Contrasting effects of Western vs. Mediterranean diets on monocyte inflammatory gene expression and social behavior in a primate model

Dietary changes associated with industrialization substantially increase the prevalence of chronic diseases, such as obesity, type II diabetes, and cardiovascular disease, major contributors to the public health burden. The high prevalence of these chronic diseases is often attributed to an 'evolutionary mismatch' between human physiology and modern nutritional environments. Western diets enriched with foods that were scarce throughout human evolutionary history (e.g., simple sugars and saturated fats) promote inflammation and disease relative to diets more akin to ancestral human hunter-gatherer diets, such as a Mediterranean diet. Peripheral blood monocytes, precursors to macrophages and important mediators of innate immunity and inflammation, are sensitive to the environment and may represent a critical intermediate in the pathway linking diet to disease. We evaluated the effects of 15 months of whole diet manipulations mimicking human Western or Mediterranean diet patterns on monocyte polarization using a well-established model of human health, the cynomolgus macaque (Macaca fascicularis). Monocyte transcriptional profiles differed markedly between the two diets, with 40% of transcripts showing differential expression (FDR < 0.05). Monocytes from Western diet consumers were polarized toward a more proinflammatory phenotype. Compared to the Mediterranean diet, the Western diet shifted the co-expression of 445 gene pairs, including small RNAs and transcription factors associated with metabolism and adiposity in humans, and dramatically altered behavior. For example, Western-fed individuals were more anxious and less socially integrated compared to the Mediterranean-fed subjects. These behavioral changes were also associated with some of the effects of diet on gene expression, suggesting an interaction between diet, central nervous system activity, and monocyte gene expression. The results of this study provide new insights into evolutionary mismatch at the molecular level and uncover new pathways through which Western diets alter monocyte polarization toward a proinflammatory phenotype.

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Mediterranean Diet Reduces Monocyte Inflammatory Gene Expression and Influences Social Behavior in Nonhuman Primates

10.1101/2020.01.27.917567 ◽

2020 ◽

Cited By ~ 1

Author(s):

Corbin S.C. Johnson ◽

Carol A. Shively ◽

Kristofer T. Michalson ◽

Amanda J. Lea ◽

Ryne J. DeBo ◽

...

Keyword(s):

Gene Expression ◽

Mediterranean Diet ◽

Molecular Mechanisms ◽

Expression Profiles ◽

Western Diet ◽

Primate Model ◽

Inflammatory Gene Expression ◽

Inflammatory Gene ◽

Increased Risk ◽

Diet Manipulation

AbstractWestern diet consumption is associated with inflammation, cardiometabolic disease, and mortality in humans, while Mediterranean diet consumption confers protective effects. One likely pathway for this association is through environmentally induced changes in monocyte function, yet the underlying mechanisms remain elusive. We conducted the first randomized, long-term diet manipulation in a non-human primate model to determine whether Western- or Mediterranean-like diets alter monocyte polarization and health. Monocyte gene expression profiles differed markedly between the two diet groups, with significant differences in over 40% of expressed genes. The Western diet induced a more proinflammatory monocyte phenotype overall and upregulated specific monocyte polarization genes. Diet also disrupted the coexpression of numerous gene pairs, including small RNAs and transcription factors associated with metabolism and adiposity in humans. Diet altered affiliative and anxiety-associated behaviors and mediation analysis showed that the diet-altered behaviors contributed significantly (∼50% of the effect of diet on gene expression) to 25% of the differentially expressed genes, suggesting that diet effects on central mechanisms also modulate monocyte gene expression. Together, these results identify both behavioral and molecular mechanisms underlying the health benefits of a Mediterranean diet regimen.Significance StatementSome of our largest public health burdens are driven by dietary changes associated with industrialization, but we still know very little about the molecular mechanisms underlying this link. Characteristic “Western diets” have been associated with increased risk for diseases related to chronic inflammation, while Mediterranean diets have anti-inflammatory benefits. Here, we identify causal effects of diet on inflammatory gene expression where consumption of the Mediterranean diet reduced inflammatory gene expression in monocytes. Additionally, our diet manipulation induced behavioral changes associated with anxiety and social integration, where Mediterranean-fed animals exhibited more positive affiliative behaviors and reduced anxiety. These behaviors were associated with 25% of the diet-affected genes, suggesting an important behavioral route through which diet can impact immune function.

