Subject Category: Clinical and Systematic Review

Continuing Medical Education Am J Gastroenterol 2017; 112: 1221–1231; doi:10.1038/ajg.2017.129; published online 16 May 2017

Bloating and Abdominal Distension: Old Misconceptions and Current Knowledge

Juan R Malagelada MD1, Anna Accarino MD1 and Fernando Azpiroz MD1

1Digestive System Research Unit, University Hospital Vall d'Hebron; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, Spain

Correspondence: Juan R Malagelada, MD, Digestive System Research Unit, Hospital General Vall d'Hebron, 08035 Barcelona, Spain. E-mail:

Received 1 November 2016; Accepted 7 March 2017
Advance online publication 16 May 2017

Take the CME quiz here



Bloating, as a symptom and abdominal distension, as a sign, are both common functional-type complaints and challenging to manage effectively. Individual patients may weight differently the impact of bloating and distension on their well-being. Complaints may range from chronic highly distressing pain to simply annoying and unfashionable protrusion of the abdomen. To avoid mishaps, organic bloating, and distension should always be considered first and appropriated assessed. Functional bloating and distension often present in association with other manifestations of irritable bowel syndrome or functional dyspepsia and in that context patients tend to regard them as most troublesome. A mechanism-based management bloating and distension should be ideal but elucidating key operational mechanisms in individual patients is not always feasible. Some clues may be gathered through a detailed dietary history, by assessing bowel movement frequency and stool consistency and special imaging technique to measure abdominal shape during episodes of distension. In severe, protracted cases it may be appropriate to refer the patient to a specialized center where motility, visceral sensitivity, and abdominal muscle activity in response to intraluminal stimuli may be measured. Therapeutic resources focussed upon presumed or demonstrated pathogenetic mechanism include dietary modification, microbiome modulation, promoting gas evacuation, attenuating visceral perception, and controlling abdominal wall muscle activity via biofeedback.



Bloating has been defined as a feeling of increased abdominal pressure that may or may not be accompanied by objective abdominal distension, i.e., visible enlargement of the waist. Conversely, the latter may occur without associated bloating sensation. Thus, bloating is a sensation and distension a sign but either one may produce significant distress (1, 2). Although the distinction between bloating and distension is nowadays well established, both terms have been used imprecisely in previous literature.

Bloating and abdominal distension may be manifestations of organic disease and potential causes should be considered first in the differential diagnosis. Acute infectious enteritis may be associated with severe bloating and abdominal distension in the early stages, often before the onset of diarrhea. Celiac disease and other conditions associated with malabsorption often present with bloating and concomitant abdominal distension. Acute or subacute bowel ischemia resulting from left sited cardiac failure or mesenteric insufficiency may manifest with bloating before the true cause of the clinical picture becomes self-evident. In the early stages of ascites formation in patients with liver cirrhosis, bloating may be a prominent clinical feature. Of course neoplastic conditions and any mechanical impediment to normal aboral flow of content along the gastrointestinal tract may be associated with symptoms of bloating and abdominal distension.

In clinical practice, bloating not associated with definite organic aetiologies is what often brings patients to request medical consultation. As such, it may present as a cardinal symptom or main complaint, constituting a broad and imprecisely defined category termed functional abdominal bloating/distension by the Rome IV committee (3), but more often as part of other functional disorders such as functional dyspepsia or irritable bowel syndrome (IBS) (4). Indeed, bloating is a highly prevalent manifestation in IBS patients and for many it is their most bothersome symptom (5, 6).

In functional dyspepsia, patients may describe a bloating sensation centered in the upper abdomen, often postprandial and sometimes associated with visible upper abdominal distension. Dyspeptic bloating may be undissociable from the characteristic epigastric fullness that constitutes a key symptom in the postprandial distress syndrome subgroup of functional dyspepsia. Dyspeptic patients may describe it with the even more imprecise but common term “indigestion” or “slow digestion” in the French literature. By contrast, upper abdominal bloating associated to gastroparesis tends to be accompanied by nausea and vomiting, not so frequent in the postprandial distress syndrome. Chronic belchers may present bloating as a trigger of belch-aerophagia sequences (a feature often unrecognized by the patient) or as a consequence of inflating their stomachs by pumping in air. In patients with IBS bloating tends to manifest as a diffuse abdominal sensation that is frequently described by patients as “wearing tight clothes”.


The clinical relevance of bloating as a symptom is highly variable. A lot of the people get bloated (7) but levels of concern differ. Healthy individuals may occasionally get bloated, particularly after indulging in large, heavy meals or in association with an overload of fermentable foodstuffs. This type of bloating may be annoying but rarely elicits any concern as it is usually short lasting, maximum a few hours and ends when the individual expels stool and/or gas. Furthermore, the recall of similar past events reassures the affected person by predicting prompt resolution (8). However, there are individuals with unrealistic expectations about tolerance to sporadic food binges who will consult, not out of true concern about the significance of their postprandial bloating but to obtain from the specialist a preventive drug or measure that would allow them to continue overindulging as they please without experiencing the punishment of bloating.

Bloating and flatulence, defined as evacuation of large volumes of gas per anus, often coexist but are definitely not the same. Experimental evidence indicates than increasing the amount of fermentable substrate in the colon, for instance by administering a poorly absorbable oligosaccharide such as lactulose to healthy individuals, results in rapid generation of excess gas (mostly H2 and CO2) flatulence (9), and bloating (10). Interestingly, ingestion of low fermentable psyllium fiber may induce a similar bloating sensation without excess intestinal gas production and hence without increased flatulence (11). This effect of bulk, dissociated from flatulence, is often acknowledged by bloated patients who indicate that ingestion of large amounts of fiber, particularly crude, aggravates their bloating even if their stool frequency increases.



Bloating and abdominal distension may be produced by different mechanisms, sometimes coinciding in the same individual (1). Recognizing the predominant operative mechanism(s) in a given patient help plan effective treatment (Tables 1 and 2).

Bloating and distension associated with accumulation of luminal gas and/or fluid

Aerophagia, that is excessive swallowing of air, sometimes compounded by rapid ingestion of carbonated drinks, may potentially induce bloating and distension due to the lag between gas swallowing and spontaneous gas venting. However, this is usually not the case for two reasons. First, aerophagics tend to be belchers as well and even if they fill up their stomachs with air (esophageal belchers excluded) they do not accumulate enough quantities at a given time to produce bloating and distension. The second reason is that air advancing from the stomach into the upper small bowel is promptly cleared. CO2 and O2 rapidly diffuse through the permeable intestinal wall and N2, which is poorly absorbed is rapidly propelled distally and expelled through the anus (2).

