They discovered EPHA6 and MUC4 as two likely gene candidates. Additionally, they discovered evidence that Genes to Diet in Inflammatory Bowel Disease in a portion of the colon may raise the risk of IBD in people utilizing genetic variation data for IBD, Crohn’s disease, and ulcerative colitis that is readily available to the general public.
The term “inflammatory bowel disease” (IBD) refers to a collection of gastrointestinal tract illnesses marked by both acute and chronic inflammation. These are complicated, multiple illnesses that are partially inherited. IBD is becoming more common in developing nations, though, which shows that environmental variables like food are potentially important contributors to disease risk. According to the evidence, eating a Western diet high in saturated fat, processed carbs, and food additives increases the risk of IBD. While dietary components like omega-3 fatty acids, medium chain triglycerides, and non-digestible carbohydrates improve these parameters and intestinal health, dietary components like omega-6 fatty acids, long chain fatty acids, protein, and digestible carbohydrates may contribute to IBD pathogenesis by altering intestinal microbiota, increasing intestinal permeability, and promoting inflammation.
However, there are discrepancies across research and it is challenging to definitively pinpoint the precise effects of food on intestinal homeostasis due to the dearth of prospective studies, small sample numbers, and the variability of disease subtypes. For IBD patients, there are no set clinical dietary guidelines. Exclusionary diet therapies, however, have demonstrated some effectiveness in symptom relief or remission induction, indicating further study is necessary to completely understand how diet affects disease behavior or interacts with other IBD risk factors to promote illness. This review focuses on the connections between various dietary elements and IBD risk in human clinical trials and IBD models with genetic susceptibility.
Inflammatory bowel disease (IBD), a group of conditions characterised by persistent, recurrent inflammation of the digestive system, including Crohn’s disease (CD) and ulcerative colitis (UC). Even while CD and UC have symptoms that are similar, each subtype’s location and histologic characteristics are unique. Unpredictably worsening and intermittent disease symptoms are followed by remission intervals of various lengths. Ages 20 to 40 are the most common for disease onset, which causes lifelong illness. Although Canada and Europe now have the greatest illness incidence rates, rates are rising everywhere, showing that IBD is quickly becoming a global disease.
As a result of the interaction between an individual’s genetic make-up, environmental triggers, and changes in the intestinal flora, IBD is a complex and multifactorial illness that causes chronic intestinal inflammation . The genetics of IBD is the aspect of these that we know the most about. Over 160 loci associated to higher IBD susceptibility have been discovered by genome-wide association studies. These loci suggest a wide range of genes implicated in the pathogenesis of IBD, including those that regulate immune system function, lymphocyte activation, and gut epithelial defense
But the exponential increase in IBD incidence over the past fifty years cannot be entirely attributed to genetics. IBD is thought to be related to a variety of environmental variables, including smoking, nutrition, medicines (including oral contraceptives and non-steroidal anti-inflammatory drugs), geography, and socioeconomic status, according to epidemiological and clinical evidence. Another piece of evidence supporting the idea that lifestyle choices and environmental variables play a significant role in the pathophysiology of IBD is the shifting pattern of IBD incidence over time and space. The adoption of a Western diet and lifestyle can be linked to the rising prevalence of IBD patients seen in emerging countries. Studies indicating that people moving from low incidence regions to nations with greater IBD prevalence are at an increased risk of acquiring IBD further reaffirm the role of environmental variables in illness initiation.
According to the degree of polymerization, carbohydrates may be divided into four categories: mono- and disaccharides (also known as simple sugars, like glucose, fructose, and sucrose), oligosaccharides (such as fructooligosaccharides or FOS, and galactooligosaccharides or GOS), and polysaccharides (such as starch, cellulose, and inulin). Their capacity for metabolism in the small intestine may also be used to group them. In the small intestine, hydrolyzed carbohydrates (simple sugars, starch) are absorbed. Inulin, plan, FOS, and GOS are examples of resistant starches that cannot be hydrolyzed in the small intestine and are instead fermented by the microbiota in the large intestine. Insoluble fiber (such cellulose or bran) also has a laxative effect, passes through the digestive track relatively undamaged, and adds weight to intestinal contents.
When it was shown that CD patients in the United Kingdom had more cornflakes for breakfast than healthy controls55, carbohydrates were first recognised as a dietary risk factor for IBD. Since then, several studies have linked low dietary fiber and excessive sugar consumption as risk factors for IBD, namely CD9. Similar to what is seen with dietary fat, the type of carbohydrate taken is crucial in deciding whether it will have a favorable or unfavorable impact on the etiology of IBD.
