24. Microbial Symbioses With Humans: The Human Microbiome and Its Impact

Microbial Symbioses With Humans

Definitions: Microbiome vs. Microbiota

The human body hosts a vast array of microorganisms that interact with each other and with their host, forming complex symbiotic relationships. Understanding the terminology is essential for studying these interactions.

• 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 themselves but also their genetic material and interactions.

• Microbiota: The specific types of organisms present in a given habitat (e.g., human skin, gastrointestinal tract, mouth). Microbiota refers to the composition, while microbiome includes function and genetics.

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

Methodologies for Probing the Human Microbiome

Metagenomics

Modern microbiology uses advanced techniques to study the diversity and function of the human microbiome.

• Metagenomics: The study of genetic material recovered directly from environmental samples, allowing identification and quantification of microbial groups without the need for culturing.

• Process: Sample collection → DNA extraction → DNA library preparation → DNA sequencing → Sequence analysis and genome reconstruction.

• Applications: Reveals microbial diversity, abundance, and potential functions in the human body.

Overview of the Human Microbiome

Major Habitats and Diversity

The human microbiome varies by body site, with each habitat supporting distinct microbial communities.

• Skin: Dominated by Propionibacterium, Staphylococcus, and Corynebacterium.

• Saliva: Contains Streptococcus, Prevotella, Veillonella, and others.

• Urogenital Tract: Lactobacillus is predominant, especially in females.

• Gastrointestinal Tract: Rich in Bacteroides, Firmicutes, and other groups; most diverse overall.

Body Site	Dominant Genera
Skin	Propionibacterium, Staphylococcus
Saliva	Streptococcus, Prevotella
Urogenital Tract	Lactobacillus
GI Tract	Bacteroides, Firmicutes

Gastrointestinal Microbiota

Development and Function

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.

• Major Sites: Stomach, small intestine, large intestine.

• Large Intestine: Functions as an in vivo fermentation vessel, with microbiota using nutrients from food digestion. Most microbes are found in the lumen, some in mucosal layers.

• Bacterial Diversity: Fecal samples show dominance of Bacteroidetes and Firmicutes.

Products of Intestinal Microbiota and Immune Education

Gut microbes contribute to host metabolism and immune system development.

Process	Product/Enzyme
Vitamin synthesis	Thiamine, riboflavin, pyridoxine, B12, K
Amino acid synthesis	Asparagine, glutamate, methionine, tryptophan, lysine, others
Gas production	CO2, CH4, H2
Odor production	H2S, NH3, indole, butyric acid
Glycosidase reactions	β-glucosidase, α-galactosidase
Steroid metabolism	Esterified, dehydroxylated, oxidized steroids

Oral Microbiota

Composition and Growth

The oral cavity is a complex microbial habitat with antimicrobial enzymes in saliva, but nutrient-rich surfaces promote localized microbial growth.

• Major Genera: Streptococcus, Actinomyces, Veillonella, Prevotella.

• Biofilm Formation: Dental plaque is a biofilm that can lead to dental caries and periodontitis.

Microbiota of the Respiratory Tract

Upper vs. Lower Respiratory Tract

Microbial colonization is limited to the upper respiratory tract; the lower tract is typically sterile.

• Upper Respiratory Tract: Microbes are trapped in mucus and expelled or destroyed in the stomach.

• Lower Respiratory Tract: No naturally resident microbiota; infections are usually due to transient pathogens.

Urogenital Tracts and Their Microbes

Urogenital Tract

The urogenital tract is generally sterile except for the distal urethra and vagina, which can harbor microbes.

• Kidneys: Typically sterile in both sexes.

• Pathogen Growth: Changes in pH or other conditions can allow pathogens like Escherichia coli and Proteus mirabilis to proliferate, causing urinary tract infections (UTIs).

Vaginal Microbiota

The adult female vagina is weakly acidic (pH ~5) and contains glycogen, supporting the growth of Lactobacillus acidophilus, which ferments glycogen to produce lactic acid and maintain acidity.

• Function: Lactic acid production inhibits growth of pathogens.

Skin Microbiota

Factors Influencing Composition

The skin microbiota is shaped by environmental factors, skin type, temperature, and personal hygiene.

• Microenvironments: Dry skin, moist skin, sebaceous (oily) skin.

• Major Genera: Staphylococcus, Propionibacterium, Corynebacterium.

Skin Type	Dominant Microbes
Dry	Betaproteobacteria, Flavobacteriales
Moist	Staphylococcus, Corynebacterium
Sebaceous	Propionibacterium

Colonization, Succession, & Stability of Gut Microbiota

Birth and Feeding Influences

Initial colonization and development of the gut microbiota are influenced by birth mode and infant diet.

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

• Breast Milk vs. Formula: Breastfed infants develop a different gut microbiome, often richer in Bifidobacterium, compared to formula-fed infants.

Disorders Attributed to Gut Microbiota

Inflammatory Bowel Disease (IBD)

IBD is characterized by chronic gut inflammation and dysbiosis (microbial imbalance).

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

• Dysbiosis: Disruption of normal microbial homeostasis.

Gut Microbiota and Obesity

Microbiota composition is linked to obesity in both animal models and humans.

• Mouse Models: Normal mice have more fat than germ-free mice; genetically obese mice have different 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 produce acids that erode tooth enamel, leading to caries. Periodontal disease can contribute to systemic conditions such as cardiovascular disease and arthritis.

Antibiotics and the Human Microbiome

Impact of Antibiotics

Oral antibiotics affect all gut microbes, not just pathogens. Early-life antibiotic use increases risk of IBD and other dysbiosis-related disorders.

• Antibiotic Resistance: Overuse can promote growth of resistant organisms like Clostridioides difficile.

Fecal Transplants

Therapeutic Use

Fecal transplants involve transferring microbiota from a healthy donor to a patient, often used to treat recurrent C. difficile infections with high success rates.

Probiotics and Prebiotics

Definitions and Applications

Probiotics are live microorganisms that confer health benefits, while prebiotics are indigestible carbohydrates that nourish beneficial gut bacteria.

• Common Probiotic Bacteria: Lactobacillus, Bifidobacterium.

• Prebiotics: Examples include inulin, fructooligosaccharides.

Probiotic Inhibition of Staphylococcus aureus

Mechanism of Action

Probiotics can inhibit pathogenic bacteria such as S. aureus by interfering with quorum sensing and virulence gene expression.

• Example: Blocking of Agr system signaling by probiotic-derived molecules prevents expression of virulence factors.