Indeed, a series of experimental studies previously performed in our laboratory showed that the normal gut is extremely efficient in propelling caudally a mixture of gases mimicking the composition of venous blood gases that were infused into the upper small bowel. Normal people are able to propel intestinal gas and expel it rectally at about the same rate as it is infused with only a relatively small volume remaining inside the gut at a given time (12). Under these conditions only a small minority of healthy subjects retains enough gas to develop bloating and/or perceptible distension. Conversely, a much higher proportion of individuals with functional abdominal symptoms, such as IBS, functional bloating or functional dyspepsia, show impaired gas disposal. Such patients tend to retain a relatively large proportion of the infused gas and consequently develop uncomfortable abdominal distension (13). Additional studies in healthy volunteers compared the effects of pharmacological gut motor inhibition and restrained voluntary evacuation on gas dynamics (14). In the former, distension was unaccompanied by discomfort whereas the latter produced both. The results suggested that, under the experimental conditions described, abdominal distension depends on the volume of gas retention whereas symptom perception depends on gut motor activity and the mechanism of retention. The symptom bloating appears to represent the clinical expression of an imbalance between gut tone and the volume of content. Such imbalance increases bowel wall tension and the latter generates the uncomfortable sensation of bloating. Intraluminal lipids accentuate gas retention and the bloating sensation (15) an observation that probably explains the symptomatic aggravation by fatty meals observed clinically. These experimental results provide a theoretical framework for the pharmacologic treatment of bloating.

Not only gas but other physical intraluminal components may distend the intestines. The volume of water within the small bowel may be substantially increased by slowly absorbed carbohydrates such as fructose and mannitol in association with perceived bloating sensation in IBS patients (16, 17). Direct distending effects of excess retained stool in constipated individuals are another plausible possibility. Thus, a direct cause and effect relation between intraluminal gas and bloating has not been established and it is quite possible that intraluminal substrates other than gas (fluid and/or solid) may also elicit bloating as in the previously referred experiment with psyllium overload in healthy volunteers (11).

Bloating and distension associated with increased generation of intestinal gas

As pointed out earlier, flatulence and bloating do not necessarily present simultaneously in the same individual but excess gas generation may, under the right conditions, produce any of these two manifestations.

As opposed to excessive air intake that follows the oral route and may advance caudally, excess gas generation takes place inside the gut itself (18). The quantitatively important gases produced endogenously are CO2, H2, and CH4. Theoretically, during the postcibal period considerable quantities of CO2 are produced by bicarbonate neutralization of gastric acid entering the duodenum but CO2 rapidly diffuses through the small intestinal wall and too little would remain in the lumen to produce significant bowel distension. Intraluminal fermentation of dietary and endogenous substrates which takes place mostly in the colon is the main source of bowel gas. We have estimated in healthy individuals that ~69% of the total gas present in the gut is located in the colon. However, only 23% of the gas produced in the colon is eventually expelled by anus, the rest being eliminated by other routes such as transmural disposal or bacterial consumption or Mego et al. (19).

The permeability of the bowel wall to gas diffusion is modified by blood flow and inflammation, among other factors, and plays a modulatory role on accumulation of gas generated inside the bowel itself. We know that in the colon small/frequent/fast waves that act like a squeegee may propel gas rapidly past other luminal contents, basically stool, and expel it and flatus (20). Thus, whether newly generated colonic gas remains or not inside the colon depends on wall physical permeability and the type of motor activity. Exercise is another important factor as it favours antegrade movement and evacuation of intraluminal gas (21). In addition, intraluminal gas consumption by specialized catabolizing bacteria (22) counter balances gas generation in the colon due to fermentation of food residues. Bacterial gas consumption by colonic methanogenic, sulfate reducing, and acetogenic bacteria is quantitatively substantial.

Gas production increases rapidly after each meal containing non-absorbable, fermentable substrates (23, 24). We have recently shown that both accumulation of fermentable residues from successive meals as well as the quantity of fermentable residue present between individual meals determines total gas production rates in healthy humans (25). Thus, the total amount of fermentable residues present in the colon at a given time is quite relevant. This may explain why constipation tends to be associated with bloating and flatulence and, conversely, why clearing the colon of retained residue improves these unwanted consequences (1). The distribution of liquid/solid residue within the colon appears to be rather uniform and stable although it tends to displace caudally into the pelvic colon during the postprandial period (26). However, even though colonic transit has been reported to be sluggish in bloated IBS patients (27) comparison of colonic non-gaseous content and distribution between healthy individuals and patients with bloating and abdominal distension shows no significant differences (26, 28).

It has been postulated that increased gas production or decreased gas consumption in patients with bloating and flatulence may occur due to variations in colonic microbiota (29). However, when similar loads of fermentable carbohydrates are ingested by patients with IBS and healthy controls, both groups produce comparable volume of gas (30, 31). Moreover, in a recent study comparing volume and distribution of intraluminal gas between normal and patients with functional disorders complaining of abdominal bloating and distension we observed no significant differences overall, although in some individuals aberrant gas distribution or gas accumulation, albeit in small amounts, is detectable during bloating episodes. Indeed, during symptomatic events such as bloating and distension episodes, intracolonic gas volume appears to be increased, albeit slightly (26, 32). Therefore, although differences in colonic gas volume between asymptomatic and symptomatic periods are usually minimal, the mechanism of visceral hypersensitivity appear to be sufficient to both increase conscious perception (bloating), and activate unperceived, yet aberrant, viscero-somatic reflexes that expand the abdominal girth (distension).

In contrast to functional bloating and distension, patients with advanced intestinal neuropathy and enteric dysmotility develop symptomatic abdominal distension through a substantially different mechanism. Ineffective peristalsis resulting from disturbed enteric motility produces marked pooling of intestinal gas together with other luminal content (33) which becomes directly responsible for the observed abdominal distension.

