Human Microbiome 2

📘 Key Terminology

  • Microbiota: The living microorganisms (bacteria, fungi, viruses, etc.) found in a specific environment (e.g., gut, skin).

  • Microbiome: The collective genomes of all microorganisms in an environment, including their structures, metabolites, and environmental interactions.

⚖ What is “Normal”?

  • The microbiome is dynamic – it changes over time.

  • Influenced by:

    • Age

    • Environmental factors

    • Personal history

  • There's no single “normal” microbiome – multiple healthy versions exist.

  • Different body sites have different microbial communities (site-specific).

🌍 Site-Specific Differences

  • Urban vs Indigenous populations → Indigenous groups have greater microbial diversity.

  • Geographical location/diet affects microbiome makeup.

  • Lower diversity is linked (but not proven to cause) obesity.

⚠ Dysbiosis

  • Dysbiosis = microbial imbalance which:

    • May cause disease

    • May result from disease

  • Can occur throughout the body, but most often discussed in the gastrointestinal tract.

  • Linked to:

    • Asthma

    • Crohn’s disease

    • IBD (Inflammatory Bowel Disease)

    • Type 1 Diabetes

👶 Microbiota & Ageing

Development Through Life:

  • Infants: Low microbial diversity

  • By Age 3: Diversity increases and stabilises

  • Pregnancy: Temporary changes in microbiota, unrelated to BMI or diet

  • Old Age: Shift in microbial community, linked to increased disease risk

👶 Microbiota in Newborns

Colonisation Process:

  1. Before birth: Infant is considered sterile.

  2. During birth: Exposure to maternal vaginal/skin flora.

  3. Post-birth:

    • Influenced by delivery method, feeding type, environment.

    • Skin-to-skin contact matters.

Key Influencers:

  • Vaginal Delivery: Infants acquire vaginal and gut flora.

  • Caesarean Section (CS):

    • ↓ Bacteroides, Lactobacillus, Bifidobacterium

    • ↑ Clostridium difficile, Staphylococcus

🍼 Breastfeeding vs Bottle Feeding

Breastfeeding:

  • Promotes healthy gut via:

    • Prebiotics (HMOs)

    • Immunoglobulins, cytokines, enzymes

    • Live bacteria: Bifidobacterium, Lactobacillus, Streptococcus

  • ↓ harmful bacteria like Clostridia and Bacteroides

Bottle Feeding:

  • Formula is nutritionally regulated, but lacks complex bioactives

  • Often fortified with:

    • Prebiotics: e.g., GOS, FOS, stimulate Bifidobacterium

    • Probiotics: e.g., Lactobacillus, shown to reduce colic and diarrhoea

👩‍⚕ Managing Dysbiosis in Infants

  • Strategies:

    • Vaginal seeding (applying maternal vaginal fluids to CS-born infants)

    • Probiotic supplementation (e.g. Lactobacillus reuteri)

🧬 Other Influences on Microbiota

  • Environment, pets, air quality, hygiene

  • Early exposure to animals linked to stronger immunity and reduced allergy/asthma

📊 TEDDY Study Findings (T1D Focus)

  • Long-term study on infants’ microbiomes:

    1. Developmental phase (3–14 months)

    2. Transitional phase (15–30 months)

    3. Stable phase (31–46 months)

  • More Bacteroides = ↓ SCFA-producing bacteria

  • Healthy children had more SCFA-producing genes

👵 The Elderly

Age-Related Changes:

  • ↓ Immune system, ↑ infection risk

  • Common dysbiosis factors:

    • ↓ stomach acid, urine flow, mucus clearance

    • Hormonal changes (e.g., oestrogen)

    • Altered GI motility and mucus production

Changes by Site:

Site

Decreased

Increased

GI Tract

Bifidobacteria

Clostridia, Enterobacteria

Urinary Tract

—

Colonisation

Oropharynx

—

Gram-negatives (E. coli, Klebsiella)

Skin

—

Streptococci

Eye

—

Coryneforms, Gram-negatives

Oral Cavity

—

Staphylococci, Enterobacteria

💥 Effects of Age-Related Dysbiosis

  • Associated with conditions of:

    • Brain, heart, immune, endocrine, and musculoskeletal systems

  • Chronic inflammation from microbiota = “inflamm-ageing”

🧴 The Skin Microbiome

  • Resident microbes: Long-term inhabitants (e.g. Staphylococcus spp.)

  • Transient microbes: Temporary colonisers

  • Conditions: Dry, acidic, oxygen-rich → limits microbial growth

  • Hands: High variability, hard to define “normal”

🦟 Scabies

  • Caused by Sarcoptes scabiei mite

  • Symptoms: Rash due to allergic reaction

  • Spread easily in crowded conditions

  • Treated with antiparasitic medication

😮‍💨 Respiratory Tract Microbiota

Upper Respiratory Tract (URT):

  • Contains:

    • Staphylococcus aureus

    • Streptococcus pneumoniae

    • Corynebacterium, Neisseria

  • Protected by mucous secretions

Lower Respiratory Tract (LRT):

  • Previously considered sterile

  • Defence mechanisms:

    • Cilia, mucus, IgA, macrophages

Smoking & Vaping:

  • Smokers’ lungs: Diverse microbiota

  • Reduced diversity in people with lung disease (e.g. dominated by Pseudomonas)

  • Vaping increases Haemophilus, and leads to higher inflammation than smoking

👄 Oral Microbiota

  • Rich bacterial population due to:

    • Food, saliva, epithelial debris

  • Habitats evolve with age

Dental Plaque:

  • Microbial biofilm on tooth surfaces

  • Bacteria secrete sticky substances

  • Produce acid → damages enamel → tooth decay

🍽 Gastrointestinal Microbiota

Distribution:

  • Stomach: Acid limits microbes (H. pylori is an exception)

  • Small intestine: More bacteria distally

  • Large intestine: High density (10¹¹–10¹² per gram), 60% of faecal mass

Site Variation:

  • Microbes differ:

    • Along GI tract

    • Between mucosal surface and lumen

    • Anaerobes dominate in the lumen

🧠 Gut Functions

  • Healthy microbiota enriched in:

    • Bifidobacterium, Lactobacillus

    • SCFA producers → reduce inflammation, regulate immunity, control glucose

📊 Enterotypes

  • Three main microbiota “types” (clusters):

    1. Type 1: High Bacteroides

    2. Type 2: Low Bacteroides, high Prevotella

    3. Type 3: High Ruminococcus

  • Influenced more by long-term diet than age, sex or geography

💩 Faecal Transplants

  • Used to treat C. difficile infections

  • May influence:

    • Weight gain/obesity

    • Risk of Alzheimer’s (emerging research)