Tag: diet and mental health

Researchers Discover Immune Mechanism Linking Changes in Gut Microorganisms and Behavior after Chronic Stress

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Stress is inevitable, but it can disturb our body’s physiological signaling mechanisms when it becomes chronic. These mechanisms are interlinked with the Microbiota Gut-brain axis (MGBA) and influence the diet-mental health relationship (DMHR) in many ways. Being a major immune organ and highly colonized with the microbiome, our gut experiences certain immune inflammatory responses due to stress, which affect the gut microbiome composition and contribute to the onset of depression and anxiety. 

A new study led by researchers at Johns Hopkins has strengthened our understanding of the role of specific gut immune cells in microbiota composition and influencing the brain’s responsiveness to stress. This early-stage experiment on mice found that a specific type of white blood cells, gamma-delta T lymphocytes, play a key role in the cellular mechanism leading to adverse behavioral changes under chronic stress. After chronic stress, some mice in the experiment developed social avoidance behavior, i.e., they started avoiding contact with other mice. These mice had reduced diversity of microorganisms in their guts and increased concentrations of gamma-delta T lymphocytes in their intestines and in the membranes surrounding their brains. Under equal chronic stress conditions, mice without gamma-delta T lymphocytes did not develop social avoidance behavior (Zhu et al., 2023). The study was published in Nature Immunology.

 

After chronic stress, some mice in the experiment started avoiding contact with other mice. They had reduced microbial diversity and increased concentrations of gamma-delta T lymphocytes in their gut and surrounding their brain

 

Chronic stress

Chronic stress is a consistent sense of feeling pressured and overwhelmed over a long period of time. There are many possible sources of chronic stress in modern society. These include bad living conditions and homelessness, bad family and social relations, negative interactions between work and family, adverse work conditions, illness, and many others (Armon et al., 2014; Goodman et al., 1991; Tsukerman et al., 2020). Chronic stress slowly drains a person’s psychological energy and has damaging effects on both health and well-being.

Chronic stress and the gut microbiota

Physiologically, chronic stress induces immune changes and inflammation, leading to psychiatric disorders such as depression and anxiety (Hodes et al., 2014). These immune changes include changes to the gut microbiota – the trillions of microorganisms that live in the human intestinal tract (Figure 1). 

 

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Figure 1. Chronic stress leads to immune changes, inflammation, depression, and anxiety

 

Gut microorganisms play a key role in digesting food, but they are also incredibly important for various other processes, such as the differentiation of certain immune cells (Zhu et al., 2023). Differentiation is when immature and unspecialized cells transform into specialized, mature cells that perform specific bodily functions. It is one of the critical processes of life. When a person is under stress, the body reacts with inflammation, that in turn affects the composition of microorganisms in the gut but also creates physiological changes that reach the brain and affect cognition and behavior.

Due to this, studying physiological changes associated with chronic stress is very important for understanding the development of the most common psychiatric disorders and finding effective ways to treat them. However, research ethics and practical considerations impose very strict limits on what types of studies can be conducted on humans. That is why studies of the physiology and biochemistry of chronic stress are often done on animals, particularly mice, using specific research protocols. One research protocol used to induce chronic stress in mice for research purposes is the chronic social defeat stress protocol.

What is chronic social defeat stress?

Chronic social defeat stress is a protocol (procedure) in which a mouse is exposed to a larger aggressive mouse in an enclosed space. This is followed by a confrontation between the two mice in which the mouse undergoing this treatment is defeated and forced into a subordinate position (social defeat). Typically, this procedure is repeated daily over ten days (Figure 2). 

 

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Figure 2. Chronic Social Defeat Stress Protocol

 

The chronic social defeat stress protocol produces effects similar to depression in exposed mice. It also produces a number of other easily detectable effects such as increased weight of spleen of these mice, lower preference for sucrose, and others. That is why it is extensively used in research on mice (Golden et al., 2011).

 

The chronic social defeat stress protocol produces effects similar to depression in exposed mice. 

 

The current study

Study author Xiaolei Zhu and his colleagues wanted to explore the cellular mechanisms behind social avoidance behaviors caused by chronic stress. They were particularly interested in the role a specific type of white blood cell called the gamma-delta T lymphocyte has in these changes and in the changes in the composition of gut microorganisms caused by stress.

What are gamma-delta T lymphocytes?

Gamma-delta T lymphocytes (γδ T-cells) are a specific type of white blood cells in the body. Still, they are found in high concentrations in various mucosal tissues called meninges, including intestines and membranes surrounding the brain. Lymphocytes are involved in the body’s immune responses. Studies have shown that gamma-delta T lymphocytes located in the meninges regulate anxiety-like behaviors and memory. Furthermore, research indicated that gamma-delta T lymphocytes in the intestines could travel to the meninges under certain conditions. This has led scientists to assume that these gamma-delta T lymphocytes from the gut may be involved in brain function changes when inflammation occurs (Zhao et al., 2018; Zhu et al., 2023) (Figure 3).

 

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Figure 3. Gamma-delta T lymphocytes are in intestinal mucosal tissue and membranes around the meninges. 

 

The experiment

The study authors applied the chronic defeat stress protocol on a group of mice. Afterward, researchers examined the social behavior of these mice (towards other mice, using a social interaction test). They noticed that some of these mice started avoiding contact with other mice in a test situation, i.e., manifested social avoidance behavior, while others did not. They named the group of mice that showed social avoidance behavior the susceptible group. In contrast, the group of mice that did not show social avoidance behavior was named the resilient group. Researchers kept a third group of the same genetic strain of mice as controls and did not expose them to the chronic social defeat protocol (see Figure 4).

