Nutrition in Pediatric IBD: Comparison
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Please note this is a comparison between Version 1 by Claudio Romano and Version 2 by Catherine Yang.

Inflammatory bowel disease (IBD) refers to a heterogeneous group of disorders encompassing Crohn’s disease (CD), ulcerative colitis (UC) and unclassified inflammatory bowel disease (IBD-U), characterized by a chronic inflammation of the intestinal tract with a relapsing-remitting behavior, and variably presenting with abdominal pain, diarrhea, rectal bleeding and weight loss. Dietary factors and malnutrition play a primary role in the onset and management of pediatric IBD. Moreover, an appropriate diet can decrease the risk of IBD flares, and an age-adequate nutritional status can decrease the risk of complications and surgery in the long-term stage of the disease. Enteral nutrition has a significant impact on mucosal inflammation in CD, and clinical response to oral polymeric diet is associated with down-regulation of mucosal pro-inflammatory cytokines. Nutritional strategies, such as exclusive enteral nutrition or CDED diet, have shown to be more effective than steroids in inducing clinical remission in pediatric patients.

  • enteral nutrition
  • inflammatory bowel disease

1. Introduction

Inflammatory bowel disease (IBD), mainly represented by Crohn’s disease (CD) and ulcerative colitis (UC), are life-long and systemic disorders with a gut predominance, variably presenting with abdominal pain, diarrhea, rectal bleeding and weight loss. It is well known that IBD has a multifactorial etiology, but despite the ongoing scientific efforts, pathogenesis and pathophysiology are still unclear. The prevailing hypothesis accounts a complex interaction between an exaggerated immune response in genetically predisposed individuals and environmental factors along with intestinal flora alterations, eventually sustaining an anomalous chronic inflammation [1][2]. In the last decades, the incidence of IBD has significantly grown in industrialized countries, in children as in adults, and the increasing “westernization” of lifestyle seems to be associated with a higher risk of IBD. Indeed, several studies have been conducted in the past to evaluate the precise role of nutrition (and malnutrition) and diet composition in immune-mediated diseases risk, leading to the development of a new discipline, referred to as “clinical nutrition”. Clinical nutrition is defined by European Society for Clinical Nutrition and Metabolism (ESPEN) as the “discipline that deals with the prevention, diagnosis and management of nutritional and metabolic changes related to acute and chronic diseases and conditions caused by a lack or excess of energy and nutrients”[3]. It encompasses all the diseases in which nutrition plays a main role, not only as a promoter, but also as a therapeutic tool. For what IBD is concerned, the relation between diet composition and disease onset, course and management is supported by scientific evidence: i) epidemiological studies found an association between specific dietary habits and nutrients with an increased risk of IBD; ii) some foods and dietary components are potentially capable to either enhance or reduce the severity of inflammation; iii) for some pediatric patients with an established diagnosis of CD, exclusive enteral nutrition (EEN) can be considered a primary induction treatment with efficacy in achieving mucosal healing; iv) exclusion diets could treat or prevent disease flares; v) in IBD children, especially in CD children, malnutrition and nutrients deficiencies are often present at diagnosis; vi) early nutritional strategies can lead to a better disease control, as well as catch-up growth, bone mineral density improvement and adequate pubertal development[4][5][6]. The most common therapeutic choices for pediatric IBD consist of systemic and topical corticosteroids, amino salicylate and immunosuppressants (such as thiopurines or methotrexate). Starting from the past decade, use of biologic therapies has significantly increased for their clear efficacy also in pediatric setting. Beside this, non-pharmacological management of pediatric IBD has evolved over years and dietary changes are currently considered major therapeutic tools[6][7].

2. Nutrition and Diet and Intestinal Inflammation

The role of the diet composition in the intestinal inflammation has long been controversial, due to sometimes limited and conflicting data resulting from retrospective and case-control studies. The increasingly “westernization” of lifestyle, mostly characterized by a high consumption of animal proteins and fats along with a poor intake of fruit, vegetables and fibers is associated with a higher risk of IBD[8][9]. There is enough evidence to support that a low intake of omega-3 (n-3) and a high one of omega-6 (n-6) polyunsaturated fatty acids (PUFAs) is associated with an increased risk of CD. N-6 PUFAs (i.e., linoleic acid) are precursors to proinflammatory eicosanoids, whereas dietary n-3 PUFAs inhibits the formation of proinflammatory prostaglandins and leukotrienes through the arachidonic acid pathway, so their chronic imbalanced consumption may eventually lead to a pro- inflammatory state, oxidative stress and impaired intestinal mucosal permeability[10]. On the other side, a long-term intake of dietary fiber, particularly derived from fruit, has been associated with lower risk of CD, while no or conflicting association with UC has been found [11]. The most recent ESPEN guidelines recommend a diet rich in fruit and vegetables and low in n-6 PUFAs[12]. Western diet increases the risk of disease through food additives like emulsifiers and saturated fats, maltodextrins, carrageenin and carboxymethylcellulose, that have been associated with impaired intestinal permeability[13][14][15][16].

