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GASTROENTEROLOGY 2005;129:1060 –1078

SPECIAL REPORTS AND REVIEWS

Abdominal Bloating

FERNANDO AZPIROZ and JUAN–R. MALAGELADA

Digestive System Research Unit, Hospital General Vall d’Hebron, Autonomous University of Barcelona, Barcelona, Spain

Abdominal bloating is a common and significant clinical problem that remains to be scientifically addressed. Bloating is one of the most bothersome complaints in patients with various functional gut disorders. However, in the current standard classification, abdominal bloat- ing is merely regarded as a secondary descriptor, which masks its real clinical effect. Four factors are involved in the pathophysiology of bloating: a subjective sensation of abdominal bloating, objective abdominal distention, volume of intra-abdominal contents, and muscular ac- tivity of the abdominal wall. The primer to elicit subjec- tive bloating may be any of the other 3 factors, or the sensation may be related to distorted perception. All of these mechanisms may play an independent role or may be interrelated. Gas transit studies have evidenced that patients with bloating have impaired reflex control of gut handling of contents. Segmental pooling, either of gas or of solid/liquid components, may induce a bloat- ing sensation, particularly in patients with altered gut perception. Furthermore, altered viscerosomatic re- flexes may contribute to abdominal wall protrusion and objective distention, even without major intra-abdominal volume increment. Bloating probably is a heterogeneous condition produced by a combination of pathophysiolog- ical mechanisms that differ among individual patients and that in most cases are subtle and undetectable by conventional methods. Further advances in the patho- physiology and clinical forms of bloating are warranted to develop mechanistic strategies rather than the cur- rent empiric treatment strategies for comprehensive and effective management of this problem.

B loating, like some other descriptors for abdominal sensations, is an ambiguous term that alludes both

to the subjective sensation and to the objective abdom- inal distention. The ambiguity of the English term is shared by other languages. Furthermore, bloating means different things to different patients (and to their doc- tors). Some use the term bloating to refer to the sensation

of a swollen/distended abdomen, and others use it to refer to the sensation of a full belly, the feeling of abdominal pressure or wall tension, or the sensation of excess gas. Yet others use it for various apparently unrelated sensa-

tions, such as needing to burp; nausea; crampy, gurgling, or rumbling stomach; or needing to go to the bathroom. Many patients with bloating, approximately 24%, report no visible abdominal distention. 1 As clinicians, when inquiring about bloating, do we really know what we are specifically asking the patient? In this review, we primarily focus on bloating, meaning the subjective sensation of abdominal distention, and, among other aspects, we will also address whether the subjective sensation of the patient corresponds with ob- jective distention of the abdomen. In the current gold standard classification of functional gut disorders, abdominal bloating and distention are merely regarded as secondary descriptors. 2,3 Thus, pa- tients with bloating as their predominant complaint are dispersed among different categories, such as functional dyspepsia and irritable bowel syndrome (IBS), and lumped together with nonbloating patients. 2,3 Only pa- tients who do not meet the criteria that define these categories, ie, by exclusion, are categorized as having functional bloating. 3 In the past few years, various clin- ical studies have raised the significance of abdominal bloating as an important, troublesome, and poorly un- derstood clinical problem. It is also highly prevalent. The sensation of abdominal bloating may affect 10%–30% of the population in community-based studies. 3 In a survey of US householders, 15.9% of the adult population re- ported abdominal bloating or distention within the month before the interview, and in more than 75% of them, the symptom was moderate or severe. 4 Bloating is one of the most common and bothersome complaints in a large proportion of patients with various functional gut disorders, such as functional dyspepsia 5,6 and IBS, 79 and it is frequently associated with constipation 10,11 and di- arrhea. 1 The importance of bloating is placed in perspec- tive by considering the enormous economic burden im- posed by this type of functional gut disorder. 12

Abbreviation used in this paper: IBS, irritable bowel syndrome. © 2005 by the American Gastroenterological Association

0016-5085/05/$30.00

doi:10.1053/j.gastro.2005.06.062

September 2005

Despite its clinical, social, and economic importance, bloating remains substantially ignored, without a proper clinical classification, a known pathophysiology, or an effective treatment. 13 It is not even clear to what extent individual patients’ complaints of bloating correlate with objective evidence of abdominal distention, and the un- certainty regarding the subjective or the objective origin of the complaints further adds to the confusion. In summary, bloating is a common and highly significant clinical problem that remains to be scientifically ad- dressed.

