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Cenni, S.;  Sesenna, V.;  Boiardi, G.;  Casertano, M.;  Nardo, G.D.;  Esposito, S.;  Strisciuglio, C. The Mediterranean Diet and Inflammatory Bowel Diseases. Encyclopedia. Available online: https://encyclopedia.pub/entry/40309 (accessed on 29 March 2024).
Cenni S,  Sesenna V,  Boiardi G,  Casertano M,  Nardo GD,  Esposito S, et al. The Mediterranean Diet and Inflammatory Bowel Diseases. Encyclopedia. Available at: https://encyclopedia.pub/entry/40309. Accessed March 29, 2024.
Cenni, Sabrina, Veronica Sesenna, Giulia Boiardi, Marianna Casertano, Giovanni Di Nardo, Susanna Esposito, Caterina Strisciuglio. "The Mediterranean Diet and Inflammatory Bowel Diseases" Encyclopedia, https://encyclopedia.pub/entry/40309 (accessed March 29, 2024).
Cenni, S.,  Sesenna, V.,  Boiardi, G.,  Casertano, M.,  Nardo, G.D.,  Esposito, S., & Strisciuglio, C. (2023, January 17). The Mediterranean Diet and Inflammatory Bowel Diseases. In Encyclopedia. https://encyclopedia.pub/entry/40309
Cenni, Sabrina, et al. "The Mediterranean Diet and Inflammatory Bowel Diseases." Encyclopedia. Web. 17 January, 2023.
The Mediterranean Diet and Inflammatory Bowel Diseases
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The Mediterranean diet is considered one of the healthiest dietary patterns worldwide, thanks to a combination of foods rich mainly in antioxidants and anti-inflammatory nutrients. Many studies have demonstrated a strong relationship between the Mediterranean diet and some chronic gastrointestinal diseases, such as inflammatory bowel diseases.

Mediterranean diet inflammatory bowel disease

1. Introduction

The Mediterranean diet (MD) is a term coined by Ancel Keys in the 1960s, describing the dietary pattern of the people living in the Mediterranean area, which is structured on a daily consumption of specific food groups included in a standardized food pyramid [1]. The MD is characterized by a high intake of vegetables, fruits, nuts, legumes, low processed cereals, whole grains, and olive oil, as well as a moderate consumption of fish and poultry, and a low intake of sweets, red meat, and dairy products, especially in the form of aged-cheeses [2][3][4]. The proportionally low content of saturated lipids as well as the high content of monounsaturated fatty acids and omega-3 polyunsaturated fatty acids, due to the use of olive oil as the main seasoning, make the MD a dietary pattern with anti-inflammatory and antioxidant properties [2][5][6][7]. Butyrate and other short-chain fatty acids produced from fibres and starches found in fruits and vegetables, which are prevalent in this type of diet, have a key role in downregulating inflammation and promoting innate immunity [3][8][9]. On the other hand, a low-fibre diet can in fact damage the mucous layer, leading to an increased barrier permeability and direct bacterial translocation across the epithelial membrane [3][8][10]. Moreover, the MD is a low-sugar, low-saturated-lipid, and almost additive-free diet, which t avoids dysbiosis and induces a reduction of the levels of plasmatic inflammatory markers, such as tumour necrosis factor-α, interferon-y and high sensitivity C-reactive protein (hs-CRP) [3][8][9]. On the other hand, the Western diet, with its high-fat intake can worsen the damage, especially in the overweight and obese patient. Indeed, adipose tissue has been demonstrated to be an important source of pro-inflammatory cytokines, which can sustain inflammation in many organs, including the gut [1][3]. Inflammation is the natural immune response to tissue damage in the human body [11]. It is initially protective for the removal of the injurious stimuli and damaged tissues, as well as the initiation of tissue healing [11]. However, it becomes problematic when there is overnutrition, which makes inflammation chronic. This is because the nutrition from the degradation of the damaged tissue, together with the excessive nutrition, will be mostly turned into lipid intermediates and deposited in healthy non-adipose tissues, causing lipotoxicity and further tissue damage [12][13]. Thus, over-nutrition will lead to a vicious cycle of excessive lean mass (such as protein) broken down and lipid intermediates piling up, fueling chronic inflammation. For its positive influence on gut microbiota and the immune system, the MD is now proposed not only as a potential tool in the management of different medical conditions, but also for health promotion and prevention globally [14]. Epidemiological evidence, in fact, has demonstrated that adherence to the MD can greatly reduce the risk of overall mortality and the incidence of many conditions such as cancer, diabetes, respiratory and cardiovascular diseases [15][16], inflammatory and functional diseases and obesity [17][18].