Even early life dietary patterns can be considered risk factors. Breast milk is rich in secretory IgA (sIgA), leukocytes and antimicrobial factors (lysozyme, lactoferrin, nucleotides), and promotes immune system maturation and T-lymphocytes pool creation, as well as immune response against infections[17]. It has been suggested that an early discontinuation of breastfeeding may facilitate the onset of several chronic conditions later in life, such as metabolic and autoimmune diseases. A recent meta-analysis comparing the exposure to breast milk among patients with CD and UC and controls confirmed an inverse association between breastfeeding and the risk of developing IBD[18]. Moreover, a dose depending effect has been hypothesized, with higher protection for longer-lasting breast milk exposure[18]. Additionally, since microbiome has been proven to differ according to the type of early diet, with relatively higher proportion of Firmicutes and Actinobacteria in breast-fed infants, it seems reasonable to assume that dysbiosis during the first months of life may negatively impact on immunological functions of the host microbiota[19][20][21].

Indeed, IBD has been consistently associated with gut dysbiosis, variably determined by specific foods and dietary habits. While commensal microbiome is physiologically abundant in Firmicutes, Bacteroidetes, Actinobacteria and Proteobacteria, IBD patients typically exhibit a low concentration of Firmicutes, such as Bifidobacterium, Clostridia and especially Faecalibacterium prausnitzii, whose protective role has been theorized for the possibility to stimulate anti-inflammatory cytokines (including IL-10). Conversely, increased concentrations of Escherichia Coli and other Enterobacteriacee has been found[22][23]. Even metabolic pathways are altered, because short chain fatty acids (SCFAs), such as acetate, propionate, and butyrate, normally produced by commensal bacteria through fermentation of food components, have been found reduced in IBD compared to controls. Further evidence includes reduced tryptophan metabolism and disrupted bile acids metabolism, with low bile acids production, classically associated with anti-inflammatory activities and T-cells regulation. All these alterations eventually contribute to a decreased bacterial diversity, altered host barrier, increased permeability and subsequent intestinal inflammation.

3. Nutritional strategies in the treatment of Inflammatory Bowel Diseases

It is recognized that dietary factors and malnutrition play a primary role in the onset and management of pediatric IBD. An appropriate diet can decrease the risk of IBD flares, and an age-adequate nutritional status can decrease the risk of complications and surgery in the long-term stage of the disease. Enteral nutrition has a significant impact on mucosal inflammation in CD, and clinical response to oral polymeric diet is associated with down-regulation of mucosal pro-inflammatory cytokines.

Exclusive enteral nutrition (EEN) is the most important nutritional intervention in pediatric IBD, consisting of a complete liquid formula as the unique source of daily energy requirement for a period of 6-8 weeks. Consensus guidelines of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and European Crohn’s Colitis Organization (ECCO), as well as North American guidelines, recommend EEN as the first-line therapy for mild to moderate pediatric CD to induce remission both in the first flare-up and during relapses of symptoms[24][25][26]. The main indication for EEN is represented by active luminal CD, with solely inflammatory behavior (B1 according to Paris classification) and low-to-medium risk at diagnosis, regardless of the disease location[25]. EEN advantages include: (i) high rates (up to 80%) of clinical remission; (ii) steroids sparing; (iii) correction of malnutrition and micronutrients deficiency; (iv) lean body mass increase; (v) improvement of growth and height Z scores; (vi) decreased longer term need for steroid and anti-TNF therapies; (vii) improvement of quality of life (QoL). EEN is delivered through the administration of enteral nutrition (EN) formulas, avail- able in a wide range of commercial formulations. A nutritionally balanced polymeric formula should be the preferred choice in patients with intestinal sufficiency and in the absence of other medical conditions (e.g., co-existence of a cow’s milk allergy).

Further nutritional strategy is represented by the Crohn’s Disease Exclusion Diet (CDED), a validated dietary intervention firstly conceived in 2014 by Sigall-Boneh and colleagues, combining PEN with a specific exclusion diet.[27] The rationale of CDED is the avoidance of certain foods and dietary components (such as additives like emulsifiers or maltodextrins, food preservatives, etc), mostly belonging to western diets, deemed to act as triggers for intestinal inflammation, dysbiosis, altered intestinal mucous layer and impaired barrier function. CDED owes its progressive diffusion both to the high efficacy in terms of clinical remission and to its variability, leading to a better acceptance by patients.[28] The foods are classified into three main groups: mandatory foods, allowed foods and not allowed foods. CDED is then designed in 3 phases: the first two induction phases lasting 6 weeks each, while the third one starting from the 13th week and referred to as “maintenance phase”. During the first phase, 50% of nutritional requirement is given in the form of a polymeric formula, poor in lactose and fibers (e.g., Modulen, Nestlè), while the remaining 50% is supplied by mandatory foods, source of high-quality proteins, pectin, resistant starch and other beneficial fibers, all necessary for the production of SCFAs. During the second phase the percentage of calories provided by the liquid formula is lowered to 25%, more foods are permitted with higher inclusion of fruits and vegetables and little quantities of bread, red meat and legumes (found to potentially aggravate symptoms). The third and last phase still consists of 25% polymeric formula and does not have a specific duration, allowing the patient to continue with a controlled diet, rich in healthy foods, with the final aim of better controlling the disease in the long term. [27][28]

Further exclusion diets have been proposed, including  the Crohn’s Disease Treatment With Eating Diet (CD-TREAT), the Specific Carbohydrate Diet (SCD), the Diet Low in Fermentable Oligo-, Di- and Monosaccharides and Polyol (FODMAPs), the Paleolithic Diet, and the Vegan Diet. Although some of them have shown interestingly results, further studies are necessary in order to establish their real efficacy. [29][30][31]

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