Does a gluten-free diet reduce IBS symptoms? Original paper

The majority of people with irritable bowel syndrome (IBS) relate their symptoms to the intake of certain foods.^[1] A key component of IBS treatment involves excluding specific food components that exacerbate symptoms from the diet. Although people with IBS commonly identify gluten-containing foods as a trigger of gastrointestinal symptoms, a gluten-free diet is not widely recommended for people with IBS.^[2]

In this 2-week randomized crossover trial, 20 participants with IBS and 18 control participants without IBS (38 participants total, average age of 25; 90% women, 10% men) consumed a gluten-free diet and either sprinkled gluten (14 grams per day) or rice flour powder over their meals. To increase dietary adherence, gluten-free meal boxes were given to all the participants along with a list of foods they were allowed to eat. There was a washout period of at least 2 weeks between interventions, and the participants consumed their usual gluten-containing diet during this period. People who identified gluten as a trigger of gastrointestinal symptoms at baseline were excluded from the study.

The primary outcome was the change in IBS symptoms (measured using the IBS-Severity Scoring System). The secondary outcomes were changes in bowel habits (measured using a stool diary based on the Bristol Stool Form scale), anxiety and depression symptoms (measured using questionnaires), and fecal microbiota composition and metabolite profile.

Subgroup analyses were performed based on the response to the interventions. “True responders” were participants with IBS who experienced a decrease of at least 50 points on the IBS-Severity Scoring System after the gluten-free diet, while “nonresponders” were those who did not meet this threshold. “Placebo responders” were people with IBS who experienced a decrease of at least 50 points on the IBS-Severity Scoring System after the gluten-containing diet.

In the participants with IBS, compared to baseline, the gluten-free diet improved IBS symptoms, and the gluten-containing diet nonsignificantly improved IBS symptoms. There was no difference between diets for changes in IBS symptoms. Also, the participants with IBS reported fewer loose stools during the gluten-free diet than the gluten-containing diet (19.2% vs. 27.4%). There were no changes in IBS symptoms or bowel habits in the healthy controls.

In all participants with IBS, nonresponders, and healthy controls, there were no differences between interventions for changes in anxiety and depression symptoms. However, in true responders, anxiety and depression symptoms decreased after the gluten-free diet compared to the gluten-containing diet.

Fecal microbiota composition did not differ between interventions in all participants with IBS, nonresponders, or placebo responders. However, in true responders, there were small changes in fecal microbiota composition after the gluten-free diet compared to the gluten-containing diet. Changes in fecal metabolites did not differ between interventions in any group. In comparisons between groups, the gluten-free diet had different effects on fecal microbiota composition in true responders compared to nonresponders. Also, the gluten-free diet had different effects on fecal metabolites in all participants with IBS compared to controls and in true responders compared to nonresponders. Modeling based on the participants’ fecal metabolites profile at baseline indicated that the response to the gluten-free diet could be predicted with high probability.

The researchers did not prespecify the subgroup analyses according to true responders, nonresponders, and placebo responders. They also did not adjust for multiple comparisons, despite the inclusion of numerous outcomes, which increases the risk of false-positive results. Therefore, the secondary outcomes, in particular, should be interpreted with caution.

Of the 20 participants with IBS, 6 were true responders and 5 were placebo responders. While it was found that true responders experienced reductions in anxiety and depression symptoms after the gluten-free diet, these analyses were not conducted for placebo responders, so it’s unclear whether placebo responders experienced improvements in anxiety and depression symptoms after the gluten-containing diet.

Wheat grains are made up of several components, including different proteins such as gluten, which is the main storage protein. Wheat is a commonly reported trigger of symptoms in people with IBS,^[3] and these side effects are often attributed to gluten, leading many people with IBS to consume a gluten-free diet.^[4]

However, wheat also contains amylase-trypsin inhibitors and fructans (a type of oligosaccharide), both of which may cause symptoms in people with IBS.^[5] In the case that a gluten-free diet improves IBS symptoms, it’s unclear which of the removed food components (i.e., gluten, amylase-trypsin inhibitors, or fructans) is primarily responsible for the improvement in symptoms.

Some evidence suggests that any benefit of a gluten-free diet is related to the reduction in fructans, as opposed to gluten.^[6][7][8][9] In a 1-week randomized crossover trial, participants with IBS consumed a low-FODMAP, gluten-free diet and 3 daily portions of rice porridge that contained either gluten (a total of 17.3 grams per day), FODMAPs (a total of 50 grams per day), or no additives (placebo).^[9] It was found that the IBS symptom score was higher in the FODMAP condition than the gluten and placebo conditions, and there was no difference between the gluten and placebo conditions. This suggests fructans, which are excluded in the low-FODMAP diet, are primarily driving the increase in IBS symptoms following wheat consumption, as opposed to gluten.