 

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Figure 4. Susceptible vs. resilient vs. no exposure

 

After the procedure, researchers collected stool samples from the mice and conducted their genetic analysis in order to identify the compositions of microorganisms present in the guts of these mice. This procedure is called the metagenomic sequencing of the gut microbiota. They also used a procedure called flow cytometry to determine the number and characteristics of gamma-delta T lymphocytes in the gut and in the meninges of these mice.

Comparison with humans

Parallel with this experiment, researchers investigated the differences in the composition of gut microbiota in humans diagnosed with major depressive disorder and healthy individuals by analyzing their stool samples. They found that a lower abundance of the Lactobacillus group of bacteria in the gut was associated with higher depression and anxiety symptoms. They confirmed this using three different assessments of depression and anxiety symptoms (the Montgomery-Asberg depression scale, the Hamilton Depression scale, and the Hamilton Anxiety Scale)(Zhu et al., 2023). Based on this, study authors assumed that concentrations of these bacteria in the gut might play a role in the vulnerability to stress in mice and humans. They decided to look for differences in the abundance of Lactobacillus bacteria in different groups of mice in their experiment.

Susceptible mice had a reduced abundance of Lactobacillus johnsonii bacteria in the gut! (See Figure 5).

 

%learn about nutrition mental health %The Center for Nutritional Psychology Figure 5. Humans + Mouse experiment showing a lower abundance of lactobacillus in gut bacteria = with higher depression and anxiety

 

A comparison of the gut microbiota of susceptible mice, resilient mice, and the control group showed that susceptible mice had less diverse microbial populations in the gut. The gut microbiota of susceptible mice differed from the gut microbiota of resilient mice and the control group on a number of bacterial species. As researchers expected, one of these species was Lactobacillus Johsonii. Their concentration was reduced in susceptible mice’s guts compared to resilient mice and the control group.

Susceptible mice had increased concentrations of gamma-delta T cells in both meninges and intestines

Given the previously described relationship between Lactobacillus bacteria and immune responses, researchers examined whether concentrations of gamma-delta T lymphocytes were increased in mice exposed to the chronic social defeat stress treatment. Results showed that susceptible mice had increased concentrations of gamma-delta T lymphocytes in their colons and meninges (membranes surrounding the brain) compared to resilient and healthy mice.

 

Susceptible mice had increased concentrations of gamma-delta T lymphocytes both in their colons and their meninges 

 

In susceptible mice, many of the gamma-delta T cells in brain membranes came from the gut!

Researchers then wanted to know whether the gamma-delta T cells found in the meninges of susceptible mice were cells that differentiated there or those cells that traveled from the gut. They identified differences between these two types of gamma-delta T cells and measured their concentrations. Results showed that, in resilient mice and the control group, gamma-delta T lymphocytes found in the meninges were indeed differentiated. However, in susceptible mice, there were fewer such cells, but many gamma-delta T lymphocytes came from the gut.

 

In susceptible mice, there were fewer such cells, but there were lots of gamma-delta T lymphocytes that came from the gut

 

Social avoidance after the chronic social defeat stress does not develop in mice without gamma-delta T lymphocytes.

Finally, researchers wanted to test whether the gamma-delta T lymphocytes were responsible for the social avoidance behavior after exposure to chronic social defeat. They repeated the procedure on a new group of special mice that did not have the gamma-delta T cells. As researchers expected, these mice did not develop social avoidance behavior after exposure to the chronic social defeat stress protocol.

Conclusion

The study showed that a certain type of white blood cells – gamma-delta T lymphocytes and their accumulation play a key role in changes to behavior induced by stress. In the context of MGBA-DMHR, it also demonstrates interactions between gut microbiota, the body’s immune responses, and the brain when an organism is stressed. Given that many of the physiological processes in mice are similar to those in humans, these findings contribute to the scientific understanding of physiological mechanisms of behavioral changes that chronic stress and related disorders in humans. These insights can help develop novel ways to treat and prevent major depressive disorder and other stress-related disorders. They can also open new approaches to diagnosing individual susceptibility to stress and increasing resilience.

The paper “Dectin-1 signaling on colonic gamma-delta T cells promotes psychosocial stress responses” was authored by Xiaolei Zhu, Shinji Sakamoto, Chiharu Ishii, Matthew D. Smith, Koki Ito, Mizuho Obayashi, Lisa Unger, Yuto Hasegawa, Shunya Kurokawa, Taishiro Kishimoto, Hui Li, Shinya Hatano, Tza-Huei Wang, Yasunobu Yoshikai, Shin-ichi Kano, Shinji Fukuda, Kenji Sanada, Peter A. Calabresi, and Atsushi Kamiya.

For more research in the Microbiota Gut-Brain Axis — Diet-Mental Health Relationship (MGBA-DMHR), visit CNP’s Nutritional Psychology Research Library (NPRL) Microbiota Gut-Brain Axis—Diet-Mental Health Relationship research category, or enroll in NP 120: Microbiota Gut-Brain Axis and the DMHR (available in May 2023).

References

Armon, G., Melamed, S., Toker, S., Berliner, S., & Shapira, I. (2014). Joint Effect of Chronic Medical Illness and Burnout on Depressive Symptoms Among Employed Adults. Health Psychology, 33(3), 264–272. https://doi.org/10.1037/a0033712

Golden, S. A., Covington, H. E., Berton, O., & Russo, S. J. (2011). A standardized protocol for repeated social defeat stress in mice. Nature Protocols, 6(8), 1183–1191. https://doi.org/10.1038/nprot.2011.361

Goodman, L., Saxe, L., & Harvey, M. (1991). Homelessness as psychological trauma. American Psychologist, 46(11), 1219.

