Normal flora

Normal Flora and Host-Microbe Interactions

Concept of Normal Flora

The human body is not sterile; it is home to a vast and complex community of microorganisms. Normal Flora (also called the normal microbiota or commensals) are the microorganisms that live on or inside the body of a healthy person without causing disease under normal circumstances.

• The majority of normal flora are bacteria and some yeasts.
• Viruses, protozoa, and helminths (worms) are generally considered pathogens, not normal flora.
• These organisms can become opportunistic pathogens if they are introduced to a different part of the body or if the host becomes immunocompromised.

Types of Normal Flora

• Resident Flora: These are microorganisms that are almost always present in a particular area of the body at a given age. They are fixed types of microorganisms that, if disturbed (e.g., by soap or antibiotics), will promptly re-establish themselves. They are like the permanent residents of a neighborhood.
• Transient Flora: These are microorganisms that are present at a given time and then disappear. They are "temporary visitors" that may be present for hours, days, or weeks but do not establish a permanent colony because of competition from resident flora and the body's defense mechanisms.

Anatomic Distribution of Normal Flora

Normal flora colonize body surfaces that are exposed to the external environment. Internal organs and tissues like the blood, brain, muscles, and lungs are normally sterile.

Skin Flora

The skin is a complex environment with dry, moist, and oily areas, each hosting different microbes. The dominant group is Gram-positive bacteria because they are more resistant to drying and high salt concentrations (from sweat).

• Key residents include Staphylococcus epidermidis, Micrococcus species, and diphtheroids (like Propionibacterium acnes, which is linked to acne).
• Staphylococcus aureus can also be found, particularly in moist areas like the nostrils and perineum.

Oral and Upper Respiratory Tract Flora

The mouth is a rich habitat for microbes. The pharynx and nose are also heavily colonized.

• The mouth contains numerous species, especially Streptococcus species (like Streptococcus mutans, which contributes to dental caries by forming biofilms called plaque).
• Anaerobes thrive in the gingival crevices (the space between teeth and gums).
• The pharynx can be a colonization site for potentially pathogenic bacteria like Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis, which may not cause illness in a healthy carrier but can cause disease if they spread.

Gastrointestinal (GI) Tract Flora

The density and composition of flora change drastically along the GI tract.

• Stomach: Has very few microbes due to its high acidity (low pH). Most are transient. Helicobacter pylori is an important exception that can survive the acid and is a major cause of stomach ulcers.
• Small Intestine: The duodenum is sparsely populated, but microbial numbers increase toward the ileum.
• Large Intestine (Colon): Contains the largest microbial population in the body (10⁹ to 10¹¹ bacteria per gram of feces). It is predominantly (>99%) populated by anaerobes like Bacteroides, Clostridium, and facultative anaerobes like E. coli.

Urogenital Flora

• Vagina: The flora is dominated by Lactobacillus species in women of reproductive age. These bacteria ferment glycogen to produce lactic acid, creating an acidic pH (around 4.5) that prevents the overgrowth of pathogens like the yeast Candida albicans. The flora changes with age and hormonal levels.
• Urethra: The distal (outer) part of the urethra is colonized by a sparse mixed flora. The rest of the urinary tract (bladder, ureters, kidneys) is sterile.

The Roles and Importance of Normal Flora

Benefits to the Host

Nutritional Benefits:

• Gut bacteria synthesize and secrete essential vitamins that humans cannot produce or get in sufficient quantities from diet alone. Key examples include Vitamin K (crucial for blood clotting) and several B-complex vitamins (like B12, biotin, riboflavin, and folate).
• They also aid in the digestion and absorption of certain carbohydrates (like fiber) that human digestive enzymes cannot break down, releasing beneficial short-chain fatty acids (SCFAs).

Protection Against Pathogens (Competitive Exclusion):

• Normal flora prevent colonization by harmful pathogens by competing for limited attachment sites on epithelial surfaces.
• They also compete for essential nutrients, effectively "starving out" potential invaders.
• This process creates a biological barrier, making it much harder for pathogens to establish an infection.

