Introduction to Human Microbiome

Human Microbiome Introduction

• The human microbiome is a complex ecosystem made up of all microorganisms residing on and within human tissues and biofluids, including their associated anatomical locations.

Terminology

• Microflora: An outdated term, originally used when only two kingdoms (Animalia and Planta) were recognized. Microbiomes were classified under Planta.
• Microbiota: Refers to the total number of microorganisms found in a specific area.
• Microbiome: Encompasses the genomes of microbiota. This term is used when examining microbial genomes.
• Metagenomics: Involves the direct study of genetic material obtained from microbial communities. This approach analyzes the collective DNA of multiple microbes within a sample.

Interesting Facts

• The intestinal microbiota boasts roughly 3.3 million genes, significantly exceeding the 22,000 genes found in the human genome.
• Genetic similarity among humans is high, at 99.9%. However, the human microbiome exhibits significant individual variation, with differences between individuals' intestinal and skin microbiome ranging from 80-90%.
• The prevalence of specific microbes varies across body locations. E. coli is typically found in the gut of healthy individuals, while Staphylococcus epidermitis colonizes the skin.

Classification of Microbiota

• Resident (or constant) microbiota: Refers to fixed types of microorganisms consistently found in a specific area at a particular age.
• Transient microbiota (or facultative): Non-pathogenic or potentially pathogenic microorganisms that temporarily inhabit the skin or mucous membranes for hours, days, or weeks. These microbes transit through a specific region and reside there for a short time.

Ecological Niches

• Each ecological niche on the human body is defined by a distinct location with a characteristic group of microbes.
• The variety of microbial species differs significantly between different areas of the body.
• An adult body harbors approximately 10¹³ bacteria, with 350 species identified in the large intestine.
• Ecological niche formation is influenced by two factors:
  • Bacterial adherence: Adhesins help bacteria overcome barriers like saliva, food chewing, gastrointestinal juices, and intestinal peristalsis.
  • Environmental conditions: Factors like oxygen levels, humidity, nutrients, temperature, and pH play a role.

Microbiota Imbalance and Disease

• Disruptions in the microbial balance within specific regions of the body can contribute to disease development.
  • Example 1: Changes in the oral microbiome can lead to dental caries (tooth decay).
  • Example 2: Alterations in the skin microbiome have been linked to ectopic dermatitis (a skin condition).

Fetal Sterility and Colonization

• The fetus is sterile, meaning it has no resident microorganisms before birth.
• Colonization of newborns begins during delivery:
  • Within 4-12 hours: Nonhemolytic bacteria, including Viridian streptococci, become the first colonizers.
  • Within 24-48 hours: The intestinal tract microbiota develops, introducing microbes like Lactobacillus, Bifidobacterium spp., and coliform bacteria.

Maternal and Postnatal Factors Influencing Microbiota

• Maternal factors: Can impact the newborn's microbiota:
  • Gut microbiota of the mother
  • Vaginal infections
  • Periodontitis (gum disease)
• Postnatal factors: Influence microbiota after birth:
  • Antibiotics
  • Breast-feeding
  • Host genetics
  • Environment
  • Diet (especially crucial after the first year of life).

Interaction of Microorganisms and the Host

• Microbes can interact with the host in various ways:
  • Transient colonization: Microbes temporarily inhabit the host.
  • Permanent colonization: Microbes establish a permanent presence.
  • Disease production: If the interaction becomes pathogenic, disease can occur.
• Disease arises when microbial interactions with the host cause damage, characterized by harmful processes within the human body.

Causative Agents of Infectious Diseases

• Strict pathogens: Microorganisms always associated with human diseases:
  • Mycobacterium tuberculosis
  • Neisseria gonorrhoeae
  • Francisella tularensis
  • Plasmodium spp.
  • Rhabdovirus
• Opportunistic pathogens: Microbes that are usually part of the normal microbiota. These organisms typically don't cause disease in their usual location but can become pathogenic when introduced into unprotected areas like the bloodstream or tissues.
  • Staphylococcus aureus
  • Escherichia coli
  • Candida albicans

Risk Factors for Opportunistic Infections

• These factors increase susceptibility to opportunistic infections:
  • Immunodeficiency
  • Chronic diseases (e.g., diabetes)
  • Gastric ulcers
  • Stress
  • Antibacterial treatment
  • Malnutrition
  • Avitaminosis (vitamin deficiency).

