The bacteria that live in people’s intestines pump toxins to deter microbial intruders. But each person’s intestine comes with its own set of toxins: individualized “access code” microbes must resolve to survive, scientists report October 30, 2019, in the journal Nature.
The findings suggest that there is no single approach for all living probiotics or biotherapeutics, microbial supplements that promote the growth of healthy bacteria, says study co-author Joseph Mougous, a researcher at the University’s Howard Hughes Medical Institute (HHMI). from Washington (UW). Your team’s work is a first step to discover how scientists could adapt beneficial microbes to different people.
Over the past decade, Mougous’ team has resolved the details of a bacterial defense mechanism called type VI secretion system. It is like a molecular syringe that hits toxins in neighboring cells. Toxins break cell walls, cut membranes and chew the energy source of cells.
Bacteria use immunity genes to neutralize these toxins and protect themselves. Invaders that lack the correct genes start from the intestine. Mougous’ team had thought that immunity genes and toxins joined in pairs, like a lock and a key. But an analysis of data from more than 1,000 human fecal samples revealed something surprising.
The immunity genes of the intestinal bacterium Bacteroides fragilis far outnumber the toxin genes. The team discovered that all those additional immunity genes belonged to other bacteria. These bacteria had stolen B. fragilis genes to protect themselves from their toxins. That means genes must be crucial for bacteria to survive in the intestine, says Mougous, something scientists did not know before.
Experiments in the laboratory showed that immunity genes are grouped into stretches of DNA that can jump from a bacterial strain to a bacterial strain. In laboratory dishes and in live mice, the bacteria that received these genes immediately became resistant to B. fragilis toxins.
In addition, human fecal samples had unique combinations of immunity genes and toxins, according to the team. “So, what it takes to survive in a person’s microbiome might not be the same in another person’s microbiome,” says Mougous.
The results could help explain why it is so difficult for people to play with their microbiome compositions, he says. “Generalized approaches to colonize the intestine with certain bacteria may never succeed, and they may need to be individualized.”
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