Diet in irritable bowel syndrome

Food allergy occurs in 6–8% of children and 1–4% of adults [46]. The food allergy reaction, which is mediated by immunoglobulin E, occurs within 2 hours of ingesting the offending food item, and manifests as swelling, itching, hives, wheezing, nausea, vomiting, diarrhoea, abdominal pain and collapse. There is no evidence that such an allergic reaction takes place in IBS [47-54]. A large proportion of IBS patients complain of subjective intolerance to various foods [20,21,52,55-60]. Food intolerance is a non-toxic, non-immune-mediated reaction to bioactive chemicals in food such as histamines, sulphites and monosodium glutamate, with symptoms usually manifesting outside the gastrointestinal tract. There is no documented proof that such intolerance occurs in IBS [42,54].

Non-coeliac gluten sensitivity (NCGS) has recently received attention from the mass media and the general public, and has become confused with the popular speculation that the high carbohydrate content of wheat is responsible for negative health aspects such as obesity [61]. NCGS is defined as having gastrointestinal and extra-gastrointestinal IBS-like symptoms without coeliac disease or wheat allergy, but with the symptoms being relieved by a gluten-free diet (GFD) and relapsing on gluten challenge [62-69]. The prevalence of NCGS has been reported as 0.55–6% of the USA population [64,70].

For more than 3 decades, patients with abdominal pain, diarrhoea and small-intestine biopsy findings with no significant changes have experienced symptom relief on a GFD with return of the symptoms after a gluten challenge [71,72]. Similar results have been reported in patients with non-celiac IBS-like symptoms [73-75]. This was confirmed by double-blind randomized placebo-controlled studies [76,77]. There is disagreement as to whether or not NCGS patients have low-grade inflammation and abnormal intestinal permeability [74,77-82].

It is noteworthy that in studies showing beneficial effects on symptoms in NCGS [74,76,77], those effects were actually the result of wheat withdrawal rather than withdrawal of gluten [83]. In a placebo-controlled, crossover study of patients with IBS-like symptoms on a self-imposed GFD [84], the gastrointestinal symptoms consistently and significantly improved when consuming a diet with reduced fermentable oligo-, di-, monosaccharides and polyols (FODMAPs), and these symptoms were not worsened by either a low- or high-dose challenge with gluten. It therefore seems that the carbohydrate content (fructans and galactans) of wheat rather than gluten is responsible for triggering NCGS symptoms. Furthermore, in those who believed that they had NCGS, 24% had uncontrolled symptoms despite consuming a GFD, 27% did not follow a GFD alone, and 65% avoided other foods that contain high levels of FODMAPs [85]. These findings lend further support to the idea that NCGS symptoms are not triggered by the gluten in wheat.

The basic description of NCGS [67] is the same as that of IBS. Both NCGS and IBS patients have the same gastrointestinal and extra-gastrointestinal symptoms that are triggered by wheat consumption. NCGS patients have been reported to have high frequency of immunoglobulin G (IgG)/immunoglobulin A (IgA) antigliadin antibodies (AGA) and a stronger association with human leucocyte antigen-DQ2 (DQ2) and -DQ8 (DQ8) [76]. The prevalence of positivity for IgG/IgA AGA, with negative tissue transglutaminase or deamidated gliadin peptide antibodies, in the blood of IBS patients has been reported to be 5–17% [86-88] or as high as about 50% [65,89]. Serum AGA has been reported to have a good sensitivity but a low specificity for coeliac disease [90], and 12–15% of serum samples from healthy subjects are positive for AGA [86,87,90,91]. Moreover, DQ2 and DQ8 are common in the general population. It appears that NCGS patients are IBS patients with a self-diagnosis and who self-treat with a GFD. It is noteworthy in this context that 20–70% of IBS patients complain of subjective intolerance to various foods [20,21,52,55-60].

The triggering of symptoms in IBS patients by certain foodstuff has been attributed to indigestible and poorly absorbed short-chain carbohydrates, FODMAPs [42,92-94] and FODMAPs intake is hypothesized to be one factor among others for IBS aetiology. These short-chain sugars include fructose, lactose, sugar alcohols (sorbitol, maltitol, mannitol, xylitol and isomalt), fructans and galactans [42]. FODMAPs occur in a wide range of foods, including wheat, rye, vegetables, fruits and legumes [95-97]. A significant proportion of these carbohydrates enter the distal small intestine and colon, where they exert osmotic effects in the large-intestine lumen, increasing its water content and providing a substrate for bacterial fermentation, with consequent gas production [92,95,98]. The produced gas causes abdominal distension and abdominal pain/discomfort. FODMAPs have been found to trigger gastrointestinal symptoms in IBS, and a low-FODMAPs diet reduces the symptoms and improves the patient’s quality of life [23,29,93,94,99-102]. Recent studies have shown that the mechanisms by which FODMAPs exert their effects are more complicated than originally thought. A low-FODMAPs diet appears to induce favourable changes in the intestinal microbiota [103] and gastrointestinal endocrine cells [104-107].

