Week Three Lecture 6: Normal Human Microbiota: A dlicate Balence Of Power

Colonization

• is the ability of a microorganism to affix itself to a host surface or an environmental habitat, where it can then replicate

  • Certain microbes colonize certain body environments

  • Where they colonize depends on their ability to survive in different environmental conditions

the human microbiome or microbiota (areas)

All the bacteria, archaea, fungi, and protozoa that inhabit our bodies

• Microbes and their human hosts “talk” to each other through chemical signals, including hormones

• These chemical signals alter the gene expression and physiology of microbes

How and When Do We Become Colonized By Microbes?

• Either in the womb or at the time of birth

  • The placenta may not be sterile but this is debated

Exposure to microbes in your environment leads to the formation

• of a microbiome

• Exposure to microbes continues to happen throughout our lives, which alters our microbiomes constantly

• Our microbiomes can become “dysregulated” and cause disease!

Our microbiome is critically important to our health

• Sometimes called a “virtual organ system”

• Directly influences which microbes can cause infection at certain body sites

• The presence of some microbes in our microbiome prevent other microbes from colonizing 

  • “Good Bacteria vs Bad Bacteria”

 Human Microbiota: Location and Shifting Composition: Certain body regions are typically sterile

• Cerebral spinal fluid

• Blood

• Some organs

Other body regions have diverse and robust microbiomes

Areas of our body that have high exposure to the outside environment typically have

heavily populated microbiomes

Some of the organisms in our microbiomes are also potential pathogens

antagonism

Some microbes purposely prevent the ability of pathogens to infect body systems

Microbiome can be changed by

• Changes in diet

• Changes in stress levels

• Antimicrobial treatments

• Exposure to animals and other humans

Skin Microbiome

• The average human adult has over 2 square meters of skin (epidermis) populated by 10¹² microorganisms. 

• Areas may be dry, moist, salty, or acidic.

  • This makes it difficult for some organisms to colonize the skin

  • Many are Gram-positive because they are more resistant to drying and salt

• Skin has an acidic pH due to organic acid secretions by sweat glands that inhibit some microbial growth

• The skin harbors persistently colonizing (normal) and transient colonizing microbiota

The eye microbiome

• Eyes produce antimicrobial factors like lysozyme, but are colonized by many types of bacteria.

• mostly transient microbiome

Nasopharynx

the area from the nose to oral cavity

Oropharynx

the area between the soft palate and the upper edge of the epiglottis

The Oral microbiome

• Within hours of birth, a human infant’s mouth is colonized with non pathogenic Neisseria species, Streptococcus, Actinomyces, Lactobacillus, and some yeasts.

• These organisms come from the surrounding environment such as the mother’s skin and garments.

  • It's been theorized that babies delivered vaginally have vastly different initial microbiomes compared to babies delivered by C-section

teeth microbiome

• As teeth emerge, anaerobes such as Prevotella and Fusobacterium colonize.

• Streptococcus mutans and Streptococcus salivarius form a glycocalyx that firmly adheres them to the oral surfaces and each other.

  • These organisms secrete acid that demineralize and dissolve tooth enamel

Most of the oral microbiota are

harmless

• Dental procedures may permit bacteria to enter blood vessels and be transported to the heart, where they grow vegetations that cause symptoms of subacute bacterial endocarditis. 

  • Caused by bacteremia – presence of bacteria in the bloodstream

the respiratory tract microbiome

• Many organisms that enter the nasopharynx are trapped in the nose cilia and don’t make it to the trachea 

• Microorganisms that make it into the trachea are trapped by mucus produced by the ciliated lining of the airway. 

• The ciliated mucous lining of the trachea, bronchi, and bronchioles makes up the mucociliary escalator, which sweeps foreign particles up and out of the lungs.

• The lung microbiome can contribute to the development of lung mucosal immunity, or add to the severity of chronic airway diseases

The Stomach microbiome

• Stomach contents are acidic, which is lethal to bacteria.

• The mucous lining of the stomach is less acidic and supports the growth of Helicobacter pylori.

• In most of the population Helicobacter pylori is harmless. 

  • Thought to colonize over half of the world’s population in the stomach

• H. pylori may incite inflammation of the stomach epithelium, causing gastritis or gastric ulcers.

the intestine microbiome

• Normal human intestine has 10¹¹–10¹³ bacteria per gram of feces.

• Populated by anaerobes and facultative anaerobes (1000 to 1 ratio)

Different areas of the intestines are ideal for different microbial species because each section have unique environmental factors

• Jejunum: slightly alkaline from secretions of the pancreas and gallbladder (bile)

• Ileum and cecum: slightly acidic, less bile

• Colon slightly acidic

• The intestine is anaerobic because the organisms in this environment utilize all of the available oxygen quickly

Gastrointestinal tract microbiota is

• very diverse

• Most resident organisms present in the intestines are harmless if they stay where they belong

Functions of the gut microbiota

• Ferment unused energy substrates

• Train the immune system

• Prevent growth of pathogenic bacteria

• Regulate the development of the gut

• Produce vitamins for the host

• Produce hormones to direct the host to store fats

is there link to gut microbiome and obesity

there has been some studies yes

Genitourinary Tract microbiome

• considered to be sterile

  • Kidneys

  • Ureters

• Bladder is not sterile

  • Has its own microbiota

  • Can be introduced to foreign organisms by catheters

• vaginal tract is heavily colonized

  • Very acidic environment

  • Increase of pH can lead to infection, Male genital tract also has a unique microbiome

Benefits of a Microbiome

• Members of our microbiota are often beneficial (mutualistic) and help in the following ways.

  • Digesting food

  • Synthesizing compounds (such as vitamins)

  • Interfering with colonization by pathogens by 

    • competing for attachment sites

    • competing for food sources

    • synthesizing antimicrobial compounds

raining and enhancing function of the immune system by producing

• Immunomodulins that modify the secretion of cytokines

  • Immunomodulins are bacterial proteins made by organisms growing on mucosal surfaces to influence the immune response of the host

Benefits of a Microbiome?

• double-sided

  • Enterotoxins produced by some Gram-negative pathogens damage the small intestine of the host and cause diarrhea.

Enterotoxins

may also protect against colorectal cancer by activating membrane calcium channels in intestinal epithelial cells. Increasing calcium transport turns on an antiproliferative pathway that slows cell division.

Risks of a Microbiome

• Microbiota may escape from their niche and cause infection and disease.

Opportunistic pathogens among the microbiota cause disease in

• immunocompromised hosts.

  • Opportunistic pathogens rarely cause disease in healthy hosts

• Compounded by acquired antibiotic resistance

  • The older we are, the more likely it is that some organisms in our microbiome have developed antibiotic resistance

Microbiome Dysbiosis

• occurs when the balance of members of the gut microbiome is altered. 

  • Dysbiosis is now thought to be the cause of some human diseases

  • C. difficile can grow unabated when dysbiosis happens, going from a harmless microbiota member to a serious infection risk!

• Infections, antibiotics, new foods, and emotional stress can all produce dysbiosis.

Probiotics

• are thought to restore balance to the microbial community and return the host to good health.

• New treatment available called fecal microbiota transplant (FMT)

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