Lecture A6 + A7 - The Mucosal Microbiota - Mutalists of the Gut

Question 1

Where do the highest densities of microbes assemble in the human body and why?

Answer 1

Gut microbiota.
Stomach is too acidic, the small intestine has a higher pH than the stomach but there is fast flow. Transit is slow in the colon so bacteria can multiply, also anaerobic environment which is good for microbes.

Question 2

What is a mutualist relationship?

Answer 2

We provide them with and nutrients in the form of complex dietary glycans and they play a key role in maintaining health and nutrition.

Question 3

Describe detoxification by the gut microbiota?

Answer 3

Anything taken into our bodies (food drugs etc) gets to the colon, microbes there can metabolise it into something that is active or inactive or a different metabolite.D

Question 4

Describe biosynthetic activity by the gut microbiota.

Answer 4

Not all vitamins and essential minerals come from our diet, some are made by the microbiota.

Question 5

Describe immune maturation by the gut microbiota.

Answer 5

Making sure the immune response only responds to pathogens.

Question 6

Describe metabolic activity by the gut microbiota.

Answer 6

Breaks down the indigestible fibres into short chain fatty acids that are an energy source for the colonocytes as well as several other benefits for the body.

Question 7

Describe the protective action of the gut microbiota.

Answer 7

Excludes pathogens by competing for resources and produce anti-microbials.

Question 8

What if the microbiota-gut-brain axis?

Answer 8

There is bi-directional signalling between the brain and the microbiota.
The microbiota can induce endocrine, immune and neural pathways.

Question 9

Name some examples of neurotransmitter production by bacteria.

Answer 9

Bacillus spp: acetylcholine, dopamine and NA.
Enterococcus spp: histamine and serotonin.
Lactobacillus spp: acetylcholine, dopamine, GABA, histamine and serotonin.

Question 10

What is the gut microbiota best considered as?

Answer 10

The indispensable metabolic organ that facilitates the transformation of nutrients and energy from ingested food and produces numerous metabolites that signal through their cognate receptors to regulate host metabolism behaviour.

Question 11

How can gut microbiota play a role in disease?

Answer 11

Imbalances (dysbiosis) of the microbiota have been implicated in many serious disease states.
Many are non-communicable chronic diseases.
Many characterised by chronic intestinal inflammation.

Question 12

Name some serious disease states that the gut microbiota can be involved in.

Answer 12

IBD
Obesity
Diabetes
Colon cancer
Heart/kidney/liver failure
Autoimmune disease
Infectious disease (cholera)

Question 13

Describe the composition of the adult gut microbiota.

Answer 13

Stool samples used as hard to get samples from anywhere else in the gut.
Predominantly Firmicutes and Bacteroidetes but also proteobacteria (E. coli) and acintobacteria (G +ve).

Question 14

How is the composition of the adult gut microbiota carried out?

Answer 14

Mainly by either 16s rRNA amplicon sequencing and whole genome ‘shotgun’ sequencing.

Question 15

What were the main findings of the gut microbiome sequencing studies?

Answer 15

Aggregate microbiota - 1000 bacterial species but each person has max 50-100 different species that are very different between individuals, suggesting distinct microbiota.
There is no keystone group of essential species that everyone shares.
Longitudinal studies indicate adult microbiota is relatively stable over time.

Question 16

What produces SCFA and what do they influence?

Answer 16

Fermentation of dietary fibre but gut firmicutes and bacteroidetes produces SCFA butyrate, propionate and acetate.
These influence host metabolism in multiple ways by acting on G-protein coupled receptors expressed by enteroendocrine cells.

Question 17

How does diet have an effect on health?

Answer 17

Through metabolites produced by microbiota.
Components of our diet are metabolised by the gut microbiota into products that drive health and disease.
Glycans are a major source of food for the gut microbiota.

Question 18

Name some glycans from the diet that are not digested by human enzymes and are available to the gut microbiota.

Answer 18

Dietary fibre - MAC (microbiota accessible carbohydrates).
Oligosaccharides such as raffinose.
Plant cell wall polysaccharides such as b-glycans, mannans.
Storage polysaccharides.
Insulin-type fructans.

Question 19

What are CAZymes for?

Answer 19

Encoded in the human gut microbiota for breaking down dietary fibre.

Question 20

How are SCFA important health promoting molecules?

Answer 20

SCFA are a waste product of glycan fermentation.
They regulate aspects of intestinal motility, hormone secretion, energy homeostasis, maintenance of gut barrier and anti-inflammatory pathways.

Question 21

Describe butyrate.

Answer 21

SCFA mainly produced by firmicutes.
Main energy course of colonocytes.
Anti-cancer - induces apoptosis in cancer cells.
Activates intestinal gluconeogenesis.
Beta-oxidation of butyrate by colonocytes consumes O2 which is essential to maintain anaerobic environment of gut and prevent dysbiosis.

Question 22

Describe propionate.

Answer 22

SCFA mainly from bacteroidetes.
Acts on beta-cell function to maintain healthy glucose homeostasis.
Lowers serum cholesterol.
Influence on gut hormones and satiety.

Question 23

Describe acetate.

Answer 23

SCFA from most gut bacteria.
Suppression of pathogens (lowers pH).
Increase butyrate production.
Affects cholesterol metabolism and lipogenesis.

Question 24

What does a high fibre diet promote?

