Glossary
1 A B C D E F G H I K L M N O P R S T V Y Β
1
16S rRNA gene — A gene encoding a component of the bacterial and archaeal ribosome. Because it is universal, evolves slowly, and contains both conserved and variable regions, it serves as a molecular barcode for identifying prokaryotic organisms. The basis of 16S rRNA gene sequencing.
16S rRNA gene sequencing — A technique for identifying bacteria and archaea in a sample by extracting DNA, amplifying the 16S rRNA gene using PCR, sequencing the amplified fragments, and comparing them to reference databases. Also called amplicon sequencing. Revolutionised microbiome research from the 2000s onward.
A
Agar plate — A shallow dish containing a gel-like nutrient medium (agar) on which bacteria can be grown as visible colonies. Invented in the laboratory of Robert Koch in the late nineteenth century and still widely used in clinical microbiology.
Alphaproteobacteria — A class of bacteria believed to be the evolutionary ancestors of mitochondria, the energy-producing organelles in eukaryotic cells.
Alternative splicing — The process by which different combinations of a gene's exons are joined together, allowing a single gene to produce multiple different proteins. A major reason the human body can make far more protein variants than it has genes.
Amino acid — One of the small molecular building blocks of proteins. Twenty standard amino acids are used by living cells; the order in which they are strung together, specified by the genetic code, determines each protein's structure and function.
Amplicon sequencing — See 16S rRNA gene sequencing.
Archaea — One of the three domains of cellular life, alongside Bacteria and Eukarya. Archaea are single-celled prokaryotic organisms that resemble bacteria in size and shape but differ fundamentally in their cell membrane chemistry, cell wall composition, and molecular biology. In the human microbiome, the most commonly detected archaeon is the methanogen Methanobrevibacter smithii.
Ascomycota — The largest phylum of fungi (the "sac fungi"), named for the sac-like ascus in which sexual spores form. Includes the yeasts Saccharomyces and Candida, the moulds Aspergillus and Penicillium, and most lichen-forming fungi. The most important fungal phylum in the human microbiome.
ATP (adenosine triphosphate) — A small molecule that serves as the universal energy currency of living cells. Energy released from nutrients is used to build ATP; the cell then spends ATP to power processes such as muscle contraction, nerve signalling, and DNA replication. Most ATP in eukaryotic cells is produced by mitochondria.
Azole antifungals — A major class of antifungal drugs (including fluconazole, itraconazole, voriconazole, and the topical agents clotrimazole and miconazole) that block an enzyme in the ergosterol synthesis pathway, starving the fungal membrane of its essential sterol.
B
Bacillota — A major phylum of bacteria (formerly called Firmicutes), typically the most abundant phylum in the adult human gut. Includes important genera such as Faecalibacterium, Roseburia, Ruminococcus, Clostridium, and Lactobacillus. Many Bacillota are specialist fibre degraders and major producers of short-chain fatty acids.
Bacillus (pl. bacilli) — A rod-shaped bacterium. Not to be confused with the genus Bacillus, which is a specific group of rod-shaped, spore-forming bacteria.
Bacteria — One of the three domains of cellular life. Bacteria are single-celled prokaryotic organisms characterised by ester-linked membrane lipids and, in most species, cell walls containing peptidoglycan. They are the dominant organisms at most human microbiome sites.
Bacteriocin — A small antimicrobial peptide produced by bacteria that kills or inhibits closely related bacterial species. Bacteriocins are one mechanism by which established gut communities resist colonisation by newcomers.
Bacteriophage (phage) — A virus that infects bacteria. Bacteriophages are the most abundant biological entities on Earth and play a major role in shaping microbial communities, including the human microbiome. See also: Prophage, Lysogeny.
Bacteroidota — A major phylum of bacteria (formerly called Bacteroidetes), dominant in the human gut. Key genera include Bacteroides (versatile carbohydrate degraders associated with Western diets) and Prevotella (associated with high-fibre, plant-rich diets).
Baltimore classification — A system for classifying viruses into seven groups based on their genome type (DNA or RNA, single- or double-stranded) and replication strategy (specifically, how they produce messenger RNA). Proposed by David Baltimore in 1971.
Base pair — Two complementary nucleotide bases joined across the two strands of the DNA double helix: adenine (A) always pairs with thymine (T), and guanine (G) with cytosine (C). Genome sizes are measured in base pairs.
Basidiomycota — The fungal phylum (the "club fungi") that includes most mushroom-forming species as well as the medically important yeasts Malassezia (dominant on human skin) and Cryptococcus (a cause of meningitis). Named for the club-shaped basidium on which sexual spores form.
Biofilm — A structured community of microorganisms attached to a surface and encased in a self-produced protective matrix. Biofilms — bacterial and fungal — form on teeth, medical devices such as catheters, and mucosal surfaces, and are far harder to eradicate than free-floating cells.
Butyrate — A four-carbon short-chain fatty acid produced by bacterial fermentation of dietary fibre in the colon. Butyrate is the primary energy source for colonocytes (the cells lining the colon), promotes anti-inflammatory regulatory T cell differentiation, and helps maintain the low-oxygen environment that anaerobic gut bacteria require. See also: Short-chain fatty acids.
C
Capsid — The protein shell that surrounds and protects the genetic material of a virus.
Capsule (bacterial) — A slimy outer layer of polysaccharides surrounding some bacterial cells. The capsule helps bacteria evade the immune system and adhere to surfaces, including human tissues.
