Human Microbiome Overview

Human Microbiome Terminology

• Microflora is an outdated term used when only two kingdoms (Animalia and Planta) were recognized.
• Microbiota refers to the total number of microorganisms found in a specific area.
• Microbiome encompasses the genomes of the microbiota, studied through genome examination.
• Metagenomics is the direct study of genetic material from microbial communities, analyzing DNA from multiple bacteria simultaneously.

Human Microbiome Facts

• The intestinal microbiota harbors 3.3 million genes, vastly exceeding the approximately 22,000 genes in the human genome.
• Humans share 99.9% genetic similarity, but their intestinal and skin microbiomes differ by 80-90%, highlighting the unique individuality of individual microbiomes.
• The human microbiome exhibits regional diversity, with E. coli prevalent in the gut of most healthy individuals and Staphylococcus epidermitis inhabiting the skin.

Microbiota Classification

• Resident or constant (obligatory) microbiota: Fixed types of microorganisms permanently residing in a given area at a specific age.
• Transient microbiota (facultative): Non-pathogenic or potentially pathogenic microorganisms temporarily inhabiting the skin or mucous membranes for hours, days, or weeks.

Ecological Niches

• Each body region with a characteristic set of microbes constitutes an ecological niche.
• The types of microorganisms vary across different areas of the body.
• The human body harbors an estimated 10^13 bacteria, with 350 species in the large intestine.
• Bacterial adherence (via adhesins) and exposure to microorganisms influence the formation of ecological niches.
• Individuals can be categorized as carriers, carrying microorganisms that may or may not cause disease, and classified into two groups:
  • Acute carrier: Exhibiting a short-term carrier state.
  • Chronic carrier: Carrying specific microbes for prolonged periods, for example, individuals carrying Staphylococcus aureus (20-40%), Streptococcus pneumoniae (40-70%), or Salmonella typhi (a lower percentage).
• Exposure to a microorganism can result in:
  • Transient colonization: The microbe temporarily resides in the individual.
  • Permanent colonization: The microbe becomes a permanent resident.
  • Disease: The interaction between the microbe and the human host leads to a pathogenic process, causing damage to the host.

Causative Agents of Infectious Diseases

• Strict pathogens: Microorganisms consistently associated with disease in humans, such as Mycobacterium tuberculosis, Neisseria gonorrhoeae, Francisella tularensis, Plasmodium species, and Rhabdoviruses.
• Opportunistic pathogens: Typically harmless members of the normal microbiota that can cause disease when introduced into vulnerable sites (e.g., bloodstream, tissues), examples include Staphylococcus aureus, Escherichia coli, and Candida albicans.

Risk Factors for Opportunistic Infections

• Immunodeficiency
• Chronic diseases (e.g., diabetes)
• Gastric ulcers
• Stress
• Antibacterial treatment
• Malnutrition
• Avitaminosis

Skin Microbiota

• Transient microbiota: Superficial, temporary residents.
• Resident microbiota: Constant inhabitants of deeper skin layers.
• Approximately 10^3-10^4 microbes reside per square centimeter.
• Common skin microbiota members include:
  • Staphylococcus epidermidis (90%)
  • Corynebacterium
  • Cutibacterium acnes
  • Malassezia
  • Candida

Factors Influencing Skin Microbiota

• Detergents: Reduce transitory and superficial microbiota by 90%, with recolonization occurring within 8 hours.
• Disinfectants: Eliminate resident microbiota.
• Sex
• Age
• Climate
• UV rays
• Hygiene
• Profession
• Diseases

Skin as a Defense Barrier

• Intact skin serves as the first line of defense against microbial invasion.
• Skin's dryness makes it unsuitable for many microbial growth.
• Skin microbiota is sustained by nutrients provided by sweat and sebaceous glands.
• Sweat glands:
  • Eccrine glands: Secrete sweat.
  • Apocrine glands: Secrete sweat and nutrients, more active after puberty.
  • Sweat contains:
    • Lysozyme: Breaks down peptidoglycan, a bacterial cell wall component.
    • Lactic acid: Lowers pH to 3-5, inhibiting bacterial colonization.
• Sebaceous glands:
  • Attached to hair follicles.
  • Secrete sebum, supporting microbial growth up to 10^6 per square centimeter.

Skin Mycobiome

• The skin mycobiome refers to the fungal species inhabiting the skin.
• Fungi constitute 30% of the skin microbiota, with Malassezia strains dominating.
• Malassezia species, including M. globosa, M. restricta, and M. furfur, represent over 90% of fungal populations in most skin niches.
• The role of Malassezia on the skin is controversial, linked to both healthy skin and conditions like dandruff and eczema.

