The Microbe-Human Ecosystem

Chapter 33: The Microbe-Human Ecosystem

  • Lectures by: UCLA Prof. Berthet

Introduction to Fermented Foods and Beverages

  • Questions raised:

    • What microbes are utilized in creating favorite fermented foods and beverages?

    • How did humans discover these fermented food and beverage processes?

Terminology

  • Microbiome:

    • All the genes found within an organism's microbiota.

  • Microbiota:

    • The community of microorganisms residing in and on an organism.

  • Holobionts:

    • Refers to hosts (including humans) and the microbes living symbiotically with them, showing co-evolution.

  • Microbial Niche:

    • Influenced by factors such as location within the body, age, sex, diet, and environmental conditions.

  • Microbial-Free Areas:

    • Internal organs such as the brain, blood, cerebrospinal fluid, and muscles typically lack microorganisms.

  • Surface Tissues:

    • Skin and mucous membranes are frequently colonized by various microbes as they engage with the external environment.

Early Colonization

  • Importance of colonization in newborns:

    • Vaginal delivery allows exposure to maternal microbiota from the birth canal.

    • Cesarean delivery exposes newborns to microbes primarily from caretakers.

  • Bifidobacteria Role:

    • Able to transport polymeric sugars from human breast milk across their plasma membrane, fermenting these sugars to provide essential calories to infants and lower gut pH, which inhibits pathogen growth.

  • Microbiota Development:

    • The microbiota community is dynamic and evolves post-birth, stabilizing by age three.

    • A diverse microbiome is critical for health.

Adult Human Microbiota

  • Generally stable throughout life, with changes related to physical or lifestyle shifts.

  • Major Bacterial Phyla in Human Microbiota:

    • Actinobacteriota

    • Bacteroidota

    • Fusobacteriota

    • Firmicutes

    • Proteobacteria

    • Verrucomicrobiota

  • Other microorganisms including archaea, fungi, and viruses also inhabit the human body.

Specific Microbial Ecosystems in the Body

Skin Microbiota

  • Dominant Species: Staphylococcus epidermidis

  • Environment:

    • Characterized by slight acidity and high sodium chloride concentrations.

    • Some areas are oily due to sebum, while others are dry, supporting diverse microbial life.

  • Key Functions:

    • Aids in gene expression in keratinocytes leading to antimicrobial peptide (AMP) production, which provides defense against pathogens.

    • Uses Microbe-Associated Molecular Patterns (MAMPs) to bind with TLR-2 receptors for pathogen recognition.

    • Employs Bacterial Interference for pathogen growth inhibition.

Oral Microbiota

  • Initial colonization occurs shortly after birth from environmental sources.

  • Anaerobic genera such as Porphyromonas, Prevotella, and Fusobacterium become prevalent in the anoxic gaps of teeth and gums and as teeth emerge, Streptococcus parasanguinis, S. mutans, and S. salivarius attach to dental enamel and mucosal surfaces.

  • Contributions:

    • Involved in dental plaque formation, dental caries, gingivitis, and periodontal diseases.

Stomach Microbiota

  • Most microorganisms are destroyed under acidic gastric conditions, but some can survive.

    • Notable survivors include Streptococcus, Staphylococcus, Lactobacillus, and mucosal yeasts like Candida.

  • Microbes may survive if they pass quickly through or are ingested with food particles resistant to gastric pH.

  • Functions include:

    • Production of Vitamin K from E. coli.

    • Emerging evidence indicates gut microbiota impacts human behavior, a field rapidly evolving.

Large Intestine (Colon) Microbiota

  • One of the most densely populated microbial ecosystems.

  • People from industrialized regions exhibit distinct core microbiomes compared to those with plant-based diets.

  • The gut microbiome collectively holds metabolic, immunological, and endocrine roles.

Small Intestine Microbiota

  • Divided into three sections:

    • Duodenum: Contains few organisms due to stomach acid, bile, and pancreatic juices.

    • Jejunum: Hosts Enterococcus faecalis, lactobacilli, and Candida albicans.

    • Ileum: Flora resembles that of the colon; the pH shifts to more alkaline.

Host Metabolism

  • The gut microbiota helps convert food into usable calories.

  • Research indicates overweight individuals typically have higher levels of Firmicutes and lower levels of Bacteroidetes.

  • Attention has shifted to metabolomes - the substances secreted by these microorganisms.

  • Bacteria ferment food monomers into short-chain fatty acids, some of which may induce weight gain.

