Microbial Symbioses with Humans Notes

Overview of the Human Microbiome

  • The human microbiome is the functional collection of different microbes in our body.
  • Microbiota refers to the types of microorganisms present in a microbiome.
  • A healthy adult carries, on average, 2-5 pounds of weight from their microbiome.
  • Microbial genetic repertoire (microbiome) is approximately 100-times greater than that of the human host.
  • Estimated ratio of microbial cells to human cells is approximately 1:1

The Human Microbiome Project

  • Launched in 2007 and continued through 2016 with a budget of $170 million.
  • Aimed to establish a baseline of what constitutes a "healthy" microbiome.
  • Characterized microbiomes of healthy human subjects across five major body sites using 16S and metagenomic sequencing.
  • Now known more broadly as the International Human Microbiome Consortium (IHMC).

Microbial Habitats

  • Skin: Left and right retroauricular crease, left and right antecubital fossa
    • Common microbes: Propionibacterium, Staphylococcus, Corynebacterium, Anaerococcus, Streptococcus
  • Oral: Attached gingivae, hard palate, throat, palatine tonsils, tongue dorsum, buccal mucosa, supragingival plaque, subgingival plaque, saliva
    • Common microbes in Saliva: Streptococcus, Pasteurellaceae, Prevotella, Veillonella, Fusobacterium, Neisseria, Actinomyces, Porphyromonas
  • Nasal: Anterior nares
  • Gut: Gastrointestinal tract, feces
    • Major bacteria: Bacteroidetes, Firmicutes, Lentisphaerae, Proteobacteria, Tenericutes, Verrucomicrobia
  • Urogenital: Vagina (posterior fornix, mid vagina, vaginal introitus)
    • Common microbes: Lactobacillus, Prevotella, Gardnerella, Atopobium, Sneathia, Bifidobacterium, Megasphaera, Anaerococcus

Factors Shaping the Human Microbiome

  • Microbiota associations are flexible and determined by several factors (Turnbaugh, P. J., et al, 2007).
  • Core microbiome: Stable associations over time.

Gastrointestinal Microbiome

  • Major Bacteria Present: Prevotella, Streptococcus, Veillonella, Helicobacter, Proteobacteria, Bacteroidetes, Actinobacteria, Fusobacteria, Firmicutes
  • Esophagus:
  • Stomach: Secretion of acid (HCl), digestion of macromolecules, pH 2
  • Small Intestine:
    • Duodenum
    • Jejunum (103-104 cells/g): Continued digestion, absorption of monosaccharides, amino acids, fatty acids, water, pH 4-5
    • Ileum (108 cells/g): Absorption of bile acids, vitamin B12, pH 7
  • Large Intestine: (1011-1012 cells/g)
    • Appendix, Anus

Microenvironments in the Large Intestine

  • Bacteria are predominant (obligate anaerobes predominate).
  • Clostridium and Bacteroides are dominant groups.
  • Acts as a fermentation vessel.
  • Conversion to feces occurs here.

Bacterial Diversity of the Large Intestine

  • Bacteroides and Clostridium
  • Degradation of plant fiber (cellulose and pectin).
  • Degradation of starch and resistant starch (whole grains) generates beneficial short-chain fatty acids (SCFAs).
  • Degradation of polysaccharides from the mucin layer.

Products of Intestinal Microbiota

  • Vitamin synthesis: Thiamine, riboflavin, pyridoxine, B12, K
  • Amino acid synthesis: Asparagine, glutamate, methionine, tryptophan, lysine, and others
  • Gas production: CO2, CH4, H2
  • Odor production: H₂S, NH3, amines, indole, skatole, butyric acid
  • Organic acid production: Acetic, propionic, butyric acids
  • Glycosidase reactions: β-Glucuronidase, β-galactosidase, β-glucosidase, α-glucosidase, α-galactosidase
  • Steroid metabolism (bile acids): Esterified, dehydroxylated, oxidized

Gut Microbiome and Immune System

  • The human microbiome, particularly in early life, provides critical signals that guide the maturation and calibration of the immune system.

Oral Cavity

  • The oral cavity provides a variety of microbial habitats, each colonized by species that grow primarily as biofilms (Baker, J. L., et al, 2024).

Oral Microenvironments

  • Streptococcus and Actinomyces are the pioneer colonizers of a freshly cleaned tooth surface, followed by successive adherence by species of Veillonella, Prevotella, Fusobacterium, and other genera.
  • Streptococcus and Actinomyces spp. are attracted to statherin in saliva (4-6h).
  • Colonization of Veillonella, Prevotella and other bacteria.
  • Statherin is a salivary protein that prevents precipitation of salts in saliva.