Skin Microbiota

• Transient microbiota: Found on the surface of the skin.
• Resident microbiota: Constantly present in deeper layers of the skin.
• Approximate microbial density: 10³-10⁴ microbes per square centimeter.
• Common residents include:
  • Staphylococcus epidermidis (about 90% of the population)
  • Corynebacterium
  • Cutibacterium acnes
  • Malassezia
  • Candida

Factors Influencing Skin Microbiota

• Detergents: Temporarily decrease transient and superficial resident microbiota by 90%, but recolonization happens within 8 hours.
• Disinfectants: Can kill resident microbiota.
• Sex: Affects skin microbiota composition.
• Age: Microbiota changes with age.
• Climate: Geographical location has an influence.
• UV rays: Exposure to UV radiation can alter skin microbiota.
• Hygiene: Levels of hygiene impact microbial abundance and types.
• Profession: Certain occupations can expose individuals to specific microbes.
• Diseases: Diseases can influence skin microbiota.

Skin as a Defense Barrier

• Intact skin serves as the first line of defense against microbial invasion. Its dryness is generally unfavorable for microbial growth, but it also provides nutrients through:
  • Sweat glands:
    • Eccrine glands secrete sweat.
    • Apocrine glands secrete sweat and nutrients. They become more active after puberty.
    • Sweat secretions include:
      • Lysozyme: Cleaves the bond between N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM) in peptidoglycan, weakening bacterial cell walls.
      • Lactic acid: Lowers pH to 3-5, creating an environment unfavorable for microbial growth.
  • Sebaceous glands: Connected to hair follicles.
    • Secrete sebum (skin oil).
    • Microbes can multiply to densities of up to 10⁶ per square centimeter.

Skin Mycobiome

• Refers to the fungal species inhabiting the skin.
• Fungi make up around 30% of the skin microbiota, with Malassezia strains comprising the majority:
  • M. globosa
  • M. restricta
  • M. furfur
  • Others
• Malassezia species represent more than 90% of the fungal population in most skin niches.
• The role of Malassezia remains controversial, as it has been linked to both healthy skin and conditions like dandruff and eczema.

Human Virome

• Encompasses all the viruses found in or on human organs, including the skin.
• Human stool contains at least 10⁹ virus-like particles (VLPs) per gram.
• Bacteriophages constitute 96.1% of human gut viral populations.
• The human virome potentially influences human health, not just disease.

Microbiota of Nasopharynx and Oropharynx

• Nasopharynx:
  • Microbial count: 10⁵ per milliliter.
  • Inhabitants:
    • Staphylococcus epidermidis
    • Corynebacterium
    • Propionibacterium
    • Haemophilus parainfluenzae
  • Pathogens:
    • Staphylococcus aureus
    • Streptococcus pneumoniae
    • Haemophilus influenzae
    • Neisseria meningitidis
• Oropharynx:
  • Microbial count: 10⁷ per milliliter.
  • Inhabitants:
    • Staphylococcus
    • Streptococcus
    • Corynebacterium
    • Propionibacterium
    • Neisseria spp.
    • Branhamella catarrhalis
    • Bacteroides
    • Fusobacterium (anaerobes)
    • Enterococcus
  • Pathogens:
    • Streptococcus (α-hemolytic)
    • Corynebacterium diphtheriae
    • Klebsiella pneumoniae
    • Pseudomonas aeruginosa

Microbiota of the Oral Cavity

• Microbial abundance:
  • Saliva: 10⁸ per milliliter.
  • Teeth plaque: 10¹¹ per gram.
• Common inhabitants:
  • Streptococcus:
    • S. salivarius
    • S. sanguis
    • S. milleri
    • S. mutans
  • Staphylococcus
  • Enterococcus
  • Veilonella
  • Neisseria
  • Bacteroides orale
  • Fusobacterim nucleatum
  • Leptrotrichia buccalis
  • Actinomyces
  • Vibrio
  • Spirocheta:
    • Treponema orale
    • Borrelia buccalis
    • Leptospira dentium
  • Candida albicans
  • Saccharomyces
  • Prevotella malinogenica
  • Porphyromonas gingivalis, etc.