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From the Table to the Tumor: The Role of Mediterranean and Western Dietary Patterns in Shifting Microbial-Mediated Signaling to Impact Breast Cancer Risk

Nutrients ◽

10.3390/nu11112565 ◽

2019 ◽

Vol 11 (11) ◽

pp. 2565 ◽

Cited By ~ 8

Author(s):

Tiffany M. Newman ◽

Mara Z. Vitolins ◽

Katherine L. Cook

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Mediterranean Diet ◽

Dietary Patterns ◽

Gut Microbiome ◽

Western Diet ◽

Diet Pattern ◽

The Mediterranean ◽

The Impact

Diet is a modifiable component of lifestyle that could influence breast cancer development. The Mediterranean dietary pattern is considered one of the healthiest of all dietary patterns. Adherence to the Mediterranean diet protects against diabetes, cardiovascular disease, and cancer. Reported consumption of a Mediterranean diet pattern was associated with lower breast cancer risk for women with all subtypes of breast cancer, and a Western diet pattern was associated with greater risk. In this review, we contrast the available epidemiological breast cancer data, comparing the impact of consuming a Mediterranean diet to the Western diet. Furthermore, we will review the preclinical data highlighting the anticancer molecular mechanism of Mediterranean diet consumption in both cancer prevention and therapeutic outcomes. Diet composition is a major constituent shaping the gut microbiome. Distinct patterns of gut microbiota composition are associated with the habitual consumption of animal fats, high-fiber diets, and vegetable-based diets. We will review the impact of Mediterranean diet on the gut microbiome and inflammation. Outside of the gut, we recently demonstrated that Mediterranean diet consumption led to distinct microbiota shifts in the mammary gland tissue, suggesting possible anticancer effects by diet on breast-specific microbiome. Taken together, these data support the anti-breast-cancer impact of Mediterranean diet consumption.

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A Comparison of Gene Expression Changes in the Blood of Individuals Consuming Diets Supplemented with Olives, Nuts or Long-Chain Omega-3 Fatty Acids

Nutrients ◽

10.3390/nu12123765 ◽

2020 ◽

Vol 12 (12) ◽

pp. 3765

Author(s):

Virginie Bottero ◽

Judith A. Potashkin

Keyword(s):

Gene Expression ◽

Alzheimer’S Disease ◽

Fatty Acids ◽

Transcription Factors ◽

Mediterranean Diet ◽

Differentially Expressed ◽

Omega 3 Fatty Acids ◽

Omega 3 ◽

The Mediterranean ◽

Long Chain

Background: The Mediterranean diet, which is rich in olive oil, nuts, and fish, is considered healthy and may reduce the risk of chronic diseases. Methods: Here, we compared the transcriptome from the blood of subjects with diets supplemented with olives, nuts, or long-chain omega-3 fatty acids and identified the genes differentially expressed. The dietary genes obtained were subjected to network analysis to determine the main pathways, as well as the transcription factors and microRNA interaction networks to elucidate their regulation. Finally, a gene-associated disease interaction network was performed. Results: We identified several genes whose expression is altered after the intake of components of the Mediterranean diets compared to controls. These genes were associated with infection and inflammation. Transcription factors and miRNAs were identified as potential regulators of the dietary genes. Interestingly, caspase 1 and sialophorin are differentially expressed in the opposite direction after the intake of supplements compared to Alzheimer’s disease patients. In addition, ten transcription factors were identified that regulated gene expression in supplemented diets, mild cognitive impairment, and Alzheimer’s disease. Conclusions: We identified genes whose expression is altered after the intake of the supplements as well as the transcription factors and miRNAs involved in their regulation. These genes are associated with schizophrenia, neoplasms, and rheumatic arthritis, suggesting that the Mediterranean diet may be beneficial in reducing these diseases. In addition, the results suggest that the Mediterranean diet may also be beneficial in reducing the risk of dementia.

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A MEDITERRANEAN DIET INTERVENTION ALTERS AGE-ASSOCIATED PHYSIOLOGY IN A NOVEL NON-HUMAN PRIMATE MODEL

Innovation in Aging ◽

10.1093/geroni/igz038.264 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S68-S68

Author(s):

Noah Snyder-Mackler ◽

Carol Shively ◽

Corbin Johnson ◽

Kristopfer Michalson ◽

Susan Appt ◽

...