Hodes, G. E., Pfau, M. L., Leboeuf, M., Golden, S. A., Christoffel, D. J., Bregman, D., Rebusi, N., Heshmati, M., Aleyasin, H., Warren, B. L., Lebonté, B., Horn, S., Lapidus, K. A., Stelzhammer, V., Wong, E. H. F., Bahn, S., Krishnan, V., Bolaños-Guzman, C. A., Murrough, J. W., … Russo, S. J. (2014). Individual differences in the peripheral immune system promote resilience versus susceptibility to social stress. Proceedings of the National Academy of Sciences of the United States of America, 111(45), 16136–16141. https://doi.org/10.1073/pnas.1415191111

Tsukerman, D., Leger, K. A., & Charles, S. T. (2020). Work-family spillover stress predicts health outcomes across two decades. Social Science & Medicine, 265, 113516. https://doi.org/10.1016/j.socscimed.2020.113516

Zhao, Y., Niu, C., & Cui, J. (2018). Gamma-delta (γδ) T Cells: Friend or Foe in Cancer Development. Journal of Translational Medicine, 16(1), 1–13. https://doi.org/10.1186/s12967-017-1378-2 

Zhu, X., Sakamoto, S., Ishii, C., Smith, M. D., Ito, K., Obayashi, M., Unger, L., Hasegawa, Y., Kurokawa, S., Kishimoto, T., Li, H., Hatano, S., Wang, T. H., Yoshikai, Y., Kano, S. ichi, Fukuda, S., Sanada, K., Calabresi, P. A., & Kamiya, A. (2023). Dectin-1 signaling on colonic γδ T cells promotes psychosocial stress responses. Nature Immunology. https://doi.org/10.1038/s41590-023-01447-8

 

Blue Zones and Their Role in the Diet-Mental Health Relationship (DMHR): A Three Part Series Exploring the Interplay of Diet, Longevity, and Mental Health.

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Editor’s Note: This article, the second in this three-part series, dives deeper into the dietary habits of Blue Zone regions and highlights the physiological impact of nutrition on aging bodies. The next and final article will explore the interplay of diet and mental health in the context of abnormally aging populations. 

As introduced in What is a Blue Zone, Blue Zones are geographic territories that produce abnormal numbers of centenarians: their residents are ten times more likely to reach age 100 than the average US citizen (Buettner & Skemp, 2016). These five regions — Ikaria, Greece; Okinawa, Japan; Sardinia, Italy; Loma Linda, California; and Nicoya, Costa Rica — encompass nine shared lifestyle characteristics that help explain exceptional longevity. These are called the Power 9 (Buettner & Skemp, 2016), and were reviewed in the previous article. 

 

Blue Zone residents are ten times more likely to reach age 100 than the average US citizen.

 

Of these nine characteristics, food is involved in three — the 80% rule, plant slant, and wine at 5 — two of which speak to the actual dietary composition of Blue Zone meals. Evidence supports a correlation between healthy dietary patterns and a decreased risk of early death, begging the further inspection of diet as a factor in the atypical longevity of Blue Zone residents (Harmon et al., 2015). 

When evaluating diet and its impact on longevity, nutritional epidemiologic studies have begun to assess populations through overall dietary patterns instead of tracking a single nutrient or food (Cespedes & Hu, 2015). Human beings do not habitually consume nutrients or food in isolation, and tracking dietary patterns produces a more realistic idea of how diet influences lifespan and health outcomes (Cespedes & Hu, 2015). Therefore, examining  Blue Zones, we explore whole dietary patterns and their commonalities. 

 

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The traditional village of Evdilos, in Ikaria island, Greece. Courtesy of Shutterstock Images.

 

Ikarian cuisine largely revolves around Mediterranean diet principles (Buettner & Skemp, 2016). The Mediterranean diet is characterized by a high intake of fruits, vegetables, whole grains, legumes, herbs, and olive oil, a moderate intake of fish, poultry, dairy products, and red wine, and a low intake of sweets and red meat (Davis et al., 2015). Green vegetables and wild plants cooked in olive oil act as main meals rather than side dishes, complimenting the finding that Ikarian individuals’ fruit and vegetable consumption often exceeds dietary recommendations (Panagiotakos et al., 2011) 

 

Green vegetables and wild plants cooked in olive oil act as main meals rather than side dishes.

 

Given their Mediterranean-inspired dietary habits, the high life expectancy of Ikarian individuals is not shocking. Adherence to a Mediterranean diet has been significantly associated with a reduced risk of mortality: 9% from cardiovascular disease, 6% from cancer, and 13% from Parkinson’s disease and Alzheimer’s disease (Sofi et al., 2008). Additionally, in an Ikarian-focused study, long-term fish consumption was independently associated with the improved kidney function of elders (Chrysohoou et al., 2013). 

By growing much of their own diet, Ikarian individuals have been able to keep up with traditional Mediterranean eating habits into the 21st century, which may play a central role in their longevity (Legrand et al., 2021).

 

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Okinawa, Japan. Courtesy of Shutterstock Images.

 

The traditional Okinawan dietary pattern is anchored majorly by root vegetables (specifically sweet potatoes), yellow and green leafy vegetables, legumes, and soy-based foods (Willcox et al., 2014). It emphasizes the intake of low-GI grains and high fiber-rich foods while stressing minimal consumption of meat and dairy products (Willcox et al., 2014). A typical meal includes miso-soup topped with tofu, fish, pork, or vegetables paired with fresh jasmine tea (medicinal plants hold significant importance to their diet) (Willcox et al., 2014).  

Okinawan cuisine is largely plant-based, as staple foods there have always been locally grown due to financial strains (Willcox et al., 2014). Sweet potatoes in particular became a main source of caloric consumption due to their ability to survive severe climates (Willcox et al., 2014).

The high phytonutrient nature of the Okinawan diet may play a protective role in longevity, as antioxidants have the ability to buffer against oxidative stress: a set of chain reactions that impact the development of diseases such as arthritis, diabetes, dementia, and cancer (Tan et al., 2018; Willcox et al., 2013). The diet’s low glycemic load and low saturated fat content further reduce the known effects of oxidative stress (i.e., cardiovascular disease and other chronic illnesses), potentially aiding in the extension of Okinawan lifespans (Willcox et al., 2013). 