Cell membrane (plasma membrane) — The thin, flexible lipid bilayer that encloses every living cell, separating its interior from the external environment. Studded with proteins that control the transport of molecules in and out of the cell.
Cell theory — The foundational principle that all living organisms are composed of cells, that the cell is the basic unit of life, and that all cells arise from pre-existing cells. Formulated by Schleiden, Schwann, and Virchow in the mid-nineteenth century.
Cell wall — A rigid or semi-rigid structure outside the cell membrane of most prokaryotes, many fungi, and all plants. In bacteria, the cell wall is composed of peptidoglycan. In archaea, it may consist of an S-layer or other materials. In fungi, it is made of chitin and glucans.
Central dogma of molecular biology — The principle, formalised by Francis Crick, that genetic information flows from DNA to RNA to protein. Retroviruses provide a famous partial exception, copying RNA back into DNA with reverse transcriptase.
Chaperone (protein) — A protein that helps other proteins fold into their correct three-dimensional shapes and prevents misfolded proteins from aggregating. Part of the cell's quality-control machinery.
Chitin — A tough polymer of N-acetylglucosamine that forms the scaffold of the fungal cell wall — and, quite separately, the exoskeletons of insects and crustaceans. One of the chemical signatures distinguishing fungi from plants (cellulose walls) and bacteria (peptidoglycan walls).
Chloroplast — An organelle found in plant and algal cells, responsible for photosynthesis. Chloroplasts are descended from ancient cyanobacteria that were engulfed by an early eukaryotic cell (see Endosymbiosis).
Chromatin — The combined complex of DNA and its packaging proteins (histones) in the eukaryotic nucleus. How tightly chromatin is wound determines whether the genes within it are accessible for reading — a key layer of gene regulation.
Chromosome — A structure composed of DNA (and, in eukaryotes, associated histone proteins) that carries genetic information. Bacterial chromosomes are typically single, circular DNA molecules. Eukaryotic chromosomes are linear and housed within the nucleus.
Coccus (pl. cocci) — A spherical bacterium. Examples include Staphylococcus and Streptococcus.
Codon — A group of three consecutive bases in messenger RNA that specifies a single amino acid (or a stop signal) during protein synthesis. The dictionary linking codons to amino acids is the genetic code.
Colonisation resistance — The ability of an established microbial community to prevent the colonisation of new organisms, including pathogens. Mechanisms include nutrient competition, production of antimicrobial compounds (bacteriocins), bile acid modification, and immune priming. First described by van der Waaij et al. (1971).
Colonocyte — An epithelial cell lining the colon. Colonocytes derive 60–70% of their energy from butyrate, a short-chain fatty acid produced by gut bacteria.
Colony — A visible clump of genetically identical microbial cells, grown on a solid medium from a single ancestor cell. Colonies are the basis of classical culture-based microbiology.
Competitive exclusion — An ecological principle stating that two species competing for exactly the same resource in a stable environment cannot coexist indefinitely — one will outcompete the other. In the gut, competitive exclusion is a key mechanism of colonisation resistance.
Conidium (pl. conidia) — An asexual fungal spore produced at the tip of a specialised hypha. Aspergillus releases conidia in enormous numbers; every person inhales hundreds daily, which healthy immune systems clear without incident.
Conjugation — A process by which one bacterium transfers DNA — typically a plasmid — to another bacterium through direct cell-to-cell contact via a pilus. A major mechanism of horizontal gene transfer and antibiotic resistance spread.
Culturing — The process of growing microorganisms outside their natural environment on nutrient media under controlled laboratory conditions. While essential for clinical diagnostics and detailed characterisation, standard culture methods recover only a fraction of the species present in complex microbial communities.
Culturomics — A high-throughput approach to microbial culture that uses dozens to hundreds of different growth conditions — varying nutrient media, atmosphere, temperature, and incubation time — to recover species that standard methods miss. Colonies are identified using MALDI-TOF mass spectrometry. Pioneered by Didier Raoult and colleagues from 2012.
Cyanobacteria — Photosynthetic bacteria responsible for producing much of the oxygen in Earth's atmosphere. Ancient cyanobacteria gave rise to chloroplasts through endosymbiosis.
Cytoplasm — The gel-like material inside a cell, enclosed by the cell membrane. Contains water, salts, organic molecules, and (in prokaryotes) the cell's DNA and ribosomes. In eukaryotic cells, the cytoplasm refers to the material outside the nucleus but within the cell membrane.
Cytoskeleton — A network of protein filaments within eukaryotic cells that provides structural support, enables cell movement, and serves as tracks for intracellular transport. Includes microfilaments, intermediate filaments, and microtubules.
D
Dectin-1 — A pattern recognition receptor on innate immune cells (macrophages, dendritic cells, neutrophils) that detects the β-glucan of fungal cell walls and triggers antifungal immune responses. Many pathogenic fungi mask their β-glucan to evade it.
Dikarya — The fungal group comprising the two large phyla Ascomycota and Basidiomycota — so named because their cells often carry two genetically distinct nuclei for a period before sexual fusion. Contains the great majority of described fungal species.
Dimorphism (fungal) — The ability of some fungi to switch between a single-celled yeast form and a filamentous hyphal (mould) form depending on conditions. In Candida albicans, the switch to the invasive hyphal form is a key step from harmless colonisation to disease.
