Therapy of IBS: Is a Low FODMAP Diet the Answer?

Irritable bowel syndrome (IBS) is the most prevalent functional gastrointestinal disorder with a worldwide prevalence of 11%. It is characterized by abdominal pain and altered bowel habits in the absence of underlying unique pathology. The condition is associated with poor quality of life and high use of healthcare resources required for management. The low FODMAP diet (LFD) is a recognized treatment for symptom management of IBS; however, approximately 30% of patients do not respond. The aim of this review was to understand the effectiveness and application of the LFD compared with other dietary and non-dietary interventions. Ten studies were included, eight of which assessed the LFD against other dietary interventions including traditional dietary advice, modified National Institute for Health and Care Excellence guidelines, a high FODMAP diet, gluten-free diet and Mediterranean diet, generalized dietary advice, probiotics, and a sham diet. Two studies compared a LFD to non-diet interventions of gut directed hypnotherapy or yoga. The findings clearly support the LFD as an effective treatment in IBS, and although it highlights the role for microbiota and current psychosocial state, it remains challenging to identify what combination of treatments may be best to ensure a personalized approach and overall higher response rates to IBS therapy.


INTRODUCTION
Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder with an estimated worldwide prevalence of 11.2% (1). The condition is characterised by recurrent abdominal pain and altered bowel habits as per the diagnostic Rome IV criteria (1). IBS is associated with decreased quality of life, social productivity, and work performance. Furthermore, IBS not only poses a financial burden to the individual through the cost of seeking medical advice but also impacts the healthcare system by time and resources acquired by patients (2). Nearly 40% of primary care and gastroenterologist visits can be attributed to IBS (3).
Diet, specifically the widely recognized low fermentable, oligosaccharide-, disaccharide-, monosaccharide-, and polyol (FODMAP) diet (LFD), has been a cornerstone therapy for IBS. The LFD involves three phases; a 'FODMAP restriction phase' lasting 4-8 weeks, a 're-introduction and challenge phase' lasting 6-10 weeks, and a 'personalization phase' where tolerated FODMAPs are returned to the diet (4). Several studies have shown the diet to be efficacious in the management of IBS symptoms (5,6). However, data still suggest that approximately 30% of individuals do not respond to this management option (7). Furthermore, the safety of the LFD has been questioned in regard to its nutritional adequacy, decreased fiber intake, and potential negative impact on the gut microbiome (8).
The major mechanistic pathways via which FODMAPs induce symptoms in IBS are via osmotic load and colonic gas production in the setting of visceral hypersensitivity and have been reviewed in depth elsewhere (9). In addition, the gut-brain axis has emerged as an important mechanistic pathway directly modulable through various therapies. This axis is a bidirectional interconnection of the vagal and sacral parasympathetic and sympathetic efferent nerves interacting with the enteric nervous system. The higher brain center can receive signals from the enteric intrinsic, external vagal, and spinal afferents. Dysregulation of this pathway can be attributed to depression, anxiety, and psychological stress (10). Signals relayed between the gut and the brain suggest that IBS is responsive to cognitive and emotive triggers such as stress, anxiety, and depression. Given that psychosocial factors are seen in a high proportion of individuals with IBS, it could explain the refractory response to dietary management of IBS in some patients. Abnormalities in the central sensory processing in IBS patients has become the target for non-dietary related therapies. Psychological therapies (including cognitive therapy and gutdirected hypnotherapy) have shown promise in significantly improving IBS symptoms in adults suffering IBS (11).
Despite several treatment options showing good efficacy for IBS management, particularly in the case of the LFD, there is still much to understand about tailoring the right treatment (whether psychotherapy or diet should be employed as a first line therapy, or a combination of both) to the individual patient. Therefore, the aim of this review was to assess the effectiveness of the LFD compared with non-dietary treatments, in reducing symptoms and improving bowel function, as well as safety considerations such as nutritional adequacy and effects on the colonic microbiota. The findings will provide insight into strengths, limitations, and application of the LFD compared with other dietary and non-dietary interventions, thereby addressing gaps in the literature and future directions for the management of IBS.

