Plate Nº 84 · recorded October 2, 2026
Health & Medicine ResearchReported finding
Too Little Salt May Harm Memory Just as Much as Too Much
A mouse study with humanized gut bacteria found both very low and very high salt diets impaired memory — through loss of synaptic proteins and inflammation, respectively.
By Marcus Bennett4 min read799 words
In brief
- Mice fed either a 0.1% low-salt or 8.0% high-salt diet for 14 weeks performed worse on memory tests than mice on a normal 0.5% salt diet.
- Low salt reduced key hippocampal synaptic proteins (SYN1, PSD95, BDNF) and CREB activation; high salt raised inflammatory signals, lowered propionate and butyrate, and increased intestinal oxidative stress.
- The study used 32 male mice colonized with gut bacteria from 10 healthy human donors, published in Food Research International (2026).
Most health advice about salt comes down to one message: eat less of it. But a new study in mice suggests the story is more complicated. Both severely restricting salt and eating far too much of it impaired memory in animals carrying human gut bacteria — just through different biological routes.
Researchers published their findings in Food Research International. The study focused on what scientists call the gut–metabolite–brain axis: the two-way communication system between gut bacteria, the chemical compounds those bacteria produce, and the brain.
Memory problems in both directions
Mice fed either a low-salt or a high-salt diet performed worse than mice on a normal diet on two kinds of memory tests: short-term working memory and long-term recognition memory.
The researchers also examined the hippocampus, the brain's memory center. Both extreme diets lowered levels of key synaptic proteins — SYN1, PSD95 and BDNF — and suppressed activation of a molecule called CREB. In plain terms, these are the molecular tools neurons use to build memories and adapt to new information. When the diets weakened these tools, the brain's ability to form memories suffered.
Why the salt question matters
Excessive salt intake is a well-documented global public health problem. Ultraprocessed foods, which are typically high in sodium, make up roughly 60% of total calories in the U.S. diet, with similar patterns in other countries. As a result, many people consume far more than the recommended limit of 2 grams of sodium per day.
A large body of research already links high salt intake to high blood pressure, cardiovascular disease, and even direct damage to the central nervous system. Public health guidelines widely promote cutting salt to protect the heart. What has remained poorly understood, however, is how severe, long-term salt restriction affects brain function.
Earlier experiments on this question relied on standard laboratory mice, whose natural gut bacteria differ substantially from those of humans. To make their results more relevant to human biology, the researchers behind the new study turned to a "humanized" mouse model.
How the study worked
The team started with 32 healthy male mice and gave them antibiotics to clear out their natural gut bacteria. They then transplanted gut microbiomes from fecal samples donated by 10 healthy humans into the mice.
With the animals' guts colonized by human bacteria, the researchers randomly split them into three groups. For 14 weeks, each group ate one of three custom diets. The normal-salt group received a standard diet containing 0.5% salt. The low-salt group got 0.1% salt, modeling severe sodium restriction. The high-salt group received 8.0% salt, modeling extreme consumption.
The researchers then ran a battery of behavioral tests. A Y-shaped maze measured short-term spatial memory. An object-recognition test — swapping a familiar object for a new one — measured long-term recognition memory. Tracking how much time mice spent in the open center of a square arena measured anxiety-like behavior and general movement.
Two diets, two mechanisms
The results pointed to two distinct routes by which salt extremes damage the brain.
In the low-salt group, memory impairment tracked with the drop in essential hippocampal synaptic proteins. Too little salt appears to starve the brain of vital chemical signals that gut bacteria normally supply.
The high-salt group showed a different pattern. The diet significantly increased pro-inflammatory signals circulating in the blood and shifted the gut microbiota toward a pro-inflammatory state. It did this partly by lowering fecal levels of two beneficial bacterial products, propionate and butyrate. These changes increased markers of oxidative stress — a kind of cellular damage — in the intestine, which the researchers note can trigger higher anxiety-like behavior.
In other words, too little salt disrupts the brain's supply lines, while too much salt causes inflammatory damage.
Important caveats
The findings are preliminary in several respects. The study involved 32 male mice, so the results may not extend to females or to humans directly, even with the humanized microbiome model. A 14-week diet in a mouse is also difficult to translate into human dietary advice. And the study modeled extreme sodium restriction and extreme consumption — not the moderate reduction most salt guidelines recommend.
Still, the results suggest that balance, rather than minimization, may be the right framing for salt and brain health.
Future studies could pin down the lowest safe level of salt intake and test whether restoring specific gut microbe metabolites — such as propionate and butyrate — can reduce memory and thinking problems linked to a salt imbalance.
More information: Anji Chen et al, Long-term low-salt and high-salt diets differentially disrupt the gut–metabolite–brain axis and induce cognitive impairment, Food Research International (2026). DOI: 10.1016/j.foodres.2026.119719
via Medical Xpress (Source)
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