 

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Alley of Castelsardo old city in Sardinia, Italy. Courtesy of Shutterstock Images.

 

The classic Sardinian diet is considered a variant of the Mediterranean diet, as it stresses the consumption of carbohydrate foods and olive oil. However, it differs in its emphasis on meat (Pes et al., 2022). Sardinian dietary patterns, influenced by the city’s history of animal husbandry, involve the high consumption of animal products such as cheese, pork fat, and poultry meat (Pes et al., 2022). As sheep and goats contributed to Sardinia’s economic stability, dairy products such as soft sour cheeses are also prevalent (Pes et al., 2021). 

 

Sardinian dietary patterns involve the high consumption of animal products such as cheese, pork fat, and poultry meat. 

 

Positive associations between daily functioning and eating sheep, goat, and poultry meat have been found. The consumption of poultry alongside vegetables, for instance, is associated with a risk reduction of cardiovascular diseases, obesity, and type 2 diabetes mellitus (Marangoni et al., 2015; Pes et al., 2021). Additionally, the diet’s high antioxidant content, stemming largely from red wine, may impact lower cardiovascular mortality through compounds in the wine  — resveratrol, and proanthocyanidins  — that counteract age-related inflammation (Corder et al., 2006). 

 

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Costa Rica scenery, looking towards the Nicoya Peninsula from Monteverde. Courtesy of Shutterstock Images.

 

The general dietary pattern in Nicoya revolves around four foods eaten with high frequency: Gallo Pinto, tortillas de maiz, Cuajada, and Galla pinto con huevos (Nieddu et al., 2020). Popular dishes incorporate legumes, rice, potato, and cassava (a nutty-flavored, starchy root vegetable) (Link & Elliott, 2021; Pies et al., 2022). These carbohydrate-based foods have a low glycemic index, possibly promoting a delayed onset of various metabolic diseases (Rosero-Bixby et al., 2014). The frequent consumption of traditional foods such as rice and beans showcases an adherence to whole foods (Rosero-Bixby et al., 2013). While overall the residents of Nicoya eat a plant-based diet, the consumption of animal proteins is still relatively high. Nieddu et al. (2020) found that at least half of the oldest Nicoyans ate three to five servings of meat per week, and about 25% consumed meat daily. 

 

While overall the residents of Nicoya eat a plant-based diet, the consumption of animal proteins is still relatively high.

 

Something unique to the Nicoya diet is the high calcium and magnesium content of their drinking water (Buettner & Skemp, 2016). This not only helps protect against heart disease but also promotes strong bones, a crucial component of healthy aging (Buettner & Skemp, 2016). Also notable is their high fruit consumption — mango and papaya specifically are known to promote high levels of antioxidants (Pes et al., 2022).

 

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Loma Linda, California on a map. Courtesy of Shutterstock Images.

 

Loma Linda’s large Adventist community takes their diet directly from the Bible: they consume a largely vegetarian diet filled with leafy greens, nuts, and legumes (Buettner & Skemp, 2016). Fraser (1999) found that Adventist vegetarians eat an average of 3.5 servings of meat substitutes per week, often derived from soy, as well as copious amounts of fruit, which increases antioxidant and dietary fiber intake (Fraser, 1999).    

This surge in dietary fiber through the consumption of vegetables, fruits, grains, and nuts is associated with lowered blood cholesterol and may offer protection against colon and rectal cancer, potentially explaining Loma Linda Adventists’ longevity (Howe et al., 1992; Soliman, 2019). The consumption of these foods combined with reduced meat intake may also decrease the risk of diabetes mellitus, hypertension, and arthritis (Fraser, 1999), facilitating healthier aging.  

It is important to note that abstinence from smoking and generally limited alcohol intake might serve as confounding variables in exploring the longevity of Adventists (Montgomery et al., 2007). In other words, diet alone may not explain the above-average longevity of Adventists, as various lifestyle factors also impact healthful aging. Nonetheless, the lifespan for California Adventists is 7.3 years longer for men and 4.4 years longer for women than the general population in California, calling for the continued exploration of how diet influences abnormal aging (Fraser & Shavlik, 2001). 

 

Overall Themes 

What commonalities can we extract from the five independent Blue Zones? Each diet is influenced by unique religious, historical, cultural, and environmental factors, making it hard to combine them all under a single pattern (Pes et al., 2022). Nonetheless, there are a few takeaways we can make. 

 

Each diet is influenced by unique religious, historical, cultural, and environmental factors, making it hard to combine them all under a single pattern. 

 

First: the self-produced nature of the food consumed. Whether it be the fishermen of Ikaria catching the evening’s dinner or Okinawan elders growing yellow and green vegetables, much of the food prepared comes from local sources. This may be due to most of the Blue Zones’ more geographically isolated nature as well as financial constraints.  

Second: the antioxidant-rich tendencies of the diets. Though from different sources (i.e., fruit in Nicoya, vegetation in Loma Linda, or wine in Sardinia), all the diets offer high amounts of antioxidants. 

Third: the consumption of potatoes and carbohydrates with a low glycaemic index. If not low in the glycaemic index to begin with, the carbohydrates consumed are prepared in specific ways to lower the overall index (i.e., potatoes are boiled in Sardinia as opposed to fried). 

Fourth: the inclusion of legumes and nuts. Though not all vegetarian, there are many plant-based themes among the five Blue Zone diets, including their use of legumes and nuts as protein sources.

 

What now? 

It is clear that diet impacts longevity, as foods hold the power to either protect against or increase the risk of morbidity as well as health issues such as cardiovascular diseases, cancers, and arthritis. Knowing that nutrition impacts longevity from a physiological standpoint begs the question of how it indirectly influences longevity through its connection with mental health. The diet-mental health relationship within Blue Zone territories will be explored in this series’s third and final article.  