METHODS
A literature search was conducted using the Medline, Scopus, Cinahl and Embase databases. Search terms included "irritable bowel syndrome," "IBS," "fodmap," "diet," "cognitive behavioral therapy," "complementary and alternative medicine," "hypnotherapy," and "herbal medicine." Intervention studies were included, being either randomized or non-randomized comparative trials that assessed the LFD against another intervention (dietary or otherwise). This inclusion criteria were set so that the LFD could have a clear comparison against another treatment modality. Studies were included if they assessed an adult population, and there was no limitation on year or the therapy the LFD was being compared to. No limitations were placed on IBS subtype. Data reviewed within these studies included diagnostic criteria (Rome III or Rome IV), intervention duration, assessment of symptom measures, changes to gut microbiome, type and overall effectiveness of the intervention implemented (education and resources), gaps in the literature, and future research directions within an IBS population.

RESULTS
Ten studies were included in this review, which assessed the LFD against other treatments ( Table 1). Six of these studies compared the LFD against other dietary interventions including traditional dietary advice (12), modified National Institute for Health and Care Excellence (NICE) guidelines (13), high FODMAP diet (14), gluten-free diet and Mediterranean diet (15), generalized dietary advice and (8,16). Two studies compared the LFD to probiotics (17,18) and two studies compared a LFD to non-diet interventions-gut directed hypnotherapy (19) or yoga (20). One study (17) used a factorial design with participants allocated to either the shame diet/ probiotic, sham diet/placebo, the LFD/probiotics, or the LFD/ placebo; however, no interaction effect for symptoms or microbiota changes were noted, so data for the LFD compared to probiotics was not reported. Therefore, only results for the LFD compared to the sham diet have been included in the current analysis.

Symptom Severity
Five studies (12,(14)(15)(16)(17) used the IBS-SSS to compare symptom severity in a LFD compared to other dietary treatment. The IBS-SSS is a five-item questionnaire scored using a VAS. One study (12) found IBS-SSS improved symptoms in each group with no significant difference between groups (p = 0.20). In the remaining studies, the LFD demonstrated superior efficacy in reducing IBS-SSS scores in comparison to traditional dietary advice, a high FODMAP diet (HFD), a gluten-free diet, generalized healthy eating, and a sham diet.
Two studies (8,13) used scoring systems other than the IBS-SSS to assess changes in symptoms. For both studies, the LFD had a greater reduction in symptoms overall at the end of intervention compared to baseline after a minimum of 4 weeks. One study (8) showed a greater reduction for each individual question and globally with a composite score of the questions on the LFD.

Bristol Stool Form Scale
Five studies assessed bowel habits using the Bristol stool form scale as a measure of stool consistency and frequency (12,13,(15)(16)(17). Overall, there was a trend toward the LFD improving stool consistency (13,17) and frequency (16). One study reported the LFD having the greatest improvement in IBS-D subtype (15).
None of the remaining interventions produced an effect on stool form or number of bowel motions (12,15).

IBS Subtype Response to Treatment
The IBS-D subtype showed a positive response to the LFD at 1 week (13) and 6 weeks (16). One study (14) showed that at 4  Improvements in all symptoms were observed from baseline to 6 weeks for hypnotherapy, LFD and combination treatment with no difference across groups (p = 0.67) While both gut-directed hypnotherapy and LFD were equally efficacious in the short (6 weeks) and longer term (6 months), gut-directed hypnotherapy showed a greater benefit on psychological indices compared to LFD Combining two equally efficacious therapies did not necessarily confer added benefits for IBS patients (Continued) weeks, the LFD had the following changes; 14 of 16 IBS-D showed an improvement in bowels, 7 of 10 with IBS-C showed bowel improvement, and of eight with IBS-M, two participants showed improvement, one worsened, and two had no changes. The remaining participants were all IBS-U, undefined at baseline (15). These findings suggest that the LFD benefits each IBS subtype, most consistently for IBS-D.