It has been reported that changing from typical Australian food to a low-FODMAPs diet changed the intestinal microbiota [103]. Thus, a low-FODMAPs diet in healthy subjects and IBS patients reduced the total bacterial abundance, while a typical Australian diet increased the relative abundance of butyrate-producing Clostridiun cluster XIVa and the mucus-associated Akkermansia muciniphia, and reduced Ruminococcus torques [103].

Several types of endocrine cell in all segments of the gastrointestinal tract of IBS patients are abnormal [108-129]. The gastrointestinal endocrine cells interact and integrate with each other, with the enteric nervous system and with the afferent and efferent nerve fibres of the central nervous system, in particular the autonomic nervous system [42,130-132]. These cells regulate several functions of the gastrointestinal tract, including sensation, motility, secretion, absorption, local immune defence and food intake (by affecting appetite) [42,131-134]. The abnormalities in the gastrointestinal endocrine cells are considered to play a major role in the development of symptoms in IBS, and therefore represent future targets for treatment [43,135]. Switching from a typical Norwegian diet to a low-FODMAPs diet was shown to lead to normalization of the endocrine cells in the stomach and large intestines [104-107].

A low intake of dietary fibre was initially believed to be the cause of IBS [136]. In clinical settings the increase in dietary fibre intake in IBS patients has been found to increase abdominal pain, bloating and abdominal distension. A meta-analysis of 12 trials revealed that IBS patients treated with increased fibre intake had no improvement in symptoms compared to placebo or a low-fibre diet [137]. However, it has been reported that water-soluble fibre—but not insoluble fibre—improves the symptoms [138,139].

As mentioned above, IBS patients tend to avoid certain food items that they associate with the onset of their symptoms. There has been some concern that the onset of IBS symptoms upon ingesting certain foods would reduce the amount of food consumed and thereby lead to malnutrition [30]. However, whereas an association between low BMI and IBS in 367 patients with IBS has been reported [140], in another report most of the 330 IBS patients examined were either normal or overweight [20]. In a recent comprehensive review, the association between IBS and obesity was found to be controversial, and the author concluded that obesity and IBS might be linked [141].

Appetite is regulated by a large number of hormones, several of which are secreted by gastrointestinal endocrine cells [142]. The gastrointestinal hormones exert their effects by acting upon the appetite control centre in the hypothalamus [142]. The arcuate nucleus (ARC) lies in the median eminence, which lacks a complete blood barrier, making the ARC particularly susceptible to hormones circulating in the blood [142-145]. The ARC is the centre that integrates the neurological and blood-borne signals [142-145]. The brain reward system in the midbrain controls hedonic feeding (i.e. the consumption of palatable food), which is modulated by blood-borne signals [145].

The following five gastrointestinal endocrine cell types that secrete hormones that regulate appetite are abnormal in patients with IBS: ghrelin, cholecystokinin (CCK), peptide YY (PYY), enteroglucagon (oxyntomodulin) and serotonin (Table 1 and Figures 1, 2, 3, 4 and 5) [108-110,112-115,132,146-149]. The endocrine cells in the oxyntic mucosa are the main source of circulating ghrelin, although small amounts do occur in the small and large intestines as well as in the ARC of the hypothalamus [144,150-153]. Ghrelin has several roles, such as regulating the release of pituitary growth hormone and accelerating gastric and intestinal motility [150-166]. Moreover, ghrelin increases appetite and feeding; central or peripheral administration of ghrelin stimulates the consumption of food and body weight gain [150]. CCK stimulates gallbladder contraction, intestinal motility and pancreatic exocrine secretion, and inhibits gastric motility and food consumption [131]. The anorexigenic action of CCK occurs via the CCK-B (CCK-2) receptor, which is the predominant receptor type in the brain [167-183]. PYY release is proportional to the composition (including calorie content) of a particular meal, and its infusion reduces the consumption of food [184,185]. PYY binds to Y2 receptors localized on the presynaptic terminals of neuropeptide Y and to agouti-related protein neurons in the hypothalamus, which causes inactivation of these neurons, resulting in anorexia [186]. Moreover, PYY is the main regulator of the ileal brake and consequently inhibits the consumption of further food once nutrients reach the terminal ileum [187-194]. Enteroglucagon reduces gastric motility and secretion [195-200] and, similar to PYY, the amount released into the bloodstream is proportional to the calories ingested [201,202]; however, enteroglucagon seems to have only a modest anorexigenic effect [145]. Serotonin has also been reported to have an anorexigenic effect [203].

Whereas the ghrelin cell density is increased in IBS patients with diarrhoea as the predominant symptom (IBS-D), it is reduced in IBS patients with constipation as the predominant symptom (IBS-C). It is therefore reasonable to assume that IBS-D patients would have a greater appetite and food intake than those with IBS-C. In both IBS subtypes, the densities of the four endocrine cell types that produce anorexigenic hormones—namely CCK, PYY, enteroglucagon and serotonin—are reduced. Thus, the changes in the gastrointestinal endocrine cells regulating appetite in IBS patients favour an increase in food consumption. BMI and appetite in IBS patients have not been studied in detail, and the available data are controversial. It is not clear whether IBS patients have a greater appetite, which is opposed by the avoidance of eating because of worsening of symptoms upon eating. Further studies are needed to clarify this issue.