DNA (deoxyribonucleic acid) — The molecule that carries genetic information in all cellular life and many viruses. DNA consists of two complementary strands wound into a double helix. See Primer Chapter 3 for a detailed explanation.
DNA methylation — An epigenetic mechanism in which small chemical tags (methyl groups) are attached to cytosine bases in DNA. Heavy methylation of a gene's control region typically silences the gene without changing its sequence.
DNA replication — The copying of a cell's DNA before cell division. The two strands of the double helix separate and each serves as a template for a new partner strand, yielding two identical copies. Rare copying errors are the source of mutations.
Domain — The highest level of biological classification. Life is divided into three domains: Bacteria, Archaea, and Eukarya.
Dysbiosis — A disruption in the composition or function of a microbial community, often associated with disease. Markers of gut dysbiosis include reduced diversity, loss of beneficial species, and expansion of Pseudomonadota (Proteobacteria). The term is widely used but somewhat imprecise, as no single "healthy" community composition has been definitively established.
E
Echinocandins — A class of antifungal drugs (caspofungin, micafungin, anidulafungin) that inhibit the enzyme building β-1,3-glucan, dismantling the structural scaffold of the fungal cell wall. The only major antifungal class that does not target ergosterol.
Electron microscopy — A family of imaging techniques that use beams of electrons rather than visible light to achieve much higher magnification and resolution than optical microscopy. Includes transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Essential for visualising viruses and subcellular structures.
Endogenous retrovirus (ERV) — A retroviral sequence permanently integrated into the germline genome of its host species and inherited from generation to generation. Human endogenous retroviruses (HERVs) make up roughly 8 per cent of the human genome. Most are no longer functional, but some have been co-opted for essential host functions (e.g., syncytin in placental development). See also: Provirus, Retrovirus, Syncytin.
Endoplasmic reticulum (ER) — An extensive network of folded membranes in eukaryotic cells. The rough ER is studded with ribosomes and synthesises proteins for export or membrane insertion. The smooth ER is involved in lipid synthesis and detoxification.
Endosymbiosis — The evolutionary process by which one organism lives inside another, with both partners eventually becoming mutually dependent. The origin of mitochondria and chloroplasts in eukaryotic cells is explained by endosymbiosis: free-living bacteria were engulfed by an ancestral cell and, over billions of years, became permanent organelles. Recent research suggests the origin of complex cells was even richer than a single such event, involving gene contributions from several bacterial groups and from giant viruses over a long period (see Giant virus).
Enteric nervous system (ENS) — The network of approximately 500 million neurons embedded in the walls of the gastrointestinal tract. Sometimes called the "second brain," the ENS can coordinate digestion, motility, and local immune responses independently of the brain. Organised into two main plexuses: the myenteric plexus (controls peristalsis) and the submucosal plexus (regulates secretion and blood flow).
Enterochromaffin cell — A specialised epithelial cell in the gut lining that produces serotonin. Approximately 90% of the body's total serotonin is produced by enterochromaffin cells, and their serotonin synthesis is regulated in part by gut bacteria.
Enterotype — A proposed classification of the human gut microbiome into distinct community types characterised by the dominance of particular genera (e.g., Bacteroides or Prevotella). First described by Arumugam et al. (2011). The concept remains debated: current evidence suggests continuous gradients rather than strictly discrete types.
Envelope (viral) — An outer lipid layer surrounding the capsid of some viruses, derived from the membrane of the host cell.
Enzyme — A protein (occasionally an RNA) that speeds up a specific chemical reaction without being consumed by it. Virtually every metabolic process in every organism — including the microbial fermentation of dietary fibre — depends on enzymes.
Epigenetics — Changes in gene activity that do not involve altering the DNA sequence itself — the cell's system of bookmarks and annotations on the genome. Main mechanisms include DNA methylation and histone modification. Microbial metabolites such as butyrate can influence the epigenetic state of human cells.
Ergosterol — The sterol that regulates fluidity and stability in fungal cell membranes, playing the role that cholesterol plays in animal cells. Its uniqueness to fungi makes it the target, direct or indirect, of most antifungal drugs (azoles, allylamines, polyenes).
Ester linkage — A type of chemical bond found in the cell membranes of bacteria and eukaryotes, linking fatty acids to glycerol. Contrast with the ether linkages found in archaeal membranes.
Ether linkage — A type of chemical bond found in the cell membranes of archaea, linking branched hydrocarbon chains to glycerol. Ether linkages are more chemically stable than ester linkages, which may contribute to the ability of some archaea to survive extreme conditions.
Eukarya (Eukaryota) — The domain of life encompassing all organisms whose cells contain a true nucleus and membrane-bound organelles. Includes animals, plants, fungi, and protists.
Eukaryotic cell — A cell that possesses a membrane-bound nucleus and internal organelles (e.g., mitochondria, endoplasmic reticulum). All animals, plants, fungi, and protists are composed of eukaryotic cells. Contrast with Prokaryotic cell.
Exon — A segment of a gene that remains in the messenger RNA after splicing and (in protein-coding genes) is translated into protein. Exons make up only about 1.5 per cent of the human genome.
Extremophile — An organism that thrives in extreme environmental conditions, such as very high or very low temperatures, high salinity, high acidity, or high pressure. Many extremophiles are archaea, though extremophilic bacteria and eukaryotes also exist.
F
Flagellum (pl. flagella) — A long, whip-like appendage used by many bacteria (and some eukaryotic cells) for locomotion. Bacterial flagella rotate like propellers; eukaryotic flagella undulate in a wave-like motion.
