Microbial Symbioses with Humans

Introduction to Microbial Symbioses

  • All sites on a human body containing microorganisms are part of a microbiome.

  • Microbiome: Functional collection of various microbes situated within a particular environmental system, e.g., the human microbiome.

  • Microbiota: Refers to all microbes present in a specific microhabitat, such as skin microbiota.

  • Distinct microhabitats host different microbes, illustrating vast microbiota differences between skin and oral environments.

24.1 Overview of the Human Microbiome (1 of 4)

  • Estimated that there are approximately 100 trillion microbes in the human microbiome, which exist in complex communities.

Figure 24.1: Microbial Habitats of the Human Body

  • Microbial habitats include various regions such as the skin, gut, vagina, and oral cavity.

24.1 Overview of the Human Microbiome (2 of 4)

  • Future benefits of understanding the human microbiome include:

    • Development of biomarkers for disease predisposition prediction.

    • Designing targeted therapies and personalized drug therapies.

    • Developing probiotics.

  • Initial studies indicate complex interactions between the host and its microbiota.

24.1 Overview of the Human Microbiome (3 of 4)

  • Experimental Protocols and Body Target Sites:

    • The majority of bacteria in the human body cannot be cultured; however, advanced sequencing techniques have enabled identification of diverse microbiota in different body sites.

    • Numerous studies have been conducted to uncover the characteristics of normal microbiota.

Figure 24.2: Overview of Major Microbial Populations in Body Sites Sampled by Human Microbiome Projects

24.1 Overview of the Human Microbiome (4 of 4)

  • Ongoing integrated projects aim to address fundamental questions about the human microbiome:

    • Is there a core human microbiome shared among individuals?

    • What is the correlation between microbiota composition at body sites and host genotype?

    • Do variations in the human microbiome correlate with health differences?

    • Are variations in specific bacterial populations significant concerning health and disease?

24.2 Gastrointestinal Microbiota (1 of 8)

  • Humans are monogastric omnivores.

  • Gut microbes significantly influence early development and predisposition to various diseases.

  • Gut colonization begins at birth.

24.2 Gastrointestinal Microbiota (2 of 8)

  • The human gastrointestinal (GI) tract comprises:

    • Stomach

    • Small intestine

    • Large intestine (totaling about 400 m² surface area).

  • Key roles include food digestion, nutrient absorption, and production of vitamins by indigenous microbial flora.

24.2 Gastrointestinal Microbiota (3 of 8)

  • The Stomach and Small Intestine:

    • Microbial populations vary across the GI tract, influenced by diet and environmental conditions.

    • Stomach and duodenal acidity inhibits many organisms, but some microbiota thrive in a healthy stomach.

    • Common bacteria in gastric fluid include Firmicutes, Bacteroidetes, and Actinobacteria.

    • Acid-resistant Helicobacter pylori was found in a significant percentage of the world’s population and typically resides in gastric mucosa.

24.2 Gastrointestinal Microbiota (4 of 8)

  • Intestinal Microorganisms:

    • Conduct several vital metabolic reactions producing notable compounds.

  • The Large Intestine:

    • Functions as a fermentation vessel, where microbiota metabolize nutrients from digested food.

    • Microbial species predominantly reside in the lumen of the large intestine with some within mucosal layers.

24.2 Gastrointestinal Microbiota (5 of 8)

  • Summary of Gut Microbiota:

    • Majority of human gut bacteria fall into three main phyla:

    1. Firmicutes

    2. Bacteroidetes

    3. Proteobacteria

    • The composition may impact metabolism and an individual's likelihood of obesity.

24.2 Gastrointestinal Microbiota (6 of 8)

  • Gut Enterotypes:

    • Individuals demonstrate variation in gut microbiota, yet each maintains relative stability.

    • Three enterotypes identified:

    1. Type #1 enriched in Bacteroides

    2. Type #2 enriched in Prevotella

    3. Type #3 enriched in Ruminococcus

    • They are distinct concerning function and phylogenetics, potentially influencing dietary and therapeutic responses.

