Micro Exam 4

Our resident microbiota…

the human microbiome, colonizes us for the long term and does not generally cause disease

Holobiont

a human plus all resident microbiota

Hygiene hypothesis

• antibiotics & lifestyle that ↓ microbial exposure predisposes people to autoimmune disease

• antibiotics disturb microbiota and, thus, the co- evolutionary relationship between our immune system and the symbionts we host

Normal flora

• Large and diverse collection of microbes living on and in the body

• Also known as resident or indigenous biota

• Include an array of bacteria, fungi, protozoa, and viruses

• organisms have a profound effect on human biology

Human cells contain 21,000 protein-encoding genes; microbes that inhabit humans contain

8-20 million genes

All healthy people harbor potentially dangerous pathogens, but

in low numbers

The Human Microbiome Project

• Composition of the host microbiome impacts the success of viral infections like influenza and HIV

• The gut microbiome can influence many aspects of human health

• The human microbiome influences the effectiveness of anticancer treatments and other treatments directed at the host

Sites Definitively Known to Harbor Normal Microbiota:

• Skin and adjacent mucous membranes

• Upper respiratory tract

• Gastrointestinal tract, including mouth

• Outer portion of urethra, bladder, and urine

• External genitalia

• Vagina

• External ear canal

• External eye (lids and conjunctiva)

• Breast milk

Additional Sites Now Thought to Harbor At Least Some Normal Microbiota (or Their DNA)

• Lungs (lower respiratory tract)

• Placenta, amniotic fluid, and fetus

Sites in Which DNA From Microbiota Has Been Detected

• Brain

• Bloodstream

Benefits of normal biota:

• Influence the development of organs

• Prevent the overgrowth of harmful microorganisms

Microbial antagonism

• The general antagonistic effect “good” microbes have against intruder microorganisms

• Microbes in a steady, established relationship are unlikely to be displaced by incoming microbes

A growing number of doctors and scientists believe fetuses are seeded with normal microbiota __ ______

in utero

We know exposure occurs during birth when the baby becomes colonized with the mother’s ________ biota

vaginal

Breast milk contains around ____ species of bacteria and ________ that babies cannot digest

600

sugars

Breast milk contains around 600 species of bacteria and sugars that babies cannot digest

• Sugars used by healthy gut bacteria

• Breast milk may be necessary for maintaining a healthy gut microbiome in the baby

• Intestinal flora starts w/ E. coli & Streptococci

• becomes primarily:

bifido bacterium

lacto bacillus

Breastmilk produces…

>200 different oligosaccharides (vary in conc. & content) = complex & dynamic

_______can’t imitate breastmilk

formula

Research: Identified 2…

oligosaccharides and incorporated into formula

Beneficial Properties of Bifidobacterium & Lactobacillus (adults & babies)

• maintain the normal intestinal balance

• improve lactose tolerance

• antitumorigenic activity

• reduce serum cholesterol levels

• promotes calcium absorption

• synthesis of B complex vitamins

• reduce or prevent the excretion of rotaviruses

Probiotics

• oral administration

• living microorganisms

• promote health and reestablish natural balance

• host specific

Prebiotics

nondigestible dietary fiber (inulin

promotes growth of probiotics)

probiotic microorganisms:

– Maintain desirable microbial community

– Stabilize gut barriers

– Produce of inhibitory substances

– Stimulate immune response

Attributes of probiotic bacteria:

• Nonpathogenic

• No toxin produced

• Effective

• Easily cultured

• Withstand acid & bile

Industry standards:

• Easy to produce in high conc.

• No off flavors

• Must retain function during manufacture, transport, storage

Good sources of prebiotics

(inulin, pectin, fiber): onions, garlic, leeks, apples,

bananas, cocoa, flaxseed, bran, oats

Skin

• Most diverse part of the body & has 3 distinct microbiomes: 1) moist, 2) oily, 3) dry

• periodic drying

skin: slightly acidic pH (~____) – bacterial metabolism releases acids

6.5

sweat =

high [salt] that causes osmotic stress

lysozyme

breaks β 1-4 linkages between NAG & NAM

P. acnes (protective strains) on normal skin:

produces protective thiopeptides which block other gram + bacteria

Oil Glands

secrete complex lipids → partially degraded by the enzymes from certain gram + bacteria (Propionibacterium acnes) =