Delivery of Dietary Intervention
Given the LFD approach is comprehensive due to the elimination, reintroduction, and personalization of the diet, there are potential risks if the diet is not implemented safely. Alterations to gastrointestinal microbiota and nutritional adequacy have been noted after just 4 weeks of a LFD, which is concerning given that the initial restriction phase is usually 6 weeks (4). Personalized dietary advice from a dietitian has been positively associated with compliance and success (21). In all studies evaluating the LFD compared to other dietary intervention, it was promising to see all involved the expertise of a dietitian in delivering the LFD diet (8,(12)(13)(14)(15)(16). Additionally, a major factor in determining the success of the LFD was the provision of written resources to facilitate implementing the diet (22). There were varying degrees of contact with the dietitian where some participants received 45 to 90 min on a single occasion or up to four sessions in either an individual or group setting. In some studies, there was limited contact with the dietitian to replicate clinical practice. Commonly noted feedback to study personnel were that participants found the diet relatively easy to follow, but the translation of low FODMAP foods into recipes was difficult. One study, which had the low FODMAP food resource prepared in accordance with Iranian culture, found that adherence was considered difficult; however, it was not reported as a problem in the trial (16). Adherence with the LFD was associated with achieving a clinically important value of a reduction in IBS-SSS ≥50 (12).
For the other dietary interventions, there was insufficient detail provided to ascertain whether participants received the same level of care as those receiving a LFD. Therefore, the quality of dietetic care is less comparable to those who received LFD intervention, and there is insufficient insight what participants were specially instructed to do to elicit symptomatic relief.

Effects on Microbiome Overall Analysis
Changes in the dietary content of fermentable carbohydrates have previously been shown to have a major influence on the gut microbiota composition. Alpha and beta diversity were not different after the implementation of a HFD or LFD from baseline to end of intervention and the result was consistent across IBS subtypes (14). There were no significant differences in the alpha diversity for the LFD compared to the sham diet (p = 0.401). The LFD compared to the sham diet did not produce a difference in beta diversity either (p = 0.575) (17). At a taxonomic level, the genus Aldercreutzia, Dorea, and the family Actinomycetaceae were lower after following a HFD (p = 0.02, p = 0.05, and p = 0.04, respectively). However, after just 3 weeks, the LFD produced fecal samples with higher Actinobacteria richness and diversity compared with the HFD group (p = 0.046 and p = 0.02, respectively) (14). Several bacterial groups decreased after following the HFD, with the exception of the Bifidobacteriaceae family and unclassed family within the Lachnospiraceae family, which increased (14). On a species level, the LFD compared with the sham diet produced lower absolute abundance of Bifidobacterium (p = 0.08). The LFD did not produce a difference in relative abundance of the Streptococcus species or the Lactobacillus species compared to the sham diet between baseline and follow-up (17). These findings suggest that the alpha and beta diversity may not be impacted by the implementation of a LFD; however, at a species level, the results are inconsistent.

Subgroup Analysis
When the IBS subtypes IBS-M and IBD-D (both groups having some diarrhoea) were analyzed, there was a greater bacterial richness in those following the LFD compared to the HFD (p = 0.047). Actinobacteria diversity was increased (p = .013), and Firmicutes, Clostridiales, and Actinobacteria richness was greater (p = 0.029, p = 0.023, and p = 0.029, respectively) (14).

Symptom Severity
Symptom severity was measured using the GSRS (17). The LFD produced a 117-point decrease on the IBS-SSS compared to the probiotic with an 82-point decrease. Probiotics did not produce a statistically significant overall symptom improvement using the GSRS (p = 0.66), but the LFD was significant (p = 0.020) (17).

Bristol Stool Form Scale
Pedersen et al. did not use the Bristol stool form scale.

Delivery of Dietary Intervention
One study compared a LFD to probiotic use whereby participants were seen by either a dietitian or nutritionist (18). Dietary counselling was provided for up to one hour (18) with a complex list of appropriate foods provided by a dietitian (18). Dietary compliance was regularly checked and contact with the dietitian was encouraged (18). Probiotics were administered in capsules (18) whereby participants consumed two capsules each day.

Effects on Microbiome
Data on the LFD and probiotic on microbiome was not reported (18).

IBS Subtype Response to Treatment
The IBS-D subtype showed a positive response to the LFD at 6 weeks (18). In addition, IBS-M subtype showed a positive response to the LFD and LGG probiotic at 6 weeks. The IBS-C subtype did not have a positive response to the LFD, probiotic intervention, or a normal diet (18).

Symptom Severity
For two studies comparing a LFD to non-dietary treatments, there was a significant decrease in symptoms for the LFD from baseline to end of intervention (p < 0.001) (19) and (p < 0.001 and p < 0.001 for yoga and a LFD, respectively) for IBS-SSS scoring (20). For both studies, there were no significant differences between the groups at baseline compared to end of intervention.

Bristol Stool Form Scale
Neither of the studies that assessed non-dietary interventions used the Bristol stool form scale as an outcome.