Immune System Stimulation and Development:

• The constant presence of normal flora stimulates the development and maturation of the host's immune system, particularly in the gut (Gut-Associated Lymphoid Tissue or GALT).
• This "training" helps the immune system to differentiate between harmless commensals and dangerous pathogens.
• The exposure to flora leads to the production of natural antibodies that may cross-react with and provide protection against related pathogens encountered later in life.

Production of Antimicrobial Substances:

• Many gut bacteria produce substances that inhibit or kill other, more harmful bacteria.
• Lactobacillus species in the vagina produce lactic acid, creating a low pH environment that prevents the overgrowth of yeast like Candida albicans.
• Gut bacteria can produce fatty acids, peroxides, and highly specific antibiotic-like proteins called bacteriocins (e.g., colicins produced by E. coli), which are lethal to closely related bacteria.

Detoxification:

• Some normal flora can metabolize and detoxify certain harmful compounds that are ingested in food or produced during metabolism.

Harmful Effects and Disadvantages of Normal Flora

Opportunistic Infections: This is the most significant disadvantage. Normal flora can cause serious endogenous (originating from within) infections if:

• The Host is Immunocompromised: A weakened immune system due to HIV/AIDS, chemotherapy, immunosuppressive drugs (for transplants), or malnutrition allows normally harmless flora to become pathogenic.
• Flora are Introduced to a Sterile Site:
  • A break in the skin from a wound or surgery can allow Staphylococcus aureus to enter the bloodstream, causing bacteremia or sepsis.
  • Perforation of the intestine (e.g., from an ulcer or injury) can release gut flora like Bacteroides fragilis into the abdominal cavity, causing peritonitis.
  • E. coli from the gut is the most common cause of Urinary Tract Infections (UTIs) when it ascends the urethra.

Carcinogenic Potential:

• While rare, some normal flora have been linked to cancer. For example, chronic inflammation caused by certain gut bacteria may contribute to the development of colorectal cancer.
• Helicobacter pylori, which can be part of the stomach flora, is a known carcinogen linked to stomach cancer.

Source of Cross-Infection:

• Normal flora from a healthcare worker can be transmitted to a vulnerable patient, where it can cause a nosocomial (hospital-acquired) infection. This is a major reason for strict hand hygiene protocols.

Symbiotic Relationships

Symbiosis (from Greek, meaning "living together") is a close and long-term biological interaction between two different species. The organisms involved are called symbionts. These relationships are critical in understanding how microbes interact with their hosts.

Mutualism (+/+):

• Definition: A relationship where both organisms benefit. It is a win-win situation.
• Example 1 (Classic): E. coli in the human colon gets a stable, nutrient-rich environment, and in return, it produces Vitamin K, which is essential for human blood clotting.
• Example 2: Ruminant animals like cows have microbes in their rumen that digest cellulose from grass, which the cow cannot do on its own. The microbes get food, and the cow gets nutrients from the digested cellulose.

Commensalism (+/0):

• Definition: An association where one organism benefits, and the other is largely unaffected (neither harmed nor helped).
• Example 1: Staphylococcus epidermidis living on human skin gets nutrients from dead skin cells and secretions, but it typically does not harm or benefit the human host.
• Example 2: Many bacteria in the human mouth live as commensals, feeding on food particles without causing any issues in a healthy individual with good oral hygiene.
• Note: The line between commensalism and mutualism/parasitism can be blurry. A commensal can become an opportunistic pathogen if circumstances change.

Parasitism (+/-):

• Definition: A relationship where one organism (the parasite) benefits at the expense of the other (the host), which is harmed.
• This is the relationship all pathogenic microorganisms have with their hosts. The degree of harm can range from mild (like in the common cold) to severe and fatal (like in Ebola).
• Example 1: Plasmodium falciparum, the protozoan that causes malaria, lives in and destroys human red blood cells, causing severe disease.
• Example 2: Mycobacterium tuberculosis lives inside human lung cells, causing tissue damage and the disease tuberculosis.