Individual perception and focussed attention

Conscious perception of both bowel and abdominal distension probably play a determinant role in symptomatic bloating (34). That is, the same degree of bowel and abdominal distension may be either unperceived, produce minor discomfort or significant pain depending on the degree of conscious sensitivity. Indeed, visceral hyperalgesia, a common feature of IBS and functional bloating may largely account for the “bloating” sensation that, as noted earlier, occurs in the presence of normal or only mildly increased amounts of intraluminal gas or other bowel content. Bloating as a sensation may constitute an expression of discomfort just below the threshold for pain as suggested by physiological studies in healthy volunteers that are ramp-distended with intraluminal balloons. Conscious perception of intraluminal content is likely to be substantially increased by the physiological phenomenon of spatial summation whereby distending stimuli applied simultaneously at different sites, result in a marked increase in the perception score (35). Regional tolerance is another important factor. We have shown, for instance, that exogenous gas infused into the colon is better tolerated that gas infused into the small bowel (36). Furthermore, the gut normally tolerates well the usual postprandial load of food, liquid, and gas, suggesting that postprandial accommodation is physiologically achieved without increasing gut wall tension (32). Normal propulsion of intraluminal content which may cause transient bowel distension ahead of the propagating contraction is also unperceived. Hence, it seems quite plausible that visceral hypersensitivity associated with functional bowel disorders converts these events, not normally sensed by healthy individuals, into bloating and other symptoms (37).

It is important to recognize that perception and reflex responses to stimuli arising from the gut are functions regulated at various levels along the brain–gut axis. Thus, both perceived and unperceived gut stimuli are modulated by complex neuro-hormonal mechanisms that act peripherally (where inflammation, sensitization, and other local factors may act as amplifiers and modifiers) but also along autonomic and medullar connecting pathways to the brain (where sympathetic arousal, descending inhibitory mechanisms and other mechanisms participate). At a central level, emotion and cognitive pain modulation are deeply interlinked, probably explaining the importance of the psychological status (stress and anxiety) on central reception and representation of nociceptive signals from the gut (38). It is also apparent that central activity may influence local gut conditions. It has been shown for instance that anxiety and depression facilitate gut inflammation (39). Furthermore, recent evidence indicates that in about 1/3 of patients with IBS, psychological distress develops after first appearance of gut symptoms suggesting that anxiety and depression may not necessarily be the primary drivers of the functional syndrome (40).

In the experience of bloating, disturbed emotional and cognitive pain modulation seem to play a facilitatory role. Individual differences in conscious perception of a given gut stimulus probably account for the wide range of bloating intensities and other features that may be observed in response to standardized bowel stimuli in experimental human studies. More to the point, an intraluminal distending stimulus may elicit symptoms in one individual (allodynia) and remain unnoticed by others.

Reflex responses to unperceived stimuli

Unperceived stimuli may be similarly modulated and upgraded by the central nervous system. Thus, abnormal viscero-somatic reflex responses that produce abdominal distension may operate, at least in theory, in the absence of pain.

Extraintestinal tissues within the abdominal cavity may also potentially influence the perception of bloating and abdominal distension. Intraabdominal adipose tissue accumulation is probably important. Several studies have shown that rapid weight gain aggravates symptomatic bloating, and conversely, weight loss tends to be associated with improvement. Several mechanisms may be at play. First, intraabdominal fat accumulation may constrain bowel expansion during luminal distension by gas or fluid, hence stimulating visceral and peritoneal sensory receptors. Second, adipose tissue accumulation in the epiplon or mesentery may have a pro-inflammatory action, on account of its capacity to release inflammatory cytokines, and thus contribute to intestinal hypersensitivity (41). Third, unwanted abdominal distension by fat may contribute to focus patient’s attention on the region and exacerbate the symptomatic response as it is known that attention or distraction substantially modify conscious perception of abdominal stimuli (42).

In females, another relevant factor to consider is the menstrual cycle. Abdominal bloating and discomfort frequently develop during the perimenstrual period (and sometimes ovulation as well) in normal otherwise asymptomatic females (43, 44) and the aggravating influence of the menstrual cycle in females suffering from bloating and distension is frequently observed clinically. The mechanism remains unclear although enhanced visceral sensitivity in the premenstrual phase is probably a relevant factor (45).

Bloating and abdominal distension are also much influenced by meals and evacuation. Many patients acknowledge that the bloating sensation increases during the postprandial period (46) and hence they tend to feel more comfortable during fasting. It is conceivably that a combination of gas and chyme pooling at various levels of the gastrointestinal tract enhances gut sensorial stimulation during digestion (an effect apparent in many normal individuals after binge eating) thus exceeding the threshold of conscious perception and even raising above the threshold for discomfort. These effects may be potentiated by chemical stimulation by specific food components, such as fat, that appears to intervene via CCK-dependent mechanisms (47). Bloaters may, therefore, distend more and feel more uncomfortable after meals, particularly after consumption of fatty foods. Bloaters may also acknowledge worsening of their symptomatology when they become constipated and accumulate a large quantity of stool inside their colon. Relief may follow evacuation although it is true that other patients indicate that passing stools does not necessarily relieve their bloating sensation. Pharmacological agents that relieve constipation have shown some effectivity in ameliorating bloating in constipated individuals but it is difficult to discern to what extent unloading of retained stool vs. direct neuropharmacological effects of these agents are responsible for the improvement. In patients with constipation due to functional outlet obstruction bloating tends to correlate with rectal balloon expulsion impairment (48).

Relation between bloating and flatulence

The relation between bloating and flatulence is somewhat ambiguous. Bloated patients often express the conviction that they would feel much relieved if they could expel “retained” gas per anus and/or mouth. Sometimes this may be the case but bloated patients may also acknowledge that forcefully expelling flatus does not diminish their bloating sensation or distension. It is unclear why this is the case since, intuitively, gas evacuation should reduce bowel distension. A possible explanation is the location of the retained gas stimulus that induces the bloating sensation. We have previously shown that gas accumulating inside the small bowel is more likely to induce abdominal discomfort than in the colon (15). Conversely, patients complaining of flatulence may not feel bloated unless they voluntarily inhibit expelling gas for social or other reasons. We have previously shown that voluntary anal contraction to restrict evacuation of retained bowel gas produces, even in normal individuals, uncomfortable abdominal distension (14).

In most episodic bloaters there is a very apparent circadian rhythm (49) that modulates their bloating sensation and abdominal distension (8). Patients tend to wake up in the morning with no or minimal bloating. After breakfast and particularly during the afternoon and early evening the bloating sensation worsens and abdominal distension becomes more apparent (50). However, some bloaters do not manifest the aforementioned circadian rhythm and remain permanently bloated, and distended though long periods configuring a more severe clinical picture. In some patients, particularly women, dressing up with tight clothes aggravates their abdominal discomfort and the distension becomes more inconvenient and self-conscious, increasing patient’s uneasiness. Moreover, in some patients the unsatisfactory self-appearance produced by abdominal distension has adverse psychological consequences and may aggravate underlying anxiety/depression.