 

References
Buettner, D., Skemp, S. (2016). Blue zones: lessons from the world’s longest lived. American Journal of Lifestyle Medicine, 10(5), 318-321. https://doi.org/10.1177/1559827616637066

Cespedes, E.M., Hu, F.B. (2015). Dietary patterns: from nutritional epidemiologic analysis to national guidelines. The American Journal of Clinical Nutrition, 101(5), 899-900.
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Chrysohoou, C., Pitsavos, C., Panagiotakos, D., Skoumas, J., Lazaros, G., Oikonomou, E., Galiatsatos, N., Striggou, M., Xynogala, M., Stefanadis, C. (2013). Long-term fish intake preserves kidney function in elderly individuals: the Ikaria study. Journal of Renal Nutrition, 23(4), e75-e82. https://doi.org/10.1053/j.jrn.2012.09.002

Corder, R., Mullen, W., Khan, N.Q., Marks, S.C., Wood, E.G., Carrier, M.J., Crozier, A. (2006). Red wine procyanidins and vascular health. Nature, 556. https://doi.org/10.1038/444566a

Davis, C., Bryan, J., Hodgson, J., Murphy, K. (2015). Definition of the Mediterranean diet; a literature review. Nutrients, 7(11), 9139-9153. https://doi.org/10.3390/nu7115459

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Tan, B.L., Norhaizan, M.E., Liew, W.P.P., Rahman, H.S. (2018). Antioxidant and oxidative stress: a mutual interplay in age-related diseases. Frontiers in Pharmacology, 9, 1162. https://doi.org/10.3389/fphar.2018.01162

Willcox, D.C., Scapagnini, G., Willcox, B.J. (2014). Healthy aging diets other than the Mediterranean: a focus on the Okinawan diet. Mechanisms of Ageing and Development, 136-137, 148-162. https://doi.org/10.1016/j.mad.2014.01.002

Willcox, D.C., Willcox, B.J., Todoriki, H., Suzuki, M. (2013). The Okinawan diet: health implications of a low-calorie, nutrient-dense, antioxidant-rich dietary pattern low in glycemic load. Journal of the American College of Nutrition, 28(sup4), 500S-516S. https://doi.org/10.1080/07315724.2009.10718117

 

 

 

 

 

Blue Zones and Their Role in the Diet-Mental Health Relationship (DMHR): A Three-Part Series Exploring the Interplay of Diet, Longevity, and Mental Health.

Posted on by CNP Super Admin

Editor’s Note: We begin our three-part series with an overview of the nine common characteristics that underlie Blue Zones. The second article will dive deeper into how diet and mental health may impact longevity.

In 2016, to explore the secrets to longevity, National Geographic Fellow and American Author Dan Buettner located five geographic locations on Earth yielding higher-than-average populations of people living beyond 100 years old, referred to as “centenarians.” The locations are Ikaria, Greece; Okinawa, Japan; Sardinia, Italy; Loma Linda, California; and Nicoya, Costa Rica (Buettner & Skemp, 2016). Buettner coined the term “Blue Zones,” defining them as communities that produce individuals who are ten times more likely to reach age 100 than the average

US citizen and prompting questions about what contributes to such extraordinarily healthful aging (Buettner & Skemp, 2016).

 

Blue zones are communities that produce individuals who are ten times more likely to reach age 100 than the average US citizen.

 

With the help of demographers, scientists, and anthropologists, Buettner identified nine common lifestyle characteristics among the Blue Zones that impact longevity: the Power 9 (Buettner & Skemp, 2016). These include: move naturally, purpose, downshift, 80% rule, plant slant, wine at 5, right tribe, loved ones first, and belong (Figure 1). His idea is that if genes dictate about 20% of life expectancy and lifestyle governs about 80%, the Power 9 can provide a blueprint for creating healthier populations and a higher human life expectancy worldwide (Herskind et al., 1996).

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Figure 1. Power 9 Blue Zone Characteristics

Power 9 characteristics can be sorted under four umbrella components — move naturally, right outlook, eat wisely, and connect.

Component 1: Move Naturally

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Rather than engaging in the exercise habits commonly seen in Western culture (e.g., high-intensity cardio, weight-lifting, marathon running), Blue Zone residents live in environments that foster daily, mindless movement. For example, Sardinians, often employed as shepherds, walk around five miles a day or more in tending to their animals (Buettner & Skemp, 2016). For others in Blue Zone communities, this routine movement may look like tending to a garden or walking across town for social commitments. 

 

Rather than engaging in the exercise habits commonly seen in Western culture, Blue Zone residents live in environments that foster daily, mindless movement. 

 

This movement leads to positive mental and physical outcomes. For instance, a 2021 study concluded that the more time Sardinians spent gardening, the better physical health they reported (Ruiu et al., 2022). The takeaway? Exceptionally long-living individuals move their bodies daily and in intuitive ways.

Component 2: Right Outlook

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Purpose

While the idea of “finding purpose” may hold varying names — the Okinawans call it “Ikiagi” and the Nicoyans call it “plan de Vida,” for example — the concept serves as a central theme within Blue Zones (Buettner & Skemp, 2016). Both “Ikiaki” and “plan de Vida” translate loosely to “why I wake up in the morning,” implying recognition of a life purpose. Buettner and Skemp (2016) found that having a life purpose may be worth up to seven years of additional life expectancy, which was supported by an association between a stronger purpose in life and decreased mortality found in a later study (Alimujiang et al., 2019). The discovery of such an individualized purpose appears to play a central role in the longevity of Blue Zone residents.

 

 Both “Ikiaki” and “plan de Vida” translate loosely to “why I wake up in the morning,” implying recognition of a life purpose.

