🪱Microbiomes Unit 6 – Microbiomes: Impact on Health and Disease

Key Concepts and Definitions

• Microbiome refers to the collective genomes of all microorganisms in a particular environment, including bacteria, archaea, viruses, and fungi
• Microbiota describes the community of microorganisms themselves, while microbiome encompasses their collective genomes
• Symbiosis is a close and long-term biological interaction between two different organisms, which can be mutualistic (beneficial to both), commensal (beneficial to one, neutral to the other), or parasitic (beneficial to one, harmful to the other)
• Dysbiosis is an imbalance in the composition of the microbiome, often associated with disease states
• Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host
• Prebiotics are non-digestible food components that promote the growth and activity of beneficial microorganisms in the gut
• Metagenomics is the study of genetic material recovered directly from environmental samples, allowing for the analysis of microbial communities without the need for cultivation

Microbiome Composition and Diversity

• Human microbiome is composed of trillions of microorganisms, including bacteria, archaea, viruses, and fungi
• Bacterial phyla Firmicutes and Bacteroidetes dominate the gut microbiome, while Actinobacteria and Proteobacteria are also present
• Gut microbiome composition varies along the gastrointestinal tract, with higher diversity in the colon compared to the stomach and small intestine
• Skin microbiome is dominated by Staphylococcus, Corynebacterium, and Propionibacterium, with variations depending on the skin site (sebaceous, moist, or dry)
• Oral microbiome includes Streptococcus, Actinomyces, and Veillonella, among others, and plays a role in oral health and disease
• Vaginal microbiome is typically dominated by Lactobacillus species, which help maintain a low pH and prevent pathogen growth
• Microbial diversity is essential for a healthy microbiome, as it contributes to resilience and stability of the ecosystem

Microbiome Development and Factors Influencing It

• Microbiome development begins at birth, with mode of delivery (vaginal or cesarean) influencing initial microbial colonization
  • Vaginally delivered infants acquire microbes from the mother's vaginal and fecal microbiota
  • Cesarean-delivered infants are exposed to skin and hospital environment microbes
• Breastfeeding promotes the growth of beneficial bacteria, such as Bifidobacterium and Lactobacillus, in the infant gut
• Introduction of solid foods and weaning lead to a shift in the gut microbiome composition, with an increase in diversity and abundance of adult-like microbes
• Age-related changes in the microbiome occur throughout life, with a decline in diversity and stability in the elderly
• Diet significantly influences the gut microbiome, with high-fiber, plant-based diets promoting a more diverse and healthier microbiome compared to high-fat, low-fiber diets
• Antibiotics can disrupt the microbiome, leading to a decrease in diversity and potential overgrowth of opportunistic pathogens
• Environmental factors, such as geography, hygiene, and living conditions, also shape the microbiome composition

Functions of the Microbiome in Human Health

• Microbiome plays a crucial role in nutrient metabolism, breaking down complex carbohydrates, proteins, and lipids
• Synthesis of essential vitamins (K and B vitamins) by the gut microbiome contributes to the host's nutritional status
• Microbiome helps maintain the integrity of the intestinal barrier, preventing the translocation of pathogens and toxins
• Modulation of the immune system by the microbiome is essential for the development of a balanced immune response
  • Microbiome promotes the development of regulatory T cells and the production of anti-inflammatory cytokines
  • Interaction with the microbiome helps the immune system distinguish between commensal and pathogenic microbes
• Microbiome influences the production of neurotransmitters (serotonin, GABA) and communicates with the central nervous system through the gut-brain axis
• Competitive exclusion by the microbiome prevents the overgrowth of opportunistic pathogens, maintaining a healthy microbial balance
• Metabolism of xenobiotics and drugs by the microbiome can affect their bioavailability and toxicity

Dysbiosis and Its Consequences

• Dysbiosis is characterized by a shift in the relative abundances of microbial taxa, often with a decrease in diversity and stability
• Factors contributing to dysbiosis include antibiotic use, poor diet, stress, and infections
• Dysbiosis can lead to increased intestinal permeability ("leaky gut"), allowing the translocation of microbes and their products into the bloodstream
• Chronic inflammation is a common consequence of dysbiosis, as the immune system is constantly stimulated by the altered microbiome
• Dysbiosis may contribute to the development of metabolic disorders, such as obesity and type 2 diabetes, by altering energy harvest and storage
• Altered production of short-chain fatty acids (SCFAs) in dysbiosis can affect intestinal health and immune regulation
• Dysbiosis has been implicated in the pathogenesis of various gastrointestinal disorders, such as inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS)

Microbiome-Related Diseases and Disorders

• Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is associated with a dysbiotic gut microbiome and abnormal immune response
• Irritable bowel syndrome (IBS) patients often display altered gut microbiome composition and increased intestinal permeability
• Clostridium difficile infection (CDI) occurs when the normal gut microbiome is disrupted, allowing the overgrowth of the pathogenic C. difficile bacteria
• Obesity and metabolic disorders have been linked to a dysbiotic gut microbiome, with reduced diversity and altered metabolic functions
• Allergic diseases, such as asthma and atopic dermatitis, may be influenced by early-life microbiome development and reduced microbial exposure
• Neurological and psychiatric disorders, including autism spectrum disorder (ASD) and depression, have been associated with microbiome alterations and gut-brain axis dysfunction
• Cardiovascular diseases, such as atherosclerosis, may be affected by the microbiome's role in lipid metabolism and inflammation
• Certain cancers, particularly colorectal cancer, have been linked to dysbiosis and the production of pro-carcinogenic metabolites by the microbiome

Research Methods and Technologies

• 16S rRNA gene sequencing is a widely used method for identifying and characterizing bacterial communities based on the variable regions of the 16S rRNA gene
• Shotgun metagenomics involves sequencing the entire genetic material in a sample, allowing for the analysis of microbial functions and strain-level identification
• Metatranscriptomics focuses on the expressed genes in a microbial community, providing insights into active functions and responses to environmental changes
• Metaproteomics studies the proteins produced by the microbiome, giving a more direct view of the functional activity of the community
• Metabolomics analyzes the small-molecule metabolites produced by the microbiome and host, helping to understand the metabolic interactions between them
• Gnotobiotic animal models, such as germ-free mice, allow for the study of microbiome effects in a controlled environment
• Organoids, three-dimensional cell culture systems, can be used to study host-microbiome interactions in a more physiologically relevant context
• Computational tools, such as bioinformatics pipelines and machine learning algorithms, are essential for analyzing and interpreting the vast amounts of data generated by microbiome studies

Future Directions and Potential Applications

• Personalized medicine approaches that take into account an individual's microbiome composition and function may lead to more targeted and effective therapies
• Microbiome-based diagnostics could be developed for the early detection and monitoring of diseases associated with dysbiosis
• Fecal microbiota transplantation (FMT) has shown promise in treating recurrent C. difficile infection and may be explored for other microbiome-related disorders
• Engineered probiotics and targeted prebiotics could be designed to modulate the microbiome composition and function for therapeutic purposes
• Microbiome-based interventions may be developed for the prevention and treatment of metabolic disorders, such as obesity and type 2 diabetes
• Psychobiotics, probiotics that influence the gut-brain axis, could be used to treat neurological and psychiatric disorders
• Manipulation of the microbiome may be used to enhance the efficacy and reduce the side effects of cancer immunotherapies
• Integration of microbiome data with other omics data (genomics, transcriptomics, proteomics) will provide a more comprehensive understanding of host-microbiome interactions and their role in health and disease