🪱Microbiomes Unit 4 – The Human Microbiome

What's the Human Microbiome?

• Refers to the collective genomes of all microorganisms residing in and on the human body
• Includes bacteria, archaea, fungi, and viruses living in a symbiotic relationship with their human host
• Estimated to contain trillions of microbial cells, outnumbering human cells by a ratio of approximately 1.3:1
• Plays crucial roles in human health, including nutrient metabolism, immune system development, and protection against pathogens
• Composition varies between individuals, influenced by factors such as diet, age, genetics, and environment
• Considered a "hidden organ" due to its extensive influence on human physiology and well-being
• Research on the human microbiome has expanded rapidly since the launch of the Human Microbiome Project in 2007

Key Players: Meet Your Microbes

• Bacteria are the most abundant and diverse members of the human microbiome
  • Firmicutes (Lactobacillus, Clostridium) and Bacteroidetes (Bacteroides) are the two dominant bacterial phyla
  • Other important bacterial phyla include Actinobacteria (Bifidobacterium), Proteobacteria (Escherichia), and Verrucomicrobia (Akkermansia)
• Archaea, single-celled organisms distinct from bacteria, are also present in the human microbiome
  • Methanogens, such as Methanobrevibacter smithii, are the most common archaeal species found in the gut
• Fungi, though less abundant than bacteria, contribute to the microbiome's diversity
  • Candida, Malassezia, and Saccharomyces are common fungal genera found in the human microbiome
• Viruses, particularly bacteriophages (viruses that infect bacteria), play a role in shaping the bacterial community
  • Bacteriophages can influence bacterial populations through lytic and lysogenic cycles
• Protozoa, single-celled eukaryotic organisms, are also present in the human microbiome, albeit in lower numbers

Home Sweet Home: Microbiome Habitats

• The gut microbiome, residing in the gastrointestinal tract, is the most extensively studied and diverse habitat
  • Dominated by Firmicutes and Bacteroidetes, with a high concentration of microbes in the colon
  • Plays a vital role in digestion, nutrient absorption, and immune system development
• The skin microbiome varies across different body sites (dry, moist, and sebaceous regions)
  • Dominated by Actinobacteria (Propionibacterium), Firmicutes (Staphylococcus), and Proteobacteria
  • Helps maintain skin barrier function and protects against pathogens
• The oral microbiome, found in the mouth, includes bacteria colonizing teeth, gums, and tongue
  • Streptococcus, Actinomyces, and Veillonella are common oral bacterial genera
  • Maintains oral health and prevents tooth decay and gum disease
• The vaginal microbiome, dominated by Lactobacillus species, helps maintain a low pH environment
  • Protects against urogenital infections and supports reproductive health
• Other important microbiome habitats include the respiratory tract, urinary tract, and nasal passages

Microbiome Development: From Birth to Adulthood

• The human microbiome begins to develop during birth, with the mode of delivery (vaginal or cesarean) influencing initial microbial colonization
  • Vaginal delivery exposes the infant to the mother's vaginal and fecal microbes, while cesarean section leads to colonization by skin and environmental microbes
• Breastfeeding plays a crucial role in shaping the infant gut microbiome
  • Breast milk contains prebiotics (human milk oligosaccharides) that promote the growth of beneficial bacteria like Bifidobacterium
  • Formula-fed infants exhibit a more diverse gut microbiome compared to breastfed infants
• The introduction of solid foods during weaning marks a significant shift in the gut microbiome composition
  • Increased diversity and abundance of Firmicutes and Bacteroidetes as the infant's diet becomes more complex
• The microbiome continues to develop and stabilize throughout childhood and adolescence
  • Factors such as diet, antibiotic use, and environmental exposures influence microbiome composition
• In adulthood, the microbiome reaches a relatively stable state but can still be influenced by lifestyle factors
  • Long-term dietary patterns, probiotics, and prebiotics can modulate the adult microbiome
• The elderly microbiome undergoes changes, with reduced diversity and increased vulnerability to dysbiosis
  • Age-related factors, such as changes in diet, medication use, and immune function, contribute to these alterations

Balancing Act: Maintaining a Healthy Microbiome

• A balanced and diverse microbiome is essential for maintaining overall health
  • Ensures proper functioning of metabolic, immunological, and neurological processes
• Diet plays a critical role in shaping and maintaining a healthy microbiome
  • High-fiber foods (fruits, vegetables, whole grains) promote the growth of beneficial bacteria
  • Fermented foods (yogurt, kefir, sauerkraut) contain live microbes that can contribute to microbiome diversity
• Probiotics, live microorganisms consumed through food or supplements, can help restore or maintain a healthy microbiome
  • Commonly used probiotics include Lactobacillus and Bifidobacterium species
• Prebiotics, non-digestible food components that stimulate the growth of beneficial bacteria, support microbiome health
  • Examples include inulin, fructooligosaccharides (FOS), and galactooligosaccharides (GOS)
• Avoiding unnecessary antibiotic use is crucial for maintaining a balanced microbiome
  • Antibiotics can disrupt the microbial community, leading to reduced diversity and potential overgrowth of opportunistic pathogens
• Regular exercise, stress management, and adequate sleep also contribute to a healthy microbiome
  • These factors influence gut motility, immune function, and overall host physiology, which in turn impact the microbiome