Keyword(s):

Mediterranean Diet ◽

Acute Stress ◽

Western Diet ◽

Autonomic Response ◽

Biological Aging ◽

Physiological Measures ◽

Primate Model ◽

Biological Similarity ◽

Associated Function

Abstract Diet modifications are some of the most well-established aging interventions. For decades we have known that caloric restriction can dramatically increase lifespan and healthspan in organisms ranging from yeast to primates. More recently, other dietary modifications, including varying nutrient composition, have been experimentally shown to alter healthspan and lifespan. However, limitations inherent in human trials, such as diet adherence and heterogeneity of other lifestyle factors, mitigate our ability to identify the mechanisms through which diet alters healthspan and lifespan. Here, we conducted a randomized, long-term, whole-diet manipulation in a nonhuman primate, where cynomolgus macaques consumed either a Mediterranean or Western diet for 15 months. We hypothesized that individuals fed a Western diet would exhibit accelerated rates of cellular and physiological aging relative to their Mediterranean-fed counterparts. Indeed, we found that Western diet-fed animals exhibited increases in physiological measures that also increase with age, including body weight, fasting insulin, and triglycerides. Animals eating a Mediterranean diet, on the other hand, had a more sensitive and tuned autonomic response, and reduced HPA responses to an acute stress challenge. Probing further, we found that diet strongly affected monocyte function, altering the expression of 40% of expressed genes, leading to a more proinflammatory monocyte phenotype in Western diet fed animals. Experiments are underway to explore effects of diet on other markers of biological aging. Together, these data provide the first controlled evidence that Western and Mediterranean diets can alter aging-associated function in a species with clear biological similarity and relevance to humans.

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Diet, psychosocial stress, and Alzheimer’s disease-related neuroanatomy in female nonhuman primates

10.1101/2020.09.25.313593 ◽

2020 ◽

Author(s):

Brett M. Frye ◽

Suzanne Craft ◽

Thomas C. Register ◽

Rachel N. Andrews ◽

Susan E. Appt ◽

...

Keyword(s):

Mediterranean Diet ◽

Nonhuman Primate ◽

Psychosocial Stress ◽

Western Diet ◽

List Type ◽

Nonhuman Primate Model ◽

Primate Model ◽

Brain Volumes ◽

Increase Risk ◽

The Brain

ABSTRACTINTRODUCTIONAssociations between diet, psychosocial stress, and neurodegenerative disease, including Alzheimer’s disease (AD), have been reported, but causal relationships are difficult to determine in human studies.METHODSWe used structural magnetic resonance imaging in a well-validated nonhuman primate model of AD-like neuropathology to examine the longitudinal effects of diet (Mediterranean versus Western) and social subordination stress on brain anatomy, including global volumes, cortical thicknesses and volumes, and twenty individual regions of interest (ROIs).RESULTSWestern diet resulted in greater cortical thicknesses, total brain volumes and gray matter, and diminished cerebrospinal fluid and white matter volumes. Socially stressed subordinates had smaller whole brain volumes but larger ROIs relevant to AD than dominants.DISCUSSIONThe observation of increased size of AD-related brain areas is consistent with similar reports of mid-life volume increases predicting increased AD risk later in life. While the biological mechanisms underlying the findings require future investigation, these observations suggest that Western diet and psychosocial stress instigate pathologic changes that increase risk of AD-associated neuropathologies, whereas Mediterranean diet may protect the brain.RESEARCH IN CONTEXTSystematic review: The authors reviewed the literature with PubMed and Google Scholar and found a number of publications which are cited that suggest that AD pathogenesis begins well before the onset of symptoms.Interpretation: Our findings support the hypothesis that Western diet and psychosocial stress may instigate neuroinflammatory responses that increase risk of later developing AD-like neuropathologies, whereas the structural stasis in the Mediterranean diet group may represent a resilient phenotype.Future directions: The manuscript serves as a critical first step in describing risk and resilient phenotypes during middle age in a nonhuman primate model of AD-like neuropathology. This report lays the groundwork for ongoing efforts to determine whether neuroinflammatory profiles differed across diet and stress groups. Future studies should aim to understand the temporal emergence of functional disparities associated with the changes in brain structure observed here.HIGHLIGHTSGlobal brain volumes changed in response to Western, but not Mediterranean, diet.Western diet increased cortical thickness in multiple regions relevant to AD.Mediterranean diet did not alter cortical thicknesses relevant to AD.Brain regions associated with AD risk differed between low and high stress monkeys.Psychosocial stress may modulate the effects of diet on the brain.

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Wine: An Aspiring Agent in Promoting Longevity and Preventing Chronic Diseases

Diseases ◽

10.3390/diseases6030073 ◽

2018 ◽

Vol 6 (3) ◽

pp. 73 ◽

Cited By ~ 11

Author(s):

Eleni Pavlidou ◽

Maria Mantzorou ◽

Aristeidis Fasoulas ◽

Christina Tryfonos ◽

Dimitris Petridis ◽

...

