A minor injury, severe infection, or even the flu can send your body in a completely different direction. Some people recover quickly, but others become seriously ill or die. Scientists call this pathway the disease pathway, and it is shaped by many factors, including age, gender, medical history, and biology.
Dr. Janelle Ayers of the Salk Institute has been studying why people react so differently to illness and injury. Her work focuses on how the body can be guided away from disease and death and towards recovery and survival.
Inflammation and disease survival
Inflammation is often a major factor in the body’s decline during infections and injuries. It is essential for defense because it alerts the immune system and transports immune cells to where they are needed. However, excessive inflammation can damage tissues and lead to death.
Infections can cause particularly harmful inflammation, so the Salk team studied infected mice. They found that adding the amino acid methionine to an animal’s diet can protect it from wasting, blood-brain barrier problems, and death associated with inflammation.
The benefits came from unexpected channels. Methionine improves kidney filtration, indicating that the kidneys may play a larger role in helping the body recover from infections than previously realized.
The survey results are cell metabolismsuggesting that small changes in nutrition can have a large impact on disease outcome. Methionine supplementation may cause inflammatory conditions, kidney disease, renal failure, and patients undergoing dialysis, but further research is needed.
“Our study shows that small biological differences, including dietary factors, can have large effects on disease outcomes,” says senior author Ayers, a professor at Salk University, holder of the Salk Institute Legacy Chair, and a fellow at the Hughes Medical Institute. “The discovery of a kidney-driven mechanism that limits inflammation, together with the protective effects of methionine supplementation in mice, points to the potential of nutrition as a mechanism-based medical intervention that can direct and optimize the pathways people take against disease-causing insults.”
Mechanism of inflammation
Inflammation is the immune system’s response to a threat. The threat could be a pathogen in the body, or something as simple as debris. Immune cells move toward the problem and promote healing.
When these immune cells arrive, they increase the body’s alarm signals through proteins known as pro-inflammatory cytokines.
The body must carefully balance inflammation. Too little inflammation can lead to uncontrolled threats, and too much inflammation can damage healthy tissue. Much of the research in this area has focused on how immune responses are turned on and off.
Ayers’ team is considering another issue. Rather than focusing solely on immune switches, they are studying how the body modulates the intensity of inflammation by controlling the release and accumulation of proinflammatory cytokines.
“Pro-inflammatory cytokines are often what ultimately lead to disease and death,” says first author Katia Troha, Ph.D., a postdoctoral fellow in Ayers’ lab. “The immune system must balance inflammation to attack invaders without harming healthy cells in the body. Our job is to find the mechanisms the immune system uses to do that so we can target them to improve patient outcomes.”
Methionine and renal filtration
To investigate how the body manages cytokine levels, the researchers used a mouse model of systemic inflammation caused by the pathogen Yersinia pseudotuberculosis.
One of the first changes they observed was a reduction in eating in infected mice, suggesting that the animals’ metabolism had changed. To better understand their nutritional status, researchers measured amino acids circulating in their blood. Amino acids are the building blocks of proteins and support healthy cell function throughout your body.
Infected mice had lower levels of methionine, an essential amino acid that humans normally get from food. Troha then fed another group of mice a diet supplemented with methionine. Unexpectedly, these mice were protected from infection.
Additional experiments revealed that methionine acts on the kidneys to reduce cytokine levels in the blood. It increased the filtering capacity of the kidneys, improved blood flow, and helped the body remove pro-inflammatory cytokines in the urine.
Importantly, this process removed excess cytokines without interfering with other important parts of the immune response.
The researchers also tested whether methionine had similar effects in other conditions. Methionine also protected mice in models of sepsis and kidney injury, suggesting that methionine may also be relevant in other inflammatory disease settings.
nutrition, kidneys, recovery
When Salk scientists added methionine to the diet of infected mice, the mice underwent a completely different disease course. Their kidney function improved and they were protected from wasting, blood-brain barrier dysfunction, and death. At the same time, they were able to fight and kill pseudotuberculosis Yersinia.
Results from sepsis and kidney injury models suggest that the effects may extend beyond a single infection. This indicates that methionine may be a tool in infectious and inflammatory conditions, especially in people with kidney disease, kidney failure, or on dialysis.
“Our findings add to the body of evidence that common dietary elements can be used as medicines,” Ayers says. “Investigating these basic defense mechanisms reveals surprising new ways to put people who are otherwise destined to develop disease and die on a path to health and survival. Something as simple as a supplement with dinner may one day be the difference between life and death for patients.”
The researchers stress that while the results are promising, efficacy in humans has not yet been tested. Therefore, you should not start taking methionine supplements based on this study alone.
Future research will further explore how methionine works, whether other amino acids produce similar or complementary effects, and how the findings may impact people.
Other authors include Shrikaar Kambhampati, Arianna Insenga, and Salk’s Christian Metallo.
This research was supported internally by two Salk Women and Science Award and Collaboration grants, a Salk Innovator Award, the Howard Hughes Medical Institute, a Pioneer Fund Postdoctoral Fellowship, and the National Institutes of Health (AI144249, AI14929), the Keck Foundation, the NOMIS Foundation, and the Raleigh Medical Institute.
