This relationship is likely an ancient one. Mucus is universal to animals from corals to fish to humans, and phages are universal to mucus. Perhaps this was how the very first animals defended themselves against infections. They developed mucus to concentrate phages that were plentiful in their environment, and the viruses in turn helped their hosts to control the microbial multitudes around them. It was a mutually beneficial relationship between animal and virus, and one that continues today.
But the latest experiments from Barr’s team, many of which were done by his colleague Sophie Nguyen, suggest that this relationship between animals and phages is even more intimate. The phages aren’t just sitting atop human gut cells, acting as bouncers. They are actually being trafficked through the cells themselves. The team even used powerful microscopes to confirm the presence of phages within the cells. “A cell is enormous compared to a phage,” says Barr. “It’s like finding a cup of coffee by sectioning a skyscraper.”
In the experiment, just 0.1 percent of the total phages made it through. But based on their rate of travel, and the staggering number of them in the average human gut, the team estimated that our gut cells absorb around 31 billion phages every day. “The percentage feels like it can’t be that important but when you turn that percentage into absolute numbers, it feels biologically relevant,” says Corinne Maurice from McGill University, who also studies phages and was not involved in this study.
The team only did experiments using lab-grown cells, but Barr says there’s good reason to think that the same viral journeys take place in living bodies. For over 70 years, scientists have been “finding phages in parts of the body where they shouldn’t be,” he says, including supposedly sterile organs like the lungs. Microbiologist René Dubos found hints of this in 1943, by injecting phages into the guts of mice and finding those same viruses in the rodents’ brains.
“Phages can be detected outside the gastrointestinal tract, but there hasn’t been any real proof of how they get there,” says Lori Holtz from Washington University School of Medicine in St Louis. Many scientists believed that they were just leaking through gaps between the cells, but Nguyen’s work suggests that they are actually going through the cells themselves. In her experiments, the phages could traverse cells that line the kidneys, lungs, liver, and even the brain. “That’s absolutely astonishing in my view,” says Barr. The brain is separated from other organs by the blood-brain barrier—one of the most tightly controlled borders in the body. It’s incredibly hard for scientists to get small molecules through it. And yet, phages seem to do so.
This isn’t an infection in any meaningful way. The phages aren’t hijacking human cells to make more copies of themselves, as viruses like influenza, Zika, or Ebola might. Instead, Barr thinks that the cells are in control. They’re actively engulfing phages, and shuttling them from one end to the other. Why?