The role of different dietary patterns on irritable bowel syndrome (IBS) symptoms

The irritable bowel syndrome (IBS) is a very common gastrointestinal disorder with an unclear pathophysiology that could negatively affect the quality of life. According to the Bristol Stool Scale (BSS) that classify the consistency of faeces, four different IBS subtypes are recognized: IBS – C (constipation) in which more than 25% of evacuation are type 1 or 2 of the BSS; IBS – D (diarrhea) in which more than 25% of evacuation are type 6 or 7 of the BSS; IBS – M (mixed) in which evacuation may be type 1 or 2 or type 6 or 7 and IBS – U (undefined) in which the diagnosis is done according to symptoms and not according the stool type. It affects quality of life through gastrointestinal symptoms such as abdominal pain, bloating, altered bowel habits and meteorism and can be managed with pharmacological and non-pharmacological approaches. This syndrome affects between 5 and 15% of the Western population, especially women under 50 years of age. Different causes may be involved in this syndrome such as: stress, genetic factors, gut microbiota dysbiosis, diet, visceral hypersensitivity and an altered gastrointestinal motility. Among the non-pharmacological approaches there is the diet. In fact, more than 70% of patients report that their symptoms are exacerbated after food ingestion and choose to exclude certain foods from their diet themselves. In the literature different nutritional approaches to manage IBS symptoms are suggested such as the traditional dietary advice based on NICE and BDA guidelines, the LOW-FODMAP diet, the Mediterranean Diet, the Gluten – free diet, the lactose – free diet, the fructose – free diet. All of these nutritional approaches showed an improvement in symptoms but among diets there were differences in terms of gut microbiota changes and also adherence. Another nutritional approach is the consumption of high amylose products that provide an improvement in post prandial glycemia and insulinemia in some studies in the literature and may have also results on increasing fecal mass and promote the short chain fatty acids (SCFAs). The microbiota composition in IBS patients is different both qualitatively and quantitatively compared to the gut microbiota of healthy subjects. Studies in the literature showed a reduction in Bifidobacterium and Faecalibacterium and an increase in Lactobacillaceae, Bacteroides and Enterobacteriaceae. The aim of the experimental protocols conducted during my PhD course was to assess the effects of different nutritional protocols on symptoms in IBS subtypes. The experimental protocols concern: 1) the FRUMILOSIO project conducted in collaboration with Tuscia University, University of Molise and Bambino Gesu Hospital in Rome, 2) the evaluation of a Mediterranean nutritional protocol on symptoms and microbiota in patients with IBS - D conducted in collaboration with IDP Medica of Colleferro and LifeBrain® and 3) a lowering-FODMAPs diet on symptoms in different subtypes of IBS (DOMINO study) conducted during my Erasmus period at KU Leuven. The FRUMILOSIO project was funded by Regione Lazio (LazioInnova) and was included in the Agritech European Project. It was divided in two different studies. The first one is an ongoing study that evaluated the effects of the consumption of high amylose products (biscuits, taralli and pasta) included in a nutritional protocol based on the Mediterranean Diet on symptoms and gut microbiota in IBS – C patients, while the second one evaluated the glycemic index and the effects on postprandial glycemia in healthy volunteers of high amylose products (biscuits, taralli and bread). 32 IBS-C patients were divided in two groups: 10 in the FRUMILOSIO group and 22 in the NO FRUMILOSIO group. Taking in consideration the drop outs, currently 8 patients are allocated to the FUMILOSIO group and 17 in the NO FRUMILOSIO group. The study design included a T0-14 gastroenterological visit, a T0 visit and a T1 visit after 28 days. During the T0 – 14 visit patients were enrolled in the study and received the FAST questionnaire, the food diary and the kit to collect the sample size, at T0 the symptoms questionnaire, the food diary and the sample size were collected and a new kit to collect sample size, a new FAST questionnaire, a new food diary and the nutritional protocol for 28 days were administrated. Moreover, also the box with high – amylose foods was provided to patients allocated in the FRUMILOSIO group. The diet was the same for both groups but only in the FRUMILOSIO group the 50% of carbohydrates – rich foods was substituted by high amylose products. Results showed a significant reduction of meteorism in the FRUMILOSIO group (p=0.0003), in abdominal pain in both groups (p=0.0285 in the FRUMILOSIO GROUP and p=0.0012 in the NO FRUMILOSIO group) and in pre - evacuation abdominal pain in the NO FRUMILOSIO group (p=0.0016). We observed also an improving trend regarding the faecal type: in fact, in the FRUMILOSIO GROUP there was an increase of type 4 and a reduction of type 3 