The stimulation of intestinal bacterial overgrowth is one recent theory for the harmful effects of carbohydrates in IBD. High intakes of readily accessible carbohydrates like glucose, sucrose, lactose, or fructose are thought to overwhelm the intestine’s absorptive processes, leading to elevated luminal sugar concentrations that the microbiota uses as a source of energy. This theory is supported by the fact that IBD patients frequently show signs of fructose malabsorption or lactose intolerance. A high-sugar diet has been shown to encourage intestinal dysbiosis, the growth of bacterial pathobionts, increased intestinal permeability, and inflammation in animal studies.
A preventive function for this carbohydrate family in IBD is suggested by the concurrent declines in dietary fiber intake and the elevated risk of IBD linked with excessive sugar consumption. Dietary fibbers are non-digestible carbohydrates that may be divided into three types: mixed (like bran), soluble (like pectin), and insoluble (like cellulose). These non-digestible carbohydrates, known as prebiotics, have been shown to bypass the small intestine and instead be fermented by the microbiota in the colon to support bacterial diversity, protect mucosal barriers, and increase the production of short chain fatty acids (SCFAs), which are crucial for the preservation of intestinal homeostasis. Prebiotic treatment with dietary fibers, such as inulin, oligofructose, and resistant starch, has been shown to reduce histopathology and inflammation in both types of murine colitis models.
The impact of polysaccharide food additives, which are used as stabilizers, thickeners, texturizers, emulsifiers, sweeteners, and coating agents in processed food products, on the risk of IBD is a feature of the Western diet that has not received enough attention . IBD prevalence grew in tandem with socioeconomic and technical advancements in the 20th century that enhanced processed food production and consumption in the United States. The Federal Food and Drug Association classifies the majority of these additives as generally recognised as safe (GRAS), but a number of recent studies indicate that they may cause immune system impairment, changes to the microbiome, bacterial overgrowth, and changes in the intestinal barrier, which may make IBD more susceptible.
Effectiveness of Dietary Manipulation on IBD
Despite the patients’ strong opinion that diet influences disease activity, there are presently no accepted clinical dietary guidelines for people with IBD. This frequently results in patients empirically avoiding food components or looking for inaccurate, inadequate, or deceptive nutritional advice online. This is frequently done without the knowledge or guidance of doctors or dieticians and can result in malnutrition or serious vitamin deficits. To offer IBD patients nutritional advice based on clinical data, more precise and controlled prospective trials are required. The therapeutic efficacy of various dietary methods in IBD, however, has shown some encouraging results.
Enteral and Parenteral Nutritional Therapy
Enteral nutrition refers to a method of feeding IBD patients that involves administering a full liquid meal by a tube, catheter, or stoma directly into the gastrointestinal system. It can be used to deliver all of the diet (exclusive enteral nutrition; EEN) or just a portion of it (partial enteral nutrition; PEN). The diet can consist of one of three distinct formulas: semi-elemental, which comprises peptides, simple sugars, glucose, or starch; or polymeric, which contains complete proteins, carbs, and lipids. polymers; and elemental, which is made up of partially or entirely hydrolyzed nutrients. A limited amount of fibrous or indigestible material makes up an elemental diet (ED), which is virtually totally absorbed by the small intestine.
In Europe and Japan, EN is a first-line CD therapy. This diet is excellent in promoting CD remission in pediatric CD patients and is hypothesized to enhance mucosal healing87. Similarly, total parenteral nutrition (TPN) can put CD88 into remission. Although EN causes remission in around 60% of adult CD patients, several trials and a meta-analysis show that it is not as effective as corticosteroids for CD treatment in adults and is hence not typically advised as a first line therapy in this population36. In contrast, EN has not been shown to be effective84 in studies involving UC patients. Studies show that EN or PN do not increase the likelihood of illness remission, increase the efficacy of steroid treatment, or favorably influence inflammation in UC.
While EN and PN treatments have had some success, it’s crucial to highlight that there are significant limitations to this therapeutic strategy. The EN and PN diets are unpleasant and can cause aspiration risk, diarrheic, overhydration, hypoprothrombinemia, hypoglycemia, and skin rashes. Patient adherence to such a diet is challenging, which leads to insufficient adherence and reduced therapeutic efficacy. But for pediatric CD patients, EN and PN may be very helpful in order to achieve disease remission, minimize the need of corticosteroids, and treat undernutrition in order to enhance quality of life.
Low FODMAP diet
Bacterial overgrowth is thought to be caused by carbohydrate malabsorption, which promotes the pathogenesis of IBD by causing an excessive amount of carbohydrate fermentation in the proximal colon and distal small intestine. A diet low in fermentable oligo-, di-, and mono-saccharides and polyols (FODMAPs) was created as a result of this theory to alleviate the gastrointestinal symptoms associated with both IBD and irritable bowel syndrome (IBS). To ascertain if certain sources or dosages of FODMAPs cause symptoms, this diet involves an exclusion phase, followed by the reintroduction of each FODMAP one at a time. The low FODMAP diet has been proven to be beneficial in lowering stomach discomfort, bloating, gas, and diarrheic in both CD and UC patients who had previously been determined to have IBS, according to a small retrospective research.
