The Correlation Between Diet and Inflammation-Induced Damage

By Irene Yeh 

While inflammation serves as an important signal for immune cell response, too much of it can lead to tissue damage or even death. When immune cells arrive at the invaded area, they release proteins called pro-inflammatory cytokines. These cytokines are what lead to sickness and death. It is a delicate process figuring out the balance between creating enough inflammation to dispose of the invader and producing too much. 

To understand how the body regulates its cytokine levels, researchers at the Salk Institute conducted a study with mice by inducing  systemic inflammation using the Yersinia pseudoturberculosis (Yptb) pathogen (Cell Metabolism, DOI: 10.1016/j.cmet.2025.12.011). The team found a nutrient-mediated role for the kidneys in regulating cytokine responses during infection.  

Methionine and Kidney Function 

The team infected the mice with Yptb, and the mice quickly showed signs of decreased appetite, indicating a metabolic change. The mice’s circulating amino acids shifted, with methionine (Met) significantly decreased during infection. The researchers wanted to test the functional role of Met before and after infection, and fed the mice controlled, Met-deficient, or Met-enriched diets for 14 days before infection. Food intake and dietary conditions did not change. The results demonstrated that mice who had been fed Met-deficient diets lost weight after Yptb infection, and mice in the Met-enriched diet group gained weight compared to the control group. In other words, the mice with Met added to their diets were protected from Yptb, as well as from wasting, anorexia, and blood-brain barrier dysfunction. It must be mentioned that the mice were all male.  

The research team also measured Yptb levels in the organs, and they made a key discovery about the kidneys. The kidneys promoted host-pathogen cooperation and mitigated the costs of immune responses by limiting systemic inflammation via renal filtration of pro-inflammatory cytokines. In other studies, there has been evidence of kidneys clearing out cytokines in blood. In this study, the team extended these findings by demonstrating that kidneys regulate systemic inflammation by promoting the clearance of circulating pro-inflammatory cytokines during infection. Increased urination was associated with elevated GFR and greater cytokine reabsorption by the kidneys, indicating that the increased excretion reflected enhanced filtration instead of impaired reabsorption, damage, or renal failure. 

Additionally, the team tested out if Met can help with other conditions. They discovered that Met could help with sepsis and multi-organ damage caused by E. coli. By examining the decreased circulating pro-inflammatory cytokine levels and increased urination of these cytokines, they found that Met supplementation protected the mice from E. coli. The researchers also induced kidney injury using adenine, which triggers sterile inflammation and progressive renal failure. The result was that Met delayed mortality and exhibited less renal pathology.  

A key unanswered question is, how does increased kidney function relate to kidney growth? Studies have shown that changes in blood flow and increases in filtration by individual nephrons often occur before the kidney grows. Conversely, kidney growth leads to larger nephrons, greater glomerular surface area, and increased blood flow, which enhances the kidney’s filtering capacity. Further research is required to determine how increased filtration and kidney growth are linked during infection—and whether Met enhances other kidney functions that support survival during infection. 

Dietary Supplements Used as Medicine 

Met is essential for growth and development, but Met restriction also mimics the benefits of calorie restriction, including improved health and lifespan. As such, it has gained traction as a form of dietary intervention. None of the studies that support the benefits of Met restriction mention how it can potentially affect physiological stressors such as infection. More research needs to be conducted to fully explore how Met works, as well as if other amino acids have similar or complementary mechanisms. 

Nevertheless, the results are promising of using a dietary supplement as a form of medicine. Instead of taking a drug that may have unpleasant side effects, the ability to simply take a supplement after a meal could make a huge difference.