Abdominal shape

Normal individuals react to intestinal gas distension by contracting their anterior abdominal muscles and relaxing the diaphragm. By this reflex manoeuvre they increase the total capacity of the abdominal cavity without protruding their abdomen (51). We have shown that patients complaining of bloating and abdominal distension activate different viscero-somatic responses that result in thoracic expansion, diaphragm contraction, and relaxation of the inferior oblique muscles. This manoeuvre reshapes their abdominal cavity an redistributes its contents resulting in anterior wall protrusion and visible distension (Figure 1). Net intraabdominal volume shows only a modest increase (52, 53, 54). We have proposed that this abnormal viscero-somatic response to intraluminal bowel stimuli constitutes a major pathogenetic mechanism of the abdominal distension associated with bloating. The somatic abdomino-thoracic muscular activity associated to abdominal distension is appreciable even when fixing the curvature of the dorso-lumbar axis and preventing lumbar lordosis, a factor previously considered as determinant of abdominal distension events. Reshaping of the abdomen appears to develop without the patient being consciously aware of the somatic muscular activities that produce it.

Figure 1.
Figure 1 - Unfortunately we are unable to provide accessible alternative text for this. If you require assistance to access this image, please contact or the author

Abdominal imaging in a patient with functional bloating. The left panel CT image shows a non-distended period with a mild bloating sensation. The right panel shows the same patient during a bloating and distension episode. Note the abdominal protrusion with elongated spine-navel axis and the marked descent of the diaphragm. Intrabowel gas volume increased by only 22ml during the bloating episode. Reproduced by permission from Accarino et al. (53).

Full figure and legend (169K)

Interestingly, patients with severe enteric dysmotility, who markedly distend their abdomen due to retained luminal gas and fluid, show normal viscero-somatic accommodation reflexes (Figure 2) (33). Thus, abdominal distension produced by reshaping of the abdomen appears to be a feature of patients with functional disorders via abnormal viscero-somatic responses rather than a direct consequence of intestinal dysmotility (52, 55, 56). However, the later may contribute to create focal pools of luminal gas or other content that act as trigger points for the aberrant viscero-somatic responses that lead to abdominal reshaping and distension.

Figure 2.
Figure 2 - Unfortunately we are unable to provide accessible alternative text for this. If you require assistance to access this image, please contact or the author

Abdominal imaging in a patient with proven intestinal dysmotility. The left panel shows a moderately distended abdomen with a discretely increased volume of intraluminal gas. The right panel shows the same patient during a bloating and distension episode. Abdominal protrusion has increased in proportion to the marked accumulation of intraluminal gas with partially compensatory ascent of the diaphragm. Reproduced by permission from Accarino et al. (53).

Full figure and legend (158K)

Recent studies from our laboratory have also evidenced that both the chest and the abdomen contribute to the phenomenon of abdominal reshaping and distension (54). During symptomatic episodes patients elevate the costal wall and hyperinflate their lungs while, paradoxically, contracting and forcing diaphragmatic descent and simultaneously relaxing their oblique abdominal muscles allowing the anterior abdomen to protrude. However, observed intraabdominal volume increments associated with aberrant viscero-somatic distending responses are smaller than those required experimentally for induction of distending responses during asymptomatic intervals (52, 55, 56). Thus, sensitization of a viscero-somatic response during symptomatic periods may be important and potentially activated at a, so far undetermined, level of the gut-brain axis.



Taking into account the diverse mechanisms that participate in the pathogenesis of bloating and abdominal distension, it is theoretically possible to construe a therapeutic plan adapted to individual patients (Table 3). However, attempting to establish the precise contribution of these potential mechanisms in each case of abdominal bloating/distension seems farfetched. In practice, there are several levels of increasing diagnostic complexity that may be applied depending on the severity of the bloating/distension, impact on patient’s quality of life and concern, and whether or not concrete therapeutic approaches have been previously implemented. Obviously, organic causes of bloating must be considered first and evaluated according to clinical priority criteria.

Mild cases of bloating and distension may sometimes be managed just with an explanation and reassurance, whereas others warrant an in-depth pathophysiological investigation and combined therapies. Some preliminary data obtained by anamnesis can be useful. For instance, a detailed dietary history would help establish whether the patient consumes excess fermentable foods or other products that may increase intestinal gas. Assessment of bowel movement frequency and stool consistency may orient towards associated constipation but it is also pertinent to consider and exclude unapparent forms of constipation such as incomplete defecation or impaired rectal defecatory sensation (57). Distension as a major feature would tend to point towards abnormal viscero-somatic responses and reshaping of the abdomen, whereas pain associated with distension would point more towards visceral hypersensitivity. It is also important to consider associated psychopathological features that may need to be specifically addressed as part of the therapeutic plan.

More precise diagnostic assessments of bloating and distension, when indicated, may include tests to evaluate possible intolerances to lactose, fructose, and sorbitol although the clinical value of breath tests remains unproven. In addition, we have found CT scan evaluation of bloating and distension useful in providing a measure of abdominal distension and reshaping (33). The CT scan appears to be most useful to characterize distension when comparing one CT obtained at baseline conditions (no or little distension) and a CT obtained during an episode of severe distension. However, the CT method requires specific software for morphovolumentric analysis as previously described (53). Recent data our laboratory (unpublished) indicates that abdominal MRI may be especially useful for repeat imaging because it does not involve radiation. In some instances measurement of tolerance and disposal of infused jejunal gas may be quite helpful. With these technical aids it becomes possible to approach treatment focussing on the most predominant or likely mechanism among those detailed previously. Admittedly, however, the more sophisticated technologies tend to be available only at specialized medical centers. Referral of selected patients to such centers for in depth evaluation of their refractory bloating and distension is a sensible option.

Dietary therapy

The dietary therapeutic approach to bloating has two distinct but often complementary facets: avoiding food intolerances (if detected) and reducing fermentation of food residues. It has been shown that patients complaining of flatulence expel similar volumes of flatus compared to healthy individuals (albeit often in repeat smaller quantities). When they consume a diet rich in fermentable products such patients may also develop bloating and other abdominal symptoms. This probably reflects their poor tolerance of intestinal gas accumulation and for this reason dietary restriction may be useful to control their symptoms (23). Excess fermentation may also increase bloating and abdominal distension in individuals who behave as gas retainers because of their limited ability to expel flatus.

