Lecture 33: Introduction to the human microbiota and barriers to infection

microorganisms are present on almost all of our body surfaces which are collectively called the microbiome

what is the microbiota?

groups of micro-organisms living in a specific environment

• develops at birth

• usually not harmful and are needed for health

• each individuals microbiota is unique depending on their age, diet, lifetyle

what are indigenous human commensals?

• bacteria that naturally lives inside the human body without causing any harm

• beneficial for bacteria and the host

• provides some protection against pathogens (no space for pathogens to grow)

what is the gut microbiome used for?

• essential for breakdown of our food

• synthesise essential vitamins B12 and k

• research suggests its also involved in obesity, allergies, mental health and immune disorders

how can indigenous human commensals act as opportunistic pathogens? give examples

can cause harm when disturbed, all only cause harm during these conditions

• Burns patient: Pseudomonus aeruginosa

• colonic bacteria: UTI, E.coli (gram -ve)

• skin flora: wound infection- staphylococcus sp. (gram +ve)

• oral flora: tooth decay- streptococcus sp.(gram +ve)(bacteria imbalance in mouth)

how is the human microbiota involved in the skin?

3 microenvironments:

• dry skin(arms and legs)

• moist skin(armpits)

• areas rich in sebaceous glands

more moist = more bacteria

• thick peptidoglycan wall making it resistant to drying

They have natural G+ colonisers of bacteria

• staphylococcus and streptococcus

• don’t usually cause disease but skin wound can lead to infection (staphylococcus aureus)

what is MRSA?

Methicillin-resistant staphylococcus aureus

• antibiotic resistant

how is the microbiota involved in the upper respiratory tract?

Nose and throat

• moist and aerobic so it has extensive bacterial flora(lots of natural colonisers)

Natural colonisers:

• streptococcus and staphylococcus

Streptococcus pneumoniae and others are usually found in the back of the throat and dont cause problems but can cause bacterial meningitis

how is the microbiota involved in the lower respiratory tract?

Lungs

• usually sterile and we dont want bacteria there

• common site of infection

• streptococcus can cause pneumonia

• mycobacterium tuberculosis can cause tuberculosis

• most common infections here

how is the microbiota involved in the mouth(oral cavity)?

complex microbial ecosystem LOTS of bacteria

• Gingival groove(teeth+gums)- anaerobes - cause gum disease

• Tooth enamel- facultative aerobes - some cause plaque and tooth decay - Streptococcus

• cheeks and gums- facultative aerobes - some colonise saliva - Streptococcus(microaerophile)

how is the microbiota involved in the digestive system?

STOMACH: least amount of bacteria

• Acidic with lots of enzymes

• helicobacter pylori lives in acidic conditions and causes stomach ulcers

SMALL INTESTINE:

• duodenum has less bacteria as still acidic with enzymes

• illeum less acidic with more bacteria

LARGE INTESTINE:

• microbiome exists here

• gram +ve and -ve

• anaerobes and facultative anaerobes

• Enterococcus faecalis causes bloodstream infections

• has E COLI

how is the microbiota involved in the urinary tract?

• kidneys, ureters and bladder are usually sterile as it can cause kidney infections

• urethra is lighyl colonised by staphylococcus epidermidis

  • frequent site of UTI infections due to Escherichia coli

how is the microbiota involved in the adult female genital tract?

• complex microbiota

• depends on age, childbirth, menopause and menstrual cycle

• usually acidic

• Lactobacillus stops other infections growing

• Candida albicans is a yeast which when overgrown needs antibiotics(thrush)

what are the non-specific defences against infection

• indigenous microbiota

• barriers: skin, mucosal surface, blood and tissues

commensals: the pathogen must compete with natural microflora for adhesion sites and food

what can be taken to support gut microbes?

PROBIOTICS:

• live microorganisms that prevent/treat conditions

• recolonise good bacteria

PREBIOTICS:

• chemicals that induce growth/activity of microorganisms

• promote health

both havent undergone clinical trials and are sold as food supplements

how is the epidermis a defence of the skin?

• physical barrier

• dry, acididc

• shedding cells to prevent bacteria that penetrate to get further

• indigenous bacteria therefore less colonisation

how is the sweat gland a defence of the skin?

• has lysozyme

how is the sebaceous gland a defence of the skin?

(associated with hair follicles)

• lysozyme breaks down peptidoglycan cell wall and gram +ve cell walls in bacteria

how is the skin associated lymphoid tissue(SALT) a defence of the skin?

• induces local inflammatory response

How is mucus a defence of the mucosal surfaces?

• traps bacteria

• produces mucin

• lysozyme kills G +ve bacteria

• lactoferrin binds to iron and moves free iron around so bacteria wont use it

• lactoperoxidase kills bacteria

How is epithelium a defence of the mucosal surfaces?

• physicaly barrier

• shedding cells

• cilia

• indigenous bacteria decreases colonisation

How is mucosal associated lymphoid tissue(MALT) a defence of the mucosal surfaces?

• induces local inflammatory response if bacteria gets that far

what are all the barriers to infection

Trachea

Lungs

digestive tract

genital tract

eyes

skin

blood and lymph

stomach

urinary tract

what are the non specific defences of the blood and tissue?

what cells do phagocytosis and what happens during?

Monocytes, Macrophages and Neutrophils

1. bacteria is identified and it adheres

2. bacteria is ingested and then lysozyme fuses with the vesicle and forms a phagolysosome

3. bacteria is digested and then discharged

what do lysosomes contain?

• digestive enzymes

• defensins

• enzymes of respiratory burst

what is the complement system?

• a biochemical cascaed involving more than 30 proteins in the blood and tissues which is activated following infection

• Destroy pathogens (e.g., bacteria, viruses)

• Mark pathogens for destruction (opsonization)

• Recruit immune cells to sites of infection (inflammation)

• Help antibodies and phagocytic cells clear microbes and damaged cells

what is mannose binding lectin?

• a soluble factor produced following infection by the liver

• it binds to patterns on microbial surfaces not specific antigens( structures it recognises )

• increases complement activation and increases opsonisation

• positive feedback

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