Phage Abundance and Diversity
Bacteriophages vastly outnumber bacteria in most environments, including the human gut, where densities reach 10^8–10^9 per gram of faeces. The most abundant biological entity in human faeces is crAssphage, discovered in 2014, infecting Bacteroides uniformis. Despite this dominance, phages have historically been overlooked in microbiome research, partly due to sequencing biases (DNA/RNA extraction favors bacterial DNA).
Life Cycles: Lytic and Lysogenic
Phages employ two strategies. Lytic phages reproduce by hijacking host machinery, lysing the cell, and releasing progeny (up to 100-200 per infection). Lysogenic phages integrate DNA into the host chromosome, replicating alongside it until stress triggers excision and lysis. Temperate phages (capable of both) are especially prevalent in the gut, creating persistent relationships between phages and bacteria.
Red Queen Dynamics and Coevolution
Phages and bacteria engage in arms-race coevolution: bacteria evolve defenses (CRISPR-Cas systems, phase variation, receptor modification); phages counter-evolve avoidance mechanisms. This Red Queen dynamic—running constantly to stay in place—maintains genetic innovation and population balance. Phage predation prevents any single bacterium from dominating, promoting diversity.
The Phageome in Disease
Phage community composition (the phageome) differs in IBD, IBS, and obesity. Clooney et al. (2019) found reduced phage diversity in IBD patients. High-abundance phages may lysogenize pathobionts, transferring virulence genes (enterotoxins, adhesins) via horizontal gene transfer. Conversely, therapeutic phages target resistant pathogens when antibiotics fail.
Phage Therapy Revival
Antimicrobial resistance has revived phage therapy interest. Bacteriophage cocktails target specific pathogens (e.g., Pseudomonas aeruginosa in cystic fibrosis) without disrupting commensals as broadly as antibiotics. Phages are more specific, evolve with pathogens, and can be engineered. Clinical trials are expanding, though regulatory pathways remain underdeveloped.