Rejuvenation of the immune system
Young neighbors restored youth to the intestines of old mice
Intestinal bacteria transplantation and even vaccination with cholera toxin led to the same effect
Polina Loseva, "The Attic"
With age, the composition of the intestinal microflora in mice (as in humans) changes quite a lot. At the same time, the work of the immune system also changes: the innate immunity becomes more aggressive, and the acquired one weakens. It is still unclear what is the cause and what is the effect: whether microbes provoke changes in immunity, or vice versa. Cambridge scientists have given a new argument in favor of the first option. By transplanting intestinal bacteria from young mice to old ones, they ensured that the acquired immunity in the intestinal wall restored its activity. In order to "wake up" the immune system, even the usual neighborhood with young mice or vaccination against cholera was enough.
Intestinal microbes and the immune system are connected by a web of complex interactions. Bacteria, on the one hand, calm the immune system to avoid unnecessary inflammation in the intestine, and on the other – keep it in good shape, constantly throwing up new foreign molecules. Over time, the bacterial community is being rebuilt: the main inhabitants of the intestine are becoming fewer, and new, previously unfamiliar creatures may come in their place. And the less diverse the resulting set is, the less chance a person has to live longer.
Immunity, in turn, is also changing. In an elderly body, chronic inflammation always develops, this is the work of the innate immunity system, while the acquired immunity, on the contrary, loses its strength. In particular, lymphocytes living in the intestinal wall are less likely to divide and react worse to possible intestinal infections.
To check who is the cause of these changes – their own aging of the immune system or the influence of the microbial community – a group of researchers from Cambridge tried to restore the immune system in old mice. They settled animals aged 3 and 21 months in one cage for 30-40 days. Since mice often eat each other's feces, scientists expected that thanks to such a neighborhood, the animals would exchange intestinal bacteria. And indeed, after a month of living side by side, the microbiome of old mice became younger and in diversity became similar to the microflora of their young neighbors. At the same time, the immune system of elderly animals became more active: lymphocytes in the intestinal wall began to multiply again.
To confirm the role of microbes in intestinal rejuvenation and exclude other factors, the researchers resorted to fecal transplants: they injected a concentrate of "young" microbes into the intestines of elderly mice, and also put fresh excrement of young animals into their cells. The result was similar to the neighborhood experiment: the number of lymphocytes in the intestinal wall increased again. Interestingly, this effect did not work in the opposite direction: when young mice were transplanted with "old" microbes, their immune system did not age, and the cells continued to divide.
Finally, the scientists decided to check whether the immune system is restored after rejuvenation. To do this, they vaccinated old mice with cholera toxin. It turned out that the vaccination itself, regardless of whether "young" microbes were transplanted into mice or not, stimulates the work of immunity in the intestinal wall. Apparently, fecal transplantation also works like a vaccination: by supplying the immune system with unfamiliar antigens, it triggers an immune response. This means that in the case of humans, you can find different ways to maintain the intestinal immune system in a viable state. But since it is hardly safe to use cholera toxin for these purposes, this is another argument in favor of using fecal transplants in order to improve the health of the elderly.
Article by Stebegg et al. Heterochronic faecal transplantation boosts gut germinal centers in aged mice published in the journal Nature Communications.
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