2. The Mediterranean Diet and Inflammatory Bowel Diseases

Inflammatory bowel diseases (IBD) are chronic autoimmune disorders characterised by chronically relapsing–remitting inflammation of the gastrointestinal (GI) tract [19]. The prevalence of IBD exceeds the 0.3% in Oceania, North America and in many European countries, and the incidence of these diseases has been substantially increasing in the last decades, principally in industrialised countries, making IBD an important burden on health systems [3][19].
The etiology of IBD is still unknown; in fact, it is a multifactorial disease [19]. Recent evidence indicates that a combination of susceptible genes, environment, altered microbial flora and inappropriate immune responses might be factors involved and functionally integrated in the pathogenesis of IBD [19]. As IBD incidence and prevalence both in the adult and in the paediatric population are constantly increasing [20], new data emerging from developing countries and migration studies suggest that environmental factors might play a major role [21]. Therefore the identification of IBD environmental risk factors and new therapies remain subjects of intensive research, and diet is one of the best candidates [3][19]. The intestinal microenvironment is indeed normally influenced by many factors in which diet plays a vital role, as it impacts its function, the gut epithelial-mucosal layer, the microbial composition, and the immune homeostasis by direct and indirect mechanisms [8]. It is known that diet can play a role in the generation of inflammation, by modulating the microbiome, the function of the intestinal barrier and the mucosal layer [22]. Several epidemiological studies discuss a positive correlation between the “Western diet”, with high amounts of unsaturated fatty acids, proteins, high sugar loads and a low vegetable and fruit intake, and the risk of developing IBD [22][23]. The components of the Western diet such as animal fats, sugars, wheat proteins, emulsifiers and maltodextrins, can determine an altered bacterial clearance at the intestinal level, promoting bacterial adhesion and penetration and subsequent intestinal inflammation [23]. Roberts et al. recently highlighted a clear correlation between the annual emulsifier consumption (in food and beverages) and the incidence of IBD [24].
A paediatric study recently confirmed a profound imbalance in fat, vegetables, and fruits consumption and the development of CD, favouring this hypothesis [25]. In IBD the nutritional approach represents a valid therapeutic option by regulating the inflammatory mechanisms [26]. Exclusive enteral nutrition (EEN) is the first-line treatment for induction of remission in patients with Crohn’s Disease [26]. The latest ESPGHAN guidelines show that the patient with IBD must not be subject to particular food restrictions and that an individual diet must be assessed on the basis of the nutritional imbalances of the individual patient, in order to avoid aggravating the symptoms [26]. Several other diets have been suggested for management of IBD, including the low-FODMAPs diet, a gluten-free diet, and a vegan diet [26]. Nevertheless, none of these diets should be recommended to children and adolescents with IBD at present [26]. On the other hand, in recent years, much attention has been given to the role of MD in IBD [19][21][26].