Amensalism (-/0) (Less Common):

• Definition: A relationship where one organism is harmed, and the other is unaffected.
• Example: The mold Penicillium produces penicillin, which kills nearby bacteria. The bacteria are harmed, but the mold is not significantly affected by the bacteria's presence or absence. This is the basis of antibiotic action.

Characteristics and Spread of Infectious Disease

An infection is the successful colonization of a host by a microorganism. Infections can lead to disease, which causes signs and symptoms resulting in a deviation from the normal structure or functioning of the host. Microorganisms that can cause disease are known as pathogens.

The signs of disease are objective and measurable, and can be directly observed by a clinician. Vital signs, which are used to measure the body’s basic functions, include body temperature (normally 37 °C [98.6 °F]), heart rate (normally 60–100 beats per minute), breathing rate (normally 12–18 breaths per minute), and blood pressure (normally between 90/60 and 120/80 mm Hg). Changes in any of the body’s vital signs may be indicative of disease. For example, having a fever (a body temperature significantly higher than 37 °C or 98.6 °F) is a sign of disease because it can be measured.

Unlike signs, symptoms of disease are subjective. Symptoms are felt or experienced by the patient, but they cannot be clinically confirmed or objectively measured. Examples of symptoms include nausea, loss of appetite, and pain. Such symptoms are important to consider when diagnosing disease, but they are subject to memory bias and are difficult to measure precisely. Some clinicians attempt to quantify symptoms by asking patients to assign a numerical value to their symptoms. For example, the Wong-Baker Faces pain-rating scale asks patients to rate their pain on a scale of 0–10. An alternative method of quantifying pain is measuring skin conductance fluctuations. These fluctuations reflect sweating due to skin sympathetic nerve activity resulting from the stressor of pain.

Distinguishing Between Signs and Symptoms of Disease

Understanding this difference is fundamental to accurate clinical assessment and diagnosis. It forms the basis of how a healthcare provider documents a patient's condition.

Signs: These are objective and measurable indicators of disease that can be directly observed or measured by a clinician, regardless of what the patient says.

• Key Examples: Fever (a measured temperature of 38.5°C), high blood pressure, a visible rash, edema (swelling), abnormal heart sounds heard with a stethoscope, elevated white blood cell count from a lab test, or a positive rapid diagnostic test for malaria.

Symptoms: These are subjective feelings or experiences reported by the patient. They cannot be directly measured or observed by a clinician and rely on the patient's personal account.

• Key Examples: Pain, nausea, headache, fatigue, chills, itching, dizziness, or a general feeling of being unwell (malaise).

Nomenclature of Disease Conditions

A specific group of signs and symptoms characteristic of a particular disease is called a syndrome. Many syndromes are named using a nomenclature based on signs and symptoms or the location of the disease.

Classifying Diseases

Infectious vs. Non-infectious Diseases

Infectious Disease: Caused by a pathogenic microorganism. Can be communicable or non-communicable.

An infectious disease is any disease caused by the direct effect of a pathogen. A pathogen may be cellular (bacteria, parasites, and fungi) or acellular (viruses, viroids, and prions). Some infectious diseases are also communicable, meaning they are capable of being spread from person to person through either direct or indirect mechanisms. Some infectious communicable diseases are also considered contagious diseases, meaning they are easily spread from person to person. Not all contagious diseases are equally so; the degree to which a disease is contagious usually depends on how the pathogen is transmitted. For example, measles is a highly contagious viral disease that can be transmitted when an infected person coughs or sneezes and an uninfected person breathes in droplets containing the virus. Gonorrhea is not as contagious as measles because transmission of the pathogen (Neisseria gonorrhoeae) requires close intimate contact (usually sexual) between an infected person and an uninfected person.

Non-infectious Disease: Not caused by a pathogen. The causes are varied, as detailed in the table below.

