FMT, Microflora, and Human-Microbial Interactions

Fecal Microbial Transplantation (FMT) for C. difficile

• FMT is a treatment for C. difficile infections that restores good bacteria to the colon.
• FMT is achieved by replacing bad bacteria with beneficial bacteria from a donor's stool.
• Colonoscopy is a common method to introduce bacteria into the body during FMT.
• FMT cures 20% to 60% of treated patients.
• Stool samples from healthy donors are screened to ensure they are free of infectious diseases.

Microflora

• Microflora refers to the microbial communities living in a specific environment.
• For example, the human gastrointestinal microflora.
• Dysbiosis is an imbalance in an individual's microflora relative to a healthy state and is the antonym of Eubiosis.

Location of Microorganisms

• Certain body areas provide ideal environments for microbial growth.
• Skin, oral cavity, gastrointestinal tract, respiratory tract, and urogenital tract typically host microorganisms.

Normal Human-Microbial Interactions

• Normal microflora shares a symbiotic relationship with the human body.
• Hosts and their microflora are sometimes referred to as a super-organism
• Microorganisms associated with the human body are divided into three groups, benign/neutral, beneficial, and opportunistic.
• Benign or neutral microorganisms are the most common group, preventing pathogen growth through competition by space, resources, and antimicrobial compound production.
• Beneficial microbes produce nutrients like vitamins used by the body.
• Opportunistic pathogens cause diseases under favorable conditions, such as a compromised immune system or damaged microflora.
• An example of an opportunistic pathogen is Staphylococcus epidermidis, which can cause infection if it enters inner tissues.

Microflora of the Skin

• The skin acts as a barrier and responds to threats, and microbes can survive there even with a powerful immune system.
• Normal skin microflora communicates with the immune system.
• Skin microbiota structure and function are studied to understand skin health and develop skin disease therapies.
• Human skin functions as an ecosystem with bacteria, fungi, protists, and viruses.
• There are over 200 genera of bacteria and fungi, including a few yeast species, that live on the skin.
• Gram-positive bacteria are predominant because they can survive the skin's dry and salty environment.
• Vaginal birth leads to colonization by microbes from the mother's vagina.
• Cesarean birth results in a skin flora more similar to the mother's skin.
• Skin-to-skin contact is encouraged to transfer microbes from mother to baby.
• Studies show an average of 150 bacteria species on human hands, with only 17% similarity between hands on the same person.
• Gender, time since hand washing, and dominant hand affect microbial composition.
• Family members exhibit similar microbial communities.
• Pet owners show great similarity with the microbial communities of their pets.
• Resident microbes live on the skin long-term.
• Transient microflora reach the skin through contact but cannot establish themselves due to competition or washing.
• The amount of moisture, weather, health, age, and hygiene defines skin microflora composition and diversity.
• An example: in HIV patients with compromised normal skin microflora, pathogenic fungi like Candida can colonize and cause infections
• Example: Young children ofter carry more potentially pathogenic gram-negative bacteria.

Microflora of the Gastrointestinal Tract

• The GI tract hosts 10^14 microbial cells, which constitutes 99% of the human microflora.
• The stomach's high acidity (pH 2) prevents microbes from entering the GI tract.
• The small intestine's flora is similar to the stomach near the stomach, but microbial populations increase as pH increases further down.
• The large intestine features very high microbe density
• Intestinal microflora produces vitamin K, vitamin B12, and certain essential amino acids.
• The body removes and replaces about 30% of the GI microflora with feces dry mass daily.
• Factors affecting gut microflora include antibiotics, illness, stress, diet, and age.
• Negative impacts are higher when taking an oral antibiotic.
• Oral antibiotics can cause diarrhea by killing normal microflora.
• Furthermore, antibiotic consumption could give antibiotic-resistant strains such as Staphylococcus aureus, Clostridium difficile, and Candida an advantage.
• There are between 3500 to 35,000 bacterial species in the human gut.
• Ethnicity and diet affects GI microflora, but it is relatively stable throughout one's life.
• There is a link between gut microbe composition and obesity, as well as increased body fat during pregnancy.
• Changing gut bacteria is suggested to be linked to types of cancer.
• High fat and protein diets may alter GI microflora to produce more cancerogenic compounds.
• Diets rich in carbohydrates might benefit the host.
• Modifying one's Gl microflora is a possible strategy to treat certain illnesses.

