High altitudes, typically above 2,500 meters, have lower air pressure and oxygen levels, which can cause serious health problems, including reduced sperm quality in people and animals. New research now shows that gut bacteria and their metabolites drive testicular inflammation and sperm cell death at high altitudes. 

The findings, published in Cell Host & Microbe, reveal a gut-testis interplay that may explain why low oxygen environments reduce male fertility at high altitudes.

In addition to low air pressure and oxygen levels, gut imbalances, diet, and microbial metabolites can also affect sperm. However, how gut changes at high altitudes cause sperm damage—and which bacteria and metabolites are involved—remains unclear.

So, researchers led by Jianchun Zhou at the Army Medical University in Chongqing, China, set out to study how sperm quality is affected by high-altitude low-oxygen conditions.

High-altitude conditions

In experiments with mice, males living at the equivalent of 5,800 meters produced fewer pregnancies when mated, had smaller testes, lower sperm concentration and motility, and showed structural damage in the sperm-producing tubules compared to males living at lower altitutdes. 

High-altitude low-oxygen conditions increased the levels of a bacterium called Clostridium symbiosum, which produces a metabolite called succinate. Giving mice either C. symbiosum or succinate lowered sperm quality, while a modified version of the bacterium that cannot make succinate did not. 

Succinate travels from the gut to the testis and harms sperm development by activating a type of immune cells that promote inflammation. These immunce cells release inflammatory molecules that trigger cell death in sperm-producing cells and boost inflammation, the researchers found.-

Improving sperm quality 

The gut microbiota from people living at high altitudes had higher levels of C. symbiosum and succinate than the microbiota of people living at low altitudes. And mice receiving gut microbiota from people living at high altitudes showed higher succinate levels, more inflammatory immune cells in their testes, and reduced sperm quality compared to mice receiving gut microbiota from people living at lower altitudes.

However, removing inflammatory immune cells or reducing succinate levels prevented sperm damage in mice, the researchers found.

The findings reveal a “gut-testis immune axis” and suggest that gut bacteria can indirectly harm sperm through immune signaling, the authors say. The results, they add, “provide insights into the potential targets for improving male sperm quality in [high-altitude] regions.”