24.2 Gastrointestinal Microbiota (7 of 8)

  • Products of Intestinal Microbiota:

    • Metabolites from gut microbiota influence host physiology significantly. Notable roles include:

    • Vitamin Production

    • Steroid Modification

    • Amino Acid Biosynthesis

Table 24.2: Biochemical/Metabolic Contributions of Intestinal Microorganisms

  • Processes and their products include:

    • Vitamin Synthesis: Thiamine, riboflavin, pyridoxine, B₁₂, K.

    • Amino Acid Synthesis: Asparagine, glutamate, methionine, among others.

    • Gas Production: CO₂, CH₄, H₂.

    • Organic Acid Production: Acetic, propionic, butyric acids.

    • Steroid Metabolism: Modifications to bile acids and steroids for amino acid synthesis inferred from gut metagenomic pathways.

24.2 Gastrointestinal Microbiota (8 of 8)

  • Immune System Development:

    • The immune system's proper function depends on microbial stimulation.

    • Early exposure to diverse microorganisms is critical for developing immune tolerance to beneficial microbes and recognizing harmful pathogens.

    • Ongoing research identifies biologically active compounds produced by human microbiota.

24.3 Oral Cavity and Airways (1 of 2)

  • The oral cavity is a complex, heterogeneous microbial habitat.

  • Saliva contains antimicrobial enzymes, yet nutrients near surfaces promote microbial growth.

  • Tooth structure:

    • Consists of a mineral matrix (enamel) covering dentin and pulp.

    • Biofilm formation on teeth (dental plaque) consists of an ordered microbial assembly.

Figure 24.7: Bacterial Diversity of Saliva

24.3 Oral Cavity and Airways (2 of 2)

  • Microenvironments of the Respiratory Tract:

    • Microbiota flourish in the upper respiratory tract. Most bacteria enter through air but are trapped in mucus and ejected or killed in the stomach.

    • The lower respiratory tract typically lacks normal microbiota in healthy individuals; only small particles reach lungs, which may include pathogenic microbes leading to conditions like pneumonia.

24.4 Urogenital Tracts and Their Microbes (1 of 2)

  • Altered pH in urinary tracts can allow pathogens (e.g., E. coli, Proteus mirabilis) to multiply and cause infections, particularly urinary tract infections in women.

24.4 Urogenital Tracts and Their Microbes (2 of 2)

  • The female vagina is weakly acidic with significant glycogen content.

  • Lactobacillus acidophilus ferments glycogen, resulting in lactic acid production that helps maintain an acidic local environment.

24.5 The Skin and Its Microbes (1 of 2)

  • The skin hosts approximately 1 million resident bacteria per square centimeter, totaling around 1 trillion microorganisms on an average adult's skin.

  • Variations in skin surface chemistry and moisture lead to three microenvironments:

    1. Dry skin

    2. Moist skin

    3. Sebaceous skin

Figure 24.15: Overview of the Skin Microbiota

24.5 The Skin and Its Microbes (2 of 2)

  • Microbial composition is influenced by environmental factors (e.g., weather) and host factors (e.g., age, hygiene).

  • Each skin microenvironment supports a unique microbiota composition, illustrated through heat maps.

Figure 24.17: Staphylococcus, Propionibacterium, and Corynebacterium Distributions on Human Skin

24.6 The Human Virome (1 of 2)

  • The human body contains a vast array of viruses, including animal viruses, bacteriophages, and possibly plant viruses. Various viruses can cause mild to severe diseases.

  • Most prevalent viruses across body sites are bacteriophages rather than animal viruses.

24.6 The Human Virome (2 of 2)

  • Role of Bacteriophages in Human Health:

    • Bacteriophages are vital in offering protection against particular pathogens, especially on mucosal surfaces, where they are abundant.

    • Estimated that bacteriophages outnumber bacteria in the mucosa by a factor of 20.

    • Their existence signifies a potential symbiotic relationship and offers host-independent immunity.

24.7 Human Study Groups and Animal Models (1 of 3)

  • Human Microbiome Study Groups contribute substantially to understanding the human microbiome's functions.

  • The Human Microbiome Project (HMP) surveyed medical students for baseline knowledge of healthy microbiomes.

  • Subsequent studies indicated more diversity in non-US subjects and highlighted gaps in dietary or lifestyle data.