The Specific Carbohydrate Diet
The Specific Carbohydrate Diet (SCD), which forbids the ingestion of complex carbs, starches, grains, and dairy while allowing consumption of the monosaccharides present in certain fruits, homemade yoghurt, and honey, looks to be another elimination diet that is beneficial for IBD patients. Drs. devised this diet. For the treatment of celiac disease, Sidney and Merrill Haas developed a method in 1924 that was later used with UC patients89. SCD is based on the idea that poorly absorbed carbohydrates can lead to bacterial fermentation in the small intestine and increase intestinal permeability60, much like the low FODMAP diet does. Promising outcomes have been seen in two investigations of pediatric CD patients, while additional research is required. According to a retrospective analysis of CD patient records, all illness symptoms disappeared within three years.
Lactose intolerance is more common in CD patients than in healthy controls, and it is also connected with the length of the illness93. Reduced lactase synthesis leads to impaired lactose digestion, which is referred to as lactose intolerance. According to one study, methane levels in breath were higher in IBD patients in remission and their lactase levels were lower, indicating lactose intolerance and an increase in methanogenic bacteria in their microbiota94. According to patient demographics, lactose intolerance may be influenced by heredity. The incidence of lactose intolerance is highest (more than 90%) among Asians and Native Americans, is moderate (60–70%) in people of black, Jewish, Hispanic, and Southern European heritage, and is at its lowest (10–15%) in those of Northern/Western European descent95. A lactose-free alternative is available for people who are lactose intolerant.
The combinatorial nature of risk in these people makes it impossible to ascertain the specific contributions of each factor to disease pathogenesis, which presents a difficulty to understanding IBD susceptibility. Diet has a part in influencing the gut microbiota, which in turn affects how food is digested. In addition to what is eaten, where it is digested, how it is broken down, and the metabolites created all have an impact on gut health. Understanding how nutrition affects IBD pathogenesis is crucial since it is one of the few risk variables that is entirely under one’s control, despite its complexity. The findings of these research also offer vital insights for patients who frequently suffer from malnutrition because they are afraid to eat things that could make their sickness symptoms worse.
The effect of dietary elements on intestinal permeability and the necessity of maintaining a strong intestinal barrier for gut homeostasis are additional recurring themes. The formation of SCFA, such as butyrate, as a result of fiber or prebiotic starch consumption enhances intestinal barrier function. On the other hand, intestinal permeability rises as a result of poor absorption of carbohydrates, consuming too much fat, or injury from certain dietary additives.
The impact of nutrition on the make-up and operation of the intestinal microbiome and gut health is also a growing topic of research. In practically all of the dietary categories examined48, the recurring themes of diet-induced microbial dysbiosis or pathobiont growth have been connected to intestinal inflammation.
Role of Vitamins in Inflammatory Bowel Disease
The lack of vitamin D has been identified as a significant contributor to the pathophysiology of IBD in various studies . Its hormonal form dihydroxy vitamin D, also known as calcitriol, is crucial for several immune pathways and is regulated by the nuclear vitamin D receptor (VDR) found in immune cells such T and B lymphocytes, monocytes, and macrophages. Vitamin D is a liposoluble vitamin. Immune cell differentiation, gut microbiota regulation, gene transcription, and barrier integrity are all affected by vitamin D . An increased risk of infection is linked to a decrease in blood vitamin D levels .
Patients with IBD may also be more likely to get a Clostridium difficile infection, according to some research. In order to prevent infection, vitamin D influences the synthesis of antimicrobial substances such cathelicidins and modifies the microbiome . VDR controls ‘s biological activity and plays a part in IBD’s genetic, immunological, environmental, and microbial components. According to a research by Dionne . dramatically reduces M1-type macrophages’ proinflammatory activity while leaving M2-type macrophages’ anti-inflammatory activity unaffected. In the study, the level of the anti-inflammatory cytokine remained unaffected .
Vitamin D-Related Genetics
It has been demonstrated in numerous candidate gene approach and genome-wide association studies (GWAS) that vitamin D status is partly determined by genetic factors. Several genes and genetic variants located in or near those genes, such as DHCR7, GC, CYP2R1, CYP24A1 and VDR, have been recognized as significant modulators of vitamin D level and bioavailability . The indicated genes code for proteins or enzymes that are involved in the transport and metabolism of vitamin D. These include the DHCR7 gene, which codes for skin-specific cholecalciferol synthesis enzymes, the GC gene, which codes for a vitamin D-binding protein, the CYP2R1 gene, which codes for a 25-hydroxylase, and the CYP24A1 gene, which codes for a 24-hydroxylase. inactivation of vitamin D metabolites.