Intro to Gut Microbiology Flashcards
What is the normal flora of the gut?
Flora normally present in all surfaces and mostly (99%) in the gut
What is meant by resident flora?
commensal organisms that are there for life
microbial melting pot
What is transient flora?
temporarily reduced, carried or changed due to environmental factors
- not permanent flora
Give an example where the flora changes in the body
organisms in baby’s gut change during weaning
e.g. baby to adult - weaning
Bifidobacterium (>90% of the flora) and utilises breast milk (gram +ve)
diet; environment; stress; hormones; age; transit time causes change from bifiobacterium →adult microbiota
Explain how baby faecal transition occurs
- Sterile meconium (first time baby
defecates; green coloured) - facultative anaerobes (baby acquires
microbial flora) - Strictly anaerobic gut (O₂ free environment
in colon) - Bifidobacterium
- After weaned off milk microbes change to
adult-like gut microbiota (bacteroides)
Describe the biological features of bifidobacterium
Gram +ve Rod; branched
Produce lactic acid; prevent growth of G-ve bacteria that may try colonising baby’s gut
Metabolises breast milk → nutrients for baby and energy for itself
Describe the transition of bacteria when acquiring adult microbial flora
Weaning:
Bifidobacterium → bacteroides, clostridia & eubacteria (adult-like gut microbiota) anaerobic organisms living in lower half of colon
What is commensal flora?
one organism derives food or other benefits from another organism without hurting or helping it
Which part of the normal flora is commensal
No one species of gut flora is a commensal, but together the flora may be regarded as commensal (no harm to host)
What is the significance of the normal flora?
A combination of organisms produces normal flora allowing normal physiology of gut
Describe the distribution of bacteria in the gut
Bacteria distributed throughout GI Tract
Fewer in stomach due to high Acidity
More complex and larger mixture of bacteria as we progress through duodenum & ileum (esp. Terminal ileum)
Describe the flora in the colon
Colon: anaerobic environment, contains facultative and obligate anaerobes
Very large amount of complex mixtures of bacteria
E.g. bacteroides, clostridia, E.coli
How does disease affect the gut flora
Microbiome alterations (dysbiosis) are associated with disease states
How does Inflammatory Bowel Disease affect the distribution of bacteria?
In patients with inflammatory bowel disease, the distribution of bacteria is very different
Generalised diversity changes and species differ
What can cause gut flora dysbiosis?
Crohn’s disease Inflammatory bowel disease – ulcerative colitis Irritable bowel syndrome – IBS Clostridium difficile Colon Cancer Allergy Celiac disease (gluten) Diabetes – type I and II Obesity (Bacteroidetes/Firmicute ratios) Mental health and depression
How can we test faeces microbiota?
Take a DNA extraction, sequencing one of the genes encoded in bacterial genome that encodes for the 16s ribosomal RNA
What structural defences are present in the gut?
Seamless epithelium, tight junctions; High turnover
Describe the mechanical host defences of the gut
Peristalsis, chewing, fluid movement through gut, prevents pathogens adhering to gut
What biochemical defences are in the gut?
Gastric acid, bile, mucous are highly toxic to bacteria
What are the immunological defences of the gut?
Secretory IgA in lumen of mucosal surfaces binds to bacteria preventing epithelial binding, intraepithelial lymphocytes
What issues can be caused by microbes in the gut?
Spread of infections to the body
damage of barriers; pH change; overgrowth, AIDS
What are the benefits of the gut flora?
- Colonisation Resistance
- Metabolites produced of benefit to host
- Normal development of immunity
- Aids digestion
How is colonisation resistance beneficial to the gut?
- blocks pathogens
- gut full of commensals = hard for pathogens to get in,
reproduce & cause disease - Hard because niche taken up by commensals
What beneficial metabolites are produced in
Vit K, B12, organic acids
Enhanced utilisation of amino acids
Butyrate for colonocytes – maintain anaerobiosis
What is the effect of normal immunity development?
Increases tolerance; antigenic stimulation, Tregs, IL17
How does the gut flora aid digestion?
Fermentation of sugars (10% of energy released from colon);
Gas? H2 or methane; regulation of fat storage
What are probiotics?
organisms we think will contribute to a healthy biome
What are the functions of the probiotics?
Best probiotics produce lactic and organic acids
~10% absorbable energy from dietary fibre;
↑ diversity of polysaccharides for metabolism
Give examples of probiotics
Lactobacillus acidophilus,
Bifidobacteria - B.longum,
Bacteroides thetaiotaomicron
Some Streptococci
What are the clinical uses of probiotics?
Control of diarrhoea in infants
Relieve constipation
Improve digestion of lactose
What are prebiotics?
nutrients that alter the gut ecosystem
What is the role of prebiotics?
Encourage good microbes to grow e.g. breast milk - ‘bifidus factor’
certain oligosaccharides
e.g. fructooligosaccharides
fermented in colon by probiotic organisms
promotes growth of probiotes
What is a bacteriocin?
a protein produced by bacteria of one strain and active against those of a closely related strain
What is microbial antagonism?
When some organisms inhibit growth of other organism to limit growth of competitors and pathogens
e.g. bacteriocins
What causes a loss of flora?
bacterial / pathogen overgrowth
What disrupts the normal flora the most?