Human Virome

• The human virome encompasses all viruses residing within or on human organs, including the skin.
• Human stools contain at least 10^9 virus-like particles (VLPs) per gram.
• Bacteriophages comprise 96.1% of the human gut viral populations.
• The human virome potentially influences human health, beyond disease.

Microbiota of Nasopharynx and Oropharynx

• Nasopharynx:
  • Microbe amount: 10^5 per milliliter.
  • Microbes: Staphylococcus epidermidis, Corynebacterium, Propionibacterium, Haemophilus parainfluenzae.
  • Pathogens: Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis.
• Oropharynx:
  • Microbe amount: 10^7 per milliliter.
  • Microbes: Staphylococcus, Streptococcus, *Corynebacterium, Propionibacterium, Neisseria species, Branhamella catarrhalis, Bacteroides, Fusobacterium, Enterococcus.
  • Pathogens: Streptococcus (α-hemolytic), Corynebacterium diphtheriae, Klebsiella pneumoniae, Pseudomonas aeruginosa.

Microbiota of Oral Cavity

• Microbe amount in saliva: 10^8 per milliliter.
• Microbe amount in teeth plaque: 10^11 per gram.
• Microbes: Streptococcus salivarius, S. sanguis, S. milleri, S. mutans, Staphylococcus, Enterococcus, Veilonella, Neisseria, Bacteroides orale, Fusobacterim nucleatum, Leptrotrichia buccalis, Actinomyces, Vibrio, Spirocheta (including Treponema orale, Borrelia buccalis, Leptospira dentium), Candida albicans, Saccharomyces, Prevotella malinogenica, Porphyromonas gingivalis, etc.

Dental Caries

• Polyaethiologic disease, meaning multiple factors contribute to its development.
• Caries refers to tooth disintegration, starting at the surface and progressing inward.
• Demineralization of the enamel surface is caused by acidic byproducts of bacterial fermentation.
• Subsequent decomposition of the dentin and cement follows.

Microbial Mechanism of Caries

1. After a meal, a thin layer of saliva (microbe pellicle, around 0.1 micrometer) forms on the tooth surface.
2. The microbe pellicle provides a site for bacteria to attach.
3. Over time, microbes multiply and ferment carbohydrates, producing glucan and fructan, lowering pH and promoting anaerobic conditions.
4. The resulting environment favors facultative anaerobes and even anaerobes.
5. Lactobacillus bacteria, producing lactic acid, further acidify the environment.
6. The high concentration of lactic acid leads to demineralization, initiating dental caries.
7. Dental caries is also a biofilm, shielding bacteria from immune cells and antibiotics.

Gastrointestinal Microbiota

• Stomach:
  • pH: 1-3.
  • Microbe amount: 10^1-10^3 colony-forming units per milliliter (CFU/ml).
  • Oxygen partial pressure (PO2): 77 mmHg.
  • Microbes: Lactobacillus, Streptococcus, Staphylococcus, Enterobacteriaceae.
• Duodenum:
  • Microbe amount: 10^1-10^3 CFU/ml.
  • PO2: 33 mmHg.
  • Microbes: Lactobacillus, Streptococcus, Staphylococcus, Enterobacteriaceae.
• Small Intestine (jejunum and ileum):
  • pH: 6-7.
  • Microbe amount: 10^4-10^7 CFU/ml.
  • PO2: 33 mmHg.
  • Microbes: Bifidobacterium, Bacteroides, Lactobacillus, Streptococcus, Enterobacteriaceae.
• Colon:
  • pH: 7.
  • Microbe amount: 10^10-10^11 CFU/ml.
  • PO2: < 33 mmHg.
  • Microbes: Fusobacterium, Eubacterium, Clostridium, Peptostreptococcus, Bifidobacterium, Streptococcus, Bacteroides, Lactobacillus, Enterobacteriaceae.

Gut-Brain-Microbiota Axis

• Variations in gut microbiota play a significant role in the development of neuropsychiatric disorders.
• Communication along this axis is bidirectional.
• Antibiotic treatment for gastrointestinal diseases can increase the risk of depression and anxiety symptoms.
• Gut microbes provide neuroactive compounds and immune modulators, including serotonin, dopamine, γ-aminobutyric acid, acetylcholine, histamine, and short-chain fatty acids.

Urogenital Microbiota

• Vagina:
  • Microbe amount: 10^9 per milliliter.
  • Microbes: Staphylococcus epidermidis, Peptostreptococcus, Neisseria species, Corynebacterium species.
• Urethra:
  • Microbes: Staphylococcus epidermidis, Streptococcus, Corynebacterium species.