Free fatty acid receptor (FFAR) — A family of cell-surface receptors (including FFAR2/GPR43 and FFAR3/GPR41) that are activated by short-chain fatty acids. Expressed on immune cells, adipocytes, enteroendocrine cells, and neurons, these receptors provide a direct molecular link between microbial metabolism and host physiology.
G
Gene — A stretch of DNA that carries the instructions for making a functional product, usually a protein (via messenger RNA) or sometimes an RNA molecule itself. The human genome contains roughly 20,000 protein-coding genes.
Gene regulation — The system of controls that determines which genes are switched on or off, and how strongly, in a given cell at a given time. Explains how cells with identical genomes — a neuron and a liver cell, say — can look and behave utterly differently.
Genetic code — The set of rules by which the sequence of bases in DNA and RNA is translated into the sequence of amino acids in proteins, read in three-base codons. Nearly universal across all life — strong evidence for a common ancestry.
Genome — The complete set of genetic material of an organism or virus. The human genome comprises about 3.2 billion base pairs of DNA; the genome of the gut bacterium E. coli about 4.6 million.
Germ-free (animal) — See Gnotobiotic.
Giant virus — A virus far larger than typical viruses — sometimes bigger than a small bacterium — carrying hundreds or even more than a thousand genes. The first to be recognised was Mimivirus (2003). Most belong to the group Nucleocytoviricota and infect eukaryotes such as amoebae and algae. Recent evidence suggests giant viruses helped carry genes into the lineage that became complex life.
Gnotobiotic — Describes an animal raised in a completely sterile environment, harbouring no microorganisms. From Greek gnotos ("known") and bios ("life"). Gnotobiotic mice are the principal experimental model for testing causal effects of specific microbes or microbial communities on host physiology.
Goblet cell — A specialised epithelial cell that secretes mucus. In the colon, goblet cells produce the MUC2 mucin that forms the two-layer mucus barrier separating the microbial community from the underlying tissue. "Sentinel" goblet cells at crypt entrances detect bacterial contact and trigger protective mucus secretion.
Golgi apparatus — A membrane-bound organelle in eukaryotic cells that sorts, modifies, and packages proteins received from the endoplasmic reticulum into vesicles for transport to their final destinations. Named after the Italian physician Camillo Golgi.
Gram stain — A staining technique developed by Hans Christian Gram in 1884 that differentiates bacteria into two major groups (Gram-positive and Gram-negative) based on differences in cell wall structure. One of the most widely used tools in clinical microbiology.
Gram-negative — Describing bacteria that lose the violet dye in the Gram stain procedure and take up the pink counterstain. Gram-negative bacteria have a thin peptidoglycan layer and an additional outer membrane containing lipopolysaccharides. Examples include Escherichia coli and Pseudomonas aeruginosa.
Gram-positive — Describing bacteria that retain the violet dye in the Gram stain procedure. Gram-positive bacteria have a thick peptidoglycan layer and no outer membrane. Examples include Staphylococcus aureus and Streptococcus pneumoniae.
Great plate count anomaly — The observation, named by Staley and Konopka (1985), that the number of microbial cells visible under a microscope in an environmental sample vastly exceeds the number that can be grown on standard laboratory media — typically by a factor of 100 or more.
H
Helical symmetry — A type of viral capsid architecture in which protein subunits are arranged in a spiral around the genome, producing a rod-like or tube-like structure. The tobacco mosaic virus is a classic example.
HERV (human endogenous retrovirus) — See Endogenous retrovirus.
Histone — A spool-like protein around which eukaryotic DNA is wound. Histones help package the long DNA molecule into compact chromosomes and play a role in regulating gene expression. Generally absent from prokaryotes.
Histone modification — The addition or removal of chemical groups (acetyl, methyl, phosphate and others) on the histone proteins around which DNA is wound. These modifications loosen or tighten chromatin, making genes more or less available for transcription. An epigenetic mechanism influenced by microbial metabolites such as butyrate.
Horizontal gene transfer (HGT) — The transfer of genetic material between organisms by mechanisms other than parent-to-offspring (vertical) inheritance. In bacteria, HGT occurs via conjugation, transformation, and transduction. It is a major driver of antibiotic resistance spread.
Hypha (pl. hyphae) — A microscopic, branching filament that is the basic growth form of moulds and many other fungi. Hyphae grow at their tips, secreting digestive enzymes ahead of themselves; a tangled mass of hyphae is a mycelium.
I
Icosahedral symmetry — A type of viral capsid architecture with twenty triangular faces, approximating a sphere. This is the most common capsid shape among viruses and provides efficient packaging of the viral genome using a minimal number of protein subunits.
Ileocaecal valve — The one-way valve separating the ileum (terminal small intestine) from the caecum (beginning of the large intestine). Passage through this valve marks the transition from the relatively sparse microbial environment of the small intestine to the densely colonised colon.
Induction (prophage) — The process by which a dormant prophage is reactivated, excises itself from the host bacterium's chromosome, and enters the lytic cycle, producing new viral particles and destroying the host cell. Induction is often triggered by environmental stress, DNA damage, or exposure to certain chemicals.
Integrase — A viral enzyme, particularly associated with retroviruses, that catalyses the insertion of viral DNA into the host cell's genome. Integrase inhibitors are an important class of antiretroviral drugs used in the treatment of HIV infection.