Aims and Methods

Our aim was to clarify the concept, clinical im- portance, and pathophysiology of abdominal bloating and, thereby, to pave the way for the comprehensive management of this problem. Specifically, we performed a critical analysis of the following topics: the pathophys- iological mechanisms involved in bloating, the various forms of presentation of bloating in clinical practice, and the current treatment options for this heterogeneous condition. To this aim, a literature review was performed based on a PUBMED search over January 1989 to September 2004 on the following terms: “abdominal bloating,” “IBS and intestinal gas,” and “IBS and flatulence.” A total of 473 articles were identified. These articles, as well as chapters on intestinal gas in standard text- books, 14 16 served as literature sources for articles pub- lished before 1989. However, only articles relevant to the areas of controversy have been quoted. The experimental evidence available on this subject is scarce; hence, this review is necessarily, to some extent, based on theoretical analysis and the authors’ interpreta- tion of existing data. References indicate the original source of information, but the referenced article may not necessarily support the concepts expressed.

Pathophysiology of Bloating:

Putative Factors and Mechanisms

Four factors are included in the pathophysiology of bloating: subjective sensation, objective girth changes, volume of intra-abdominal contents, and muscular activ- ity of the abdominal walls (Figure 1). The primer to elicit subjective bloating may be any of the other 3 factors, or the sensation may be related to distorted perception. These mechanisms, ie, abnormal perception, objective distention, intra-abdominal volume increment, and abdominal wall dystony, may play an independent role or may be interrelated. Indeed, objective abdominal distention, whether accompanied or not by a subjective

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accompanied or not by a subjective ABDOMINAL BLOATING 1061 Figure 1. Factors involved in bloating. Subjective

Figure 1. Factors involved in bloating. Subjective bloating may be related to objective abdominal distention or to distorted perception. Objective abdominal distention may be due to increased abdominal contents or to intra-abdominal content redistribution. Intra-abdominal content may increase at the expense of either intraluminal or extralu- minal volume. Changes in abdominal wall activity may induce a sub- jective sensation of bloating and/or objective abdominal distention due to content redistribution, even without a net increment in intra- abdominal volume.

sensation of bloating, may be due to changes in abdom- inal wall activity produced either by a real volume in- crement of abdominal contents or just by intra-abdom- inal content redistribution. Intra-abdominal content may increase at the expense of either intraluminal volume (ie, gas or liquid/solid gut content) or extraluminal volume (ie, tissue water increment due to edema or vascular congestion). Changes in abdominal wall activity, which are potentially related to viscerosomatic reflexes, may increase the tension of abdominal muscles, which may be subjectively interpreted as a bloating sensation but may also produce objective abdominal distention due to re- distribution of intra-abdominal contents even in the absence of net changes in intra-abdominal volume. The experimental evidence, in terms of the amount of data, supporting each one of these possible mechanisms is frankly uneven and will be analyzed below. Most of the information available relates to the role of intestinal gas in bloating, because this has been the primary focus of experimental studies on this topic. Bloating, like many other abdominal symptoms, is probably a heterogeneous condition produced by a combination of pathophysiolog- ical mechanisms that differ among individual patients. The pathophysiology of bloating will be reviewed below by analyzing the relation of bloating to objective

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Table 1. Do Patients With a Bloating Sensation Have Objective Abdominal Distention?

