[pazimzadeh]

The Old Friends hypothesis doesn't make a ton of sense to me. Viruses did not come around much later than bacteria and parasites, and definitely before the adaptive immune system.

Bacterial viruses may have been involved in the evolution of nuclei https://nyaspubs.onlinelibrary.wiley.com/doi/full/10.1111/j....

The adaptive immune system of jawed vertebrates itself probably wouldn't be around if a virus hadn't infected the gametes of our fishy ancestors https://www.nature.com/articles/29457 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2686171/

More likely is that there is a critical time window during the development of the immune system when it is trained not to react to most bacteria (which are passed on from the mother's vaginal microbiota and harmed by cesarian sections and early antibiotic use). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6904599/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4464665/

There's more and more evidence that one person's commensal bacteria can be someone else's pathogen, and that we should really think about it as a "lock and key" with your immune system rather than categorizing bacteria as inherently good or bad. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5300855/

Another rarely mentioned complication though is that the successful immune response itself likely selects for more pathogenic microbes. https://pubmed.ncbi.nlm.nih.gov/15539148/

Removing selective pressure from pathogens can actually lead to less virulent strains. https://pubmed.ncbi.nlm.nih.gov/30100182/

That may be why the body spends considerable resources feeding the microbiota at a slow pace using by secreting mucus which contains a large amount of sugars, but which are attached using an extreme amount of diverse linkages so that one bacteria cannot sweep the field and take over. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1134114/ https://www.nature.com/articles/s41522-023-00468-3

You cannot really withhold food from bacteria, they will just eat you. But if you give them a slow trickle of sugar, you remove their reason to invade you (which is is at a risk to themselves). I personally think this concept can be applied to wars and immigration, but anyway..

Why are viruses more likely to cause autoimmune diseases than parasites? Probably because viruses go inside us and set of (Th1) intracellular responses , whereas parasites set of extracellular responses (Th2). You're probably more likely to be tricked into attacking yourself when you are fighting off something inside yourself than something outside your cells.

[modeless]

The "old friends" hypothesis is not that parasites evolved to be beneficial to us. They're not literally our friends, that's why "old friends" is in scare quotes. It's that the immune system evolved in an environment where parasites were omnipresent, and it malfunctions in an environment where they are entirely absent.

For example, the IgE protein present in peanut allergy is part of the parasite-fighting machinery of the immune system. It's not supposed to be reacting to food. But when there are no parasites to fight, it doesn't just become dormant as we would like.

[pazimzadeh]

I don't disagree with that.

However the original article talks about 'peaceful' commensals and links to this post (https://rachel.fast.ai/posts/2024-04-25-microbiome-1/), with the example that "friendly" microbes may not trigger your immune system if they leak into your bloodstream because they 'look similar' to your pancreatic cells.

While critical during the development of the immune system, this idea that there are certain actually 'friendly' or peaceful bacteria is less and less supported by the literature, and overstated to the point of probably being harmful. Even probiotic strains can be harmful if your immune system is overloaded or incapacitated.

Strong immune avoidance or induction of tolerance outside of the critical window is a strategy often used by pathogens to escape host defenses.

[throwup238]

> The Old Friends hypothesis doesn't make a ton of sense to me. Viruses did not come around much later than bacteria and parasites, and definitely before the adaptive immune system, so why aren't there "commensal viruses" which fight off parasites for us?

Viruses are even harder to study than bacteria, which are already very difficult because most of them can't be cultured in a lab [1], so we just haven't studied them that much. It's a lot easier to study viruses that cause a disease because we know what to look for. The gut virome [2] alone is likely to contain a lot of commensal viruses that help us fight off parasites but our understanding is in its infancy.

[1] https://en.wikipedia.org/wiki/Microbial_dark_matter

[2] https://www.thelancet.com/journals/ebiom/article/PIIS2352-39...

[pazimzadeh]

Sorry I edited my comment before I saw your response. I agree in general, and we may find commensal viruses. It's not crucial to the argument though so I removed it.