Germ-Free (GF) Mice Studies

  • GF mice are derived from cesarean births and raised in sterile conditions.

  • They provide a framework for exploring microbial impacts on animal health by comparing them with conventional mice.

  • Findings indicate GF mice can consume more food but gain less weight compared to standard mice.

  • After fecal microbiome transplants, these previously GF mice become obese without altering diet or exercise.

Immunity and Microbiota

  • Antibiotic treatments can disrupt gut microbial communities.

  • Following antibiotics, individuals are more susceptible to gastrointestinal infections.

  • Colonization Resistance:

    • Based on competitive exclusion of harmful pathogens; microbiomes secrete toxic peptides that specifically target pathogens.

Gut Microbiota's Influence on the Central Nervous System (CNS)

  • Behavioral traits (curiosity, sociability) and mental states (anxiety, depression) differ between GF and normal mice.

  • Heritable traits aid prediction of microbiome impacts on CNS function.

  • Three proposed pathways of microbiome influence on CNS:

    1. The microbiome affects the immune system.

    2. A direct pathway exists from the gut to the brain via GI tract nerves (e.g., vagus nerve signals).

    3. Soluble products from microbes can cross the blood-brain barrier.

Metabolic Syndrome

  • Defined by the presence of at least three characteristics:

    • Large waist size.

    • High triglyceride levels.

    • High blood pressure.

    • Elevated low-density lipoprotein levels.

    • High fasting blood glucose levels.

  • Characterized by chronic, low-level inflammation linked to the microbiome via metabolic endotoxemia.

Cardiovascular Disease

  • Diet associated with cardiovascular disease commonly includes high red meat and fat content while providing insufficient fiber for gut microbes to generate anti-inflammatory short-chain fatty acids (SCFAs).

  • Promotes growth of a microbial population that metabolizes components like L-carnitine and phosphatidylcholine to generate trimethylamine (TMA).

  • TMA enters the bloodstream and reaches the liver, where it converts to trimethylamine N-oxide, accelerating atherosclerosis.

Cancer and Microbes

  • Approximately 20% of malignancies are influenced by microbial involvement.

  • Specific viruses may induce cancer by affecting host cell cycles to favor growth, leading to mutations and increased cancer risk.

  • Example: Helicobacter pylori involves proteins like CagA which affects the host cell cycle promoting proliferation and inhibits DNA repair mechanisms.

  • Some bacteria are implicated in the metastatic spread of tumors, contributing to inflammation states associated with dysbiosis.

Probiotics and Prebiotics

  • Prebiotics: Compounds that promote the beneficial effects of probiotics by enhancing their colonization.

  • Probiotics Defined:

    • “Live microorganisms that, when administered in adequate amounts, confer health benefits to the host” (as per FAO-WHO).

  • Caution on Probiotics:

    • The U.S. FDA does not rigorously regulate foods or supplements claiming to contain probiotics; thus, health benefits remain unverified.

Take Home Message

  • Understand the interactions between microbes and organisms and particularly the relationships between humans and their resident microbes.

  • Be able to explain key concepts and terminologies associated with microbial interactions.

  • Consider the implications of disruptions in the normal human microbiome across various body regions.

Guide Questions

33.1 Humans Are Holobionts

  • Define the term microbiome.

  • Explain the concept of humans as holobionts.

33.2 The Microbiome Develops from Birth to Adulthood

  • Discuss the role of bifidobacteria in infant microbiome development.

  • Predict environmental conditions favoring acidophilic, anaerobic, lactic acid-fermenting, and halophilic bacteria association.

  • Analyze factors mediating microbial diversity in the human body.

33.3 A Functional Core Microbiome Is Required for Host Homeostasis

  • Explain the gut microbiome's contribution to metabolism.

  • Assess the significance of germfree mice in understanding the human microbiome.

  • Differentiate between direct and indirect mechanisms for colonization resistance.

  • Identify three reasons the immune system relies on the microbiome for homeostasis.

  • Contrast three pathways of communication between gut microbes and the central nervous system.

33.4 Many Diseases Have a Connection with Dysbiosis

  • Describe metabolic syndrome and its metabolic endotoxemia hypothesis.

  • Discuss how a diet high in red meat connects to atherosclerosis through microbial means.

  • Outline the overarching relationship between the microbiome and cancer development.

33.5 Microbiome Manipulation Can Be Therapeutic

  • Define what constitutes a probiotic product.

  • Anticipate the applications of probiotics in disease prevention.