Importance of Microbiomes in gut: the role of phages (Introduction)

by David Turell , Saturday, March 23, 2024, 17:11 (35 days ago) @ David Turell

Our cells gobble them up:

https://www.the-scientist.com/cellular-cuisine-phages-on-the-menu-71730

"The human gut is a bustling highway for a highly diverse microbial community, including an abundance of bacteriophages that modulate the gut microbiome.1 It’s a phage-infect-bacteria world, and while bacteriophages cannot infect mammalian cells, their paths still intersect. Mammalian cells can engulf phages within the gut. Researchers have observed that different bacteriophages induce opposing reactions such as anti- or proinflammatory responses in mammalian cells.2,3 However, it is unclear how bacteriophages interact with cells and modulate these cellular and immune responses.

***

"To investigate the downstream effects of phage consumption by mammalian cells, Barr and his team applied highly purified T4 phage, a well studied bacteriophage that infects Escherichia coli, across three mammalian cell lines. The cells readily gobbled up and internalized the phages by taking large gulps of fluid through macropinocytosis, encapsulating the meal inside a small vesicle. The response—or lack thereof—surprised him.

"The bacteriophage meal did not activate the intracellular nucleic acid receptors toll-like receptor 9 or cyclic GMP-AMP synthase, which stimulate the interferon pathway and lead to inflammation. This finding suggests that the phage capsid remained intact and did not release phage DNA within the vesicle, preventing the engulfed phages from triggering the immune system.

***

"Phages upregulated and activated the protein kinase B-dependent pathway that promoted cellular growth, proliferation, metabolism, macropinocytosis, and survival. Barr believes that macropinocytosis induces a positive feedback loop, prompting the cell to engulf more phages.

"Additionally, the phages also downregulated the cyclin-dependent kinase-1 pathway, which is involved in cell division. Sated by the phage feast, the cells seemed to remain in a prolonged growth phase. The researchers used a cell proliferation assay to confirm that the inhibition of this pathway delayed the cell cycle.

***

"Mammalian cells appear well equipped to carefully ferry phages from the environment into the cell. “From the cell perspective, the compressed nucleotides are a high value nutrient that isn’t typically available extracellularly,” added Barr."

Comment: the way I view it our gut cells control the phages, so our gut biome has enough bacteria to maintain a good microbiome.