Salt changes the microbiome and memory

Scientists studied the “gut–metabolites–brain” axis: how salt changes the gut microbiota and its chemical products, and these, in turn, affect brain function. To make the results closer to human physiology, they used a “humanized” mouse model: first, they cleared their intestines of their own microbiota using antibiotics, and then they inoculated them with microbes from stool samples of 10 healthy donors.

22 mice were divided into three groups and fed different diets for 14 weeks:

• the control group received a standard diet with 0.5% salt;
• the low‑salt group received 0.1% salt (strict sodium restriction);
• the high‑salt group received 8.0% salt (extremely high intake).

Then, memory and behavior were tested. To assess short‑term spatial memory, a Y‑maze was used. Long‑term recognition memory was tested using the “novel object” test: in a familiar arena, one object was replaced with an unfamiliar one, and the time the mouse spent exploring the novelty was recorded. Anxious behavior and overall motor activity were assessed in an “open field” — a square arena where the time spent by the animals in the center was recorded (less anxious animals tend to go to the center more often) and how they moved.

As a result, memory suffered both at very low and at very high salt intake. In the hippocampus, the brain’s main memory center, both diets reduced the levels of key synaptic proteins (SYN1, PSD95) and the neurotrophic factor BDNF, and also suppressed the activation of the CREB protein. All these molecules are critically important for memory formation and neuronal plasticity, so their weakening directly reduced the brain’s ability to remember.

At the same time, the mechanisms of harm were different. With a low‑salt diet, the main damage was due to the brain being deprived of important chemical signals that are normally produced by gut bacteria. Simply put, too little salt deprived the brain of the necessary metabolites produced by the microflora.

With a high‑salt diet, the picture was different. Pro‑inflammatory signals increased in the blood, the microflora shifted towards a pro‑inflammatory profile, and markers of oxidative stress rose in the intestines. At the same time, levels of short‑chain fatty acids, propionate and butyrate, which usually support the health of the intestinal barrier and have an anti‑inflammatory effect, decreased. Such a shift is often associated with more pronounced anxious behavior.

Thus, balance is important for the health of the brain and intestines: too little salt means the brain doesn’t receive enough beneficial microbial signals, while too much salt triggers inflammation and oxidative stress. In the future, experts plan to determine the minimum safe level of salt intake and to check whether memory problems can be compensated for by restoring specific microbial metabolites.