Bacterial Diversity of Subgingival Plaque

Bacteroidetes
Actinobacteria
Saccharibacteria
Spirochaetes
Synergistetes
Firmicutes
Proteobacteria
Fusobacteria

Urogenital Tracts and Their Microbes

  • Kidneys and bladder are believed to be sterile.
  • Facultatively aerobic gram-negative bacteria can colonize epithelial cells lining the distal urethra.
  • Escherichia coli and Proteus mirabilis can cause disease if conditions such as changes in pH occur.

Vaginal Microbiome

  • Weakly acidic and contains significant amounts of glycogen (puberty vs reproductive age vs menopause).
  • At least five types of “normal vaginal communities” containing different compositions of Lactobacillus spp.

Skin Microbes

  • Propionibacterium spp. are the dominant organisms in sebaceous areas.
  • Staphylococcus and Corynebacterium spp. are the most abundant organisms colonizing moist areas.
  • Mixed representation from the phyla Actinobacteria, Proteobacteria, Firmicutes and Bacteriodetes (Grice, E. A., & Segre, J. A., 2011).

Development of the Human Microbiome

  • Birth Infant (
  • Toddler (1-3 years)
    Solid food introduction: Familial transmission, Environmental exposure, Bifidobacterium
  • Full adult diet
    Maternal factors, Postnatal factors: Environment, Familial transmission, Vaginal infection, Periodontitis, Breast-feeding, Antibiotics, Host genetics, Microbiota Lactobacillus depletion, Christensenellaceae

Impact of Birth Mode on Infant Gut Community

  • Vaginal delivery vs. Cesarean delivery significantly impacts the gut microbial composition in early infancy.
    Vaginal delivery: Proteobacteria, Actinobacteria, Bacteroides, Firmicutes
    Cesarean delivery: Other Bacteroidetes, Verrucomicrobia

Impact of Feeding on Infant Gut Community

  • Breastfeeding is associated with elevated numbers of fermentative Bifidobacterium, Lactobacillus, and Staphylococcus species.

Gut Microbial Community Structure in the First Three Years of Life

  • Enterobacteriaceae, Bacteroidaceae, Lachnospiraceae, Ruminococcaceae, Bifidobacteriaceae, Clostridiaceae, change by age (months).

Modulation of the Human Microbiome

  • Alexander Flemming 1928, Penicillium mould secretes an antibacterial substance, which he named "penicillin".
  • Increase in life expectancy for Cystic Fibrosis patients.

Antibiotics and the Human Microbiome

  • Antibiotics affect and change gut microbiota composition (Fishbein, S. R., et al, 2023).
    Bacteroidetes, Firmicutes, menters, Actinobacteria, Proteobacteria, Verrucomicrobia

  • Urgent threat: Clostridioides difficile, Carbapenem-resistant Enterobacteriales

  • Serious threat: ESBL-producing Enterobacteriales, Vancomycin-resistant Enterococcus, Drug-resistant Campylobacter, Salmonella and Shigella

Clostridioides difficile Infections

  • Antibiotic-resistant C. difficile has growth advantage.
  • Loss of community bacterial diversity.
  • C. difficile persists following antibiotic therapy.
  • C. difficile displaced following therapy.

Fecal Microbiome Transplant (FMT)

  • Involves transferring stools from healthy donors into the digestive track of C. diff patients.

Vaginal Seeding

  • A procedure that involves transferring vaginal fluids from a birthing person to a newborn baby's skin, mouth, or nose.
  • Usually performed after a C-section, when a baby doesn't come into contact with vaginal bacteria during birth.

Probiotics

  • Live microorganisms which when administered in adequate amounts confer a health benefit to their host.
  • Scientific evidence has shown they can alleviate:
    • Acne
    • Bacterial vaginosis
    • Clostridium difficile
    • Dysbiosis
    • Infectious diarrhea
    • Inflammatory bowel disease
    • Leaky gut
    • Sinus infections
    • Urinary tract infections
    • Yeast infections

Prebiotics and Synbiotics

  • Prebiotics: Non-digestible food or ingredients that promote the growth of beneficial microorganisms.
  • Synbiotics: Mixture of probiotics and prebiotics.

Probiotic Inhibition of Staphylococcus aureus Intestinal Colonization by Bacillus

  • Ingestion of a Bacillus strain present in a rural Thai environment was shown to prevent colonization by pathogenic Staphylococcus aureus.
  • The Bacillus prevents colonization by interfering with the S. aureus quorum-sensing signaling system, ultimately preventing transcription of genes encoding virulence.

Dysbiosis contributing to necrotizing enterocolitis of premature infants.

  • Necrotizing enterocolitis (NEC) is a severe inflammatory injury to the intestines of low-birthweight premature infants.
  • Probiotic feeding of commercially available species of Bifidobacterium and Lactobacillus.
  • Early treatment with these bacteria reduced the risk of death by 25%, likely by competing for space and resources with pathogenic enteric bacteria.