Lecture 38: Gut microbiome III

Question 1

Aside from bacteria, name 3 other types of organisms present in the gut microbiome.

Answer 1

Fungi, viral microbiota (bacteriophages), and helminths

Question 2

The collection of fungi in the gut microbiome is called […]

Answer 2

Mycobiome

Question 3

The collection of helminths in the gut microbiome is called […]

Answer 3

Macrobiota

Question 4

The collection of viral microbiota in the gut microbiome is called […]

Answer 4

Virome

Question 5

What are probiotics?

Answer 5

Live microorganisms which when administered in adequate amounts confer a health benefit to the host.

Question 6

Name 4 current issues with probiotics.

Answer 6

1. Inadequate studies(uncertain health benefits, concerns about data quality)
2. Limited mechanistic understanding of effects of current probiotics
3. Effectiveness of probiotic to altering a disease state is not currently provided.
4. There is the possibility of transferrable microbial properties (i.e. antibiotic resistance genes) to the gut microbiota.

Question 7

What is the effect of probiotics said to be after disease?

Answer 7

It is claimed that taking probiotics when sick can help the gut microbiota return to normal after a perturbation.

Question 8

Describe the setup and goal of the Suez et al. 2018 study.

Answer 8

They treated both humans and mice with antibiotics ciprofloxacin and metronidazole, then put them on bi-daily probiotics administration. The goal was to test whether probiotics do in fact help the gut microbiome recover after antibiotic perturbation.

Question 9

Describe the results of the Suez et al. 2018 study in mice.

Answer 9

It was found that mice without antibiotic exposure were not colonized by probiotics. For those that did receive antibiotics, probiotic colonization was mild in mucosal layers.

Question 10

Describe the results of the Suez et al. 2018 study in humans.

Answer 10

In humans, probiotic colonization was site and person-specific. Antibiotics significantly enhanced probiotic colonization in musosal layers. Overall, probiotics delay gut microbiome reconstitution and its metabolism, which is unexpected.

Question 11

How do probiotics compare to FMT in terms of mucosal microbial diversity and metabolism?

Answer 11

FMT restores mucosal microbial diversity and metablism very effectively as compared to probiotics.

Question 12

What are the 3 major helminths in the gut?

Answer 12

Nematodes, cestodes, and trematodes.

Question 13

How much of the world’s population is affected by helminth infection?

Answer 13

25%

Question 14

What is the typical effect of helminths on the body?

Answer 14

It induces Th2 response, which is a chronic immune response, allowing for decade-long infections. There is also the possibility of protection from malaria, but this is uncertain.

Question 15

What is the hygiene hypothesis?

Answer 15

It is the hypothesis that excessive hygiene in the developed world, which causes lack of exposure to helminths, might be the cause of the high prevalence of autoimmune disorders in these regions

Question 16

Name 2 roles of helminths in the gut.

Answer 16

They can alleviate bleeding in inflammatory bowel disease and can decrease the number of Bacteroides species involved in intestinal inflammation.

Question 17

How can gut helminths affect the airways?

Answer 17

Their interactions with the gut bacteria can alleviate asthma symptoms, as their metabolites can behave as neurotransmitters and affect the tissue.

Question 18

What is worm therapy? How effective is it?

Answer 18

It is when chronically ill individuals purcahse helminths to put into their guts to attempt to alleviate their disease symptoms. However, there is very little known about the details and effects of this method.

Question 19

What are bacteriophages? Where are they found?

Answer 19

They are viruses that infect bacteria that are obligatory parasites without inherent metabolism. They exist everywhere that bacteria are present.

Question 20

How prevalent are bacteriophages in microbial communities?

Answer 20

There is typically a bacteriophage:bacteria ratio of 10:1. The exception is the gut, which has a lower, 1:1 ratio (can range between 0.1:1 and 3:1).

Question 21

What are the two most prevalent phage types in the gut?

Answer 21

CrAssphages (most prevalent) and Lak phages.

Question 22

What is known about phage diversity? Why?

Answer 22

There are various types, including DNA and RNA as well as with capsids or envelopes. However, most phages remain unknown because there is no common genetic marker (such as 16S rDNA) and the databases are limited.

Question 23

What are the two major bacteriophage replication cycles?

Answer 23

The lytic cycle and the lysogenic cycle.

Question 24

Describe the lytic cycle of bacteriophages.

Answer 24

They infect the cell and inject their DNA/RNA into it, which becomes plasmids. The bacteriophage genome replicates, which produces more phages in the cell. The cell lyses and the bacteriophages break free to infect another cell.

Question 25

Describe the lysogenic cycle of bacteriophages.

Answer 25

The bacteriophage injects its genome into the cell and it integrates into the chromosome. The bacteria can then replicate as usual, including the phage genome. At any time, the cells can be induced to start phage production from the genome, which will cause lysis (like the lytic cycle).

Question 26

Of bacteriophages that undergo the lytic cycle versus the lysogenic cycle, which type is more preferable for therapies and why?

Answer 26

Lytic cycle, because their behaviour in the cell is more predictable. In the lysogenic cycle, genome replication could be induced at any time.

Question 27

What type of phages are the majority of bacteriophages in the gut?

Answer 27

The majority seem to be DNA, although this might be due to experimental bias. They are also prophages, meaning that they are integrated in bacterial cells.

Question 28

What is the impact on bacteriophages on the immune response?

Answer 28

They can modulate the immune response either directly or indirectly.

Question 29

Might we expect the virome to be the same or different between healthy and diseased individuals?

Answer 29

It will be different in terms of virome diversity. Diseased individuals will have increased phage richness, and will have an increased abundance of free phages.

Question 30

How does the balance of viral abundance/diversity and bacterial abundance/diversity vary between the infant gut and the adult gut?

Answer 30

In infants, there is higher viral abundance/diversity and lower bacterial abundance/diversity (thus higher ratio of phages:bacteria). In adults, it is the other way around, so there is a higher ratio of bacteria:phages.

Question 31

What three aspects of the gut bacteria do phages regulate?

Answer 31

Abundance, diversity, and phenotype.

Question 32

Can phages be used to manipulate gut bacterial communities?

Answer 32

Yes.

Question 33

Give an example of a health issue that can be potentially be addressed with microbiome manipulation with phages.

Answer 33

Stunting

Question 34

What is stunting?

Answer 34

It is when a child’s height-for-age is > 2 STDEV below the WHO Child Growth Standards median. It is irreversible after 2-3 years of life but is completely preventable.

Question 35

How do the microbiomes of stunted children differ from non-stunted children? When is intervention possible?

Answer 35

Non-stunted children harbour more temperate phages, while stunted children have stunted phages that allow proteobacteria to develop in an age-specific manner. Results suggest an intervention time window of 23 months.