Intron — A segment within a gene that is transcribed into RNA but cut out (spliced) before the messenger RNA is translated. Common in eukaryotic genes, almost absent from bacterial ones.
ITS sequencing — The fungal counterpart of bacterial 16S rRNA sequencing: a DNA barcoding method that identifies fungi by sequencing the internal transcribed spacer (ITS) region of their ribosomal DNA. The main tool for surveying the human mycobiome.
K
Kill the winner — An ecological model in which the most abundant bacterial species in a community (the "winner") becomes disproportionately targeted by bacteriophages, which multiply rapidly on this abundant host and drive its numbers down. This density-dependent predation helps maintain microbial diversity within ecosystems such as the human gut.
Koch's postulates — A set of criteria, developed by Robert Koch in the 1880s, for establishing that a specific microorganism causes a specific disease. The postulates require isolating the organism from a diseased host, growing it in pure culture, reproducing the disease by introducing the culture into a healthy host, and re-isolating the organism from the new host.
L
Lichen — A composite organism formed by a fungus living in intimate mutualistic partnership with a photosynthetic partner (a green alga or cyanobacterium). The fungus provides structure and protection; the partner provides food.
Light microscope — A microscope that uses visible light and glass lenses to magnify small objects. Also called an optical microscope. Can achieve magnifications up to about 1,000× and resolve structures down to approximately 0.2 micrometres — sufficient to see bacteria but not viruses or most subcellular details.
Lipid bilayer — The double-layered structure formed by phospholipids in cell membranes, with hydrophobic tails pointing inward and hydrophilic heads facing the aqueous environment on both sides.
Lipopolysaccharide (LPS) — A large molecule found in the outer membrane of Gram-negative bacteria. LPS is a potent activator of the human immune system and, when present in the bloodstream in large quantities, can trigger sepsis.
LUCA (Last Universal Common Ancestor) — The hypothetical single-celled organism from which all current cellular life on Earth is descended. LUCA is not a specific species but a theoretical ancestor of all three domains.
Lysogenic conversion — The acquisition of new phenotypic traits by a bacterium as a result of genes carried by an integrated prophage. Notable examples include the cholera toxin (encoded by the CTXφ prophage in Vibrio cholerae) and Shiga toxin (encoded by a prophage in certain pathogenic E. coli strains).
Lysogenic cycle (lysogeny) — A viral replication strategy in which the virus integrates its genome into the host cell's chromosome (as a prophage or provirus) and is replicated passively along with the host's DNA during cell division, without immediately producing new viral particles or harming the host. Under certain conditions, the integrated virus can reactivate and enter the lytic cycle. Contrast with Lytic cycle.
Lysogeny (lysogenic cycle) — A mode of viral reproduction in which the virus integrates its genetic material into the host cell's genome (becoming a prophage in bacteria) and is replicated passively as the host divides. Under stress, the virus may exit lysogeny and enter the lytic cycle, producing new viral particles and destroying the host cell.
Lysosome — A membrane-bound organelle in eukaryotic cells containing digestive enzymes that break down waste materials, cellular debris, and engulfed pathogens. Sometimes called the cell's recycling centre.
Lytic cycle — A viral replication strategy in which the virus takes over the host cell's machinery, produces large numbers of new viral particles, and then destroys (lyses) the host cell to release them. Contrast with Lysogenic cycle.
M
MALDI-TOF mass spectrometry — Matrix-Assisted Laser Desorption/Ionisation Time-Of-Flight mass spectrometry. A rapid technique for identifying microorganisms by analysing the unique pattern of proteins they contain. Widely used in clinical microbiology and in culturomics for high-throughput species identification.
Mass spectrometry — An analytical technique that measures the mass-to-charge ratio of molecules in a sample. In microbiome research, used in metabolomics to identify and quantify small molecules (metabolites) and in MALDI-TOF for microbial identification.
Messenger RNA (mRNA) — A temporary, single-stranded RNA copy of a gene, carrying its instructions from the DNA to the ribosome where the corresponding protein is built. The basis of the mRNA vaccines used against COVID-19.
Metabolite — A small molecule produced or modified by metabolic processes. In the context of the microbiome, metabolites include short-chain fatty acids, bile acid derivatives, amino acid metabolites, and signalling molecules produced by microbial communities.
Metabolomics — The large-scale study of metabolites — small molecules produced by cellular processes — in a biological sample. Uses mass spectrometry or NMR spectroscopy to identify and quantify the chemical outputs of microbial communities.
Metagenome — The collective genetic material of all microorganisms in a particular environment. The human gut metagenome, for example, contains between two and twenty million genes — far more than the approximately 20,000 protein-coding genes in the human genome.
Metagenomics — The sequencing and analysis of all DNA extracted from an environmental or biological sample, without prior culturing. Provides both taxonomic and functional information about microbial communities. Also called shotgun metagenomics.
Metatranscriptomics — The sequencing and analysis of all messenger RNA (mRNA) in a microbial community. Provides a snapshot of gene expression — which genes are actively being used — rather than merely which genes are present.
Methanogen — An organism that produces methane as a metabolic by-product. In the human gut, the most common methanogen is the archaeon Methanobrevibacter smithii, which consumes hydrogen and carbon dioxide produced by bacterial fermentation.
Microbiome — The entire habitat of microorganisms associated with a particular environment, including the organisms themselves, their collective genetic material, their metabolic products, and the environmental conditions they create and respond to. Often used interchangeably with microbiota in popular writing.
