antibiotics
- Other environmental factors may predispose to both infections and mental illness
- Infectious agents themselves, rather than antibiotic treatments, might impact on mental health
What are probiotics? (1)
Give two examples. (2)
Live microorganisms that, when administered in adequate amounts, confer a health benefit on the host.
EXAMPLES:
- Bifidobacteria
- Lactobacilli
What are prebiotics? (1)
Give two examples. (2)
Substrates that are selectively utilised by the host microorganisms (ie. food for the bacteria), conferring a health benefit.
EXAMPLES:
- Nondigestible fibre
- Galactooligosaccharide (GOS)
Describe the types of probiotic supplements which are currently on the market, and what products/research people are currently focussing on for the future. (2)
Numerous products currently available focussing on single microorganism strains (these have been extensively studied over the last decade).
Research now moving on to products featuring multiple microorganism strains.
This question relates to the following study:
The Efficacy, Safety, and Tolerability of Probiotics on Depression: Clinical Results From an Open-Label Pilot Study.
10 treatment-naive, depressed patients were given daily Lactobacillus helveticus and Bifidobacterium longum for 8 weeks.
Describe the results seen at 4 and 8 weeks. (2)
Significant improvement in symptoms at 4 and 8 weeks
This question relates to the following study:
The Efficacy, Safety, and Tolerability of Probiotics on Depression: Clinical Results From an Open-Label Pilot Study.
10 treatment-naive, depressed patients were given daily Lactobacillus helveticus and Bifidobacterium longum for 8 weeks.
They saw significant improvement in symptoms at 4 and 8 weeks.
However, give 2 drawbacks of this study which may affect validity of the results. (2)
- No control group or placebo
- No blinding
(title states an ‘open-label pilot study’)
A study aimed to assess the effects of probiotics on generalised anxiety disorder.
In 48 drug-free GAD patients, some were given SSRI+probiotic, and some were given SSRI+placebo for 8 weeks.
The probiotic contained Bifidobacterium longum, Bifidum lactis, and Lactobacillus acidophilus.
State the results of this study in terms of the following outcome measures at week 8. (3)
a) HAM-A score
b) state-anxiety score
c) WHOQOL score
a) SSRI+probiotic improved HAM-A score at week 8
b) SSRI+probiotic improved state-anxiety score at week 8
c) WHOQOL score remained unchanged at week 8
Despite some evidence suggesting that probiotics may have a beneficial affect on mood, there have also been some negative results for probiotics and mental health:
Chahwan et al (2019) - Gut feelings: a randomised, triple-blind, placebo-controlled trial of probiotics for depressive symptoms.
Give three reasons why some studies may not see a benefit of probiotics on mental health. (3)
- Hard for orally administered strains to survive pH changes through the GI tract and achieve long-term colonisation
- Host factors such as diet and baseline microbiota might influence efficacy
- Different bacterial strains may be effective in different disease subtypes
Complete the sentence regarding probiotics and mental health. (3)
There is mixed evidence for an effect of probiotics on mental health, which suggests that a combined …………………………….. approach may be needed. There are some positive preclinical findings however …………………….
There is currently ……………….. evidence to support probiotics as a stand-alone treatment for mood disorders.
HINT: second one is a phrase rather than just a couple of words
diet x probiotic
these are yet to translate to the clinic.
no
Give some examples of foods which act as prebiotics. (10)
- Garlic
- Legumes
- Apples
- Buckwheat
- Onions
- Tomatoes
- Artichokes
- Oatmeal
- Berries
- Bananas
A study assessed the effects of prebiotic supplements on gut microbiota and mental health.
It was a double-blind, placebo-controlled study in which 64 healthy young adult females were given a galactooligosaccharide prebiotic supplement daily for 4 weeks.
Describe the results at 4 weeks, in terms of the following outcome measures. (2)
a) Bacterial composition of microbiota, as assessed by amount of bacteria species in faeces
b) self-scores in anxiety
a) increased faecal bifidobacterium
b) trend for improved self-scores in high-anxiety individuals (although this was not significant)
A study assessed the effects of prebiotic supplements on gut microbiota and mental health.
72 patients with MDD who were on medication were given either a prebiotic supplement or a placebo daily for 8 weeks.
Describe the effect that the prebiotics had on the BDI (Beck’s Depression Inventory) scores. (1)
Prebiotic did not improve BDI scores
A systematic review found no benefit of prebiotics on depression.
Why might this be? (3)
- Host factors such as diet and baseline microbiota might influence efficacy
- Different prebiotics may be effective in different disease subtypes
- May require a combined approach to be effective
Give two future directions for the use of prebiotics and probiotics in treating mental health conditions such as depression and anxiety. (2)
- Test other prebiotic nutrients apart from galactooligosaccharide, such as polyphenols and omega-3 fatty acids
- Investigate use of synbiotics (synergistic combinations of probiotics + prebiotics)
