July 23, 2024

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Feasting Risks: High-Fat Diets Temporarily Suppress Immunity

Feasting Risks: High-Fat Diets Temporarily Suppress Immunity, Reversed by Fiber-Rich Recovery

Feasting Risks: High-Fat Diets Temporarily Suppress Immunity, Reversed by Fiber-Rich Recovery

Indulging in an occasional feast turns out to be an immune killer! Nature Subjournal: Brief episodes of high-fat diets can increase susceptibility to pathogenic bacteria and suppress immunity.

It’s well known that junk food brings joy! Given the choice, omnivores (such as mice and humans) often prefer energy-dense foods rich in fat over plant-based foods. This explains why many people, after several days of home-cooked meals, crave junk food or dining out!

Unexpectedly, treating yourself to a rare lavish meal can quietly harm your body.

Recently, a research team from the University Medical Center Hamburg-Eppendorf in Germany, published a study in Nature Immunology revealing that each brief transition from a regular diet rich in dietary fiber to an energy-dense “feast” alters the metabolism, transcription, and immunological landscape of the gastrointestinal tract. In simple terms, each feast comes at the cost of short-term immune suppression!

The researchers found that a sudden high-fat feast is enough to induce transient mucosal and systemic immune suppression, leading to increased susceptibility of the intestines to pathogenic bacteria and impairment of antigen-specific immunity. The good news is that this process is reversible. After reintroducing dietary fiber, immune suppression and CD4+ T cell metabolism can return to normal, ultimately rebuilding mucosal and systemic immunity.

Feasting Risks: High-Fat Diets Temporarily Suppress Immunity, Reversed by Fiber-Rich Recovery

In this experiment, researchers used an energy-dense diet pattern rich in animal fats but lacking dietary fiber (FD) to simulate common “feasts,” alternating it every 3 days with a regular diet (RD) for a total of four switches.

Each “feast attack” resulted in periodic changes in the mice’s body weight, serum cholesterol levels, energy expenditure, and core body temperature.

Additionally, the microbiota in the ileum and the transcriptome of the ileum tissue showed periodic changes. For example, at each “feast switch,” the abundance of certain intestinal bacteria increased or decreased, and differentially expressed genes (DEGs) followed a “gain-loss” pattern.

To clarify the impact of a “feast” on mucosal immunity, researchers introduced Salmonella Typhimurium into the intestinal tissue of mice. The results showed that compared to the control group on a regular diet, mice switched to the energy-dense diet had a significant increase in body weight. Moreover, there were more colony-forming units (CFUs) in the intestinal contents, ileum tissue, and liver.

Not only that, the systemic immune response was also affected. Mice switched to the energy-dense diet were unable to effectively clear systemic infections induced by Listeria bacteria and even directly impaired the immune response of antigen-specific CD4+ T cells.

In fact, short-term “feasts” further altered the immune landscape of the intestines, leading to inhibition of CD4+ T cell zones and downregulation of mucosal type III cytokines IL17a, IL17f, and IL22. The reduction in these cytokines made the intestines more susceptible to Salmonella Typhimurium and more prone to bacterial invasion.

Why does the high-fat “deceptive feast” damage immunity? Is the culprit simply excessive calorie intake? It’s not that simple. After controlling for total energy intake and comparing multiple groups of mice on different diet patterns, researchers found that the health damage caused by a sudden feast does not depend on fat, nor is it limited to a specific energy-dense diet but is concentrated in all diet patterns with extremely low dietary fiber content. Could a “low-fiber diet” be the key to unlocking the Pandora’s box?

Further exploration revealed that the effects driven by dietary fiber are actually mediated by the gut microbiota, not by high fat or high calorie intake. Researchers found that compared to the control group adhering to an RD, the concentration of acetate and butyrate, which are short-chain fatty acids (SCFAs), was lower in the cecum of mice in the FD group.

Both acetate and butyrate are common SCFAs. This finding implies that the key to mediating immune homeostasis is the types of gut bacteria that ferment dietary fiber into SCFAs. Compared to RD, FD has lower dietary fiber content, resulting in lower naturally generated SCFAs. The decrease in SCFAs changes the common basic mechanisms of type I and type III immune responses, such as the metabolism of CD4+ T cells, thereby impairing intestinal and systemic immune function.

Short-term effects of FD are mediated by microbial metabolites:

Short-term “feasts” indeed harm the immune system, but there’s no need to worry excessively. Quickly returning to a diet rich in fiber and supplementing a large amount of dietary fiber can effectively alleviate the damage to the immune system caused by feasting.

After switching back to RD for 21 days, the mice’s increased weight returned to baseline levels, the higher CFUs in the intestinal cavity improved, and the effectiveness of CD4+ T cells against antigens reversed significantly.

Therefore, after a “deceptive feast,” rapidly returning to a regular diet and replenishing a lot of dietary fiber can effectively mitigate the damage to the immune system.

Restoring RD can restore mucosal and systemic immunity:

Of course, limited to animal experiments may seem less convincing. Researchers also observed similar phenomena in a human trial. In healthy participants, they alternated between a fiber-rich diet (FRD) and a fiber-deficient diet (FPD), with each switch lasting 5 days.

The results showed that FPD significantly altered the composition of participants’ gut microbiota, reducing the number of fiber-fermenting bacteria and consequently decreasing the concentration of SCFAs in the feces. Moreover, after the “feast” diet, the peripheral blood significantly decreased the co-expression of IL-17A, TNF-α, and TH1 cells.

It seems that occasional feasts can indeed become a “fast lane” for diseases, especially during holidays or travels when there are abundant feasts, dealing a potentially “fatal blow” to the body’s immune system! Therefore, “first aid” after a feast is crucial—supplementing dietary fiber can rescue your “vulnerable” gut and immune system.

Feasting Risks: High-Fat Diets Temporarily Suppress Immunity, Reversed by Fiber-Rich Recovery

Siracusa, F., Schaltenberg, N., Kumar, Y. et al. Short-term dietary changes can result in mucosal and systemic immune depression. Nat Immunol 24, 1473–1486 (2023). https://doi.org/10.1038/s41590-023-01587-x

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