When Things Go Wrong: Dysbiosis and Disease

• Dysbiosis refers to an imbalance in the microbiome, characterized by reduced diversity and altered composition
  • Can result from factors such as antibiotic use, poor diet, stress, and infections
• Dysbiosis has been associated with various gastrointestinal disorders
  • Inflammatory bowel diseases (Crohn's disease, ulcerative colitis) exhibit reduced microbial diversity and increased abundance of pro-inflammatory bacteria
  • Irritable bowel syndrome (IBS) has been linked to alterations in the gut microbiome, with differences in bacterial composition compared to healthy individuals
• Metabolic disorders, such as obesity and type 2 diabetes, have been associated with microbiome dysbiosis
  • Reduced diversity and increased ratio of Firmicutes to Bacteroidetes observed in obesity
  • Altered microbial metabolism and increased gut permeability contribute to insulin resistance and inflammation
• Neurological and psychological disorders, including autism spectrum disorder and depression, have been linked to microbiome alterations
  • Gut-brain axis: bidirectional communication between the gut microbiome and the central nervous system
  • Microbial metabolites and neuroactive compounds produced by the microbiome can influence brain function and behavior
• Skin conditions, such as acne, psoriasis, and atopic dermatitis, have been associated with dysbiosis of the skin microbiome
  • Altered balance between commensal and pathogenic bacteria contributes to skin inflammation and barrier dysfunction
• Strategies to address dysbiosis include targeted antibiotics, probiotics, prebiotics, and fecal microbiota transplantation (FMT)
  • FMT involves transferring healthy donor feces to restore a balanced microbiome in the recipient

Microbiome Research: Tools and Techniques

• Next-generation sequencing (NGS) technologies have revolutionized microbiome research
  • 16S rRNA gene sequencing: identifies and quantifies bacterial and archaeal communities based on the 16S rRNA gene
  • Shotgun metagenomics: sequences the entire genetic material in a sample, providing insights into microbial functions and interactions
• Bioinformatics tools and databases are essential for analyzing and interpreting microbiome data
  • Platforms like QIIME, Mothur, and MEGAN enable processing, clustering, and taxonomic assignment of sequencing data
  • Databases such as Greengenes, SILVA, and RDP provide reference sequences for microbial identification
• Metabolomics, the study of small molecule metabolites, complements microbiome research
  • Identifies microbial-derived metabolites and their potential roles in host physiology and disease
• Gnotobiotic animal models, particularly germ-free mice, are valuable tools for studying microbiome-host interactions
  • Allows for controlled colonization experiments and investigation of specific microbial strains or communities
• Organoid models, derived from human stem cells, provide a platform for studying microbiome-host interactions in vitro
  • Enables testing of microbial therapies and investigation of microbiome-mediated disease mechanisms
• Imaging techniques, such as fluorescence in situ hybridization (FISH) and electron microscopy, allow visualization of microbes in their native environments
  • Provides insights into spatial organization and interactions within the microbiome

Future Frontiers: Emerging Topics and Applications

• Personalized medicine: tailoring therapies based on an individual's microbiome profile
  • Microbiome-based biomarkers for disease prediction and treatment response
  • Targeted probiotic and prebiotic interventions for specific health conditions
• Microbiome-based therapeutics: developing novel treatments derived from the microbiome
  • Engineered probiotics: genetically modified bacteria designed to deliver therapeutic compounds or perform specific functions
  • Postbiotics: bioactive compounds produced by microbes, such as short-chain fatty acids, that can be used as therapeutic agents
• Microbiome and drug metabolism: understanding how the microbiome influences drug efficacy and toxicity
  • Microbial biotransformation of drugs can impact their absorption, distribution, and elimination
  • Potential for microbiome-based strategies to optimize drug therapy and minimize adverse effects
• Microbiome and environmental health: exploring the role of the microbiome in environmental processes and bioremediation
  • Microbial communities in soil, water, and air contribute to nutrient cycling and pollutant degradation
  • Harnessing the microbiome for sustainable agriculture, waste management, and ecosystem restoration
• Microbiome and space exploration: studying the impact of space travel on the human microbiome and developing strategies for maintaining astronaut health
  • Microgravity, radiation, and confined environments can alter the microbiome and potentially impact astronaut well-being
  • Developing probiotics and other microbiome-based interventions for long-duration space missions
• Microbiome and precision nutrition: leveraging microbiome data to develop personalized dietary recommendations
  • Understanding how individual microbiome composition influences nutrient metabolism and health outcomes
  • Designing targeted dietary interventions to optimize microbiome function and prevent diet-related diseases