Excess fermentation may occur because of (a) a high intake of gas producing foods, (b) small bowel malabsorption that would deliver to the colon unusually large quantities of fermentable components or (c) variations in the metabolic activity of the microbiota. In any case a correct management approach would start by prescribing a diet low in fermentable components and indeed such diets are associated with a major and measurable reduction in flatulence, abdominal distension, and improvement in well-being (24). Unfortunately, the wide variety of foods that provide fermentable substrates for colonic bacteria make it challenging for any individual to comply long term with a diet devoid of potentially fermentable substrates. Thus, as pointed out earlier it would seem appropriate to determine first whether the patient under consideration shows reduced capability to absorb certain carbohydrates, chiefly lactose and fructose, by performing the corresponding breath tests. In clinical practice, however, psychological factors sometimes influence and may distort subjective perception of carbohydrate intolerance limiting the practical value of performing carbohydrate malabsorption tests (58).

Directly placing bloaters on a FODMAP restricted diet (avoiding lactose, fructose, fructans, polyols, and galactooligosaccharides which are the main fermentable sugars in the normal diet) has rapidly become a cornerstone of dietary management of functional bloating, including bloating associated with IBS (59, 60). However, the FODMAP diet imposes a burden on patients since it excludes many common components of a normal western diet and, therefore, compliance and benefits produced by long term adherence to a FODMAP diet remain an open question. Furthermore, restrictive diets may have potential deleterious effects on microbiota.

Microbiome modulation

Since bacterial fermentation of dietary residues is a major source of intestinal gas it seems that reducing gas-producing bacterial species and/or modifying their metabolic activity would constitute a straightforward method to reduce gas production and bowel distension but matters are more complex that it appears at first glance. First, in addition to gas producing species, there are others that actively consume H2 and CO2 to synthesize short chain fatty acids, produce methane or reduce sulfate to sulfide. Hence, the fact that broad spectrum antibiotics such as ampicillin, tetracycline, and cephalosporins fail to substantially reduce net H2 excretion in human volunteers may relate to their undiscriminate action on the intestinal flora (61). On the other hand, rifaximin a nearly unabsorbable wide spectrum antibiotic has evidenced some effectivity in relieving IBS associated bloating (62). Whether rifaximin achieves its favourable effects on bloating by diminishing small bowel bacterial overgrowth or by modifying the fermenting colonic microbiota remains uncertain. Probiotics would seem an attractive option for the treatment of bloating on account of their purported properties to modulate intraluminal fermentation, mucosal inflammation, and visceral sensitivity. Bifidobacteria seem particularly active (63, 64). However, objective evidence of clinical efficacy for probiotics remains meager.

Diet induces substantial changes on microbiota composition. In one recent study, a highly flatulogenic diet was associated with marked changes in microbiota promoting the appearance of methanobrevibacter smithii (23). Some specific non-absorbable, fermentable substrates, i.e., prebiotics, induce the proliferation of beneficial microorganisms. Initially, these substrates increase gas production, which may be bothersome in patients with functional gut symptoms but, after a 1–2 week adaptation period, gas production decreases and abdominal symptoms may improve (65). There are also significant microbial taxa differences between healthy individuals and IBS with bloating which could possibly determine a variable response to diets, antibiotics, and probiotics as well. Intestinal motility, particularly colonic propulsive activity, also influences microbiota activity and net gas generation by modulating time and degree of exposure of substrates to gas producing or gas consuming bacteria. In turn, intestinal nutrients may also influence propulsive activity and gas clearance from the bowel (66, 67). Thus, a complex interplay among nutrients, transit, and the microbiome, not yet fully elucidated, complicates dietary approaches to management of bloating and distension.

Promoting gas evacuation

Relieving constipation, if present, is a valid initial step in the management of bloating but bulk and osmotic laxatives have the potential drawback of increasing luminal distension and are best avoided in this context.

Unlike motion of fluids and solids, displacements of gas inside the gut is produced by tonic type contractions (68). Clearance of accumulated gas may be accelerated by physical exercise (21) or rapidly acting cholinomimetic agents such as parenteral neostigmine (69). Moreover, oral pyridostigmine also has shown ability to expel gas from the gut although but tachyphilaxis tends to limit clinical effectivity of this agent beyond short term use (70).

Prucalopride, a 5HT4 agonist that promotes propulsive peristalsis has been shown to reduce bloating in patients with chronic constipation (71) but it is uncertain whether the positive effect is independent of the clearing of retained stool in the colon. Linaclotide and lubiprostone induce intestinal fluid secretion and ameliorate bloating in clinical trials involving patients with constipation predominant IBS (72, 73). Linaclotide, unlike lubiprostone, has antinociceptive properties shown in experimental animal models that could possibly attenuate visceral hypersensitivity (74). In brief, it appears that improving constipation, if present, produces beneficial effects on bloating and distension but considering the relatively small amounts of gas spontaneously retained by bloated individuals, pharmacological stimulation of gas transit and evacuation would be expected to have modest therapeutic effects, at best. If gas retention is associated to functional outlet obstruction, then anorectal biofeedback may be particularly useful.

OTC and “natural” remedies

Numerous agents are promoted for the management of functional bloating emphasizing their “natural” source and innocuity. These include activated charcoal, simethicone, kiwi fruit extract, STWS (Iberogast), magnesium salts and many others. Objective evidence of efficacy is generally weak and their popularity is probably bolstered by strong placebo effects combined in some instances with laxative action.

Attenuating visceral perception

Wall tension is the main stimulus for eliciting gut discomfort and the magnitude of the perceived sensations is amplified by the phenomenon of visceral hypersensitivity that appears to be present in a substantial fraction of patients with functional abdominal pain. Thus, altered perception probably represents a key mechanism in the distress experienced by functional patients with bloating and constitutes a pharmaco-therapeutic opportunity to relieve their symptoms.

Some pharmacologic agents may be utilized to decrease gut perception of wall tension. Antispasmodic drugs have long been employed to reduce abdominal discomfort on account of their muscle relaxing properties but evidence that they specifically act on the symptom of bloating is lacking. Visceral hyperalgesia, which probably involves multiple disturbed mechanisms along the gut–brain axis would seem a more suitable therapeutic target to ameliorate the bloating sensation. Although some molecules, such as linaclotide, may include antinociceptive gut activity among their pharmacodynamic properties, no successful specific agents to attenuate gut hypersensitivity have been commercialized. Antidepressants have been employed as visceral antinociceptive agents in IBS with some success (75) although it remains uncertain whether specifically improve bloating (76). Furthermore, it is not completely clear at which neuroregulatory level they exert their therapeutic action since these agents also improve mood and control anxiety that also intervene as modulatory factors. Antidepressants that combine inhibitory affinity for norepinephrine and serotonin (SSNRI) may be more effective to reduce visceral hypersensitivity than specific serotonin-reuptake inhibitors. The older tricyclic antidepressants exhibit antihypersensitivity action but their use tends to be limited by unwanted side effects. Anxiolytic agents such as benzodiazepines may alleviate bloating possibly by acting centrally to reduce the effect of chronic stress but tachyphilaxis and potential addictive properties restrict their long term use. Psychological approaches have also been reported to produce favourable effects in IBS but the formal and more structured modalities such as hypnotherapy and behavioural modification require time and trained therapists that are not always available in usual clinical settings. Their overall reported efficacy is variable and probably depends on different factors, such as the expertize of the team and the selection of the patients (77, 78).