Dental Caries

• A multifactorial disease involving the disintegration of teeth, starting from the surface and progressing inwards.
• Demineralization of the enamel, the outermost layer of the tooth, is caused by acids produced from bacterial fermentation of sugars.
• Subsequent breakdown of dentin and cementum, the underlying tooth layers, occurs.

Microbial Mechanism of Caries

1. After meals, a thin saliva layer (0.1 micrometers), also known as microbial pellicle, forms on the tooth surface.
2. This pellicle provides an attachment site for bacteria.
3. Given time, the attached microbes multiply and break down carbohydrates, producing glucans and fructans.
4. Their metabolism leads to a decrease in pH and promotes anaerobic conditions.
5. These conditions favor the growth of facultative anaerobes and even anaerobes.
6. Lactobacillus further acidifies the environment by producing lactic acid.
7. High lactic acid concentrations contribute to demineralization, initiating dental caries.
8. Dental caries is also a biofilm, providing bacteria with protection from immune cells and antibiotics.

Gastrointestinal Microbiota

• Stomach:
  • pH: 1-3
  • Microbial count: 10¹-10³ colony-forming units (CFU) per milliliter.
  • Oxygen partial pressure (PO₂): 77 mmHg.
  • Inhabitants: Lactobacillus, Streptococcus, Staphylococcus, Enterobacteriaceae.
• Duodenum:
  • Microbial count: 10¹-10³ CFU per milliliter.
  • PO₂: 33 mmHg.
  • Inhabitants: Lactobacillus, Streptococcus, Staphylococcus, Enterobacteriaceae.
• Small intestine:
  • Jejunum and ileum:
    • pH: 6-7.
    • Microbial count: 10⁴-10⁷ CFU per milliliter.
    • PO₂: 33 mmHg.
    • Inhabitants: Bifidobacterium, Bacteroides, Lactobacillus, Streptococcus, Enterobacteriaceae.
• Colon:
  • pH: 7.
  • Microbial count: 10¹⁰-10¹¹ CFU per milliliter.
  • PO₂: < 33 mmHg.
  • Inhabitants: Fusobacterium, Eubacterium, Clostridium, Peptostreptococcus, Bifidobacterium, Streptococcus, Bacteroides, Lactobacillus, Enterobacteriaceae.

Gut-Brain-Microbiota Axis

• Variations in gut microbiota play a critical role in the development of neuropsychiatric disorders.
• Communication along this axis is bidirectional.
• Antibiotic courses for gastrointestinal diseases can increase the likelihood of depression and anxiety symptoms.
• Gut microbes produce neuroactive compounds and immune modulators, including:
  • Serotonin
  • Dopamine
  • γ-aminobutyric acid (GABA)
  • Acetylcholine
  • Histamine
  • Short-chain fatty acids.

Urogenital Microbiota

• Vagina:
  • Microbial count: 10⁹ per milliliter.
  • Inhabitants:
  • Staphylococcus epidermidis
  • Peptostreptococcus
  • Neisseria spp.
  • Corynebacterium spp.
  • Lactobacillus acidophilus
  • Lactobacillus fermentans
  • Bacteroides
  • Ureaplasma
  • Mycoplasma
  • Pathogens:
    • Gardnerella vaginalis
    • Candida albicans
    • Trichomonas vaginalis
    • Neisseria gonorrhoeae
    • Chlamydia trachomatis
• Urethra:
  • Inhabitants:
    • Staphylococcus epidermidis
    • Streptococcus
    • Corynebacterium spp.

Role of Microbiota

• Positive aspects:
  • Absorption of nutrients and breakdown of food products.
  • Synthesis of vitamin K.
  • Conversion of bile pigments and bile acids.
  • Antagonism to microbial pathogens.
  • Stimulation of the immune system.
• Negative aspects: Dysbiosis (microbial imbalance) can contribute to disease:
  • Infections: Microbiota can cause infections when they enter normally sterile areas.
  • Immune dysregulation: Microbiota can stimulate excessive immune responses, leading to disorders.
  • Metabolic conditions: Microbiota can influence metabolic processes that contribute to conditions like obesity and diabetes.

Explore the fascinating world of the human microbiome, a complex ecosystem comprised of microorganisms residing in and on our bodies. This quiz covers key terminology, such as microflora, microbiota, and metagenomics, providing insights into their roles and significance. Dive into interesting facts that highlight the vast genetic diversity found within our microbiomes.