Microflora of the Urogenital Tract

• The bladder and kidneys of a healthy person are sterile.
• Facultative aerobic bacteria colonize the urethra in healthy males and females.
• Opportunistic pathogens like Escherichia coli and Proteus mirabilis can cause urinary tract infections by multiplying.
• The vagina is colonized by a natural microflora that changes composition throughout life.
• The vagina of the adult female is weakly acidic because Lactobacillus acidophilus ferments glycogen and produces lactic acid, the acidic conditions reduce infection.
• Besides Lactobacillus acidophilus Candida, Streptococci, and E. coli can also be present in the vagina.
• Bacterial, fungal (yeast), or protist infections may result from imbalanced microflora or the introduction of exogenous pathogens.
• L. acidophilus is rare before puberty, glycogen isn't produced, and pH is neutral and microflora includes streptococci, staphylococci, and E. coli.
• Glycogen production stops after menopause and pH rises, while microflora resemble before puberty.

Microbial Pathogenesis

• Pathogenesis is the process by which a pathogen causes disease.
• Disease is tissue damage or injury caused by a pathogen that impairs host function.
• A pathogen is a microorganism that grows in or on a host, causing disease and benefiting at the host's expense.
• Pathogenicity is the ability of a pathogen to cause disease.
• Virulence measures a pathogen's pathogenicity or relative ability to cause disease.
• A more virulent pathogen can be determined using lethal dose 50 data.
• Virulence depends primarily on a pathogen's genotype.

Measuring Virulence

• Virulence is estimated experimentally using LD50 (lethal dose 50).
• Lethal dose 50 is the number of pathogen cells required to kill 50% of a host population.
• Fewer cells of a highly virulent pathogen are required to kill 50% of the target population.
• The number of cells required to kill 100% is not that different to kill 50%
• Attenuation is reducing/eliminating virulence especially when kept in lab conditions for long periods, this are often used as vaccines as it no longer causes any disease.
• Microbes lose their virulence when grown on a synthetic culture medium over time.

Steps For A Disease to Happen:

• A host must be exposed to a pathogen.
• The pathogen must attach to cells such as skin cells or epithelial cells.
• The microbe must be able to enter cells.
• The microbe needs nutrients.
• It needs to produce siderophores to retrieve iron from the host's cells.
• It must reproduce within cells and create a large population
• Symptoms emerge through multiplication.
• Extracellular structures like slime layers, capsules, fimbriae, and pili facilitate bacterial adherence.
• Virulence factors can directly and indirectly promote their pathogenicity.
• Some virulence factors include protease and lipase.
• Virulence factors are diverse, for example, Salmonella species encode a large number of virulence factors which includes toxins, siderophores, and antibiotic resistance plasmids.
• Toxicity is the ability of an organism to cause disease through a toxin that inhibits host cell function or kills host cells.
• Toxins can travel to sites within the host that are not affected by the pathogen
• Toxins are divided into either Exotoxins, or Endotoxins depending on the toxins membrane.
• A specific type of exotoxin is AB toxins.
• AB toxins consist of two subunits, A and B.
• Subunits works by binding to a host cell receptor (B subunit) and transfers damaging agent (A subunit) across the cell membrane.
• The exotoxin, Botulinum toxin (Bacterium Clostridium botulinum produces a potent AB exotoxins that affect nervous tissue.
• One milligram of Botulinum toxin is enough to kill one million pigs.
• The lipopolysaccharide portion of the outer membrane of gram-negative bacteria is an endotoxin and is released as bacterial toxin.

Host Factors

• A host's condition influences the result of pathogen-host interaction.
• Age: infectious diseases are more common in very young and old individuals -Improper diet, or high stress contribute to infection.
• Compromised hosts are more susceptible to infection.
• Host genetics is a key factor, and individuals that are immune or less susceptible exist