Answer 24

High SCFAs.
Enhanced mucus secretion and increased antimicrobial peptides.
Regulated immune response.
Decreased oxygen in the gut and unregulated tight junctions making a functioning intestinal barrier to invading organisms.
Promotes health, immune homeostasis and functional barriers.

Question 25

What does a low fibre diet promote?

Answer 25

Low SCFAs.
Reduced mucus secretions and reduced antimicrobial peptides.
Pro-inflammatory immune response.
Increased oxygen and down regulated tight junctions allowing invading microorganisms in.
Dysfunctional intestinal barrier.
Promotes dysfunctional barrier, inflammation and chronic disease.

Question 26

What do bile acids do?

Answer 26

Help with emulsification of dietary fats and lipids. Gut microbial enzymes contribute to bile acid metabolism through deconjugation and dehydroxylation reactions to generate unconjugated bile acids and secondary bile acids.

Question 27

How can eating red meat be harmful to the body?

Answer 27

Microbiota also produce harmful molecules from dietary compounds.
Choline and carnitine from red meat are metabolised into trimethylamine by gut microbiota.
TMA is oxidised into TMA N-oxidase promoting metabolic and functional changes in the host including cardiovascular and renal end organ damage.

Question 28

What can a too high in protein diet mean?

Answer 28

Too much protein = microbiota must deuse the protein. Breakdown products if the protein isn’t beneficial can lead to cytotoxic compounds being produced.

Question 29

How can a high fibre diet help with effects of meat and fat?

Answer 29

Trade off between saccharolytic and proteolytic fermentation means a high fibre diet likely inhibits protein fermentation counteracting many of the detrimental effects of meat and fat, so they are less problematic.

Question 30

How do human gut microbes metabolise xenobiotics?

Answer 30

Packed with actively metabolising microorganisms that have a transformative effect on what is ingested.
Depending on the composition of microorganisms in the gut, the subsequent products have nutritionally beneficial effects, modify pharmaceuticals or be toxic.

Question 31

What factors can influence the composition of the gut microbiota?

Answer 31

Methods of delivery at childbirth
Breastfeeding or bottle fed as a baby
Diet
Exercise and personal habits
Presence of disease
Ageing
Medications
Geography

Question 32

Describe how method of delivery at childbirth can influence the gut microbiota.

Answer 32

Babies delivered by c-section acquire a different microbiota to vaginally delivered babies. Vaginally delivered babies exposed to the mothers faecal and vaginal microbiota first and have an enriched bifidobacterium and bacteroides.
C-section babies are exposed to the skin and hospital environment microbiota first and have disrupted transmission of maternal bacteroides strains and colonisation by opportunistic pathogens.

Question 33

What are c-section babies more at risk of developing?

Answer 33

C-section babies at a higher risk for immune and metabolic disorders such as IBD, diabetes, childhood asthma and obesity.

Question 34

What is the differences between breast fed babies and bottle fed babies microbiota?

Answer 34

Breastfed = infant gut dominated by bifidobacteria.
Bottle fed = infant gut have reduced bifido levels and increased diversity.

Question 35

Why is there a difference between breastfed and bottle fed babies?

Answer 35

Human milk contains complex molecules that shape the composition of the microbiota. Antimicrobials like lactoferrin immune molecules and complex carbs known as human milk oligosaccharides.

Question 36

How can you reduce the downsides of C-section delivery?

Answer 36

Transplanting faecal matter from the mother into the baby so they can get all the essential bacteria needed that they didn’t get via birth.

Question 37

What does the association between reduced diversity and disease indicate?

Answer 37

That a species rich gut ecosystem is more robust against environmental influences as functionally related microbes in a diverse ecosystem can compensate for the function of other missing species.

Question 37

What is the evidence for effects of fibre on microbiota diversity and gut health?

Answer 37

Lower microbiota seen in obese individuals and is linked to long term low fibre intake.
Main evidence from people of traditional ‘non-industrial’ societies where levels of fibre intake are much higher than in the Western world. Have a more diverse microbiota and almost no chronic disease like IBD, CRC.

Question 38

What are the differences between traditional and industrialised gut microbiota?

Answer 38

VANISH taxa abundant in traditional, rare in industrialised.
Akkermansia munciniphila abundant in industrialised, rare in traditional.
Phylogenetic diversity high in traditional, low in industrialised.
CAZyme diversity higher in traditional.

Question 39

Describe the importance of fibre for effective mucosal barrier.

Answer 39

Colon has a thick layer of mucus to protect underlying epithelial cells.
Chronic inflammation can result from reduced barrier function allowing microbial products to translocate from intestine to systemic circulation.

Question 40

What does lack of fibre lead too?

Answer 40

Increased mucin degrading bacteria and expression of mucin targeting enzymes.

Question 41

What were the main findings of the dietary simple sugar study in mice?

Answer 41

Dietary glucose exacerbates DSS-induced colitis of gut in a microbiota dependent manner.
Likely caused by erosion of mucus barrier due to dysbiosis in the gut.

Question 42

What mucus degraders are high in industrialised gut microbiota?

Answer 42

Akkermansia muciniphila and bacteroides abundance.
Reduced CAZyme diversity also contributes as lots of CAZymes needed to degrade fibre instead of mucins.

Question 43

What strategies can be used to manipulate the gut microbiota to try and promote better health?

Answer 43

Add back live microbes
Provide microbiota with more nutrients.