Lecture 26: Gut microbiome Flashcards
What is meant by “hidden deficiency”
“The wrong mic of gut bacteria, not just starvation, could contribute to severe malnutrition”
In Malawi, 10s of thousands of children have this, with 15% being fatal
What is the gut microbiome?
~3000 bacterial species in gut. Also contains yeast fungi (“mycobiome”) and viruses (“virome”). The “bacteriome” makes up >99% of the microbiome
what is the bacteriology of different regions of the human gastrointestinal tract:
- Small intestine: 10^4-6g
- Stomach: 10^3g
- Large intestine: 10^12g
What are the three ‘biomes’ of the gut microbiome?
- Bacteriome
- Mycobiome (fungi)
- Virome
What is the gut mycobiome
1. Commensal fungi coexisting with other
'bugs'
2. Can be positive or negative
3. Low diversity compared to bacteriome
4. Dominated by yeast, making up 8 of the
top 15 most abundant genera
a. Saccharomyces
b. Malassezia
c. CandidaWhat is the gut virome
1. Human faeces contain at least 10^9 virus-
like particle per gram
2. Highly individualised
3. Vast majority of viral particles
unidentified
4. Viruses important to them carrying
antibiotic resistance genes as well as
virulence genes
5. Can modulate the microbiome
compositionWhat are the major groups of bacteria in the gut?
- Firmicutes. E.g;
a. Lactobacillus
b. Clostridium
c. Staphylococcus etc - Bacteroidetes. E.g;
a. Bacteroides
b. Prevotella - Proteobacteria. E.g;
a. Escherichia
b. Pseudomonas - Actinobacteria. E.g;
a. Bifidobacterium
90% of gut = Firmicutes and Bacteroidetes
What is meant by the evolution of microbiomes?
Different animals have unique microbiomes.
These include:
- Persissodactyla:
a. Elephant
b. Rhino
c. Horse
d. Zebra - Primates:
a. Monkeys
b. Chimpanzees - Carnivora:
a. Lions
b. Hyena - Artiodactyla:
a. Sheep
b. Cow
c. Giraffe
How does he gut microbiome develop with age?
1. Vaginally delivered infants -
microbiota is dominated by mothers
vaginal and faecal bacteria
2. C-section infants - microbiota
dominated by skin and bacteria from
hospital environment (LESS
MICROBIOTA DIVERSITY THAN
VAGINAL)
3. Microbiota changes with weaningWhat factors affect the gut microbiome?
- Genetics
- Ageing
- Diet
- Stress
- Infection
- Antibiotics
What are the beneficial and harmful effects of the gut microbiome?
Beneficial:
- Stim of host immune system
- aids digestion
- Prod short chain FAs and vitamins
- Inhibition of pathogenic bacteria
- Transformation of bioactive compounds
- Provide fixed nitrogen
Harmful:
- Prod of carcinogens
- Role in obesity and diabetes
- Involvement in inflammatory diseases
What makes up the mutualistic relationship between microbes and humans
- Microbiome provides health benefits
- We provide a home:
a. free food
b. free water
c. constant temperature
What role does the microbiome have in health and disease?
- Pathogen exclusion
- Brain development
- biotransformation of dietary components
- asthma
- cancer
- liver function
- obesity
- diabetes
- mucosal immunity
- inflammatory bowel disease
What are the molecular approaches to characterising microbial communities?
- Microbial community. From:
a. GI tract
b. Seawater
c. biofilm
d. soil - DNA isolation
- Sequence all bacterial DNA
(“metagenomic” shotgun sequencing) OR
PCR variable region of genome - 16S
rRNA (“metataxonomic”) - Next gen sequencing
- Bioinformatics
What is the microbiome variance between individuals?
- > 50% of humans share 75 species
- > 90% of humans share 57 species
“GREATER SIMILARITY BETWEEN INDIVIDUALS ON A FUNCTIONAL LEVEL”
What is ulcerative colitis (UC)?
- Form of inflammatory bowel disease (IBD)
- Specifically in large intestine
- 1/1000 un UK and western world affected
Different factors include:
a. Genetics
b. Environmental
c. Gut bacteria
What is the relationship between the gut microbiome and obesity?
- 64% of Americans overweight or obese
- Factors affecting obesity:
a. high calorie intake
b. genetic predisposition
c. Microbial metabolism
What did a study find regarding the relationship between the microbiome and obesity in mice?
“Obese mice have 50% less Bacteroidetes (major phyla in gut microbiome) than lean mice, the reverse is true for Firmicutes”
CAUSE OR EFFECT???
Another study transplanted the gut microbiome from an obese mice into a normal mice. This lead to a greater percentage increase in total body fat compared to donation of microbiota from lean donors.
What is the role of the gut microbiome in nitrogen fixation?
- new species found in human stool:
“D. diazotrophicus sp. nov” - Ability to fix nitrogen (N2 to NH3 via
nifHDK) may be an advantage in survival
in complex gut microbiome if nitrogen
becomes limited particularly in
people with low protein diet
What is the role of C. difficile in humans for biocontrol of gut pathogens
1. A superbug-major cause of hospital
acquired infections
2. Spores can persist in the hospital
environment: hands, floor, clothing,
bedding
3. Produce toxins
4. Possible food borne pathogen
5. 20,000 cases of CDI ("Closridium
difficile infection") in UKWhat is Clostridium difficile infection (CDI)
- Mild = severe diarrhoea, abdominal
pain, fever - Severe = bowel inflammation (1500
deaths in UK) - Elderly patients who have taken broad
spectrum antibiotics and immuno-
compromised patients are at most risk
(>80% of CDI reported in people >65 YO) - Clear association between disruption
of normal gut biota by antibiotic
How is CDI treated?
- Currently treatable via:
a. Metronidazole
b. oral vancomycin - Relapse occurs 20-30%
- Potential risk of antibiotic resistance
What is FMT (faecal transplant)?
- Treatment for CDI
- Procedure:
a. patient stops taking antibiotics
b. patient given enema to empty the
bowels
c. Nasjejunal (NJ) tube is inserted through
by gastroenterologist
d. Fresh faecal slurry is prepared
e. Transported to hospital and delivered
to patient via NJ tube
f. Takes 20 minutes - 92% success rate in norwich
Pros and cons of FMT treatment for CDI
+ Cheap
+ high success rate
+ Easy to administer
+ Very few side effects
- Risk transferring unknown pathogens
- Public acceptance
- Long-term impact of foreign microbiome
unknown
What is the future of FMT developments?
- Frozen donor faecal matter
- Freeze dried donor faecal capsules
- Defined mix of gut bacteria instead of
whole faecal microbiome
How does the gut microbiome affect brain function and behaviour?
- Gut microbiome associated with:
a. anxiety
b. depression
c. sensitivity to pain
d. serotonin production
e. autism
What did a study on mice find after a faecal transplant in mice regarding the gut-brain axis?
1. Recipient mice would take up
personality of donor
2. daring mice would become
apprehensive
3. timid mice would become more
exploratory
4. FMT using aged donors lead to
impaired spatial learning and memory
in young adult recipientsWhat is the gut brain axis?
- The guts mind
- “enteric nervous system”
- Gut produces more serotonin than the
brain