Keyword(s):

Human Health ◽

Chronic Diseases ◽

Mediterranean Diet ◽

Red Wine ◽

White Wine ◽

Wine Consumption ◽

Beneficial Role ◽

Pubmed Database ◽

The Mediterranean

Introduction: Moderate wine consumption is a characteristic of the Mediterranean diet. Studies around the world have shown a beneficial effect of moderate alcohol intake, especially wine, on health. This review aims to critically summarise the most recent studies that investigate the beneficial effects of moderate wine intake on human health. Methods: The PubMed database was comprehensively searched to identify trials published from 2013 to 2018 that investigated the association between moderate wine consumption and health. Results: The most recent studies confirm the valuable role of moderate wine consumption, especially red wine, in the prevention and treatment of chronic diseases such as cardiovascular disease, metabolic syndrome, cognitive decline, depression, and cancer. In the meantime, recent studies also highlight the beneficial role of red wine against oxidative stress and in favour of desirable gut bacteria. The beneficial role of red wine has been attributed to its phytochemical compounds, as highlighted by clinical trials, where the effect of red wine has been compared to white wine, non-alcoholic wine, other alcoholic drinks, and water. Conclusions: Moderate wine intake, at 1–2 glasses per day as part of the Mediterranean diet, has been positively associated with human health promotion, disease prevention, and disease prognosis.

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Phenolic compounds in fruits and beverages consumed as part of the mediterranean diet: their role in prevention of chronic diseases

Phytochemistry Reviews ◽

10.1007/s11101-015-9443-z ◽

2015 ◽

Vol 15 (3) ◽

pp. 405-423 ◽

Cited By ~ 54

Author(s):

Yolanda Aguilera ◽

Maria Angeles Martin-Cabrejas ◽

Elvira González de Mejia

Keyword(s):

Phenolic Compounds ◽

Chronic Diseases ◽

Mediterranean Diet ◽

The Mediterranean

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Developing Mediterranean and Western Diets for an Anti-Inflammatory Feeding Trial (P12-017-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz035.p12-017-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Cited By ~ 1

Author(s):

Amy Schweitzer ◽

Bobbie Barron ◽

Nga Barron ◽

Meredith McCormack ◽

Emily Brigham

Keyword(s):

Mediterranean Diet ◽

Healthy Eating Index ◽

Western Diet ◽

Omega 3 ◽

Feeding Study ◽

Funding Sources ◽

Omega 6 ◽

Strict Diet ◽

The Mediterranean ◽

Anti Inflammatory

Abstract Objectives Design a research diet that can be used to evaluate the relationship between nutrition and inflammation in a randomized, cross-over study in adults. Methods Dietary components were established for a Mediterranean menu and a Western menu based on a literature review. Three-day menu cycles were planned using the established components. Recipes were developed and adapted to meet menu goals at the 2000 calorie level. Proportional increments of menu items at the 2000 kcal level were used to establish 2500, 3000, and 3500 daily kcal levels to allow for varying energy requirements of participants. Meal plans were analyzed using Nutrition Data System for Research 2017 (NDSR). Healthy Eating Index was calculated using NDSR data. Results 100% of grains in the Mediterranean diet, none in the Western diet, were whole grains. Sweets and pastries were included in the Western diet daily but not the Intervention diet. Mean HEI score for the three-day menu cycle was 91.1 and 37.2 for the Mediterranean and Western diet, respectively. Preliminary results from three participants fed both diets for 6 days: All three participants consumed within 5% of the planned diet with the exception of one participant, who, during the Mediterranean diet cycle, consumed 64%. Mean HEI calculated for actual participant intake (n = 3, 6 days each) was: 89.7 Mediterranean, 36.4 Western Conclusions The Mediterranean diet had a 10-fold higher ratio of omega-6: omega-3 fat than Western. A three-day menu cycle was planned and met goals for an anti-inflammatory feeding study. Recruitment is ongoing to study the feasibility of providing a Mediterranean style and Western style diet to adults with asthma in Baltimore City. Mean HEI for the first three recruits was similar to that of the planned menu, indicating that lack of strict diet adherence did not alter HEI goal of the diet. Although diet design was successful, there were challenges to feeding study participants that must be considered in future feeding studies. Adequate freezer space is key in food preparation and delivery. Acceptability of foods in the Mediterranean diet may effect diet compliance in those who typically eat a Western diet. Dietary restrictions and allergies excluded potential study subjects. Funding Sources This publication was made possible by the Johns Hopkins Institute for Clinical and Translational Research (ICTR) which is funded in part by Grant Number UL1 TR001079 from the National Center for Advancing Translational Sciences (NCATS) a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the Johns Hopkins ICTR, NCATS or NIH. Supporting Tables, Images and/or Graphs

