“I am on a diet.” is probably one of the most commonly heard sentences these days. With or without a specific aim in mind, most of us have tried to be on a particular “diet” regimen. Diets, in nutrition, are defined as the sum of food consumed by a person. Nowadays, it often implies the intake or avoidance of particular food.

We can usually name the broad goals of a diet — weight loss, gut cleansing, or “healthy eating.” Yet, oftentimes, we are unaware of how these diets affect our bod­ies on a cellular level and impact how the cells get energy, function and behave. This article will focus on how diets affect our immune system specifically.

Western Diet

The Western diet is perhaps the most thoroughly re­searched diet. It is a modern-day diet rich in refined sug­ars, salt, processed meats, and saturated fats derived from animals while containing low fibre, vitamins, and minerals. Research from various disciplines has shown that the popu­larization of the Western diet and lifestyle accounts for the drastic increase in chronic inflammation and noncommuni­cable diseases worldwide, including most heart diseases and cancers.

A Western diet meal impacts both branches of the immune system: adaptive and innate immunity. Macrophages, a type of innate immune cell, are involved in engulfing and degrad­ing infected cells and foreign pathogens. These cells are par­ticularly susceptible to the stress induced by animal-derived fats in a Western diet. Obesity caused by excessive caloric intake also alters the natural localization of innate immune cells, which correlates to increased systemic inflammation.

As part of the adaptive immune system, lymphocytes, in­cluding T cells and B cells, are also impacted by obesity. The balance between two T cell subsets, Th1 and Th2, is bro­ken when the body is in an obese state, rendering the body more susceptible to inflammation. B cell concentration also increases under obesity, worsening insulin resistance.

The Western diet also affects gut microbiota composition, causing microbial imbalances in the gut. This, in turn, sab­otages gut-dependent processes and contributes to increased cardiovascular risks and autoimmune diseases.

Mediterranean Diet

In contrast to Western diets, Mediterranean diets are en­riched in vegetable-derived protein, vitamins and unsaturat­ed (healthy) fats. This diet has been associated with  anti-inflammatory effects, a decreased rate of chronic diseases and increased longevity.

A study demonstrated that macaques on a Mediterranean diet, compared to those on a Western diet, had lower expres­sions of proinflammatory genes in monocytes, the precursors of macrophages. The diet also inhibited a specific type of monocytes, M1 monocytes, and their downstream M1 mac­rophages, known to be associated with chronic diseases.

Unsaturated fats, found in olive oil and nuts in the Med­iterranean diet, can, in fact, dampen the deleterious effects caused by saturated fats and promote the functionality of innate immune cells. Fibres, another component enriched in the Mediterranean diet but lacking in the Western diet, are also crucial in regulating immune functions. Certain fibres have been found to promote the differentiation of a subset of T cells called regulatory T cells, essential for preventing autoimmune diseases. Moreover, a diet high in vitamins and fibres has also been shown to ameliorate intestinal inflamma­tion and restore bacterial composition in mouse models.

Paleo Diet

The paleolithic diet, or the cavemen diet, is a diet that attempts to resemble what human hunter-gatherer ancestors ate during the Paleolithic era. This diet avoids any processed food, grains, legumes, vegetable oils and most dairy prod­ucts and emphasizes the intake of fruits, vegetables, meat and fish. In fact, derivatives of paleo diets have been adopted and advocated for to alleviate the symptoms of some immune dis­eases.

The modified paleolithic Wahls diet is one of the two di­ets promoted for multiple sclerosis (MS). Despite the precise pathogenesis of MS being unknown, numerous studies have shown that the Wahls diet promoted mobility and improved symptoms of MS, including fatigue.

According to the Autoimmune Association, the Autoim­mune Paleo (AIP) diet is suitable for people with autoimmune or inflammatory conditions such as psoriasis, celiac disease and inflammatory bowel syndrome. AIP diet also focuses on eating more vegetables and fish, aligning with the paleo diet principles, while avoiding food that people with autoimmune diseases commonly react to.

However, so far, no studies have attempted to uncover if or how a paleo diet alters immunity on a cellular level.