while in the NO FRUMILOSIO group we observed a reduction of type 1 and an increase in type 2 of faeces. Also the macronutrient intake significantly changed. In fact, carbohydrates and fibers intake significantly increased in both groups (p=0.0318 and p=0.0126 for carbohydrates, and p=0.0010 and p=0.0001 for dietary fibers intake respectively for FRUMILOSIO and NO FRUMILOSIO group). While the protein intake significantly decreased only in the NO FRUMILOSIO group (p=0.0310) and lipid intake significantly decreased only in the FRUMILOSIO group (p=0.0251). Also the Mediterranean Diet adherence was assessed through the MDSS and it significantly increased only in the FRUMILOSIO group (p=0.0013). Regarding gut microbiota we observed a downtrend of pro – inflammatory populations (Proteobacteria) and an uptrend in the anti -inflammatory populations (Actinobacteria) in the FRUMILOSIO group while in the NO FRUMILOSIO group we observed a trend of normalization of the ratio Firmicutes/Bacteroidetes. The second study of the FRUMILOSIO projects evaluated the glycemic index of three high – amylose (HA) products (biscuits, taralli and bread) compared to control products. This study included 10 healthy volunteers and the study design provided a first enrolment visit and after that with a two – day wash out participants’glycemia was tested through a glycemic curve every 15 minutes for 2 hours. The first and the last measurement were constituted by glucose used as standard. Results showed that all HA products had a lower impact on post – prandial glycemia than control products and that HA biscuits and bread had a significant lower glycemic index compared to control counterparts (respectively, p=0.0016 and p=0.0111). We evaluated also the glycemic load (GL) and we noticed that HA biscuits and bread had a lower GL compared to control counterparts but with no significant differences. The third study, Mediterranean Diet and IBS – D, evaluated the effects of a Mediterranean Diet on IBS-D symptoms and gut microbiota. This is another ongoing study and the study design was similar to the FRUMILOSIO and IBS – C study. Nevertheless, currently 6 IBS-D subjects are included in the study we observed that both the abdominal pain intensity and the evacuation frequency significantly decreased (p=0.0048 and p=0.0005, respectively). Another interesting result without significant changes, is the Bristol Stool Scale. At T0 100% of patients had type 6 of faeces, while at the end of the study, only 17% had type 6, 33% had type 4 and 50% had type 5. Regarding food diaries, also in this case carbohydrates and fibers intake significantly increased (p=0.0317 and p=0.0088, respectively) while the lipid consumption significantly decreased (p=0.0327). The Firmicutes/Bacteroidetes ratio had a non significant change towards the optimum level from 0% at T0 to 17% of patients at T1. The fourth project was based on the DOMINO study, already published by the Translational Research Center for Gastrointestinal Disorder (TARGID) of the KU Leuven. It included 470 IBS patients enrolled in the primary care and randomized in the diet arm (FODMAP lowering diet) and in the drug arm (otilonium bromide) for 8 weeks. As a pragmatic study, patients could choose to change treatment after the week 8 until week 24 of follow up and who changed was recognized as “discontinuers”. Results showed a greater reduction in gastrointestinal symptoms (assessed through the IBS – SSS questionnaire) in the diet arm compared to the drug arm after 8 weeks and also a higher responders’ rate. Thus, a post – hoc analysis was conducted only in the diet arm stratifying the population according to the IBS subtypes to assess if there could be differences in the effectiveness of the diet according to the subtype. Results showed that from week 4 until week 24 al subtypes had a significant reduction in symptoms (p<0.0001). in the discontinuers group only the IBS-M subtype had a significant improvement at week 16. Regarding questionnaires about somatization status, anxiety and depression the IBS – D subtype had more beneficial. In fact, at 4,8 and 16 week the score significantly reduced (p<0.05) and also at week 24 (p<0.001) for somatization, while for anxiety we observed a significant reduction (p<0.05) at 16 and 24 weeks and for depression (p<0.05) only at week 24. Also in the IBS – M subtype we observed a significant reduction in somatization status at 16 weeks. Regarding quality of life we observed a significant improvement at week 8 and 16 only in the IBS-D and IBS-M subtypes (p<0.05) and at 24 weeks this result was observed in all subtypes (p<0.05 and p<0.001 only in the IBS – M subgroup). The adherence rate was comprised between 55 and 70% in all subtypes while the satisfaction rate was comprised between 45 and 53%. As different causes involved in the onset of this syndrome, a multidisciplinary treatment is necessary to identify the different IBS subtypes and the gut microbiota composition in order to define the correct nutritional protocol to reduce symptoms and to lead gut microbiota to eubiosis.