Abdominal biofeedback treatment

Whereas, the sensation of bloating is generated by a multiplicity of mechanisms that difficult specific therapy, functional abdominal distension, whether or not accompanied by bloating, appears to be the result of combined thoraco-abdominal striated muscular activity that reshapes the abdomen and causes it to protrude anteriorly. Intraabdominal volume remains constant or near constant, as reviewed earlier. The abnormal viscero-somatic muscular response that motivates protrusion, be it the result of abnormal viscero-somatic reflex activity or behavioural is potentially amenable to biofeedback therapy.

Biofeedback training is achieved with the help of abdominal EMG recordings that permit visual control of muscle activity by the patient during the treatment sessions. The patient is requested to reduce the activity of the intercostal muscles and the diaphragm while increasing the activity of the anterior abdominal muscles (54). In analogy to anorectal biofeedback, training sessions are conducted on separate days up to 3 times during a 1–2 week period. In a recent study we have shown that this biofeedback method is able to diminish diaphragmatic and intercostal muscle activity by about one fifth and to achieve ~40% reduction in the subjective sensation of abdominal distension as well as a 2.5cm reduction in abdominal girth (54).

Patients with episodic distension as their cardinal symptom may be more amenable to successful biofeedback therapy than patients with permanent distension or those in whom bloating constitutes is one more component of a complex clinical picture that includes pain, major changes in bowel function and other ancillary symptoms. Since facilitatory emotional conditions (stress, anxiety, and depression) may be involved in the sensitization of aberrant viscero-somatic responses such as bloating and distension that probably represent conductual manifestations of somatization (1, 43), these emotional aspects should be addressed simultaneously.


Conflict of interest

Guarantor of the article: Juan R Malagelada, MD.

Specific author contributions: J.R.M. wrote the review and A.A. and F.A. made suggestions, corrected and added on pertinent material.

Financial support: No financial support for this review article.

Potential competing interests: None.