24.8 Colonization, Succession, and Stability of the Gut Microbiota (1 of 2)

  • Microbial Activities in Infancy:

    • Microbial colonization begins at birth from maternal transfer.

    • Early colonizers predominantly serve as vitamin sources and are primarily facultative rather than obligate anaerobes.

    • Variability in Gut Microbiome: Vaginally delivered infants share microbiota characteristics with their mothers compared to cesarean-born infants.

    • Breastfed infants benefit from higher levels of commensal bacteria due to oligosaccharides in breast milk that support their growth.

Figure 24.20: Maturation of the Infant Gut Community

24.8 Colonization, Succession, and Stability of the Gut Microbiota (2 of 2)

  • **Stability of Adult Microbiome: **

    • Early experiences are crucial in shaping the gut microbiome. Aging and frailty relate to reduced microbial diversity.

24.9 Syndromes Attributed to the Gut Microbiota (1 of 3)

  • Inflammatory Bowel Disease (IBD):

    • Characterized by chronic gut inflammation and disruption of homeostasis (dysbiosis).

    • Antibiotic use heightens IBD risk and may allow transmissibility between family members.

    • Individuals with IBD tend to show lower gut microbiome diversity and a strong association with Western diets rich in animal proteins.

Figure 24.24: Reduced Functional Capacity in Gut Microbiome of IBD Patients

24.9 Syndromes Attributed to the Gut Microbiota (2 of 3)

  • Mouse Models:

    • Normal mice exhibit 40% more fat than germ-free mice fed identical diets.

    • Introducing normal mouse microbiota into germ-free mice results in weight gain, indicating microbiota's impact on obesity predisposition.

    • Obese mice harbor different microbiota than normal, with higher Firmicutes and methanogenic Archaea levels.

Figure 24.25a: Fermentation in the Colon of Lean vs. Obese Mice

24.9 Syndromes Attributed to the Gut Microbiota (3 of 3)

  • Human Obesity:

    • Studies did not validate mouse-based Bacteroidetes-Firmicutes relationships but showed obese humans often host more Prevotella species and methanogenic Archaea, mirroring findings in mice.

    • Dietary habits and genetics are key in determining the transmissibility and nature of gut microbiota.

24.10 Syndromes Attributed to the Oral, Skin, and Vaginal Microbiota

  • Dental Health Issues:

    • Formation of biofilms, known as dental plaque, consists of Streptococcus and other fermentative bacteria. These organisms produce acids that degrade tooth enamel leading to caries.

    • Periodontal disease may contribute to systemic health issues, including cardiovascular diseases and arthritis.

24.11 Antibiotics and the Human Microbiome (1 of 2)

  • Oral antibiotics impact all gut microbes, targeting both harmful and beneficial bacteria.

  • Early-life antibiotic use increases risks for IBD and disorders tied to dysbiosis.

  • Clostridium difficile:

    • Known for causing infections linked to antibiotic use; they are spore-formers resistant to many antibiotics.

    • Fecal transplants have emerged as a therapeutic approach to treat Clostridium difficile infections.

Figure 24.28: Antibiotic Treatment and Clostridioides difficile Infection Risk

24.11 Antibiotics and the Human Microbiome (2 of 2)

  • Fecal Transplants:

    • Aim to restore normal microbiota in patients with bacterial intestinal diseases to displace disease-causing organisms.

    • The success rate of fecal transplants from healthy donors in treating C. difficile infections has led to increased adoption of the treatment.

24.12 Probiotics, Prebiotics, and Synbiotics (1 of 2)

  • Probiotics: Live microorganisms providing health benefits, e.g., species of Bifidobacterium and Lactobacillus found in yogurt.

  • They may prevent pathogen colonization by occupying spaces/nutrients.

  • Prebiotics: Indigestible complex carbohydrates that nourish gut bacteria.

  • Examples include inulin and components of soluble fiber.

24.12 Probiotics, Prebiotics, and Synbiotics (2 of 2)

  • Synbiotics: Formulations combining probiotics and prebiotics, enhancing both components’ effectiveness.

  • Successful applications of synbiotics include treatments for sepsis in young children.