Multiple research studies agree on its preventive and therapeutic role [9][27][28][29][30][31][32]. Initial interest in this diet scheme arose from the observation of lower rates of chronic and degenerative diseases, such as IBD, in the Mediterranean region compared to Western countries [9]. There are several proposed mechanisms of action to explain the association between IBD and MD. These proposed mechanisms involve the direct effect of dietary antigens, the alteration of gut permeability, and the autoinflammatory response of the mucosa due to changes in the microbiota [27]. Several papers analysed the connection between single dietary elements and IBD development; to summarise, many studies agreed that a high intake of animal protein, linoleic acid and sweets and a low intake of fruits and vegetables were all risk factors for IBD development [28][29][30]. However, only a few of the studies focused their attention on the role of specific dietary patterns, such as MD in IBD prevention [28][29][30]. In 2016, the Epic Study was the first major European case-control study to analyse the link between adherence to the Mediterranean diet and the risk of developing UC or CD [31]. Between 1992 and 2000, the EPIC-IBD study gathered a group of 366,351 healthy people (male and female, aged 20–80 years) from seven European countries [31]. During the follow-up, which lasted from 2004 to 2010, incident cases of IBD were tracked down, and for each case, four controls were chosen [31]. For all the people enrolled, food-frequency questionnaires were administered at baseline, and an adapted Mediterranean-diet score (aMED) was calculated, to establish MD adherence [31]. Three distinct dietary patterns were separately generated for UC and CD [31]. The study showed that a diet rich in sugar and soft drinks was directly associated with UC risk when the disease was diagnosed after at least two years of diet recording; nevertheless, this bond failed if the vegetables intake was high, as if they offset each other [31]. On the other hand, the study was not able to prove any connection between diet and CD risk [31]. Subsequently, Khalili et al. gathered a group of 83,147 Swedish middle-aged male and females born between 1914 and 1952 and calculated for each of them a modified Mediterranean-diet score (mMED); incident cases of UC and CD were verified from the Swedish Patient Register [9]. Statistical analysis of this prospective cohort study showed that a higher mMED score was linked to a lower risk of developing CD (p = 0.02). Moreover, the relationship between diet and CD was confirmed, as people with poor adherence to the MD had an adjusted population-attributable-risk of 12% for later onset CD [9]. However, contrary to the work of Racine et al., no association was demonstrated between the mMED score and UC [9][31]. In addition to disease prevention, the MD seems to play a pivotal role in the management of the disease itself [32]. Its anti-inflammatory and antioxidant properties and its capacity to downregulate inflammatory pathways led researchers to investigate its effect on plasmatic and faecal inflammatory markers, such as CRP, FC and interleukins [32]. Several studies confirmed an anti-inflammatory role for MD in the healthy population, as observed in the study by Sureda et al., which concluded that a high adherence to the MD pattern was directly associated with a better profile of plasmatic inflammatory-markers (higher levels of adiponectin and lower levels of hs-CRP, TNF-α, leptin and PAI-1), particularly in healthy male adults [33]. In a six-week pilot study, Marlow et al. highlighted a small reduction of established biomarkers, such as CRP (statistically non-significant) and an altered expression of 3551 genes analysed by transcriptomics [34]. Other interesting data that emerged from this manuscript was the fact that MD could influence the microbiota composition, leading to an increase in Bacteroidetes and Clostridium clusters and to a decrease in Proteobacteria and Bacillaceae, as was seen in the normal microbiome of non-IBD patients [34]. Regarding this last topic, Illescas et al. also confirmed the protective role of the microbiota associated with the MD [35]. They concluded that following an MD lead to an increase in beneficial anti-inflammatory bacterial species, in contrast to what happens in IBD patients [35]. Moreover, Chicco et al. evaluated the impact of a short-term dietary intervention based on the adoption of the MD in 142 adult patients with a diagnosis of IBD for at least 6 months and in active follow-up [36]. After six months of a hypocaloric MD properly prescribed by a nutritionist, they observed a statistically significant reduction in BMI (UC patients p = 0.002, CD patients p = 0.023), waist circumference (CD patients p = 0.04) and a substantial improvement of liver steatosis (UC patients p = 0.016 and CD patients p < 0.001). Interestingly they also noticed a reduction of inflammatory markers such as CRP (UC patients p = 0.013, CD patients p = 0.035) and FC (UC patients p = 0.049, CD patients p = 0.035) [36]. This prospective interventional study also highlighted an important increase in quality of life (p < 0.001), which is often compromised in IBD patients. Accordingly, an MD has also been associated with an improvement in nutritional status and with a reduction of pro-inflammatory visceral fat, when associated with energy restriction [36]. This feature can be very interesting, considering that IBD patients have been shown to have an increased risk of developing non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome. The MD could also have a therapeutic role in the post-surgical phase of UC patients who undergo pouch surgery. In fact, as shown in the study of Godny et al., high adherence to an MD was directly associated with lower faecal-calprotectin levels and, in the long run, lower risk of developing pouchitis [37].
