1. Overview

• The course covers the physiopathology of the human holobiont, emphasizing the microbiota's role in health and disease.
• Located primarily in the digestive tract (gut microbiota) but applicable to the whole organism.
• Highlights include microbiota acquisition, functions, and impact on diseases.
• Approach includes technological tools (NGS, metagenomics), study design, data analysis, and clinical case studies.

2. Core Concepts & Key Elements

• Definition of holobiont: host plus associated microbes; considered a supra-organism.
• Components of microbiota: bacteria, viruses, fungi, archaea.
• Historical emergence driven by technological breakthroughs like NGS; earlier dogmatic views delayed understanding.
• Microbiota acquisition: mainly in perinatal life, with influences from delivery mode (vaginal vs. C-section).
• Microbiota develops through stages from newborn to adult; defined by enterotypes (Bacteroides, Prevotella, Ruminococcus).
• Biodiversity varies among individuals; shared functions despite taxonomic differences.
• Spatial segregation: mucus layer, epithelium, lumen.
• Barriers: physical (mucus), biochemical (antimicrobials), immunological (immune tolerance).
• Symbiosis types: mutualism, commensalism, pathogenic (pathobionts).
• Microbiota contributes to host: digestion, vitamin production, energy, detoxification, immune modulation, organ regulation.
• Systems involved: vagus nerve, bloodstream, lymphatic system.
• Dysbiosis: loss of beneficial microbes, overgrowth of pathogens, associated with diseases: cancers, metabolic (obesity, diabetes), neurodevelopmental (autism), inflammatory, skin, gut.
• Koch’s postulates adapted to microbiota-related diseases: similar dysbiosis, reintroduction triggers disease.
• Gut microbiota influences: metabolic diseases, immune system development, inflammation, neuro functions, cancer response.
• Mechanisms: microbial metabolites (SCFA, TMA), structural molecules (LPS), neurochemical mediators.
• Microbiota’s role in diseases: allergies, asthma, autoimmune, neurodegenerative, cancer, metabolic states.

3. High-Yield Facts

• Human microbiota gene count: 600,000–3 million; human gene count: 30,000.
• Microbiota weight: approximately 2 kg.
• Main gut enterotypes: Bacteroides, Prevotella, Ruminococcus.
• Biodiversity shared functions: >50% metabolic pathways common; species vary.
• Dysbiosis signatures: reduced diversity, loss of beneficial microbes, pathogen colonization.
• Koch’s adapted criteria: dysbiosis is similar across patients, microbiota transfer can induce diseases.
• Gut microbiota predicts metabolic health: diet explains more variance than genome (57% vs. 90% accuracy).
• Obesity can be transferred via microbiota; worm studies show transmissibility.
• Short-chain fatty acids (SCFA): key in modulating gene expression, energy, and immune functions.
• Microbial influence pathways: humoral, nervous (vagus), immune.
• Key microbial metabolites: SCFA, TMA, LPS.
• Diseases associated with dysbiosis: cancer, autism (+33%), allergies, inflammatory bowel diseases, neurodegenerative diseases.
• C-section increases risk for allergies, asthma, obesity, autoimmune diseases.
• Gut-brain axis involves neurotransmitter synthesis: 95% of serotonin produced in gut.
• Microbiota can modulate neuropsychological states: anxiety, depression, social behavior.
• Microbial interventions: probiotics, fecal microbiota transplants reduce symptoms in autism, obesity.

4. Summary Table

5. Mini-Schema (ASCII)

Human Holobiont
 ├─ Components of Microbiota
 │   └─ Bacteria, viruses, fungi, archaea
 ├─ Acquisition & Development
 │   ├─ Perinatal phase
 │   └─ Microbiota evolution: newborn to adult
 ├─ Microbiota Functions
 │   ├─ Digestion, vitamin synthesis
 │   ├─ Immune modulation
 │   ├─ Metabolic regulation
 │   └─ Barrier integrity
 ├─ Spatial & Structural Barriers
 │   ├─ Mucus layer
 │   ├─ Epithelium
 │   └─ Immune system
 ├─ Dysbiosis & Disease
 │   ├─ Loss of diversity
 │   ├─ Pathobiont overgrowth
 │   └─ Associated diseases: cancer, autism, obesity, allergies
 └─ Microbiota Host Interactions
     ├─ Nervous system (vagus, serotonin)
     ├─ Bloodstream (metabolites)
     └─ Immune regulation

6. Rapid-Review Bullets

• The holobiont includes host plus microbiota, a supra-organism.
• Main microbiota: bacteria, viruses, fungi, archaea.
• Acquisition begins at birth; mode (vaginal vs. C-section) impacts microbiota development.
• In adults, microbiota classified into enterotypes: Bacteroides, Prevotella, Ruminococcus.
• Biodiversity varies but functions (metabolism, immunity) are shared among individuals.
• Microbiota components: mucus, epithelium, lumen; barriers prevent pathogen invasion.
• Symbiosis: mutualism, commensalism; pathogens = pathobionts.
• Functions include digestion, vitamins, detox, immune training, organ regulation.
• Dysbiosis involves loss of beneficial microbes and overgrowth of harmful species.
• Dysbiosis linked to cancer, allergy, autism, obesity, neurodegeneration.
• Microbiota influences: gut-brain axis, immune responses, metabolic pathways.
• Serotonin 95% produced in gut; microbiota modulates neurochemical mediators.
• Obesity and metabolic diseases can be transmitted via microbiota; affected by diet.
• Intervention: probiotics, fecal transplants show therapeutic potential.
• C-section increases risks of immune and metabolic disorders.
• Gut microbiota plays role in inflammation, cancer, immune response, and neurodevelopment.