Transcript File - Science With Miss C!

The Normal Microbiota
Natural Human Flora
• What organisms are part of
normal flora
• Where do they colonize
- microbial ecosystems
• How are they able to cause
disease?
- exposure
- virulence factors
MICROBIAL COMMUNITY COMPOSITION IN A
HEALTHY HUMANS
NATURE REVIEWS | MICROBIOLOGY
VOLUME 9 | APRIL 2011 | 279
Distribution of bacterial species along the gut
Stomach
• Streptococcus
Small bowel (ileum)
• Lactobacillus
• Streptococcus
• E. coli
• Clostridium
• Bacteroides
• Eubacterium
• Vellonella
Colon
Colon
• Bacteroides
Bacteroides
• Eubacterium
Eubacterium
Clostridium
• Clostridium
Ruminococcus
• Ruminoccus
Bifidobacterium
• Bifidobacteriu
Streptococcus
Lactobacillus
m
E. •coli
Streptococcus
non -E. coli coliformes
• Lactobacillus
• E. coli
>13 500 sequences 16S rRNA
Eckburg et al., 2005 Science
A healthy microflora regulates diverse biological
roles
Behavior
- alters host behavior through its
effects on the central nervous system
Metabolism
- supplies enzymatic activities not
encoded by host
- modifies bioavailability and
bioactivity
- can induce/reduce obesity & T2D
Protection
- develops local and systemic
immunity
- regulates tolerance, allergies &
homeostasis
Gut microbes are “inherited” maternally
In utero = sterile “germ free”
Maternal vaginal,
colonic & skin
microflora
Vaginal vs C-section
Antibiotics
Initial feedings
Birth: colonization begins
Environment & host
influence species
dominance
Developing
immune system
Adult microbiota: acquired by 2 yrs
Stable?
Stability could impart resilience to disturbance to ensure
continued gut function, but in a disease context, this could
be detrimental if the gut community is pathogenic.
Microbiota is variable between individuals but each individual
microbiota is stable
Species diversity profiling
of fecal adult microbiota
14 healthy adults
Zoetendahl et al. 1998
Seksik et al. 2003
Vanhoutte et al. 2004
The faecal microbiota is specific of individuals
Denaturing/thermal gradient gel electrophoresis separates DNA by
differing thermal stability; patterns reflect bacterial diversity
Once colonized your microflora is stable throughout life.
Factors can change the microbiota composition:
dysbiosis
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Stress: (O'Mahony, 2009)
Exercise: (Matsumoto, 2008)
Inflammation: (Lupp, 2007)
Old Age: (Biagi, 2010)
Diet:
• carbohydrate reduced(Walker, 2011); high fiber diets (De Filippo
2011); high-fat, high-sugar "Western" diet (Turnbaugh 2010);
calorie-restricted diets (Santacruz 2009); vegetarianism (Liszt K,
2009); alcohol consumption (Mutlu, 2009); high fat (Mozes,
2008)
Diseases associated with gut microbial dysbiosis
 Inflammatory Bowel Disease
 Type I and II Diabetes
 Irritable Bowel Syndrome
 Celiac’s Disease
 Autism?
Does dysbiosis cause disease?
Obesity-Associated Gut Microbiota Induces Adiposity
Microflora from an obese mouse
Microflora from a lean mouse
Mice + lean microflora = resistant to the fattening effects of
high fat diets, despite eating the same amount of food.
(Turnbaugh et al, 2006 Nature).
Reduced Microbiota Diversity
with Obesity
The microbiota
diversity is reduced
in obese subjects.
Turnbaugh et al. 2009, Nature 457:480-485.
A healthy microflora balances immunological
responses
Probiotics
Bifidobacteria isolated
from the intestine
www.livingfoodsusa.com/libr
ary/probiotic.html
Probiotics: Live microorganisms when administered in adequate amounts confer a
beneficial health effect on the host
Prebiotics: compounds that promote the growth of probiotics
 Can probiotics treat or prevent disease?
 Assumed to be a safe benign treatment
 All yogurts have at least two probiotics
• Lactobacillus bulgaricus
• Streptococcus thermophilus
• Opportunist infections
– Some microbes that are non-pathogenic in normal host
can produce severe life-threatening disease in
immunodeficient – may be normal flora components
(endogenous)
• Ex. Fungal pathogens;
• Infection with organisms of known pathogenicity
– Reactivation
• Ex. TB in AIDS patients
– Exogenous
• Pathogens which normally cause mild conditions can cause lifethreatening illness in immunodeficient
Causes of Immunodeficiency
• Disease or trauma
– Ex. HIV; neoplasia; burns; compromised clearance (ex.
cystic fibrosis, obstructed urine flow)
• Therapy
– Ex. steroids, chemotherapeutic cytotoxic agents,
radiotherapy, splenectomy; prosthetic devices; catheters
• Age
– Neonates (immature immune system)
– Elderly (decrease in immunity, malnutrition
Some Common Causes of Infection in
Immunocompromised Patients
Infectious Agent
Disease
E. Coli
Urinary infections, septicemia
Pseudomonas aeruginosa
Pneumonia, septicemia
M. Tuberculosis
Pulmonary, miliary TB
C. Difficile
Diarrhea, pseudomembranous
colitis
Candida
Thrush, systemic candidiasis
Cryptococcus neoformans
Meningoencephalitis
Clostridium difficile
• Present in less than 5% of people in their normal flora at very low numbers
• Can be “acquired” through community or hospital
• Antibiotic use (particularly broad spectrum) causes disruption of normal flora →
overgrowth of C. difficile → C. difficile produces exotoxins →
– Diarrhea
– Characteristic fibrinous pseudomembrane covers colonic mucosa (hence the
name “pseudomembranous colitis”)
• Treatment: metronidazole or oral vancomycin (resistance has emerged)
• Oral fecal bacterial therapy has been successful
C. difficile is acquired the hospital: patients are exposed through contact
with the hospital environment or health care workers. After antibiotictreatment they can develop infection but only if the strain is toxigenic and
they fail to produce IgG responses.
• Bioterrorism = intentional or threatened use of
viruses, bacteria, fungi, or toxins from living
organisms to produce death or disease in humans,
animals, and plants
– Agent chosen for mass casualties
• Biocrime: agent chosen as a means for a localized
attack
• Characteristics that favour use of particular agent:
– Invisible, odourless, tasteless
– Difficult to detect
– Take hours or days before awareness that they have
been used
Examples of Intentional Uses of Biological Agents for Criminal or
Terror Intent
• 1984 in Dalles, Oregon
– Salmonella typhimurium in 10 restaurant salad bars
• 1996 in Texas
– Intentional release of Shigella dysentariae in a
hospital lab break room
• 2001 in seven eastern U.S. states
– Use of weaponized Bacillus anthracis spores delivered
through U.S. postal systems
– 22 infected persons
– Five deaths
Agents Considered a High Priority
Threat
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Yersinia pestis
Francisella tularensis
Small pox
Bacillus anthracis
Botulinum toxin
Exotic viruses (ex. Ebola, Marburg)
Genetically modified organisms