Eating Less or Not Eating at All

Fasting as a dietary option has gained popularity over the years, with the duration ranging from a couple of hours a day to multiple days as a “system cleanse.” The 16/8 intermittent fasting (IF) regimen is the most popular version of fasting. Dieters restrict their eating period to only an 8hour window, for example, from 8 am to 4 pm, and refrain from eating for the remaining 16 hours of the day.

A recent study showed that people going on a 14% caloric restriction over two years had a drastic increase in the gener­ation of new immune cells and overall decreased proinflam­matory gene expressions.

Studies have also investigated the effects of fasting during Ramadan, the month of fasting for Muslims. Over the month of Ramadan, the level of proinflammatory cytokines, the concentration of circulating leukocytes and the cell prolifera­tion rates in the body were all significantly reduced compared to before Ramadan. This suggests that IF practiced during Ramadan effectively reduced the level of inflammatory pro­cesses in the body.

IF also promotes a cellular activity called autophagy, a natural degradation method to remove dysfunctional compo­nents of the cells. Autophagy plays an essential role in regu­lating the activation and responses of specific T cells. IF also reduces biomarkers of inflammation in the body and decreas­es fat mass, which correlates to lower levels of proinflam­matory cytokines. Combining the effects of both reducing inflammation and promoting T cell activation, IF has been suggested as a possible defence mechanism against SARS-CoV2 infections.

So far, it seems like all the “healthy” diets mentioned have been shown to reduce the level of inflammatory responses in the body, on top of other pro-immune effects. However, as we will learn throughout this issue of IMMpress, gut micro­biota composition and balance are essential for maintaining health. Sudden changes in diets can often cause drastic chang­es in the gut microbiota population and behaviour, leading to unpredictable or undesirable effects. We should always keep in mind that there is no one-size-fits-all diet, and we should all ensure we understand the impact of a diet before jumping into one.


References:

Asghar, A., & Sheikh, N. (2017). Role of immune cells in obesity induced low grade inflammation and insulin resistance. Cellular immunology, 315, 18–26. https://doi.org/10.1016/j.cellimm.2017.03.001

Christ, A., Lauterbach, M., & Latz, E. (2019). Western Diet and the Immune System: An Inflammatory Connection. Immunity, 51(5), 794–811. https://doi.org/10.1016/j.immuni.2019.09.020Faris, M. A., Kacimi, S., Al-Kurd, R. A., Fararjeh, M. A., Bustanji, Y. K., Mohammad, M. K., & Salem, M. L. (2012). Intermittent fasting during Ramadan attenuates proinflammatory cytokines and immune cells in healthy subjects. Nutrition research (New York, N.Y.), 32(12), 947–955. https://doi.org/10.1016/j.nutres.2012.06.021

Hannan, M. A., Rahman, M. A., Rahman, M. S., Sohag, A., Dash, R., Hossain, K. S., Farjana, M., & Uddin, M. J. (2020). Intermittent fasting, a possible priming tool for host defense against SARS-CoV-2 infection: Crosstalk among calorie restriction, autophagy and immune response. Immunology letters, 226, 38–45. https://doi.org/10.1016/j.imlet.2020.07.001

Johnson, C. S., Shively, C., Michalson, K. T., Lea, A. J., DeBo, R. J., Howard, T. D., Hawkins, G. A., Appt, S. E., Liu, Y., McCall, C. E., Herrington, D. M., Ip, E. H., Register, T. C., & Snyder-Mackler, N. (2021). Contrasting effects of Western vs Mediterranean diets on monocyte inflammatory gene expression and social behavior in a primate model. eLife, 10, e68293. https://doi.org/10.7554/eLife.68293

Spadaro, O., Youm, Y., Shchukina, I., Ryu, S., Sidorov, S., Ravussin, A., Nguyen, K., Aladyeva, E., Predeus, A. N., Smith, S. R., Ravussin, E., Galban, C., Artyomov, M. N., & Dixit, V. D. (2022). Caloric restriction in humans reveals immunometabolic regulators of health span. Science (New York, N.Y.), 375(6581), 671–677. https://doi.org/10.1126/science.abg7292 Wahls, T. L., Chenard, C. A., & Snetselaar, L. G. (2019). Review of Two Popular Eating Plans within the Multiple Sclerosis Community: Low Saturated Fat and Modified Paleolithic. Nutrients, 11(2), 352. https://doi.org/10.3390/nu11020352

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