Microbiota — The community of living microorganisms (bacteria, archaea, fungi, protists, and viruses) inhabiting a particular environment, such as the human gut.
Microbiota-accessible carbohydrates (MACs) — Complex carbohydrates — including cellulose, hemicellulose, resistant starch, inulin, and pectins — that human enzymes cannot digest but which are fermented by gut bacteria, primarily in the colon. The term, introduced by the Sonnenburgs, is increasingly preferred over "dietary fibre" in microbiome research because it specifies that the relevant property of these molecules is their accessibility to microbial metabolism.
MicroRNA (miRNA) — A very short RNA molecule (about 22 bases) that is never translated into protein but instead regulates other genes, typically by binding to messenger RNAs and blocking their translation or triggering their destruction.
Mitochondrion (pl. mitochondria) — A membrane-bound organelle found in most eukaryotic cells, responsible for generating the majority of the cell's energy through aerobic respiration. Mitochondria are descended from ancient alphaproteobacteria that were engulfed by an ancestral cell (see Endosymbiosis) and retain their own small genome.
Monolayer (membrane) — A single-sheet membrane structure found in some archaea, in which lipid molecules span the entire width of the membrane rather than forming two separate layers. Extremely stable and resistant to harsh environmental conditions.
Mould — A fungus that grows as a network of branching filaments (hyphae) forming a fuzzy mat (mycelium). Medically important moulds include Aspergillus, Mucor, Rhizopus and Fusarium.
MUC2 — The principal mucin glycoprotein of the colonic mucus layer. One of the largest molecules produced by the human body (molecular weight >5 million daltons), MUC2 is secreted by goblet cells and forms the structural basis of both the inner (bacteria-free) and outer (bacteria-colonised) mucus layers of the colon.
Multi-omics — An integrative approach that combines two or more omics techniques (e.g., metagenomics, metabolomics, metatranscriptomics, proteomics) to build a more comprehensive picture of microbial community composition and function.
Mushroom — The large, visible fruiting body that certain fungi (mostly Basidiomycota) produce for sexual reproduction and spore dispersal. The mushroom is only a temporary structure; the main organism is the hidden mycelium below.
Mutation — A change in the sequence of an organism's DNA, arising from copying errors, chemical damage or radiation. Most are neutral or harmful, but occasionally a mutation is beneficial — mutations are the raw material of evolution and a driver of antibiotic resistance.
Mycelium (pl. mycelia) — The main body of a filamentous fungus: an interwoven network of hyphae spreading through soil, wood, food — or living tissue. Some mycelia are among the largest and oldest organisms on Earth.
Mycobiome — The fungal component of a microbiome: all the fungi (yeasts and moulds) inhabiting a particular environment such as the human gut or skin. Vastly outnumbered by bacteria, but disproportionately influential, and historically under-studied.
Mycorrhiza (pl. mycorrhizae) — A mutualistic partnership between a fungus and a plant's roots, in which the fungal network supplies water and mineral nutrients in exchange for sugars from photosynthesis. Formed by roughly 90 per cent of land plant species.
N
Negative-sense RNA — A type of single-stranded viral RNA genome that cannot be directly translated by ribosomes. It must first be copied into a complementary positive-sense RNA strand by a viral RNA-dependent RNA polymerase. Influenza virus is a negative-sense RNA virus. Contrast with Positive-sense RNA.
NMR spectroscopy — Nuclear Magnetic Resonance spectroscopy. An analytical technique used in metabolomics to identify molecules based on how their atomic nuclei behave in a magnetic field.
Non-coding RNA — Any RNA molecule that is transcribed from DNA but not translated into protein. Far from being waste, many non-coding RNAs — including microRNAs and long non-coding RNAs — have regulatory or structural functions.
Nuclear pore — A channel in the double membrane of the eukaryotic nucleus that regulates the transport of molecules between the nucleus and the cytoplasm.
Nucleoid — The region within a prokaryotic cell where the DNA is concentrated. Unlike a eukaryotic nucleus, the nucleoid is not surrounded by a membrane.
Nucleolus — A dense region within the eukaryotic nucleus where ribosomal RNA is synthesised and ribosomal subunits begin to be assembled.
Nucleotide — The basic building block of DNA and RNA, consisting of a sugar, a phosphate group and one of four bases. DNA is a chain of nucleotides; the human genome is about 3.2 billion nucleotides long per strand.
Nucleus — A membrane-bound organelle in eukaryotic cells that contains the cell's DNA. The presence of a nucleus is the defining feature of eukaryotic cells.
O
Obelisk — A recently discovered class of viroid-like circular RNA elements found in the human gut microbiome. Obelisks encode a single protein and do not fit into any previously known category of biological entity. First described by Zheludev et al. in 2024.
Obligate anaerobe — An organism that cannot survive in the presence of oxygen. Most of the dominant bacteria in the human colon are obligate anaerobes, which is why the low-oxygen environment of the colonic lumen is essential to maintaining normal gut community composition.
Oblin — A novel protein superfamily encoded by obelisks, with no detectable similarity to any previously known protein family. The function of Oblins remains unknown.
Operon — A cluster of bacterial genes transcribed together as a single unit, typically encoding proteins that work in the same pathway. The lac operon of E. coli, described by Jacob and Monod, is the classic example. Rare in eukaryotes.