 

Downshift

Downshift explores the idea of routines meant to release stress. The experience of stress is inevitable, and Blue Zone residents have created ways — unique to their religious ties and geographic regions — to release stress. For example, Adventists in Loma Linda pray, Okinawans take moments to remember their ancestors, and Ikiarians nap (Buettner & Skemp, 2016). In creating rituals to eliminate distress, bitcoin mixer individuals in Blue Zone regions defend themselves against stress-related illnesses such as coronary heart disease, cancer, and respiratory disorders (Salleh, 2008). By prioritizing outlets of escape from ambient stressors through downshift, Blue Zone residents create a culture supportive of a greater-than-average life expectancy.

 

Downshift explores the idea of routines meant to release stress. 

 

Component 3: Eat Wisely

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80% Rule 

Rather than eating until they feel they can’t take another bite, Blue Zone residents follow an 80-20 rule. This mantra, Hara Hachi Bu, created by Okinawans 2,500 years ago, encourages individuals to stop eating when they are 80% full (Buettner & Skemp, 2016). A consistent practice of this rule leads this population to consume fewer calories and consequently have lower energy intake (Fukkoshi et al., 2015). 

 

The Okinawan mantra Hara Hachi Bu encourages individuals to stop eating when they are 80% full. 

 

This practice begs individuals to practice mindfulness, as recognizing one’s satiety requires an understanding of internal cues. Blue Zone residents are encouraged to chew slowly, take deep breaths, and be present in their bodies to honor their hunger cues and avoid overeating. As stated above, by not overeating, these populations subsequently experience a lower input of calories and collateral energy, which is associated with human longevity (Willcox et al., 2006). 

 

In eating until 80% full, Blue Zone residents are pushed to chew slowly, take deep breaths, and be present in their bodies to honor their hunger cues and avoid overeating. 

 

Wine at 5

All Blue Zone populations, excluding Adventists in Loma Linda, regularly and moderately consume alcohol (Buettner & Skemp, 2016). The frequent alcohol of choice is wine, specifically, Cannonau, a red wine native to Sardinia (Buettner & Skemp, 2016). Red wine contains large amounts of antioxidants — polyphenols — which stabilize free radicals and counteract oxidative stress. The latter is a known contributor to detrimental neurological conditions such as Parkinson’s disease, Alzheimer’s disease, and depression, all of which contribute to increased mortality (Pizzino et al., 2017). Consuming quality red wine regularly and socially provides an influx of antioxidants to help defend against such diseases, likely positively contributing to longer-than-average life spans among Blue Zone residents.

 

Red wine contains large amounts of antioxidants — polyphenols — which stabilize free radicals and counteract oxidative stress. 

 

Plant Slant

Most centenarian diets are plant-based, with a significant intake of vegetables, beans, and whole grains. Ikarians, largely due to their proximity to the Mediterranean, eat a Mediterranean diet filled with lots of fruit, olive oil, vegetables, and plant-based proteins such as nuts, beans, and seeds. Adventists take their dietary habits from the Bible and consume a vegan diet full of legumes, leafy vegetables, and nuts. Nicoyans consume little to no processed foods and emphasize antioxidant-rich fruits in their diet (Buettner & Skemp, 2016). Though their diets vary slightly based upon location and community values, all Blue Zone diets have a plant-based theme associated with longevity (Norman & Klaus, 2020).

Component 4: Connect

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Right Tribe 

The idea of “finding your people” is one that lots of individuals strive to achieve. Maintaining satisfying social ties with friends and family and living a socially-oriented lifestyle can decrease feelings of loneliness and contribute to beneficial mental health outcomes (Hitchcott et al., 2017). In Okinawa, children aged five are put into moai, committed social networks that exist indefinitely (Buettner & Skemp, 2016). These social circles provide individuals with the comfort of knowing they will always have support, whether financial, emotional, or otherwise. Nurturing healthy relationships like those in moai substantially increases one’s likelihood of longevity, explaining why this effort is so important for Blue Zone folk (Holt-Lunstad et al., 2010).

Loved Ones First

Another central theme in Blue Zone territories is keeping family close. Blue Zone residents, whether living near family or in intergenerational homes, emphasize investing in their families (Buettner & Skemp, 2016). In collectivist cultures such as Japan, harmonious relationships with family play a role in supporting psychological well-being (Kitayama et al., 2020). The same goes for the strong social support from family members in Italy; it is associated with few depressive symptoms later in life (Carpiniello et al., 1989). Living with aging parents and grandparents in intergenerational homes also lowers children’s disease and mortality rates (Buettner & Skemp, 2016). Prioritizing loved ones plays a role in longevity, as committing to a partner, commonly seen throughout Blue Zones, can add up to three years of life expectancy (Buettner & Skemp, 2016).

 

Prioritizing loved ones plays a role in longevity and can add up to three years of life expectancy.

 

Belong

Most centenarians in Blue Zone communities belong to a faith-based community, and all but five of 263 Blue Zone centenarians interviewed by Buettner belonged to a specific one (Buettner & Skemp, 2016). Denomination does not interfere with the impact of belonging to such a community, as religiosity is a protective factor for aging (Krause, 2003). Attending a faith-based service four times per month can add anywhere between four and 14 years of life expectancy. Older adults who gain a sense of meaning in life from religion also tend to report higher levels of mental health benefits such as life satisfaction, self-esteem, and optimism (Buettner & Skemp, 2016; Krause, 2003). Overall, the longest-living communities tend to incline toward faith-based groups.

 

Older adults who gain a sense of meaning from religion also report higher levels of mental health benefits such as life satisfaction, self-esteem, and optimism. 

 

What now?

The association of mental health and longevity, combined with the knowledge that there are pockets of the world producing abnormal amounts of centenarians, urges the exploration of what mental health efforts Blue Zone residents are implementing into their daily lives that may be impacting mortality.