Other studies focused instead on the self-perceptive quality of life of IBD patients and its correlation with a healthy and balanced lifestyle which includes adherence to the MD [5][10]. For example, Ruano et al. reported a firm association between MD adherence and some aspects of a self-perceived mental and physical quality of life [38]. The latter can also be explained by the fact that a reduction in BMI, waist circumference and a controlled healthy lifestyle might influence the perception of quality of life of these patients. A recent study by Papada et al. tried to analyse the relationship between adherence to an MD and the quality of life of IBD patients. In a cross-sectional study, they used the MedDiet score to assess patients’ dietary habits and highlighted a statistically significant correlation between adherence to an MD and improved quality of life; collaterally they also noticed an improvement in intestinal symptoms correlated with IBD (p = 0.008) [5]. Following a healthy lifestyle such as the MD might lead to an improvement of life quality, but can also determine a mortality reduction in patients affected by CD and UC, as seen in the work of Lo et al. [10]. Similarly, Vrdoljak et al. investigated the adherence to an MD in 94 patients aged between 18 and 65 years with an IBD-diagnosis for at least 1 year. They observed that only nine participants fulfilled the criteria for MD adherence, and all of them were male (p = 0.0021) [19]. On the other hand, most of the population (90.4%) considered that proper nutrition might play an important role in their health and agreed that a more controlled and better diet could reduce their IBD symptoms [19]. Indeed, most of the participants expressed their will to expand their nutritional knowledge if proper educational programs were proposed [19]. Following this example, Taylor et al., in their single-centre cross-sectional analysis, suggested the use of an MD-adherence questionnaires, such as the thirteen-item PREDIMED Mediterranean diet score to identify pro-inflammatory dietary schemes, in order to modify the patient’s dietary scheme and ameliorate their dietary intake [39]. Although many studies have been published for the adult population, little is known about the paediatric population. D’Souza et al. analysed the preventive role of diet in the paediatric population in their case-control study, trying to determine the connection between certain dietary patterns and risk of CD in Canadian children [40]. In this published paediatric case-control study, a positive association with CD was found in girls with a diet rich in meats, fatty foods, and desserts, whereas a high intake of vegetables, fruits, olive oil, fish, grains, and nuts was inversely associated with CD in both sexes [40]. One published manuscript focused on the role of environmental factors in IBD and showed that the Mediterranean dietary pattern may exert a protective role in the development of IBD [41]. Researchers found that low adherence to an MD was higher for CD and for UC when compared with controls [41]. In addition, El Amrousy et al. proved that the reduction of inflammatory biomarkers in the paediatric population was similar to the adult one if adherence to MD was high [42]. They analysed the positive effects of an MD in IBD patients with active CD and UC; after a 12-week diet, the clinical remission rate, as well as most inflammatory markers (CRP, calprotectin, TNF- α, IL17, IL 12 and IL13) were significantly improved, in contrast to the patients who followed their regular diet [42]. Researchers investigated the relationship between inflammation and dietary behaviours in IBD children, in particular adherence to an MD, in comparison with a healthy control group [43]. It is observed that there was a different kilocalorie intake between IBD patients and the control group (p = 0.024), and comparing UC to CD, there emerged a significant difference in protein intake (p = 0.047), iron intake (p = 0.023) and vitamin D (p = 0.044), which was higher in CD patients. Interestingly, researchers found a significant association between adherence to an MD and a lower level of FC in IBD patients (p = 0.027) [43].
Table 1 summarizes the main studies regarding the impact of the MD on IBD.
Table 1. Main characteristics of the studies regarding the impact of a Mediterranean diet on Inflammatory Bowel Disease.

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