Delivery of Intervention
The participants receiving gut-directed hypnotherapy were allocated 1 h weekly sessions throughout the 6-week study duration. Each participant received the same script that was also recorded and given to the participants to listen to daily for the duration of the study. The intervention was provided by an experienced clinical hypnotherapist (19).
Participants who received the yoga intervention had twice weekly group sessions, which were 75 min in duration for a 12week period. The classes were guided by the same certified hatha yoga instructor. Specifically, participants were instructed on customised postures and breathing techniques to improve symptom control (20).

IBS Subtype Response to Treatment
There were no differences in treatment effectiveness between IBS subtypes (19,20).

DISCUSSION
This review highlights that the LFD is efficacious in the management of IBS. Despite its success, several considerations need to be addressed regarding its use. While there has been greater understanding of the LFD and its mechanism in practice with recent research, there is still a consensus that further understanding of the diet's implications are needed.
Gaps of interest include a deeper understanding on the longterm effects of the LFD on gut microbiota diversity. It should be established whether a change in the microbiota profile can be attributed to a mediated symptom response (8,14). Although recent reviews indicate that baseline microbiota may not be an accurate predictor of symptom improvement in IBS (23), the volatile organic compound profile may very accurately select responders, suggesting that understanding metabolic function of bacteria is more important for determining response to dietary interventions (24). Modulation of gut microbiota with the use of pre-and probiotics while implementing the LFD should be considered. While prebiotics can infer a symptomatic response in some individuals, it should be ascertained whether a less restrictive LFD mitigates the negative impact on the microbiota.
From a safety perspective, calorie and nutrient inadequacies have been acknowledged when following the LFD. Therefore, excessive restrictions such as the avoidance of complete food groups should be averted (25). The implementation of the LFD is extensive and requires education from a qualified nutrition professional (4). Where the LFD may not be appropriate or possible, other dietary strategies can be considered. Evidence suggests that simple strategies such as a reduction in gut stimulants (caffeine, alcohol, and spicy food) and modulation of meal size and frequency may also be effective. However, it should be noted that the NICE guidelines include recommendations such as reducing polyols, onions, cabbage, and beans and limiting fruit to three portions per day. Despite being considered as generalized dietary advice, these foods contain FODMAPs, which is why a reduction in symptoms may be concurrent if following this advice. Furthermore, dietitians instructed participants in one study who were not randomized to the LFD to limit consumption of foods that contribute to perceived detrimental symptoms (16). While the dietitians did not advise these participants to restrict FODMAPs specifically, it is unknown if any foods restricted did contain FODMAPs, which could have contributed to symptom improvement. From a practical perspective, it appears there is still a need for data on the LFD when followed for a long duration.
Cognitive considerations in IBS also warrant further investigation. The mechanisms in which gut directed hypnotherapy exert an effect on the gut are not fully understood but suggest the control and normalisation of gastrointestinal function can be made to the subconscious mind. Peters et al. found that improved psychological indices were not correlated with symptomatic benefit, although the study was not designed to evaluate mechanisms for efficacy; therefore, further understanding the mechanisms of gut hypnotherapy on symptom improvement is needed (19).
Despite results from Peters et al. that a combination of dietary and psychological interventions showed no additive benefits, areas for further research would be further exploring combining dietary and other non-dietary interventions. Tailored advice based on an individual's current dietary intake and other psychosocial factors should help to inform a management plan. Given that the gut microbiota have an established role in IBS and the gut-brain axis (26), combined dietary and cognitive treatments should be examined to determine the relationship between concurrent changes to the gut microbiota and symptom resolution.
This review highlighted a heterogeneity in LFD study designs and in IBS patient selection, including a lack of inclusion or reporting of specific IBS-subtypes. Regardless, the findings demonstrate consistencies in the evidence that the LFD is efficacious in overall symptom and bowel function improvement for each IBS subtype, allowing practical application across the distribution of IBS patterns.
In conclusion, the LFD is efficacious in reducing symptoms when compared to other dietary and non-dietary treatments, however it remains difficult to understand why some individuals respond to certain treatments while others do not. Future research should focus on identifying which treatment modality specifically or in which combination via a multimodal approach is best suited to an individual with IBS, including short-and long-term effects. Current dietary intake and symptom pattern of an individual in conjunction with current psychosocial state regarding depression, anxiety, and stress should be measured to best inform whether dietary or cognitive therapies are likely to be more effective in the management of IBS.