Interactions Between Microbes and Humans: The Human Microbiome, Infection, and Disease

Interactions Between Microbes and Humans

The Human Microbiome

The human microbiome refers to the collective genomes and communities of microorganisms that inhabit the human body. These microbes are essential for maintaining health and normal physiological functions.

• Definition: The human microbiome is the sum total of all microbes found in and on a normal human.

• Importance: It is critically important for the health and functioning of its host organism.

• Diversity: The microbiome includes bacteria (the most numerous), archaea (primitive single-celled organisms), fungi, protozoa, and some viruses.

• Microbial Abundance: The human body contains as many or more microbial cells as human cells.

Types of Microbes in the Human Body

• Colonists (Normal Biota): Microbes that colonize the body long-term without causing disease.

• Transients: Microbes that are rapidly lost and do not permanently colonize the body; most are harmless but can occasionally cause infection.

• Invaders: Microbes that invade tissues and may cause disease.

Infection and Disease

Infection occurs when microbes overcome host defenses, enter tissues, and multiply. If the cumulative effects of infection disrupt tissues and organs, the result is disease.

• Disease: Any deviation from health caused by factors such as infection, genetics, aging, or malfunction of systems or organs.

• Infectious Disease: A pathologic state caused directly by microorganisms or their products.

• Role of Microbiota: Some microbes are essential for normal development and health.

Antagonism and the Role of Normal Biota

The normal microbiota play a protective role by preventing colonization by pathogens, a phenomenon known as microbial antagonism.

• Microbial Antagonism: The antagonistic effect of "good" microbes against intruder microorganisms.

• Mechanisms: Competition for attachment sites and nutrients, and creation of an unfavorable physiological environment for pathogens.

• Compromised Hosts: Individuals with weakened immune systems (due to age, genetic defects, surgery, immunosuppressive drugs, or underlying disease) are more susceptible to infections by normal microbiota.

Colonization and Disease Causation

Pathogenic Relationships

Some microbes have a parasitic relationship with their host, leading to infection and disease. The ability of a microbe to cause disease is termed pathogenicity.

• Pathogenicity: The potential of an organism to cause disease.

• Types of Pathogens:

  • True (Primary) Pathogens: Cause disease in healthy individuals (e.g., influenza virus, malarial protozoan).

  • Opportunistic Pathogens: Cause disease when host defenses are compromised or when they colonize an unusual body site (e.g., Pseudomonas species, Candida albicans).

Virulence

Virulence is the degree of pathogenicity of a microorganism, determined by its ability to establish itself in the host and cause damage.

• Virulence Factors: Characteristics or structures that contribute to a microbe's ability to cause infection (e.g., toxins, enzymes, capsules).

• Severity: The relative severity of disease depends on the virulence of the microbe.

Portal of Entry and Infectious Dose

To initiate infection, a microbe must enter the host through a specific portal of entry and in sufficient numbers (the infectious dose).

• Portal of Entry: The characteristic route by which a pathogen enters the host (e.g., mucous membranes, skin, respiratory tract).

• Infectious Dose (ID): The minimum number of microbes required to cause infection. If the number of microbes is below the ID, infection does not occur; if greatly above, disease onset is rapid.

Portal of Entry	Organism/Disease	How Access is Gained
Skin	Staphylococcus aureus, Streptococcus pyogenes, Herpes simplex (type 1)	Via abrasions, mucus membranes, or skin
Gastrointestinal Tract	Escherichia coli, Salmonella, Hepatitis A, Giardia lamblia	Through eating contaminated food or water
Respiratory Tract	Microbes causing meningitis, influenza, rubella, chickenpox	Via inhalation of organisms
Genitourinary Tract	HIV, Trichomonas, Neisseria gonorrhoeae, herpes, syphilis	Enter through skin/mucosa of vagina/cervix

Attachment to Host and Interaction with the Microbiota

Microbes must attach to host tissues to establish infection. This is achieved through various mechanisms:

• Adhesion: Bacteria, fungi, and protozoa use fimbriae, surface proteins, and capsules; viruses use specialized receptors or spikes.

• Host Defenses: Microbes not part of the normal biota are likely to encounter resistance from the immune system, especially from white blood cells (phagocytes).

• Phagocyte Evasion: Some pathogens produce leukocidins (toxic to white blood cells) or survive inside phagocytes, allowing them to hide, grow, and spread.

Virulence Factors and Host Damage

Virulence factors are adaptations that enable pathogens to invade, establish, and cause damage in the host.

• Mechanisms of Host Damage:

  • Directly through enzymes and toxins (endotoxins and exotoxins).

  • Indirectly by inducing excessive or inappropriate host immune responses.

  • Epigenetic changes to host cells.

• Examples of Virulence Factors: Capsules (e.g., Streptococcus pneumoniae), enzymes (e.g., hyaluronidase, coagulase), toxins.

• Exotoxins: Secreted proteins that damage host tissues (e.g., hemolysins, neurotoxins).

• Endotoxins: Lipopolysaccharide (LPS) from Gram-negative bacteria outer membrane; can cause severe inflammation and tissue damage.

Host Susceptibility and Disease Outcome

• Highly Virulent Microbes: Almost always cause disease (e.g., rabies virus).

• Low Virulence/Commensals: Rarely cause disease unless host defenses are compromised (e.g., Lactobacillus in the gut).

• Opportunistic Infections: Occur when host immunity is decreased due to conditions like pregnancy, disease, or immunosuppressive drugs.

• Determinants of Infection Outcome: Microbial virulence, infectious dose, portal of entry, host genetics, prior exposure, and general health.

Koch's Postulates

Koch's postulates are a set of criteria used to establish a causative relationship between a microbe and a disease. They rely on isolating the microbe in pure culture and demonstrating its ability to cause disease in a healthy host.