Lecture 13- Lec 12 Part 2 Flashcards
Lower GIT
Comprises of small + large intestine; segment of the GI tract from the jejunum (just after the duodenum- start of small intestine) to the anus
Upper GI- involved in transport, protection, mechanical + enzymatic digestion
Lower GI; digestion, absorption, defecation + protection; slide 4
Microbiome
99% of gut= anaerobic
Anaerobic bacteria= use fermentation to break down indigestible fibres + produce nutrients
Recovery of host microbiome post stomach acid
Exposure to bile, stomach acid is neutralised
1.pH through the GIT becomes more hospitable
2.O2 levels drop as the GI tract progresses
3.Bacterial cell numbers start to recover
Mucus membranes + microbiota
Discrete bacterial communities can develop in niche microhabitats; gut lumen, colon mucosal layers + colon crypts
Bacterial community dependent on= oxygen conc, pH, antimicrobial peptides + nutrient sources available
Factors affecting gut microbiome composition
Gut microbiome constantly adapts due to genetic + external/environmental pressures
Age= factor in early years (most gram +), later life becomes gram - rods
Usually= baseline state, can change in response to= illness, meds, emotional stress, diet etc
Competition by commensal microbes
Slide 9
Offers protection;
-can restrict colonisation by pathogens through competitive exclusion
-some members also produce antimicrobial agents that inhibit growth of pathogens
Mucus + production of antimicrobial agents
Gut mucosal epithelial cells= secrete a wide range of antimicrobial agents
Gut= paneth cells- found in intestinal crypts produce granules which contain
-lysozyme= breaks down PDG
-phospholipase= phospholipase by layer in membranes
-lectins= bind to carbs, pore forming in bacteria
-defensins= small antimicrobial peptides, defend stem cells which replicate to form new villi
Gut Associated Lymphoid Tissue (GALT)
Gut mucosa= hosts the body’s largest population of immune cells
Dendritic cells in GALT= sample the intestinal contents for pathogens
DC= use dendrites to pass through the M cell + sample bacteria/antigens for PAMPs
Method; slide 11
Exclusion zone for host to maintain control
Work in conjunction with mucus to provide a bacterial “exclusion zone”. Physical separation of the small intestine surfaces + the gut microbiome
Exclusion zone not present?
- higher rates of infection + cancers due to constant inflammation
- no appropriate control
Bacterial killing by antimicrobial peptides
Defensins; host defence peptides (20-50 AA in size)
- kill bacteria entering crypts to protect stem cells + epithelium and avoid infection
Campylobacter jejuni
Opportunistic foodborne pathogen
Spiral spirochete shaped; may become coccoid under stress
Gram -
Facultative intracellular pathogen
Colonises the intestinal mucosa
Transmission- C. Jejuni
Zoonotic infection- transmitted to humans by animals
Main route of C.jejuni transmission raw/undercooked poultry
Other routes; pork, beef, contaminated water
Chickens intestinal microbiome; produces little-no clinical observations in poultry
Post slaughter;
Cross-contamination in the kitchen can be a problem
Direct (faecal-oral route) / indirect transmission
Mechanism of infection- C. Jejuni
Mechanism of infection- not understood. Surface of C.jejuni helps to evade host defences
Evasion of host defences;
- Lipooligosaccharide (LOS)= glycolipid vital for integrity of the outer membrane + resistance to bile salts. Can display molecular mimicry of host structures
- Capsule; a polysaccharide coat that may mask underlying antigens + confer resistance to phagocytosis + other innate defences
- Protein glycosylation; adds carbs moiety to a protein
- may mask bacterial antigen. Hides them from immune cells
Mechanism of infection- C.jejuni
Flagella; role in motility, adhesion & protein injection into host cells
Adhesions; outer membrane proteins- mediate attachment to epithelial cells
Protein secretion systems- flagella mediated- cell cytoskeleton rearrangement
Iron acquisition systems
Production of cytolethal distending toxin
Cytholethal distending toxin (CDT) damages the human intestine
CDT holotoxin- 3x subunits, CdtA, CdtB + CdtC; CdtB= effector
CdtA+ CdtC= bind a host cell receptor mediating entry via clathrin-coated pits= formation of vesicle
CdtB -> transits to the nucleus = causes double-strand DNA breaks + cell cycle arrest= human cell death
Infection in humans; Campylobacteriosis
Incubation period; 2-5 days after ingestion
-small + large intestines colonised
Inflammatory diarrhoea, haemorrhagic
Fever, nausea, abdominal cramps + pain= symptoms
Self limiting + symps last 5-7 days
Intestinal ulceration + perforation observed sometimes
Enrichment + detection of campylobacteriosis + treatment
Relies on collection of a faecal sample
Enrichment media may contain;
-ferrous sulphate, sodium metabisulphate + sodium pyruvate= quench toxic compounds + increase aero tolerance
-lysed horse blood= quench oxygen + provide a source of iron
Antibiotics; vancomycin, cefoperazone + trimethoprim
Identification; API, DNA sequencing
Treatment;
-self limiting
-antibiotics= erythromycin- (a macrolide)- shortens the duration of symptoms if given early
-quinolone antibiotics; ciprofloxacin/levofloxacin= no longer as effective owing to resistance
-dehydrated patients= IV + electrolyte therapy
Salmonella
Typhoidal; causes typhoid fever
Non-typhoidal; self-limiting gastroenteritis in immunocompetent individuals- food poisoning
Difference= NT salmonella doesn’t cause sepsis like TS because NTS infections are usually confined to the intestines whereas TS infections spread throughout the body
Slides 29-37
Clostridioides difficile
Slides 37-44
Fungal infections of the lower GI tract
Fungi makes up 1-2% of the intestinal microbiome- essential for digestion + protection
Reasons for fungal GI infections; immunocompromised host, antibiotic use, diet= overgrowth of fungi in the gut
Blood stream infection can result in; sepsis, septic shock + death
Obesity with bacteria
Gut microbiome from lean humans can offer protection against body fat gain in experimental mice
Slide 46
Listeria monocytogenes
Gram +
Facultative anaerobe
Psychrophile
Can cross the placental, intestinal + blood-brain barrier
Transmission;
Found in soil, water + animal digestive tracts
Bacteria can contaminate food during harvesting, processing, prep, packing, transportation or storage
Common routes;
Eating contaminated foods, mother-child transmission, pets etc
Infection in humans- listeriosis
Incubation period of 7-70 days after ingestion
Mild fever+ diarrhoea in immunocompetent pts
Self limiting + symptoms rarely diagnosed- can last days-weeks
Extra intestinal invasion in preg women
Complications of listeriosis
1- extra-intestinal spread can occur in immunocompromised-deficient patients= sepsis, meningitis, convulsions, muscle ache, loss of balance + fever
2- can migrate across the placenta- loss of the unborn foetus, pre-term labour, infection of newborn etc
Treatment=
-self limiting
Antibiotics= ampicillin, gentamicin= administered early for those with complications
Dehydrated pts= IV + electrolyte therapy
Monitor unborn child
