3110. A New Connection Between the Gut and the Brain

By Jonathan D. Grinstein, Scientific American, December 5, 2018

It is well known that a high salt diet leads to high blood pressure, a risk factor for an array of health problems, including heart disease and stroke. But over the last decade, studies across human populations have reported the association between salt intake and stroke irrespective of high blood pressure and risk of heart disease, suggesting a missing link between salt intake and brain health.

Interestingly, there is a growing body of work showing that there is communication between the gut and brain, now commonly dubbed the gut-brain axis. The disruption of the gut-brain axis contributes to a diverse range of diseases, including Parkinson’s disease and irritable bowel syndrome. Consequently, the developing field of gut-brain axis research is rapidly growing and evolving. Five years ago, a couple of studies showed that high salt intake leads to profound immune changes in the gut, resulting in increased vulnerability of the brain to autoimmunity—when the immune system attacks its own healthy cells and tissues by mistake, suggesting that perhaps the gut can communicate with the brain via immune signaling.

Now, new research shows another connection: immune signals sent from the gut can compromise the brain’s blood vessels, leading to deteriorated brain health and cognitive impairment. Surprisingly, the research unveils a previously undescribed gut-brain connection mediated by the immune system and indicates that excessive salt might negatively impact brain health in humans through impairing the brain’s blood vessels regardless of its effect on blood pressure.

This research proposes new therapeutic targets for countering stroke—the second leading cause of death worldwide—and cognitive dysfunction. Reducing salt intake is applicable to people around the globe, as nearly every adult consumes too much salt: on average 9–12 grams per day or around twice the recommended maximum level of intake (5 grams) by the World Health Organization.

The researchers used mice and found that immune responses in the small intestines set off a cascade of chemical responses reaching the brain’s blood vessels, reducing blood flow to the cortex and hippocampus, two brain regions crucial for learning and memory. This, in turn, brought a decline in tests of cognitive performance. The impairment in learning and memory was clear even in the absence of high blood pressure; they observed that the gut is reacting to the salt overload and directing immune signals that lay the basis for deterioration throughout the brain’s vital vascular complex and compromise cognitive function. While this study has only been carried out on research animals so far, the scientists believe it's likely that much of the same applies to people.

Lowering salt intake has been shown to have beneficial effects to overall health, so the researchers wanted to know whether these effects extend to this newly identified signaling cascade that begins in the gut and targets the brain’s blood vessels too, ultimately, affect cognitive function. When the mice were returned to a normal diet after being on a high salt diet, the detrimental health effects caused by excess salt intake were erased. A pharmacological intervention that disrupted the immune signals also reversed the effects.

The implications of this newly identified gut-brain connection extend to several autoimmune disorders, including multiple sclerosis, rheumatoid arthritis, psoriasis, and inflammatory bowel disease, that have been shown to activate the same immune signaling pathway implicated in this study. These autoimmune disorders have a high stroke risk and are linked to poorly functioning blood vessels in the nervous system. This research is also a demonstration that what we eat affects how we think, and that seemingly isolated parts of the body can play vital roles in brain health. These results motivate research on how everyday stressors to our digestive systems and blood vessels might change the brain and, consequently, how we see, and experience, the world.