Opisthokonta — The eukaryotic supergroup that unites animals and fungi (with some single-celled relatives), named for the single rear-mounted flagellum of their ancestral swimming cells. Its existence means you are more closely related to a mushroom than that mushroom is to a plant.
Organelle — A specialised, membrane-bound structure within a eukaryotic cell that performs a specific function. Examples include the nucleus, mitochondria, and chloroplasts.
P
Peptidoglycan — A polymer of sugars and amino acids that forms a mesh-like layer in bacterial cell walls, giving the cell structural rigidity. Absent from archaeal cell walls. The target of several classes of antibiotics, including penicillins and cephalosporins.
Peyer's patches — Organised clusters of immune tissue (lymphoid follicles) embedded in the wall of the ileum. Peyer's patches sample the microbial contents of the small intestine and are major sites of immune surveillance and education.
Phage therapy — The use of bacteriophages to treat bacterial infections. First explored in the early twentieth century, phage therapy fell out of favour in the West with the advent of antibiotics but is now experiencing renewed interest as antibiotic resistance grows. Phage therapy offers the advantage of high specificity, targeting pathogenic bacteria while leaving the beneficial microbiome intact.
Phageome — The complete community of bacteriophages associated with a particular environment, such as the human gut. The gut phageome is highly individual and relatively stable over time within a person.
Phospholipid — A lipid molecule with a hydrophilic (water-attracting) head and two hydrophobic (water-repelling) fatty acid tails. Phospholipids are the primary structural component of cell membranes.
Pilus (pl. pili) — A short, hair-like projection on the surface of many bacteria, used for attachment to surfaces or for transferring DNA during conjugation.
Plasmid — A small, circular DNA molecule found in many bacteria, separate from the main chromosome and able to replicate independently. Plasmids often carry genes for antibiotic resistance or other advantages, and can be transferred between bacteria — even between species — by conjugation.
Polyene antifungals — Antifungal drugs (amphotericin B, nystatin) that bind directly to ergosterol in the fungal membrane, punching holes that make the cell leak and die. Amphotericin B is powerful but notoriously toxic, because it can also interact with human cholesterol.
Polymerase chain reaction (PCR) — A laboratory technique that makes millions of copies of a specific segment of DNA from a small starting amount. Uses heat-stable DNA polymerase enzymes, synthetic primers, and repeated cycles of heating and cooling. Essential for 16S rRNA gene sequencing and many other molecular biology applications.
Positive-sense RNA — A type of single-stranded viral RNA genome that can be directly translated by the host cell's ribosomes, functioning as messenger RNA immediately upon entry into the cell. SARS-CoV-2 is a positive-sense RNA virus. Contrast with Negative-sense RNA.
Primer (molecular biology) — A short, synthetic strand of DNA (typically 15–30 nucleotides) designed to bind to a specific target sequence, providing a starting point for DNA replication during PCR. Not to be confused with the primer chapters of this book.
Prion — An infectious agent consisting of a misfolded form of a normal cellular protein (PrP). Prions can induce correctly folded copies of the same protein to adopt the abnormal shape, causing a chain reaction that leads to progressive, fatal brain diseases such as Creutzfeldt-Jakob disease (CJD) in humans.
Prokaryotic cell — A cell that lacks a membrane-bound nucleus and other internal membrane-bound organelles. Bacteria and archaea are prokaryotes. Contrast with Eukaryotic cell.
Prophage — The DNA of a bacteriophage that has been integrated into a bacterial host's genome during the lysogenic cycle. The prophage is replicated along with the host's DNA during cell division and can reactivate under certain conditions.
Protein — A large molecule built from a chain of amino acids folded into a specific three-dimensional shape. Proteins do most of the work of the cell: as enzymes, structural components, transporters, hormones, antibodies and more.
Protein folding — The process by which a newly made chain of amino acids coils and packs into its functional three-dimensional shape. Misfolded proteins underlie diseases including Alzheimer's, Parkinson's and the prion diseases.
Protist — An informal term for any eukaryotic organism that is not an animal, plant, or fungus. Protists are a diverse and largely unrelated collection of organisms, mostly single-celled, that include amoebae, algae, and parasites such as Plasmodium (malaria) and Blastocystis.
Provirus — The DNA form of a retroviral genome after it has been reverse-transcribed and integrated into the host cell's chromosomal DNA. The provirus is replicated along with the host's DNA during cell division and can remain latent for extended periods. In bacteria, the equivalent term is prophage.
R
Resistome — The complete collection of antibiotic resistance genes present in a microbial community. Identified through metagenomic sequencing.
Retrovirus — A family of viruses that carry their genome as single-stranded RNA and use the enzyme reverse transcriptase to convert it into DNA, which is then integrated into the host cell's genome as a provirus. HIV (human immunodeficiency virus) is the most well-known retrovirus. Retroviruses are unique in their ability to permanently alter the host's genetic material.
Reverse transcriptase — An enzyme, characteristic of retroviruses, that synthesises DNA from an RNA template — the reverse of the normal flow of genetic information (DNA → RNA). The discovery of reverse transcriptase by David Baltimore and by Howard Temin and Satoshi Mizutani in 1970 overturned the assumption that information could only flow from DNA to RNA. Reverse transcriptase inhibitors are a major class of antiretroviral drugs.
