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I have read this article about how difficult is to send ships to another possible habitable world. One aspect deals with the human bacterial companions which might be greatly affected by prolonged living in a very closed environment:

We are always teamed with many other living creatures. Eighty percent of the DNA in our bodies is not human DNA, and this relatively new discovery is startling, because it forces us to realize that we are not discrete individuals, but biomes, like little forests or swamps. Most of the creatures inside us have to be functioning well for the system as a whole to be healthy. This is a difficult balancing act, and does not work perfectly even on Earth; but divorced from Earth’s bacterial load, and thus never able to get infusions of new bacteria, the chances of suffering various immune problems similar to those observed in over-sterile Terran environments will rise markedly.

As reaching a habitable planet outside our solar system is estimated to decades, if not more than 100 years, I expect these effects to be less noticeable for short periods of time in space.

This article confirms that gut microbiome is changing while living in space, more related to microgravity rather than radiation. However, it is not clear if these effects might lead to such serious health issues that a very long trip in space is virtually impossible.

Question: Were there any noticeable immune system changes observed for people staying for long in space?

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Immune system of Russian cosmonauts after orbital space flights Rykova M.P. Human Physiology. 2013. Т. 39. № 5. С. 557-566.

The article is an overview of the results of studies of the immune systems of cosmonauts. The use of a system approach to the evaluation of the various components of the immune system made it possible to identify a number of characteristics of adaptive change, including the quantitative and functional changes of the innate and adaptive immunity. Among them the most important are: changes in in the system of Toll like receptors (TLRs) manifested as a decrease in the content of circulating monocytes and granulocytes expressing TLR2, TLR4, and TLR6, and LPS-induced cytokine production; inhibition of the functional potential of natural killer (NK)- and T-cells. The article discusses possible factors and mechanisms of the identified changes.

In russian: Как долгий космический перелет повлияет на наше здоровье (Space travel affects our health)

In a long space flight, this shift can have a significant negative impact on health: the risk of developing Th2-associated autoimmune diseases and allergies increases, and the susceptibility to diseases associated with a weakening of cellular immunity increases

В условиях длительного космического полета этот сдвиг может оказывать существенное негативное влияние на здоровье: повышается риск развития Th2-ассоциированных аутоиммунных заболеваний и аллергий, а также увеличивается восприимчивость к болезням, связанным с ослаблением клеточного иммунитета

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    $\begingroup$ So, Kim Stanley Robinson has is right when arguing that long (decades) space flights might reduce people's life span very much also due to immunity system changes. Thanks. $\endgroup$ – Alexei Dec 14 '19 at 7:52
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The answer appears to be "yes", even for those astronauts who stayed in LEO, shielded by earth's magnetic field.

Examples are weakened tumor defences: https://www.physiology.org/doi/abs/10.1152/japplphysiol.00761.2018

Reacticated virusses from stress exposure: https://www.frontiersin.org/articles/10.3389/fmicb.2019.00016/full#h1

And more when searching "astronaut immune system". Am looking forward to solutions for how to keep people alive and healthy during longer spaceflights outside of earth's shielding.

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