Certain antibiotics (e.g. ciprofloxacin) disrupt our microbiome more than others
What is the consequence of loss of flora due to antibiotics?
Leads to antibiotic associated colitis
as antibiotics reduce no. of gut flora and changed it => lead to overgrowth of clostridium difficile = pseudomembranous colitis
What is colitis?
inflammation of colon caused by introduction of antibiotics
Outline the effects of microbial antagonism
- Limits growth of competitors + pathogens
- Bacteriocins
- Reduced no. of available epithelial receptors
- Keeps pH low
- Controls oxidative potential (anaerobic growth)
- Limits pathogen growth
- Occupy all niches
- High numbers
- Waste products
What is gastroenteritis?
Acute syndrome characterised by generalised GI symptoms in any combination including:
- Nausea
- Vomiting
- Diarrhoea
- Abdominal discomfort
What is diarrhoea?
Watery / liquid stools, usually with an increase in stool weight above 200 g per day and an increase in daily stool frequency and often a sense of urgency
What are the clinical consequences of diarrhoea?
- severe dehydration, excessive fluid and electrolyte loss,
hypovolaemia; hypokalaemia; organ failure - long-term morbidity and reduced growth
What is dysentery?
Inflammatory disorder of GI Tract, usually large intestine; often associated with blood & pus (as penetrated natural barrier). As well as pain, fever and abdominal cramps
What is enterocolitis?
Inflammation involving mucosa of small and large intestine e.g. Crohn’s Disease
What is the impact of diarrhoeal diseases?
Many deaths a year (2 million)
Especially under 5’s (undergo multiple episodes a year) -> massive global health burdens (it is preventable)
What are the main causes of diarrhoeal diseases?
Infectious mciroorganisms e.g.
- Bacteria
- Viruses
- Parasites - protozoal and worms
How are diarrhoeal diseases spread?
infectious micro organisms shed in faeces and spread to new host (faecal-oral route)
What are the characteristic patterns of gut infections?
Acute watery diarrhoea
Dysentery = Acute / chronic diarrhoea + blood + pus
Poor Fat absorption = chronic diarrhoea / malabsorption
Infective proctitis : ano-rectal STIs
Which pathogen is responsible for travellers diarrhoea?
normally e. Coli
Explain how food poisoning occurs
Diarrhoea from eating food containing toxins or bacteria in food that grow inside us and produce toxins
Which patients are classed as immunocompromised hosts?
- AIDS patietnts
- immunosuppressed
- elderly or very young
What causes antibiotic related diarrhoea?
altered normal flora
What damage is caused by an infection of the GI tract?
Pharmacological
- action of bacterial toxins local or distant to site of
infection e.g. cholera
Local inflammation
- in response to superficial microbial invasion
e. g. Shigella dysentery or Campylobacter food-poisoning
Deep invasion
- to blood and lymphatics and dissemination of the
organism to other body sites – enteric fevers e.g.
Typhoid fever or Hepatitis A
Perforation/ulceration
- of mucosal epithelium peritonitis; intra-abdominal
abscess (e.g. Entamoeba)
What are the different mechanisms of diarrhoea?
Bacterial Toxins
Adherence
Penetration + invasion
Describe how bacterial toxins cause diarrhoea?
- Enterotoxins are toxins that affect the gut
- Exotoxins effect fluid/electrolyte transport by increasing
/ decreasing cAMP - Cytotoxins direct cell damage
How does pathogen adherence cause diarrhoea?
e.g. E. coli EPEC enteropathogenic adhere to cells below and damage epithelium
Explain how invasion and penetration by pathogens can lead to diarrhoeal disease
Disruption of tissue architecture and function
- enteroinvasive
Inflammation
What is the function of villus in the gut?
Main function is absorption
What is the role of crypts in the gut?
Mainly secretion
What are heat stable toxins?
Toxins that are not destroyed even when heated. If consumed, effects will prevail
What are heat liable toxins?
Heat-liable toxins are inactivated through cooking
Outline the mechanism of action of toxins in the villi causing diarrhoeal diseases
Affect electrolyte channels in the enterocytes by:
Heat labile toxin stimulate AC, causing cAMP to disregulate protein kinase → changes Cl- channel causing electrolyte imbalance and thus fluid balance
Similar with GC
Explain how mucosal injury can lead to diarrhoea
Virus / bacteria can penetrate into villi resulting in villous atrophy. There’s no absorptive capacity = anti-absorptive diarrhoea (malabsorption)
Why does damage to gut mucosal surface cause diarrhoea?
=> immediately get crypt hyperplasia to try replace villus; crypt tries to regenerate villus. At this time you get lots of secretion, so combination of atrophy and then high secretion = anti-absorptive diarrhoea, eventually recovering (takes up to 3 days)
What viruses cause gut disorders?
- Astrovirus (star)
- Calicivirus (Star of David)
- Rotavirus (wheel)
- Poliovirus (featureless)
- Norwalk SRSVs) Norovirus (ill defined lace-like
appearance)
Which properties of intestnal physiology are affected by the microbiome?
- Energy balance regulation + pathophysiology of obesity
- Modulates digestion + absorption
- ↑ energy harvesting
- Microbiome influenced by diet, antibiotics, surgery +
genes - Microbiome contributes to host metabolism + energy
homeostasis beyond nutritional processing e.g.
endocrine function and inflammatory signals