Ribosomal RNA (rRNA) — A structural component of ribosomes, the cellular machinery that translates genetic instructions into proteins. The gene encoding 16S rRNA (in prokaryotes) or 18S rRNA (in eukaryotes) is highly conserved across all life and is widely used for identifying and classifying microorganisms. Carl Woese's comparison of 16S rRNA sequences led to the discovery of the three domains of life.
Ribosome (70S / 80S) — The molecular machine that reads messenger RNA and assembles proteins. Prokaryotic ribosomes are designated 70S; eukaryotic cytoplasmic ribosomes are 80S. The "S" refers to the Svedberg unit, a measure of sedimentation rate. Several antibiotics target the 70S ribosome specifically.
RNA (ribonucleic acid) — A single-stranded relative of DNA that uses the sugar ribose and the base uracil (in place of thymine). RNA serves many roles: messenger RNA carries genetic instructions, transfer RNA delivers amino acids, ribosomal RNA forms the core of the ribosome, and some viruses use RNA as their genome.
RNA polymerase — The enzyme that carries out transcription: it reads a gene's DNA sequence and builds the corresponding RNA molecule one base at a time.
S
S-layer (surface layer) — A crystalline protein lattice that forms the outermost cell wall layer in many archaea and some bacteria. In archaea, the S-layer often serves as the primary cell wall, replacing the peptidoglycan found in bacteria.
Saprotroph — An organism that feeds by decomposing dead organic matter. Most fungi are saprotrophs, and collectively they are the planet's principal recyclers of wood and leaf litter.
Scanning electron microscopy (SEM) — An electron microscopy technique that bounces electrons off the surface of a specimen to produce three-dimensional images. Used to visualise the surface morphology of cells and microorganisms.
Selective toxicity — The principle that an antimicrobial drug should harm the pathogen while leaving the host unharmed. Achieved by targeting structures or pathways present in the pathogen but absent from host cells (e.g., peptidoglycan in bacteria, which human cells lack).
Short-chain fatty acids (SCFAs) — Small organic acids — principally acetate (2 carbons), propionate (3 carbons), and butyrate (4 carbons) — produced by bacterial fermentation of dietary fibre in the colon. SCFAs are produced in quantities of ~500–600 mmol/day and serve as the primary energy source for colonocytes, regulate immune function, influence distant organs via the bloodstream, and help maintain the anaerobic environment of the gut. They are arguably the most important class of molecules produced by the gut microbiome.
Spirillum (pl. spirilla) — A spiral-shaped bacterium.
Spore (fungal) — A tiny, hardy reproductive cell released by fungi, able to survive hostile conditions and germinate when it lands somewhere suitable. Produced both asexually (e.g., conidia) and sexually.
Syncytin — A protein essential for the formation of the human placenta, derived from the envelope gene of an ancient endogenous retrovirus. Syncytin mediates the fusion of cells in the outer layer of the placenta, enabling nutrient exchange between mother and foetus.
T
Torque teno virus (TTV) — A small, non-enveloped, single-stranded DNA virus found in more than 90 per cent of the human population. TTV causes no known disease and is considered part of the normal human virome. Its prevalence makes it a subject of interest in studies of viral commensalism and immune modulation.
Transcription — The first step in gene expression: the copying of a gene's DNA sequence into a messenger RNA molecule by RNA polymerase. See also Translation.
Transcription factor — A protein that binds to specific DNA sequences near a gene and increases or decreases how often that gene is transcribed. Combinations of transcription factors define a cell's identity.
Transfer RNA (tRNA) — A small RNA molecule that delivers a specific amino acid to the ribosome during protein synthesis, matching its three-base anticodon to the corresponding codon on the messenger RNA.
Translation — The second step in gene expression: the reading of a messenger RNA by a ribosome, three bases at a time, to assemble the corresponding protein from amino acids. See also Transcription.
Transmission electron microscopy (TEM) — An electron microscopy technique that fires electrons through an ultra-thin specimen slice, achieving nanometre-scale resolution. Used to visualise internal cellular structures, viruses, and molecular complexes.
V
Vesicle — A small, membrane-bound sac within a cell, used for transporting materials between organelles or between the cell and its environment.
Vibrio — A comma-shaped or curved-rod bacterium. The genus Vibrio includes the species Vibrio cholerae, which causes cholera.
Virion — A complete, mature viral particle outside of a host cell. A virion consists of the viral genome (DNA or RNA) enclosed in a protein capsid, and in some cases an outer lipid envelope.
Viroid — A small, circular RNA molecule that can infect plant cells and cause disease. Viroids are the smallest known infectious agents and consist of naked RNA with no protein coat.
Virome — The total community of viruses associated with a particular organism or environment, including bacteriophages, eukaryotic viruses, endogenous viral elements, and dietary or environmental viral sequences. The human virome is increasingly recognised as an important component of the microbiome that interacts with bacterial communities and the immune system.
Virus — A non-cellular biological entity consisting of genetic material (DNA or RNA) enclosed in a protein coat (capsid). Viruses cannot reproduce independently and must hijack the machinery of a host cell. They infect organisms across all three domains of life.
Y
Yeast — A fungus that lives as single, rounded cells and typically reproduces by budding. Yeasts include the baker's and brewer's workhorse Saccharomyces cerevisiae, the gut and mucosal resident Candida albicans, and the skin-dwelling Malassezia.
Β
β-glucan — A polymer of glucose that forms the structural core of the fungal cell wall. β-1,3-glucan is the main molecular pattern by which the human immune system recognises fungi (via the receptor Dectin-1) and the target of the echinocandin antifungals.