In contrast to communicable infectious diseases, a noncommunicable infectious disease is not spread from one person to another. One example is tetanus, caused by Clostridium tetani, a bacterium that produces endospores that can survive in the soil for many years. This disease is typically only transmitted through contact with a skin wound; it cannot be passed from an infected person to another person. Similarly, Legionnaires disease is caused by Legionella pneumophila, a bacterium that lives within amoebae in moist locations like water-cooling towers. An individual may contract Legionnaires disease via contact with the contaminated water, but once infected, the individual cannot pass the pathogen to other individuals.

Types of Infectious Diseases by Acquisition and Transmission

Communicable Disease: An infectious disease that can be transmitted from one person (or animal) to another, either directly (e.g., through touch or respiratory droplets) or indirectly (e.g., through contaminated water or insects).

• A disease that is very easily spread is often called a contagious disease. Measles and chickenpox are highly contagious.
• Examples: Tuberculosis, HIV, Measles, Influenza, Cholera.

Non-communicable Infectious Disease: An infectious disease that is not spread between people. It is typically acquired from an environmental reservoir or as an opportunistic infection from one's own normal flora.

• Example 1 (Environmental): Tetanus. A person gets tetanus when Clostridium tetani spores from the soil enter a deep wound. You cannot "catch" tetanus from someone who has it.
• Example 2 (Opportunistic): A bladder infection caused by a person's own E. coli from their gut.

Iatrogenic Disease: (from Greek iatros, "healer"). A disease that occurs as a direct result of a medical procedure or treatment. This implies the disease was an unavoidable or accidental consequence of necessary medical intervention.

• Example: A patient develops a wound infection after surgery because the surgical site was not properly cleaned, or develops sepsis after a procedure with a contaminated endoscope.

Nosocomial Disease: A disease acquired within a hospital or healthcare facility. Also known as a Hospital-Acquired Infection (HAI). These are often caused by drug-resistant bacteria and are a major concern in patient safety.

• Example: A patient develops a urinary tract infection from an indwelling catheter (Catheter-Associated UTI or CAUTI), or pneumonia from being on a ventilator (Ventilator-Associated Pneumonia or VAP).

Zoonotic Disease (Zoonosis): An infectious disease that is naturally transmitted from a vertebrate animal to a human.

• Example: Rabies from a dog bite, Anthrax from handling infected livestock, or Avian Influenza from infected birds.

The Stages of an Acute Infectious Disease

An acute disease typically progresses through five distinct stages. The severity of signs and symptoms directly correlates with the number of pathogens present in the body.

1. Incubation Period: The initial period between infection and the first appearance of any signs or symptoms. The length varies greatly depending on the pathogen, the initial dose, and the host's immunity.

Pathogen Load: The pathogen is beginning to multiply, but its numbers are not yet high enough to cause symptoms.

Signs and Symptoms: None. The patient is unaware of the infection but may be contagious.

2. Prodromal Period: A short period of early, mild, and general (non-specific) symptoms, such as malaise, headache, or muscle aches. This signals that the disease is starting.

Pathogen Load: Increasing rapidly.

Signs and Symptoms: Vague and general. The immune system has begun to respond.

3. Period of Illness: The disease is most severe, and the characteristic signs and symptoms are fully evident. This is the peak of the disease process.

Pathogen Load: Reaches its highest point during this phase.

Signs and Symptoms: Most severe and specific to the particular disease (e.g., jaundice in hepatitis, characteristic rash in measles). The host's immune response is fully engaged, leading to fever and inflammation.

4. Period of Decline: The number of pathogens begins to decrease, and signs and symptoms start to subside. This occurs as the immune system or medical treatment successfully overcomes the pathogen.

Pathogen Load: Decreasing.

Signs and Tymptoms: Lessening in severity. The patient is starting to feel better but is vulnerable to secondary infections due to a weakened immune system.

5. Period of Convalescence: The recovery period where the body returns to its pre-disease state and health is restored. Tissues are repaired, and strength returns.

Pathogen Load: Drastically reduced or eliminated. However, some pathogens can persist.

Signs and Symptoms: None, but the person may feel weak or fatigued. Importantly, some individuals can still be carriers and transmit the pathogen to others even during this recovery phase (e.g., in typhoid fever).