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The effects of the Mediterranean Diet on Chronic Diseases: Cardiovascular Diseases, Oxidative Stress, Dyslipidemia, Diabetes Mellitus, Blood Pressure, Cancer, Neurodegenerative Disease and Obesity

Journal of Applied and Advanced Research ◽

10.21839/jaar.2017.v2i6.122 ◽

2017 ◽

Vol 2 (6) ◽

pp. 333 ◽

Cited By ~ 1

Author(s):

Abdelhay Benyaich

Keyword(s):

Oxidative Stress ◽

Diabetes Mellitus ◽

Fatty Acids ◽

Fatty Acid ◽

Chronic Diseases ◽

Mediterranean Diet ◽

Dietary Habits ◽

The Mediterranean ◽

Fish And Shellfish ◽

The Relationship

Poor dietary habits lead to the emergence of chronic diseases such as coronary heart disease, stroke, hypertension, diabetes mellitus, dyslipidemia, cancer, dementia, obesity and oxidative stress involved through the aggression of cells by free radicals, Knowing that these diseases cause a global burden both individually and economically, Several studies focus on the relationship between diet and chronic disease. Studies suggest that the Mediterranean diet, (MD) traditional eating habits and lifestyle specific to the Mediterranean region, reduce the incidence of chronic diseases and improve longevity. The MD is known to be one of the healthiest diets, this diet is based on herbs, spices, vegetables, fruits, olive oils, cereals (preferably whole grains), legumes and nuts, fish and shellfish, white meat, so the main source of dietary fat from MD is olive oil. Moderate consumption of eggs and dairy products, and reduced consumption of red meats, processed meats and foods rich in sugars and fats. MD has a beneficial fatty acid profile with a higher content of monounsaturated fatty acids (MSFA) and a higher MSFA / saturated fatty acid (SFA) ratio than non-Mediterranean diets. High consumption of dietary fiber. a low glycemic index, anti-inflammatory effects, and antioxidant compounds, can work together to produce favorable effects on health status. MD is rich in vitamins and minerals, such as: vitamin B (B1, B2, niacin, B6, folate and B12) and antioxidant vitamins (vitamins E and C), and polyphenol, flavonoids, phytosterols, n-fatty acids 3 (alpha linoleic acid), resveratrol, quercetin, oleic acid, carotenoids and lutein. The purpose of this review is to provide an update on the current state of science regarding the relationship between the traditional Mediterranean diet and lifestyle related chronic diseases, and discuss the mechanisms involved and opportunities. in this area of research, to clarify and increase the confidence of the role of nutrition in the etiology of chronic diseases.

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Diet and Stress Impair Ovarian Function in Mid-life, Increasing Risk of Chronic Diseases of Aging in Primates

Innovation in Aging ◽

10.1093/geroni/igab046.2547 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. 682-682

Author(s):

Brett Frye ◽

Suzanne Craft ◽

Thomas Register ◽

Susan Appt ◽

Mara Vitolins ◽

...

Keyword(s):

Chronic Diseases ◽

Mediterranean Diet ◽

Repeated Measures ◽

Psychosocial Stress ◽

Cycle Length ◽

Ovarian Function ◽

Western Diet ◽

Middle Aged ◽

Ovarian Dysfunction ◽

Increasing Risk

Abstract Ovarian dysfunction increases risk for chronic diseases of aging including cardiovascular disease, depression, cognitive impairment, and bone and muscle loss which promote frailty. Psychosocial stress disrupts ovarian function and recent observations suggest that Western diet may also. Determination of causal relationships among diet, psychosocial stress, and ovarian physiology is difficult in humans. Nonhuman primates provide relevant opportunities to investigate diet and psychosocial effects on ovarian physiology and aging because, like humans, they have monthly menstrual cycles and recapitulate many aging-related processes similar to humans. We examined ovarian function in 38 socially housed, middle-aged females fed either a Western or Mediterranean diet for 26 months (~ an 8-year period for humans). During the last 12 months, we examined cycle length, peak progesterone per cycle, and frequency of anovulatory cycles using blood sampling (3/week) and vaginal swabbing (6/week). Repeated measures analysis revealed that like middle-aged women, cycle length increased, and progesterone levels fell over time, suggesting that ovarian dysfunction generally increased in our sample with time. In addition, both Western diet and the stress of low social status reduced progesterone levels, disrupting ovarian function, and increasing risk of chronic diseases of aging. This study demonstrates the additive negative effects of poor diet and psychosocial stress on ovarian physiology in mid-life and lays the groundwork for future investigations to uncover associated metabolic signatures of accelerated aging. The results also suggest that a Mediterranean diet may exert a protective influence against ovarian dysfunction and its pathologic sequelae.

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