The Power 9 provides distinct factors central to Blue Zone communities. Physical movement, mental health, diet, and social connection appear critical to uncovering the secrets of longevity and well-being. Yet many questions remain to be answered. How much influence does one factor have over the others? What role does food, specifically, play in the mental health of Blue Zone residents?

 

Physical movement, mental health, diet, and social connection appear critical to uncovering the secrets of longevity and well-being. 

 

More research on Blue Zones is expected in the upcoming years. As our understanding of the diet-mental health relationship (DMHR) evolves and becomes more central to various healthcare settings, Blue Zones may provide a unique opportunity to boost healthy living. 

The interplay of diet and mental health and its impact on longevity will be further explored in the context of Blue Zone regions in two upcoming articles.

 

References

Alimujiang, A., Wiensch, A., Boss, J. (2019) Association between life purpose and mortality among US adults older than 50 years. JAMA Network Open, 2(5). doi:10.1001/jamanetworkopen.2019.4270

Buettner, D., Skemp, S. (2016). Blue zones: lessons from the world’s longest lived. Sage Journals, 10(5), 318-321. https://doi.org/10.1177/1559827616637066

Carpiniello B., Carta M. G., Rudas N. (1989). Depression among elderly people. A psychosocial study of urban and rural populations. Acta Psychiatrica Scandinavica, 80(5), 445–450. Doi: 10.1111/j.1600-0447.1989.tb03004.x

Fastame, M.C., Hitchcott, P.K., Mulas, I., Ruiu, M., Penna, M.P. (2018). Resilience in elders of the Sardinian blue zone: an explorative study. Behavioral Sciences, 8(3), doi: 10.3390/bs8030030

Fukkoshi, Y., Akamatsu, R., Shimpo, M. (2016). The relationship of eating until 80% full with types and energy values of food consumed. Science Direct, 17, 153-156. https://doi.org/10.1016/j.eatbeh.2015.03.001

Herskind, A.M., McGue, M., Holm, N.V., Sorensen, T.I.A., Harvald, B., Vaupel, J.W. (1996). The heritability of human longevity: a population-based study of 2872 Danish twin pairs born 1870-1900. Human Gent, 97(3), 319-323. DOI: 10.1007/BF02185763

Hitchcott, P.K., Fastame, M.C., Ferrai, J., Penna, M.P. (2017). Psychological well-being in Italian families: an exploratory approach to the study of mental health across the adult life span in blue zone. Europe’s Journal of Psychology, 13(3), 441-454. Doi:

10.5964/ejop.v13i3.1416

Holt-Lunstad, J., Smith, T.B., Layton, J.B. (2010). Social relationships and mortality risk: a meta-analytic review. Plos Medicine, 7(7). https://doi.org/10.1371/journal.pmed.1000316

Kitayama S., Markus H. R., Kurokawa M. (2000). Culture, emotion, and well-being: good feelings in Japan and the United States. Cognition and Emotion, 14(1), 93–124. Doi: 10.1080/026999300379003

Krause, N. (2003). Religious meaning and subjective well-being in late life. The Journals of Gerontology, 58(3), S160-S170. https://doi.org/10.1093/geronb/58.3.S160

Norman, K., Klaus, S. (2020). Veganism, aging and longevity: new insight into old concepts. Current Opinion in Clinical Nutrition and Metabolic Care, 23(2), 145-150. doi:10.1097/MCO.0000000000000625

Pizzino, G., Irrera, N., Cucinotta, M., Pallio, G., Mannino, F., Arcoraci, V., Squadrito, F., Altavilla, D., Bitto, A. (2017). Oxidative stress: harms and benefits for human health. Oxidative Medicine and Cellular Longevity, 2017: 8416763. salgen.it doi: 10.1155/2017/8416763

Ruiu, M., Carta, V., Deiana, C., Fastame, M.C. (2022). Is the Sardinian blue zone the new Shangri-la for mental health? Evidence on depressive symptoms and its correlates in late adult life span. Aging Clinical and Experimental Research, 34, 1315-1322.https://doi.org/10.1007/s40520-021-02068-7

Salleh, M.R. (2008). Life event, stress, and illness. The Malaysian Journal of Medical Sciences, 15(4), 9-18.

Willcox, D.C., Willcox, B.J., Todoriki, H., Curb, J.D., Suzuki, M. (2006). Caloric restriction and human longevity: what we can learn from the Okinawans. Biogerontology, 7, 173-177. https://doi.org/10.1007/s10522-006-9008-z

 

Eating Fermented Foods with Live Microbes May Improve Dietary Health

Posted on by CNP Super Admin

Fermented foods—like kimchi and yogurt—and probiotic supplements have been associated with improved metabolic health and, consequently, stronger immunity and reduced risk against various cancers (Savaiano et al., 2021; Wastyk et al., 2021). What these foods and supplements have in common is the presence of living microorganisms (Montville, 2004; Jeddi et al., 2014; Ziyaina et al., 2018). In fact, raw and unpeeled fruits and vegetables, dairy, and certain proteins contain dietary microbes that have been demonstrated to benefit human health (Roselli et al., 2021; Marco et al., 2022). 

Note: this article/study does not specifically explore beneficial or pathogenic microbes; rather, the authors are interested in determining how many “live” microbes are found in foods within the Western diet. To do this, they used preexisting data to estimate microbial content by classifying the foods eaten by participants as low, medium, or high amounts.

 

Raw and unpeeled fruits and vegetables, dairy, and certain proteins contain dietary microbes that have been demonstrated to benefit human health.

 

However, compared to other macronutrients such as carbohydrates, fats, and proteins which are reported on nutrition fact labels and databases, it is not clear how much of the Western diet is actually composed of foods containing live dietary microbes and, moreover, the percentage of U.S. adults and children who consume them. Addressing this knowledge gap is not only imperative in establishing safe daily intake values of live microbes but also encourages further clinical studies to investigate the long-term health benefits they may provide.

