The microbiome refers to the total collection of microorganisms (bacteria, fungi, viruses, and archaea) and their genetic material found in and on the human body. The largest and most studied community resides in the gut, particularly the large intestine.

Key stats:

• Estimated 100 trillion microbes live in the human body.
• They represent over 1,000 different bacterial species.
• The total microbial genome (called the microbiome) contains 150 times more genes than the human genome.

These microbes are not just passengers they actively interact with our cells, influence our immune system, help digest food, and produce essential molecules.

Key NGS-based methods used in microbiome analysis:

1. 16S rRNA Gene Sequencing

• Targets a conserved ribosomal RNA gene found in bacteria and archaea.
• Enables taxonomic classification at the genus (and sometimes species) level.
• Cost-effective and suitable for large-scale profiling of microbial communities.

2. Shotgun Metagenomic Sequencing

• Sequences all genetic material in a sample, not just a marker gene.
• Offers high-resolution data on:
• Species and strain composition
• Functional gene content (e.g., antibiotic resistance, carbohydrate metabolism)
• Allows reconstruction of microbial genomes from complex samples.

3. Metatranscriptomics

• Focuses on microbial RNA, not DNA.
• Captures actively expressed genes, providing a snapshot of real-time microbial activity.
• Useful for understanding how the microbiome responds to diet, infection, or treatment.

4. Metabolomics

• Measures small molecules produced or modified by microbes.
• These include short-chain fatty acids, bile acids, vitamins, and neurotransmitter precursors.
• Metabolomic profiling links microbial function to host physiology.

Together, these “omics” technologies provide a multi-dimensional view of the microbiome, allowing researchers to connect structure to function and track how microbial communities change under different conditions see more.

Digestion and Metabolism

Gut microbes ferment dietary fibers into short-chain fatty acids (SCFAs) like butyrate, acetate, and propionate. These molecules fuel colon cells, regulate appetite, and reduce inflammation.

Immune System Development

Microbial antigens interact with immune cells in the gut, shaping immune tolerance and preventing autoimmunity. A balanced microbiome reduces risk of chronic inflammatory conditions.

Pathogen Protection

A diverse microbiota provides colonization resistance, outcompeting harmful microbes for nutrients and space and producing antimicrobial substances.

Brain-Gut Axis

Microbial metabolites can:

• Stimulate the vagus nerve
• Influence neurotransmitter synthesis (serotonin, GABA)
• Modulate behavior and stress responses

These effects highlight the importance of microbiome balance in mental health and neurodevelopment.

Probiotics and Prebiotics

Microbial therapies based on beneficial bacteria or their growth substrates are being used to improve gut health, although efficacy varies across individuals.

Fecal Microbiota Transplantation (FMT)

FMT has proven effective in treating recurrent Clostridioides difficile infections by restoring microbial diversity. Research is ongoing into its application for IBD, metabolic disorders, and neurological diseases.

Engineered Microbial Therapeutics

Synthetic biology allows for the development of designer bacteria capable of:

• Producing therapeutic molecules (anti-inflammatories)
• Targeting pathogens
• Delivering genes directly to the gut

These live biotherapeutics are entering clinical trials, and some are already being used in regulated settings.

Microbiome science is expanding rapidly into:

• Personalized medicine, where gut profiles guide diet or treatment choice
• Non-invasive diagnostics, using microbial signatures from stool or saliva
• Microbiome editing, using CRISPR or phage-based systems to eliminate harmful strains
• Microbiome restoration, using targeted prebiotic or synbiotic approaches