  1. Houghton LA, Lea R, Agrawal A et al. Relationship of abdominal bloating to distension in irritable bowel syndrome and effect of bowel habit. Gastroenterology 2006;131:1003–1010. | Article | PubMed | ISI |
  2. Azpiroz F. Intestinal gas. In: Feldman M, Friedman LS, Brand LJ (eds). Pathophysiology, Diagnosis, Management 10th edn. Elsevier: Philadelphia, USA. 2015 pp 242–250.
  3. Drossman DA. Functional gastrointestinal disorders: history, pathophysiology, clinical features, and rome IV. Gastroenterology 2016;150:1262–1279. | Article |
  4. Tuteja AK, Talley NJ, Joos SK et al. Abdominal bloating in employed adults: prevalence, risk factors, and association with other bowel disorders. Am J Gastroenterol 2008;103:1241–1248. | Article | PubMed | ISI |
  5. Lembo T, Naliboff B, Munakata J et al. Symptoms and visceral perception in patients with pain-predominant irritable bowel syndrome. Am J Gastroenterol 1999;94:1320–1326. | Article | PubMed | ISI | CAS |
  6. Maxton DG, Morris JA, Whorwell PJ. Ranking of symptoms by patients with the irritable bowel syndrome. BMJ 1989;299:1138. | Article | PubMed |
  7. Sandler RS, Stewart WF, Liberman JN et al. Abdominal pain, bloating, and diarrhea in the United States: prevalence and impact. Dig Dis Sci 2000;45:1166–1171. | Article | PubMed | ISI | CAS |
  8. Maxton DG, Martin DF, Whorwell P et al. Abdominal distension in female patients with irritable bowel syndrome: exploration of possible mechanisms. Gut 1991;32:662–664. | Article | PubMed | CAS |
  9. Furne JK, Levitt MD. Factors influencing frequency of flatus emission by healthy subjects. Dig Dis Sci 1996;41:1631–1635. | Article | PubMed |
  10. Longstreth GF, Thompson WG, Chey WD et al. Functional bowel disorders. Gastroenterology 2006;130:1480–1491. | Article | PubMed | ISI |
  11. McRorie J. Clinical data support that psyllium is not fermented in the gut. Am J Gastroenterol 2013;108:1541. | Article | PubMed |
  12. Serra J, Azpiroz F, Malagelada J-R. Intestinal gas dynamics and tolerance in humans. Gastroenterology 1998;115:542–550. | Article | PubMed | CAS |
  13. Serra J, Azpiroz F, Malagelada J-R. Impaired transit and tolerance of intestinal gas in the irritable bowel syndrome. Gut 2001;48:14–19. | Article | PubMed | CAS |
  14. Serra J, Azpiroz F, Malagelada J-R. Mechanisms of intestinal gas retention in humans:impaired propulsion versus obstructed evacuation. Am J Physiol 2001;281:G138–G143. | CAS |
  15. Serra J, Salvioli B, Azpiroz F et al. Lipid-induced intestinal gas retention in the irritable bowel syndrome. Gastroenterology 2002;123:700–706. | Article | PubMed |
  16. Marciani L, Cox EF, Hoad CL et al. Postprandial changes in small bowel water content in healthy subjects and patients with irritable bowel syndrome. Gastroenterology 2010;138:469–477 477,e1. | Article | PubMed | ISI |
  17. Murray K, Wilkinson-Smith V, Hoad C et al. Differential effects of FODMAPs (fermentable oligo-, di-, mono-saccharides and polyols) on small and large intestinal contents in healthy subjects shown by MRI. Am J Gastroenterol 2014;109:110–119. | Article | PubMed | ISI | CAS |
  18. Guarner F, Malagelada JR. Gut flora in health and disease. Lancet 2003;361:512–519. | Article | PubMed | ISI |
  19. Mego M, Bendezu A, Accarino A et al. Intestinal gas homeostasis: disposal pathways. Neurogastroenterol Motil 2015;27:363–369. | Article |
  20. Mc Rorie J, Fahey G. Invited review article: a review of gastrointestinal physiology and the mechanisms underlying the health benefits of dietary fiber: matching an effective fiber with specific patients needs. Clin Nurs Stud 2017;1:82–92.
  21. Dainese R, Serra J, Azpiroz F et al. Effect of physical activity on intestinal gas transit and evacuation in healthy subjects. Am J Med 2004;116:536–539. | Article | PubMed | ISI |
  22. Azpiroz F. Functional abdominal bloating and gas. In: Talley NJ, Kane SV, Wallace M (eds). Practical Gastroenterology and Hepatology: Small and Large Intestine and Pancreas. Wiley-Blackwell: NJ, USA. 2010 pp 470–473.
  23. Manichanh C, Eck A, Varela E et al. Anal gas evacuation and colonic microbiota in patients with flatulence: effect of diet. Gut 2014;63:401–408. | Article | PubMed | ISI |
  24. Azpiroz F, Hernandez C, Guyonnet D et al. Effect of a low-flatulogenic diet in patients with flatulence and functional digestive symptoms. Neurogastroenterol Motil 2014;26:779–785. | Article | PubMed |
  25. Mego M, Accarino A, Malagelada JR et al. Accumulative effect of food residues on intestinal gas production. Neurogastroenterol Motil 2015;27:1621–1628. | Article | PubMed |
  26. Bendezu RA, Barba E, Burri E et al. Colonic content in health and its relation to functional gut symptoms. Neurogastroenterol Motil 2016;28:849–854. | Article | PubMed |
  27. Agrawal A, Houghton LA, Reilly B et al. Bloating and distension in irritable bowel syndrome: the role of gastrointestinal transit. Am J Gastroenterol 2009;104:1998–2004. | Article | PubMed | ISI |
  28. Pritchard SE, Marciani L, Garsed KC et al. Fasting and postprandial volumes of the undisturbed colon: normal values and changes in diarrhea-predominant irritable bowel syndrome measured using serial MRI. Neurogastroenterol Motil 2014;26:124–130. | Article | PubMed | ISI |
  29. Simren M, Barbara G, Flint HJ et al. Intestinal microbiota in functional bowel disorders: a Rome foundation report. Gut 2013;62:159–176. | Article | PubMed | ISI |
  30. Ong DK, Mitchell SB, Barrett JS et al. Manipulation of dietary short chain carbohydrates alters the pattern of gas production and genesis of symptoms in irritable bowel syndrome. J Gastroenterol Hepatol 2010;25:1366–1373. | Article | PubMed | ISI | CAS |
  31. Yao CK, Tan HL, van Langenberg DR et al. Dietary sorbitol and mannitol: food content and distinct absorption patterns between healthy individuals and patients with irritable bowel syndrome. J Hum Nutr Diet 2014;27 (Suppl 2): 263–275. | Article | PubMed |
  32. Perez F, Accarino A, Azpiroz F et al. Gas distribution within the human gut: effect of meals. Am J Gastroenterol 2007;102:842–849. | Article | PubMed | ISI |
  33. Barba E, Quiroga S, Accarino A et al. Mechanisms of abdominal distension in severe intestinal dysmotility: abdomino-thoracic response to gut retention. Neurogastroenterol Motil 2013;25:e389-94.
  34. Agrawal A, Houghton LA, Lea R et al. Bloating and distention in irritable bowel syndrome: the role of visceral sensation. Gastroenterology 2008;134:1882–1889. | Article | PubMed | ISI |
  35. Serra J, Azpiroz F, Malagelada JR. Modulation of gut perception in humans by spatial summation phenomena. J Physiol 1998;506:579–587. | Article | PubMed |
  36. Hernando-Harder AC, Serra J, Azpiroz F et al. Colonic responses to gas loads in subgroups of patients with abdominal bloating. Am J Gastroenterol 2010;105:876–882. | Article | PubMed | ISI |
  37. Houghton LA, Calvert EL, Jackson NA et al. Visceral sensation and emotion: a study using hypnosis. Gut 2002;51:701–704. | Article | PubMed |
  38. Murray CD, Flynn J, Ratcliffe L et al. Effect of acute physical and psychological stress on gut autonomic innervation in irritable bowel syndrome. Gastroenterology 2004;127:1695–1703. | Article | PubMed |
  39. Ghia JE, Blennerhassett P, Collins SM. Impaired parasympathetic function increases susceptibility to inflammatory bowel disease in a mouse model of depression. J Clin Invest 2008;118:2209–2218. | PubMed | CAS |
