Lecture 37: Gut microbiome II Flashcards

1
Q

How does the North American gut microbiome compare to the microbiome of indigenous populations? Why?

A

The composition is extremely different because the diets are different. The North American diet is more processed and meat-heavy, which changes the microbiome present.

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2
Q

How does obesity impact the gut microbiome?

A

Obese individuals have higher proportions of Firmicutes:Bacteroidetes than lean individuals.

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3
Q

What method was used to determine how the gut microbiome differs between obese individuals and lean individuals? Why?

A

Because there are several confounding factors that affect humans (diet, genetics, environment), mice models are used instead, as their genetics and diet and can be controlled.

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4
Q

As opposed to a normal lean mouse, how is an obesity-prone mouse different genetically?

A

The obesity-prone mouse will be lacking in leptin, which is a hormone made by fat cells that regulates the amount of fat stored in the body (the satiety hormone)

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5
Q

Describe how it was proven that obese organisms have a different gut microbiota than lean organisms.

A

Lean mice and leptin-mutant mice were fed the same diet. The 16S rDNA method was used to look at what type of gut microbiota was present in each. It was found that obese mice had a significantly higher proportion of firmicutes:bacteriodetes in their gut.

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6
Q

Describe how it was proven that the difference in gut microbiota between lean and obese individuals is the cause of the weight difference.

A

Two mice were transferred microbiomes from a lean human and an obese human respectively, and they confirmed that the bacterial ratios were as expected. The two mice were fed identical diets and quantities of food, but the obese mice still had more body fat despite this.

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7
Q

Explain why the difference in gut microbiomes between obese and lean individuals causes a difference in weight gain when put into mice. Also explain how this was determined.

A

The microorganisms from the obese system caused more genes involved in carbohydrate metabolism to be expressed. So, for the same amount of food, obese mice were getting more energy out of it vs losing it in the feces. This was shown by fecal calorimetry, with obese mice having less energy left in their feces.

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8
Q

What is the role of diet in the establishment of lean vs obese microbiota?

A

A bad diet cannot be cancelled out by having a “lean” microbiome. Lean microbiota still can’t colonize well if exposed to a high fat and lower fiber diet.

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9
Q

What impact do antibiotics have on gut microbiota diversity?

A

It vastly reduces microbiota diversity, even in strains that are not targeted by the antibiotics.

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10
Q

In what stage of life are antibiotics particularly disruptive?

A

During early childhood.

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11
Q

At sub-therapeutic doses, antibiotics can promote […]

A

Weight gain

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12
Q

How do antibiotics affect bacterial abundance before and after exposure?

A

They decrease abundance during exposure, but the numbers usually bounce back afterwards (although the diversity does not)

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13
Q

What is a pathobiont expansion?

A

This is an unintended effect of antibiotics whereby they can promote the establishment of pathogens in healthy hosts. This doesn’t always cause disease, but sometimes can.

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14
Q

Give an example of a pathobiont expansion (drug and pathobiont)

A

Drug: clindamycin
Pathobiont: C. difficile

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15
Q

Why does taking clindamycin promote the establishment of C. difficile?

A

Because the abundance of other bacteria in the system decrease, so it gives C. difficile the chance to colonize.

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16
Q

How prevalent is C. difficile in the gut microbiome typically (without antibiotics)? How do antibiotics change this?

A

Normally, around 2% of the population are healthy carriers who have a small, harmless amount. But when they take antibiotics, this allows them to take over, and they become hard to get rid of.

17
Q

Why are C. difficile infections so hard to get rid of?

A

Because they are spore formers.

18
Q

What is the first line of treatment against C. difficile infection after antibiotic use?

A

The discontinuation of antibiotic usage and a course of Metronidazole or vancomycin (+ probiotics)

19
Q

After the first line of treatment against C. difficile, what % of patients still have recurrent C. difficile?

A

Around 25%

20
Q

What is the last resort treatment for recurrent C. difficile infections?

A

Fecal microbiota transplant (FMT)

21
Q

What is FMT?

A

It is the infusion of fecal bacteria from a healthy individual into a recipient, thus replacing their gut microbiota.

22
Q

What have the results been of research regarding the effectiveness of FMT?

A

It has been shown to be highly effective in treating recurrent C. difficile, to the point where studies were stopped because it was considered unethical not to offer the treatment to everyone.

23
Q

Name 3 current concerns about FMT.

A
  1. Total community transplant (uncertainty about the effect of transplanting a whole other microbiome + creating higher risk of other diseases by accident by introducing pathogens)
  2. Society buy-in due to taboo of fecal matter
  3. Need for defined bacterial mixtures to minimize uncertainty
24
Q

What is the major solution to the concerns about FMT?

A

A defined microbiota transplant, where it is a specific mix of microorganisms to ensure the seeding of healthy bacteria.

25
Q

How effective are defined microbiota transplants in treating chronic conditions?

A

There’s been mixed results, as there’s also a genetic factors in many chronic diseases alongside the C. difficile infection.

26
Q

Other than microbiota transplants, name 4 ways to manipulate the gut microbiome.

A

Probiotics, prebiotics, diet, and bacteriophages

27
Q

What are probiotics? Give a few examples of where they can be found.

A

Live microorganisms that are safe for ingestion and can give a health benefit. For example, yoghurt, cheese, kombucha, fermented food.

28
Q

What are prebiotics?

A

Food for microorganisms. They ensure that the right nutrients are being given for the right bacteria to grow. Prebiotics are not alive.

29
Q

The main way in which microorganisms affect the brain is via […], which come from […]

A

Short fatty acids, bacterial fermentation (they are metabolites)

30
Q

Name 3 examples of microbiota-derived SCFAs.

A

Acetate, proprionate, butyrate

31
Q

Why do gut microbiota produce SCFAs?

A

Because they undergo fermentation (anaerobic respiration), since the gut is an anaerobic environment.

32
Q

What are the major properties of SCFAs (aside from effects on brain)?

A

They have immunoregulatory properties (can be pro or anti inflammatory) and butyrate can be an energy source of enterocytes.

33
Q

How can SCFAs affect the brain? Why?

A

They can cross the blood-brain barrier and regulate neurological functions, as they have a very similar structure to neurotransmitters.

34
Q

Give 4 examples of body-wide microbial interactions (co-occuring pathologies).

A

Any of:
1. IBS and pulmonary inflammation/impaired lung function
2. Asthma and functional/structural changes in gut microbiota.
3. Changes in oral microbiome and preterm birth and abortions
4. Rheumatoid arthritis and periodontal disease
5.IBD and psoriasis