▪↑ [oil] during puberty

▪Oil metabolized into volatile fatty acids

▪↑ skin inflammation =Acne Treatment: skin probiotics

very limited flora =

nonpathogenic Corynebacteria sp. & Staphylococcus epidermidis

• blinking, tears, lysozyme

Eye current view

– All exposed mucosal surfaces populated

– Many difficult to culture

– Huge variation of bacteria on eye

eye during infection

see a ↓ in bacterial diversity and see an ↑ in Pseudomonas sp. = indicator/diagnostic for infection

Outer ear

Populated w/ bacteria often seen on the skin (Staphylococcus, Streptococcus)

Middle ear

P. aeruginosa causes swimmer’s ea

Middle ear infection: ↑bacteria & fluids=

pressure & pain

In adults there exists a bend in the Eustachian tube =

Protects against bacteria from the throat (nasopharynx)

Mouth

• Large pop with many different microbiomes: roof, teeth, gums, tongue

mouth: organisms survive mechanical removal by ________

adhering

Saliva (~109 bacteria/ml)

Streptococci, Staphylococci, Neisseria, Lactobacilli, several fungi & protozoans

mouth wipe out normal flora w/ antibiotics =

candidiasis

mouth Structure of microbiome is not random but

layered

Structure of microbiome is not random but layered

– Streptococcus sp. form 1st layer

– biofilm formation

a community of bacteria that excrete a sticky matrix for attachment and persistence (antibiotic resistant)

biofilm formation

Streptococcus sp.=

dental plaque, dental caries, gingivitis, periodontal disease

upper RT

flora similar to oral cavity (Streptococci)

historically lungs considered sterile:

– continuous stream of mucus generated by ciliated epithelial cells (ciliary escalator)

– phagocytic action of alveolar macrophages

– lysozyme in mucus

IgA

IgA protein

Antibody- specific immune response protein- found in all body secretions) = Ab protects epithelial layer

now know lung also populated by low conc. of bacteria in patches or islands

lungs coated w/ surfactant = allows movement of lungs & acts as antimicrobial peptides (AMPs)

Human Papilloma Virus (HPV):Lifetime risk of HPV infection is >__% & causes

50

Lifetime risk of HPV infection is >50% & causes:

• ano-genital warts

• cervical cancer

• 83%–95% of anal cancers

• 20%–50% of vulvar cancers

• 60%–65% of vaginal cancers

• 30%–42% of penile cancers

• spread by ____ ______even when symptoms are absent

skin contact

recurrent respiratory papillomatosus (RRP):

– causes airway obstruction→ requires frequent laser excision to remove tumors → often leads to tracheostomy & loss of ability to speak

– spread to distal airways & malignancy often fatal

HPV can be spread to the baby during childbirth resulting in

recurrent respiratory papillomatosus

Gardasil 9 – HPV Vaccine

• ~200 HPV strains (~40 infect the genital tract)

• virus-like particles (VLPs) of purified L1 protein of HPV

• types 6,11 responsible for ~ 90% genital warts

• types 16,18 (~70% cancers) 31, 33, 45, 52 & 58

(~90%cancers)

• L1 proteins produced by Saccharomyces cerevisiae fermentation & self-assemble into VLPs

• VLPs are released by yeast cell disruption and then adsorbed onto an aluminum-containing adjuvant

Gardasil 9 Induces __________ antibodies that prevent virus attachment

neutralizes

Gardasil Vaccine

3 intramuscular doses at 0, 2, & 6 months

Genitourinary tract

female genital tract

▪ complex microbiota in a state of flux due to menstrual cycle (change in hormones & blood flow)

▪ acid-tolerant lactobacillus predominate

▪ estrogen stimulates glycogen production → glycogen is then used by Lactobacillus to produce lactic acid = ↓ pH (~pH 5)

▪ preterm babies see ↓ Lactobacillus sp. & ↑ bacterial diversity

▪ sexually active= share NF with partner

Genitourinary tract low pH/acid =

prevents Candida albicans growth

Bladder infections occur predominantly in women. Why?

the structural anatomy

Large Intestine (colon)

• largets microbial population of body

– eliminated by 1) peristalsis, 2) desquamation,

and 3) movement of mucus

– replaced rapidly due to high reproductive rat

Self regulating:

– Obligate anaerobes >90% of resident flora = Bacteroides, Bifidobacterium, Fusobacterium, Clostridium perfringens

– facultative anaerobes such as Escherichia coli, Enterococci, yeasts, viruses also present