  40. Koloski NA, Jones M, Talley NJ. Evidence that independent gut-to-brain and brain-to-gut pathways operate in the irritable bowel syndrome and functional dyspepsia: a 1-year population-based prospective study. Aliment Pharmacol Ther 2016;44:592–600. | Article | PubMed | CAS |
  41. Kahn SE, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 2006;444:840–846. | Article | PubMed | ISI | CAS |
  42. Accarino AM, Azpiroz F, Malagelada JR. Attention and distraction: effects on gut perception. Gastroenterology 1997;113:415–422. | Article | PubMed | CAS |
  43. Chang L, Lee OY, Naliboff B et al. Sensation of bloating and visible abdominal distension in patients with irritable bowel syndrome. Am J Gastroenterol 2001;96:3341–3347. | Article | PubMed | ISI | CAS |
  44. Altman G, Cain KC, Motzer S et al. Increased symptoms in female IBS patients with dysmenorrhea and PMS. Gastroenterol Nurs 2006;29:4–11. | Article | PubMed |
  45. Houghton LA, Lea R, Jackson N et al. The menstrual cycle affects rectal sensitivity in patients with irritable bowel syndrome but not healthy volunteers. Gut 2002;50:471–474. | Article | PubMed | CAS |
  46. Maxton DG, Whorwell PJ. Abdominal distension in irritable bowel syndrome: the patient's perception. Eur J Gastroenterol Hepatol 1992;4:241–243.
  47. Lobo B, Serra J, D'Amato M et al. Selective CCK receptor antagonism enhances accommodation and tolerance of intestinal gas in functional gut disorders. J Gastroenterol Hepatol 2015;31:288–293. | Article |
  48. Shim L, Prott G, Hansen RD et al. Prolonged balloon expulsion is predictive of abdominal distension in bloating. Am J Gastroenterol 2010;105:883–887. | Article | PubMed |
  49. Bishehsari F, Levi F, Turek FW et al. Circadian rhythms in gastrointestinal health and diseases. Gastroenterology 2016;151:e1–e5. | Article | PubMed |
  50. Lewis M, Reilly B, Houghton L et al. Ambulatory abdominal inductance plethysmography: towards objective assessment of abdominal distension in irritable bowel syndrome. Gut 2001;48:216–220. | Article | PubMed |
  51. Villoria A, Azpiroz F, Soldevilla A et al. Abdominal accommodation: a coordinated adaptation of the abdominal walls to its content. Am J Gastroenterol 2008;103:2807–2815. | Article | PubMed | ISI |
  52. Villoria A, Azpiroz F, Burri E et al. Abdomino-phrenic dyssynergia in patients with abdominal bloating and distension. Am J Gastroenterol 2011;106:815–819. | Article | PubMed |
  53. Accarino A, Perez F, Azpiroz F et al. Abdominal distension results from caudo-ventral redistribution of contents. Gastroenterology 2009;136:1544–1551. | Article | PubMed | ISI |
  54. Barba E, Burri E, Accarino A et al. Abdomino-thoracic mechanisms of functional abdominal distension and correction by biofeedback. Gastroenterology 2015;148:732–738. | Article | PubMed |
  55. Tremolaterra F, Villoria A, Azpiroz F et al. Impaired viscerosomatic reflexes and abdominal wall dystony associated with bloating. Gastroenterology 2006;130:1062–1068. | Article | PubMed | ISI |
  56. Burri E, Barba E, Huaman JW et al. Mechanisms of postprandial abdominal bloating and distension in functional dyspepsia. Gut 2014;63:395–400. | Article | PubMed |
  57. Harraf F, Schmulson M, Saba L et al. Subtypes of constipation predominant irritable bowel syndrome based on rectal perception. Gut 1998;43:388–394. | Article | PubMed | CAS |
  58. Tomba C, Baldassarri A, Coletta M et al. Is the subjective perception of lactose intolerance influenced by the psychological profile? Aliment Pharmacol Ther 2012;36:660–669. | Article | PubMed | CAS |
  59. Shepherd SJ, Parker FC, Muir JG et al. Dietary triggers of abdominal symptoms in patients with irritable bowel syndrome: randomized placebo-controlled evidence. Clin Gastroenterol Hepatol 2008;6:765–771. | Article | PubMed | ISI | CAS |
  60. Halmos EP, Power VA, Shepherd SJ et al. A diet low in FODMAPs reduces symptoms of irritable bowel syndrome. Gastroenterology 2014;146:67–75. | Article | PubMed | ISI | CAS |
  61. Strocchi A, Levitt MD. Factors affecting hydrogen production and consumption by human fecal flora. The critical roles of hydrogen tension and methanogenesis. J Clin Invest 1992;89:1304–1311. | Article | PubMed | CAS |
  62. Pimentel M, Lembo A, Chey WD et al. Rifaximin therapy for patients with irritable bowel syndrome without constipation. N Engl J Med 2011;364:22–32. | Article | PubMed | ISI | CAS |
  63. Whorwell PJ, Altringer L, Morel J et al. Efficacy of an encapsulated probiotic Bifidobacterium infantis 35624 in women with irritable bowel syndrome. Am J Gastroenterol 2006;101:1581–1590. | Article | PubMed | ISI |
  64. Agrawal A, Houghton LA, Morris J et al. Clinical trial: the effects of a fermented milk product containing Bifidobacterium lactis DN-173 010 on abdominal distension and gastrointestinal transit in irritable bowel syndrome with constipation. Aliment Pharmacol Ther 2009;29:104–114. | Article | PubMed | CAS |
  65. Azpiroz F, Barba E, Mego M et al. Metabolic adaptation of colonic microbiota to diet. United Eur Gastroenterol J 2014;2 (5S): A436.
  66. Serra J, Azpiroz F, Malagelada J-R. Gastric distension and duodenal lipid infusion modulate intestinal gas transit and tolerance in humans. Am J Gastroenterol 2002;97:2225–2230. | Article | PubMed |
  67. Harder H, Serra J, Azpiroz F et al. Reflex control of intestinal gas dynamics and tolerance in humans. Am J Physiol 2004;286:G89–G94.
  68. Tremolaterra F, Villoria A, Serra J et al. Intestinal tone and gas motion. Neurogastroenterol Mot 2006;18:905–910. | Article |
  69. Caldarella MP, Serra J, Azpiroz F et al. Prokinetic effects in patients with intestinal gas retention. Gastroenterology 2002;122:1748–1755. | Article | PubMed |
  70. Accarino A, Perez F, Azpiroz F et al. Intestinal gas and bloating: effect of prokinetic stimulation. Am J Gastroenterol 2008;103:2036–2042. | Article | PubMed | ISI |
  71. Tack J, Stanghellini V, Dubois D et al. Effect of prucalopride on symptoms of chronic constipation. Neurogastroenterol Motil 2014;26:21–27. | Article | PubMed |
  72. Casellas F, de Torres I, Malagelada JR. Improved screening for intestinal villous atrophy by D-xylose breath test. Dig Dis Sci 2000;45:18–22. | Article | PubMed |
  73. Rao SS, Quigley EM, Shiff SJ et al. Effect of linaclotide on severe abdominal symptoms in patients with irritable bowel syndrome with constipation. Clin Gastroenterol Hepatol 2014;12:616–623. | Article | PubMed |
  74. Eutamene H, Bradesi S, Larauche M et al. Guanylate cyclase C-mediated antinociceptive effects of linaclotide in rodent models of visceral pain. Neurogastroenterol Motil 2010;22:312–e84. | Article | PubMed |
  75. Tack J, Broekaert D, Fischler B et al. A controlled crossover study of the selective serotonin reuptake inhibitor citalopram in irritable bowel syndrome. Gut 2006;55:1095–1103. | Article | PubMed | ISI | CAS |
  76. Rahimi R, Nikfar S, Abdollahi M. Efficacy and tolerability of Hypericum perforatum in major depressive disorder in comparison with selective serotonin reuptake inhibitors: a meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry 2009;33:118–127. | Article | PubMed |
  77. Webb AN, Kukuruzovic RH, Catto-Smith AG et al. Hypnotherapy for treatment of irritable bowel syndrome. Cochrane Database Syst Rev 2007, CD005110.
  78. Zijdenbos IL, de Wit NJ, van der Heijden GJ et al. Psychological treatments for the management of irritable bowel syndrome. Cochrane Database Syst Rev 2009, CD006442.


This work was supported by the Spanish Ministry of Economy and Competitiveness (Dirección General de Investigación Científica y Técnica, SAF 2013-43677-R); Ciberehd is funded by the Instituto de Salud Carlos III.