Study

Method

Result

Poynard 20

Maxton 21

Maxton 21

Sullivan 22

Lea 25

Lea 26

Tape measure Tape measure Computed tomographic scan Tape measure Plethysmography Plethysmography

No

Yes

Yes

Yes

Yes

Variable a

a Constipation-predominant yes; diarrhea-predominate no.

distention, abdominal wall dystony, abnormal percep- tion, and intra-abdominal contents. The latter issue is by far the best documented, including aspects on the role of intestinal gas, impaired handling of gut contents, the responsible area of the gut, and the intra-abdominal component that gives rise to bloating.

Does the Subjective Sensation of Bloating Really Correspond With Objective Distention?

This is a deceptively simple and key question, yet it is not easy to answer. Most patients indicate that their abdomen is or becomes episodically distended, and their claim is often corroborated by a proxy. However, the examining doctor may be mystified or uncertain and, in any case, unable to either prove or disprove the assertion. There are indeed patients whose abdomens appear to be truly distended. However, to show even the seemingly obvious may be difficult, because there are no practical office or bedside devices to reliably measure abdominal volume. Tape measures of abdominal girth have been shown to reproducibly detect even small changes in abdominal circumference induced experimentally by in- testinal gas infusion. 1719 However, tape measurement requires an immobilized patient fitted with a belt-type measuring device that remains in place during the entire experiment, and each individual serves as his or her own control. Measurements performed in the context of clin- ical research studies have not yielded uniform results

( Table 1). A multicenter study evaluating patients with

functional gut disorders (IBS and functional dyspepsia) failed to detect differences in abdominal circumference between those who reported visible abdominal distention and those who did not. 20 Using a tape measure, Maxton et al 21 showed that in women with IBS, girth signifi- cantly increased during the day. Furthermore, the an- teroposterior diameter of the abdomen measured by com- puted tomography was also shown to increase during the day. 21 Another study reported that in patients with bloating, girth, but not weight, increased during epi- sodes of visible abdominal distention. However, in this

study, measurements were performed by the patients themselves, and the variability of the changes reported (5.3 3.0 cm in girth and 1.0 0.9 kg in weight; mean SD) was quite large. 22 More recently, automated methods have been devel- oped to measure girth changes. 23,24 Preliminary results with an ambulatory technique using inductance pleth- ysmography indicate that clinical variations in girth are significantly greater in IBS patients complaining of bloating than in healthy subjects. 25 However, the rela- tionship of distention to subjective bloating is variable, showing a good correlation in constipation-predominant IBS patients, but not in diarrhea-predominant IBS. 26 Hence, it seems that subjective claims of distention represent true perceptions of a real event in a significant proportion of patients, but this may not be the case in many others. For one thing, some patients complain of bloating but readily acknowledge no physical evidence of abdominal distention. Others point toward a “distended” abdomen that the examining physician appreciates as normal. Finally, other patients, usually with persistent bloating, show a prominent, fatty abdomen associated with IBS-like symptoms that they interpret as secondary to gut distention. A prospective study reported that patients with bloating were more likely to have experi- enced recent weight gain than healthy controls, despite similar age, sex, and body mass index between groups. 22 Thus, fat accumulation in the abdomen may favor the development or awareness of bloating as a symptom.

Abdominal wall activity. The shape of the abdo-

men is determined by the disposition of the walls of the abdominal cavity, specifically, the vertebral column, which determines the configuration of the posterior ab- dominal wall, the diaphragm, and the anterolateral mus- culature. The influence of the pelvic floor, with its lim- ited mobility, is probably insignificant. Even without increments in intra-abdominal volume, a change in the relative position of the walls may produce visible, objec- tive distention. Furthermore, signals arising from the abdominal wall—for instance, because of a muscular dystony—may induce a subjective sensation of abdomi- nal bloating, even in the absence of true abdominal distention, and this could explain some cases of appar- ently imaginary bloating. Is a classic article, Alvarez 27 described in great detail a series of patients in whom pronounced abdominal dis- tention was, in his view, related to the muscular activity of the abdominal wall. This hypothesis is substantiated by the fact that in some patients, visible abdominal distention has a very rapid onset 27,28 and resolves instan- taneously by gentle abdominal palpation while asking the patient to relax, by anesthesia, 27 or by hypnotic

