Gut Bacteria Can Inject Proteins Into Human Cells (Jan 2026) Effector–host interactome map links type III secretion systems in healthy gut microbiomes to immune modulation Other
- Thread starter Michael Harrop
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This is really interesting, it's one of the few studies to look at actual direct protein interactions as a means of potential benefits of symbiotic Proteobacteria/Pseudomonadota.
Firstly, many papers treat all of them as if they were merely near-pathogens that manage to achieve harmlessness by not interacting too much with the host--which in turn implies that they aren't important for health and can be easily dispensed with. This paper argues for strain-dependence of pathogenicity or benefit, which obviously isn't captured by papers that merely report species abundance.
Secondly, there is this idea in the literature that at least in the colon, in the absence of disease, the bacteria are physically separated from human cells by the mucus layer. The movement of bacteria into direct contact with human cells is seen as a hallmark of disease. The T3SS is a "needle" sticking off of bacteria whose tip physically touches human cells, it's not something that is secreted and floats around, and is only about 80 nanometers long, which is very long for a protein but still less than 1/10 the width of a typical bacterium (the "diameter of the rod", not the long dimension). Its very existence therefore suggests a much more intimate association of the bacteria with the host than most researchers seem to envision at least in the colon. It's possible that the interaction happens mainly in the small intestine, where the barrier is known to be less robust, but the fact that healthy microbes do it at all I predict will take quite a few by surprise.
Unfortunately for such a potentially door-opening paper, I noticed that the phrase "Gram positive Bacteroidetes" is used twice. I suspect this is merely a typo and not a lack of familiarity with the gut microbiome that could make others doubt the work--I did check just to make sure there isn't some Gram-positive subclass of Bacteroidetes that I didn't know about.
Firstly, many papers treat all of them as if they were merely near-pathogens that manage to achieve harmlessness by not interacting too much with the host--which in turn implies that they aren't important for health and can be easily dispensed with. This paper argues for strain-dependence of pathogenicity or benefit, which obviously isn't captured by papers that merely report species abundance.
Secondly, there is this idea in the literature that at least in the colon, in the absence of disease, the bacteria are physically separated from human cells by the mucus layer. The movement of bacteria into direct contact with human cells is seen as a hallmark of disease. The T3SS is a "needle" sticking off of bacteria whose tip physically touches human cells, it's not something that is secreted and floats around, and is only about 80 nanometers long, which is very long for a protein but still less than 1/10 the width of a typical bacterium (the "diameter of the rod", not the long dimension). Its very existence therefore suggests a much more intimate association of the bacteria with the host than most researchers seem to envision at least in the colon. It's possible that the interaction happens mainly in the small intestine, where the barrier is known to be less robust, but the fact that healthy microbes do it at all I predict will take quite a few by surprise.
Unfortunately for such a potentially door-opening paper, I noticed that the phrase "Gram positive Bacteroidetes" is used twice. I suspect this is merely a typo and not a lack of familiarity with the gut microbiome that could make others doubt the work--I did check just to make sure there isn't some Gram-positive subclass of Bacteroidetes that I didn't know about.