Microbial Symbioses With Humans

Definitions: Microbiome and Microbiota

The human body hosts a vast array of microorganisms that interact with their host in complex ways. Understanding the terminology is essential for studying these relationships.

• Microbiome: The functional collection of different microbes (bacteria, archaea, viruses, fungi) in a particular environmental system, such as the human body. It encompasses not only the organisms but also their genetic material and interactions.

• Microbiota: The specific types of organisms present in an environmental habitat, such as human skin or the gastrointestinal (GI) tract.

• Example: The skin microbiota includes Staphylococcus and Propionibacterium species, while the gut microbiota is dominated by Bacteroides and Firmicutes.

Methodologies for Probing the Human Microbiome

Metagenomics

Modern techniques have revolutionized the study of the human microbiome, allowing for comprehensive analysis of microbial diversity and abundance.

• Metagenomics: The study of genetic material recovered directly from environmental samples, enabling identification of microbial communities without the need for culturing.

• Key Steps:

  • Sample collection (e.g., stool, saliva, skin swab)

  • DNA extraction and library preparation

  • DNA sequencing

  • Sequence analysis and genome reconstruction

• Applications: Metagenomics is used to profile the diversity and function of the human microbiome, identify novel organisms, and study microbial interactions.

Overview of the Human Microbiome

Major Microbial Groups by Body Site

The human microbiome varies significantly by anatomical site, with distinct communities adapted to local conditions.

Example: The GI tract is dominated by Bacteroides and Firmicutes, while the urogenital tract is rich in Lactobacillus.

Gastrointestinal Microbiota

Role and Colonization

The gut microbiota plays a crucial role in early development, health, and disease predisposition. Colonization begins at birth and is influenced by delivery mode and diet.

• Functions: Digestion, vitamin synthesis, immune system education, and protection against pathogens.

• Colonization: Begins at birth, with initial exposure from the mother and environment.

Large Intestine Microbiota

The large intestine acts as an in vivo fermentation vessel, supporting dense microbial populations that metabolize dietary components.

• Fermentation: Microbes use nutrients from digested food to produce short-chain fatty acids and other metabolites.

• Localization: Most microbes are found in the lumen, with some in mucosal layers.

Bacterial Diversity of Feces

Fecal samples reflect the diversity of gut microbiota, with two major phyla dominating:

Products of Intestinal Microbiota and Immune System Education

Gut microbes contribute to host metabolism and immune function through various biochemical activities.

Oral Microbiota

Composition and Function

The oral cavity is a complex habitat with diverse microbial communities. Saliva contains antimicrobial enzymes, but nutrient-rich surfaces promote microbial growth.

• Major Genera: Streptococcus, Actinomyces, Veillonella, Fusobacterium

• Biofilm Formation: Dental plaque is a biofilm that supports fermentative bacteria.

Microbiota of the Respiratory Tract

Upper vs. Lower Respiratory Tract

The respiratory tract is divided into upper and lower regions, with distinct microbial colonization patterns.

• Upper Respiratory Tract: Colonized by microbes, most of which are trapped in mucus and expelled or swallowed.

• Lower Respiratory Tract: Typically sterile, with no resident microbiota under healthy conditions.

Urogenital Tracts and Their Microbes

Urogenital Tract Microbiota

The urogenital tract has unique microbial communities and is influenced by physiological and environmental factors.

• Kidneys: Typically sterile in both males and females.

• Urethra: Can harbor potential pathogens such as Escherichia coli and Proteus mirabilis under altered conditions (e.g., pH changes).

Vaginal Microbiota

The adult female vagina is weakly acidic (pH ~5) and contains glycogen, supporting specific microbial populations.

• Lactobacillus acidophilus: Ferments glycogen to produce lactic acid, maintaining an acidic environment that inhibits pathogens.

Skin Microbiota

Factors Influencing Skin Microbiota

The skin's microbial composition is shaped by its chemical and physical properties, as well as environmental factors.

• Microenvironments: Dry skin, moist skin, and sebaceous (oily) skin each support different microbial communities.

• Major Genera: Propionibacterium, Staphylococcus, Corynebacterium

Colonization, Succession, & Stability of Gut Microbiota

Influence of Birth and Diet

Early life events shape the gut microbiome, with lasting effects on health.

• Vaginal vs. Cesarean Birth: Vaginally delivered infants acquire microbiota resembling the mother's vaginal flora, while C-section infants have more skin-associated microbes.

• Breast Milk vs. Formula: Breastfed infants develop a distinct gut microbiome compared to formula-fed infants, influenced by human milk oligosaccharides.

Disorders Attributed to Gut Microbiota

Inflammatory Bowel Disease (IBD)

IBD is associated with chronic gut inflammation and microbial imbalance (dysbiosis).

• Dysbiosis: Disruption of normal microbiota homeostasis.

• Risk Factors: Early antibiotic use increases IBD risk; IBD patients have lower microbiome diversity.

Gut Microbiota and Obesity

Microbial composition influences host metabolism and obesity risk.

• Mouse Models: Germ-free mice have less body fat than normal mice; genetically obese mice have distinct microbiota.

• Humans: Obese individuals have higher levels of Prevotella and methanogens.

Disorders Attributed to Oral Microbiota

Dental Caries and Periodontitis

Oral biofilms composed of fermenting bacteria can lead to dental caries and periodontal disease.

• Dental Caries: Acid production by fermenters erodes tooth enamel.

• Periodontal Disease: May contribute to systemic conditions such as cardiovascular disease and arthritis.

Antibiotics and the Human Microbiome

Impact of Antibiotics

Antibiotics can disrupt the gut microbiome, affecting both target and non-target organisms.

• Early Life Use: Increases risk of IBD and other dysbiosis-related disorders.

• Resistant Pathogens: Clostridioides difficile can persist and proliferate following antibiotic therapy.

Fecal Transplants

Therapeutic Applications

Fecal transplants involve transferring microbiota from a healthy donor to a patient, restoring microbial balance.

• Clinical Use: Effective in treating recurrent C. difficile infections.

Probiotics and Prebiotics

Definitions and Functions

Probiotics and prebiotics are used to support and restore healthy microbiota.

• Probiotics: Live microorganisms that confer health benefits to the host. Common genera include Lactobacillus and Bifidobacterium.

• Prebiotics: Indigestible carbohydrates that nourish beneficial gut bacteria, such as inulin and oligosaccharides.

Probiotic Inhibition of S. aureus

Mechanisms of Action

Probiotics can inhibit pathogenic bacteria through various mechanisms, including interference with quorum sensing and competitive exclusion.

• Quorum Sensing: Probiotics may block signaling pathways used by Staphylococcus aureus to regulate virulence gene expression.

• Example: Inhibition of the Agr system in S. aureus reduces toxin production and pathogenicity.