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induction (Whorwell, personal communication, Novem- ber 1995). Furthermore, distention may affect only part of the abdomen, and rapid resolution is not associated with gas evacuation. 27 However, experimental evidence of these abdominal wall hypotheses has been difficult to obtain. Computed tomography has failed to identify differences in lumbar lordosis and diaphragmatic posi- tion in patients with bloating. 21 It has also been reported that patients with bloating have weak abdominal muscles as compared with healthy controls. 22 In contrast, McManis et al 29 studied a group of patients with IBS and abdominal distention by means of surface electromyography and found that patients and healthy subjects alike increased electromyographic activ- ity in the lower abdomen while standing compared with lying supine, but there were no differences between groups. Using a more elaborate technique and simulta- neously recording the muscular activity at 8 different sites, we recently reproduced these results. 30 However, we were also able to show a dystonic response of the abdominal wall to intra-abdominal volume increments in patients with bloating. Intestinal gas retention modeled by rectal gas infusion during anal blockade increased the muscular tone of the abdominal muscles in healthy sub- jects in the upright position. Similar volumes of gas retention produced significantly greater objective ab- dominal distention and subjective symptoms in patients with bloating than in healthy subjects. Exaggerated ab- dominal distention in patients was associated with failed contraction of the abdominal musculature and even par- adoxical relaxation of the internal oblique. 30 Animal studies have shown the relevance of viscerosomatic re- flexes. For instance, chemical irritation of the colon in rats induces abdominal wall contractions that are inhib- ited by colonic distention. 31 Abnormal viscerosomatic reflex activity may also participate in the mechanism of abdominal distention and muscular wall dystony in pa- tients with bloating. Abnormal perception. Abnormal perception re- lated to cognitive interpretation, abdominal wall sensa- tions, or visceral sensitivity is probably a key contribut- ing factor to the sensation of abdominal bloating. Some patients with a normal or simply fatty abdomen, but with a distorted interpretation of reality, may believe, sometimes to the point of the obsession, that their ab- domen is distended. Suarez et al 32 elegantly showed that people who regarded themselves as severely lactose in- tolerant and complained of bloating after consumption of even small amounts of dairy products, when specifically tested in a double-blind fashion, recorded negligible symptoms when consuming 250 mL of milk, whether it was lactose hydrolyzed or not. Hence, despite their con-

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viction, the experimental evidence proved that custom- ary milk-related symptoms in these patients had an imaginary origin. However, in other cases, altered perception seems to be due to genuine hypersensitivity with impaired mod- ulation of sensory signals. 33 Hence, the bloating sensa- tion could plausibly arise from a hypersensitive abdom- inal wall (for instance, in case of abdominal wall trauma, injuries, or scars) and may give the patient the sensation of increased abdominal wall tension, which is interpreted as bloating. This mechanism may contribute to postop- erative bloating after laparotomy. Alternatively, the sen- sation may arise from abdominal viscera. Indeed, visceral hyperalgesia has been well characterized in patients with functional gut disorders, such as functional dyspepsia and IBS. 33 In these patients, physiological stimuli in the gut, normally unperceived, may induce abdominal symp- toms—specifically, bloating. Furthermore, probing stimuli in the laboratory, such as gut distention, tend to reproduce the customary symptoms, depending on the area on the gut stimulated, and in some patients they induce the sensation of bloating. 33 The area of the gut affected by the sensory dysfunction depends on the clin- ical syndrome. 34 It has been shown that patients with IBS have increased sensitivity in the large and the small bowel. 3,35 By contrast, in patients with functional dys- pepsia, the stomach seems predominantly affected. Spe- cifically, in a group of patients with postprandial bloat- ing, gastric, but not duodenal, distentions induced an exaggerated perception and reproduced the customary bloating symptom. 36 It has been recently shown that in dyspeptic patients with postprandial symptoms (most of them with dysmotility-like dyspepsia and bloating- related symptoms), fundic distention reproduced the cus- tomary symptoms better than antral distention, whereas in dyspeptic patients with ulcer-like pain during fasting, antral distention replicated their usual symptoms more closely. 37 In other studies, using different selection cri- teria, intestinal hypersensitivity has been also shown in dyspeptic patients. 2 In patients with functional gut disorders, altered sen- sitivity combines with impaired control of gut motility, and both dysfunctions may interact to produce their symptoms. 33 This also applies to bloating. Basically, intraluminal trapping of contents causing focal disten- tion in a hypersensitive area would have a synergistic effect in inducing the symptoms. Indeed, minor motility disturbances that do not compromise function may be- come clinically relevant and produce symptoms only in the presence of altered gut perception.