To quantify the level of microbes across food groups and the proportion of U.S. residents that ingest them, Marco et al. conducted a 2022 study that analyzed published dietary data from the National Health and Nutrition Examination Survey (NHANES), an ongoing study led by the CDC’s National Center for Health Statistics. NHANES study participants are selected through statistical sampling and information is collected through both in-home interviews and physical examinations at designated health centers. 

For their retrospective analysis, Marco et al. used 24-hour dietary recall results obtained from 74,466 adults and children, dating from 2001 to 2018. Their study aimed to use pre-existing data to estimate the general amounts of microbes contained in food items reported in the NHANES study, classify each item as low-, medium-, or high-microbial content, and, ultimately, approximate the percentage of U.S. adults and children who consume these live microbes.

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Figure 1. Representative image depicting the approximate levels of live microbes across different food groups and the increasing U.S. dietary intake of medium to medium-high levels of microbes from 2001 to 2018 (based on Marco et al., J Nutr, 2022).

 

They estimated that processed foods (which are usually pasteurized to remove harmful microbes), meats, seafood (raw and cooked), and peeled fresh fruits and vegetables contained low levels of microbes. Fruit juices, unpeeled fruits and vegetables (skin is still on, so microbes can live on the surface), and fermented foods like sauerkraut, miso, and kimchi have medium levels. Fermented and cultured dairy products like milk, yogurt, sour cream, and cheese were classified as high (Figure 1). 

 

Processed foods (which are usually pasteurized to remove harmful microbes), meats, seafood (raw and cooked), and peeled fresh fruits and vegetables contained low levels of microbes.

 

While their study attempted to categorize different food groups based on their microbial content through previous studies and expert opinions, Marco et al. recognize that their findings are limited by possible biases and inaccuracies in how items were classified. Nevertheless, after quantifying the levels of microbes across different foods in the Western diet, the authors approximated that greater than 50% of U.S. adults and children eat medium to medium-high amounts of live microbes, with this being an increasing trend over an 18-year period (Marco et al., 2022). 

Out of all food groups categorized, fruits, vegetables, and fermented dairy constituted the majority of live microbes in the U.S. diet based on the study’s classification system. Despite the numerous approaches and regulatory guidelines implemented to clean fruits and vegetables for human consumption, Marco et al. report them to be a notable source of microbes that can actually be providing key nutrients such as calcium, fiber, and potassium, which are lacking in the diets of adults and children (USDA and USDHHS, 2020). 

 

Out of all food groups categorized, fruits, vegetables, and fermented dairy constituted the majority of live microbes in the U.S. diet. 

 

This result is not surprising but underscores the need for further research on the validity of the study’s approach and the significance of these microbes on fruits and vegetables. In comparison, the authors expected fermented dairy products to be the major source of microbes as the process of fermentation—in which foods composed of carbohydrates convert to alcohol or organic acids used in various cuisines—relies on the biological activities of microorganisms. Ultimately, Marco et al. presented interesting results that provide a foundation for future research to better explore the relationship between the consumption of live microbes and dietary health outcomes. 

 

References

Jeddi, M. Z., Yunesian, M., Gorji, M. E., Noori, N., Pourmand, M. R., & Khaniki, G. R. (2014). Microbial evaluation of fresh, minimally-processed vegetables and bagged sprouts from chain supermarkets. Journal of health, population, and nutrition, 32(3), 391–399.

Marco, M. L., Hutkins, R., Hill, C., Fulgoni, V. L., Cifelli, C. J., Gahche, J., Slavin, J. L., Merenstein, D., Tancredi, D. J., & Sanders, M. E. (2022). A Classification System for Defining and Estimating Dietary Intake of Live Microbes in US Adults and Children. The Journal of nutrition, nxac074. Advance online publication. https://doi.org/10.1093/jn/nxac074 

Montville, R., & Schaffner, D. W. (2004). Statistical distributions describing microbial quality of surfaces and foods in food service operations. Journal of food protection, 67(1), 162–167. https://doi.org/10.4315/0362-028x-67.1.162 

Roselli, M., Natella, F., Zinno, P., Guantario, B., Canali, R., Schifano, E., De Angelis, M., Nikoloudaki, O., Gobbetti, M., Perozzi, G., & Devirgiliis, C. (2021). Colonization Ability and Impact on Human Gut Microbiota of Foodborne Microbes From Traditional or Probiotic-Added Fermented Foods: A Systematic Review. Frontiers in nutrition, 8, 689084. https://doi.org/10.3389/fnut.2021.689084 

Savaiano, D. A., & Hutkins, R. W. (2021). Yogurt, cultured fermented milk, and health: a systematic review. Nutrition reviews, 79(5), 599–614. https://doi.org/10.1093/nutrit/nuaa013 

U.S. Department of Agriculture and U.S. Department of Health and Human Services (2020). Dietary Guidelines for Americans, 2020-2025. 9th Edition. Available at DietaryGuidelines.gov.

Wastyk, H. C., Fragiadakis, G. K., Perelman, D., Dahan, D., Merrill, B. D., Yu, F. cactusmeraviglietina.it B., Topf, M., Gonzalez, C. G., Van Treuren, W., Han, S., Robinson, J. L., Elias, J. E., Sonnenburg, E. D., Gardner, C. D., & Sonnenburg, J. L. (2021). Gut-microbiota-targeted diets modulate human immune status. Cell, 184(16), 4137–4153.e14. https://doi.org/10.1016/j.cell.2021.06.019 

Ziyaina, M., Govindan, B. N., Rasco, B., Coffey, T., & Sablani, S. S. (2018). Monitoring Shelf Life of Pasteurized Whole Milk Under Refrigerated Storage Conditions: Predictive Models for Quality Loss. Journal of food science, 83(2), 409–418. https://doi.org/10.1111/1750-3841.13981 

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