A gluten-free diet may also improve IBS symptoms through a placebo effect. According to a systematic review published in 2017, approximately 40% of people with suspected gluten sensitivity show a nocebo response, meaning they report an increase in IBS symptoms when they are given a placebo that they are told is gluten.^[10]

The summarized study controlled for the effects of other food components by having all the participants consume a gluten-free diet and then sprinkling either pure gluten or rice flour over their meals. Specifically, the participants consumed vital gluten, which was prepared with a wet milling process that washes away starch (including fructans) and the majority of amylase-trypsin inhibitors. Additionally, this study controlled for placebo and nocebo effects by including a rice flour placebo, as well as having all participants consume a gluten-free diet, as opposed to comparing a gluten-free diet to some other diet. Many studies have compared the efficacy of different dietary interventions in people with IBS (e.g., low-FODMAP vs. traditional dietary advice), but this comparison poses an issue in this case when participant blinding is compromised. Many people with IBS become familiar with popular diets recommended for their condition, and as such, are able to determine which diet they have been assigned based on the foods their diet includes. This increases the probability of placebo and nocebo effects occurring. In the summarized study, 35% of participants with IBS correctly guessed when they received gluten, 20% incorrectly guessed, and 45% did not know, suggesting that blinding was adequate.

The summarized study found that a gluten-free diet improved IBS symptoms compared to baseline, while a gluten-containing diet nonsignificantly (p=0.06) improved IBS symptoms, with no difference between diets. These results indicate that removing gluten from the diet is unlikely to improve IBS symptoms in most people. However, other existing evidence is mixed.

In a multicenter study conducted in Italy, 55 of 77 participants with IBS experienced a significant improvement in general well-being following a 3-week gluten-free diet.^[11] These 55 participants then completed a 1-week double-blind, placebo-controlled, gluten crossover challenge, meaning the participants continued consuming a gluten-free diet and supplemented with either gluten (5.6 grams per day) or placebo. It was found that 18 of 53 participants with IBS had a worsening of general well-being following reintroduction of gluten.

In a separate study with a similar design, 65 of 180 participants with IBS experienced a significant improvement in gastrointestinal symptoms following a 4-week gluten-free diet.^[12] These 65 participants then continued consuming a gluten-free diet and were randomly assigned to daily consumption of either 2 slices of gluten-containing or gluten-free bread for 4 weeks. It was found that gastrointestinal symptoms were significantly worse in the group consuming the gluten-containing bread.

In a third study, 80 of 102 participants with IBS reported a significant improvement in gastrointestinal symptoms following a 6-week gluten-free diet.^[13] These 80 participants then continued consuming a gluten-free diet and were randomly assigned to supplement their diet with 52 grams of gluten or a placebo daily for 6 weeks. It was found that gastrointestinal symptoms increased in 26 of 35 participants in the gluten group and 6 of 37 participants in the placebo group, which was a significant difference between groups.

In sum, these studies indicate that a nonnegligible number of people with IBS are sensitive to gluten and experience an improvement in symptoms with a gluten-free diet. This is in agreement with the summarized study, as these results show that a subgroup (6 of 20 participants with IBS) of participants experienced a clinically meaningful improvement in IBS symptoms following the gluten-free diet, even if the researchers didn’t find a significant difference in IBS symptoms between a gluten-free and gluten-containing diet on average.

At present, the evidence base is not robust enough to recommend a gluten-free diet for people with IBS at large or particular subtypes of IBS,^[2][14] but this information may be useful for a minority of participants. A gluten-free diet may be considered as part of a “bottom-up” approach, meaning that it could be used as the initial dietary intervention in people with IBS who report that wheat and other gluten-containing foods exacerbate their symptoms.^[3]

To begin this approach, a gluten-containing diet should be consumed for 6 weeks, and the individual eating the diet should use a numerical rating scale to keep track of 1–3 main symptoms (e.g., abdominal pain, bloating, loose stool) each week. A gluten-free diet should then be consumed for 6 weeks, with similar continued weekly tracking. If at the end of 6 weeks, there is a significant improvement in IBS symptoms, as evidenced by at least a 30% reduction in at least one main symptom for at least 50% of the observation time (i.e., at least 3 of 6 weekly evaluations),^[15] the individual can undergo a gluten challenge to determine whether gluten is the primary cause of their IBS symptoms.

A gluten challenge consists of adding either gluten (8 grams per day) or a placebo to the gluten-free diet for 1 week, followed by a 1-week washout period (and a continuation of a strict gluten-free diet), and a third week on the other treatment.^[15] Throughout this process, the same main symptoms should be monitored. If there is a variation in symptoms of at least 30% between the gluten and the placebo treatments, the individual is considered to have a gluten sensitivity. If they do not, then some other food component is likely the cause of their IBS symptoms and a different approach, such as a low-FODMAP diet, could be considered.

When should a gluten-free diet be used for IBS?