Mice fed a highly processed diet are more susceptible to flu

JAlthough its role in infectious disease has long been ignored by science, diet is now known to be important in the response to infections – for example, macronutrient composition and caloric density can influence disease severity. Now, a study published this week (November 15) in Cell reports indicates that other food properties may also have an effect on how the host handles a viral infection. The authors found that mice fed a highly processed diet were more likely to die within weeks of influenza infection than mice that ate grain-based foods. The findings may have important and broader implications for research on laboratory animals, which are often fed highly processed or grain-based foods assuming they are equivalent.

See “Gut microbiome may help or hinder defenses against SARS-CoV-2”

The idea to compare the two diets arose from a collaboration between immunologist Carl Feng and nutritional biologist Stephen Simpson, both from the University of Sydney, to explore the role of nutrition in the response to infections, explains Feng. The first question they faced, he adds, was which diet to use as a control, because researchers use grain-based and purified diets interchangeably in these types of mouse studies. Both diets are equivalent in protein, carbohydrate and fat, but differ in ingredients and micronutrient/vitamin levels. Additionally, the purified diets have been ultra-processed and contain less fiber.

Their comparison led to some surprises, Feng said. Under normal conditions, female mice eating either diet showed no significant differences in metabolic responses. For example, both groups showed similar weight gain and energy expenditure. However, when the mice were infected with the influenza A virus after three weeks on the diet, some differences became visible. All of the mice on the cereal diet began to regain weight 10 days after infection, while none of those on the ultra-processed diet did. Instead, all mice in the ultra-transformed diet succumbed to infection by day 14.

Diet is more than calories.

—Ruslan Medzhitov, Yale School of Medicine

Feng and his colleagues found that this striking difference in survival was not linked to a lack of immune response to the virus. On the contrary, the ultra-processed diet impaired the recovery phase, their analyzes suggest. For example, compared to grain-fed mice, those on a highly processed diet consumed less food during the first nine days after infection, had a significantly colder core temperature after day 7, and exhibited lower glucose uptake. altered on day 9.

Based on the fact that interferon (IFN)-γ, a signaling protein released by infected cells, has been associated with hypothermia in mice, Feng and colleagues also tested its potential role in the different outcomes. between the two groups. Using a mouse mutant that lacked a receptor for this cytokine, they found that mutants on the highly processed diet regained body weight and temperature similar to wild-type mice receiving the cereal diet. This suggests that IFN-γ mediates the outcome triggered by the ultra-processed diet, say the authors, but the details of this association are unknown.

See “Gut microbes help coordinate immune activity in mice”

The difference in mortality by diet is “very impressive,” says Yale School of Medicine immunologist Ruslan Medzhitov, who was not involved in the study. “The big question now [is] what exactly makes the difference in this diet.

It’s “a very interesting article” and the overall conclusions – for example, that diet formulation plays a role in maintaining homeostasis after infection – “are strong and supported by this research”, Philip Calder , a nutritional immunologist at the University of Southampton, writes in an email to The scientist. However, he adds, these results “do not allow us to affirm that ultra-processed foods are responsible for the adverse effects” observed. These diets have significant differences in terms of vitamins and minerals, notes Calder. “Many of these micronutrients are vital for the immune system,” so the reduced amount of micronutrients in the highly processed diet “could be an alternative explanation for ultra-processing,” says Calder, who was not involved in the study. this study.

Feng acknowledges that these other variables may indeed contribute to the difference in survival between diets, and at this time, these differences cannot be conclusively attributed to the high level of processing or a specific dietary component.

Feng adds that it is currently very difficult to translate this mouse work into what might happen in humans. But he stresses the importance of this work for animal research, arguing that paying more attention to the diets used as controls will help improve the reproducibility of experiments. “For us, this is a very important message,” he says. Calder agrees: “This study highlights something really important,” which is that the two diets “are not the same and may produce different results,” and comparisons assuming they are equal “are seriously wrong and should not be done”.

Medzhitov notes that this article adds to a body of research over the past few years supporting “that diet has a significant impact on the immune system.” He adds that people in industrialized countries are probably not sufficiently aware of how our diet affects our health under different conditions. “The focus has been on increasing caloric intake and associated metabolic disease, but diet is about more than calories.”

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