Intra-abdominal contents. Abdominal distention

and bloating may be due to a pooling of intraluminal

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contents, tissue–water increment in viscera, or even free intraperitoneal content, such as ascites. Of all elements within the abdominal cavity, intraluminal gas seems to be the most versatile. Given the characteristic rapid fluctuations of nonorganic bloating, intestinal gas has been, and is still considered, the most likely candidate to explain bloating, whereas other putative causes have received much less attention. The gas hypothesis. Little is known about intes- tinal gas homeostasis, but it seems to be a finely regu- lated process. Many studies on different populations us- ing different methods have shown that despite the very large capacity of the entire gastrointestinal tract, the total volume of intraluminal gas amounts only to 100 – 200 mL. 18,38 40 This fairly constant and relatively low volume is astonishing if one considers the diverse and complicated processes of gas input and gas output. 14

background. Gas input results

from swallowing, chemical reactions, diffusion from blood, and bacterial fermentation. Gas output is achieved by eructation, absorption, bacterial consumption, and anal evacuation (Figure 2). Swallowing introduces a small amount of air into the stomach that is obviously much greater with gaseous bev- erages. Air in excess is eliminated from the stomach by belching, absorption, or emptying into the intestine. Chem- ical reactions—specifically, neutralization of acids and alka- lis in the upper gut—produce enormous quantities of car-

bon dioxide, 41 which is absorbed in the small bowel. In the colon, intraluminal bacteria play a major role in gas metabolism by both producing and consuming large amounts of intraluminal gases, and their activity consti- tutes the determinant of anal gas output. The net effect of colonic flora on gas metabolism depends on the bal- ance between gas-producing and gas-consuming micro- organisms, which varies considerably among individu- als. 14 The composition of the colonic microflora seems to be determined by early environmental conditions, but there may also be an adaptive component to alimentary habits later in life. 42,43 In approximately 90% of the general Western population, the colon harbors hydro- gen-producing bacteria that ferment undigested sub- strates, particularly carbohydrates, and release hydrogen and carbon dioxide. 44 46 Part of the colonic flora con- sumes intraluminal gases, and this may account for a considerable proportion of intraluminal gas dis- posal. 46 48 Both hydrogen and carbon dioxide are con- sumed in large quantities, and oxygen that reaches the colon is partly consumed by aerobic bacteria, thereby reducing the intraluminal content of oxygen. Most indi- viduals have a pool of sulfate-reducing bacteria that may be present throughout the colon. 46 These bacteria con-

Physiological

the colon. 4 6 These bacteria con- Physiological Figure 2. Intestinal gas metabolism. Gas input results

Figure 2. Intestinal gas metabolism. Gas input results from swallow- ing, chemical reactions, diffusion from blood, and bacterial fermen- tation. Gas output is achieved by eructation, absorption, bacterial consumption, and anal evacuation. Gas transit determines the time of exposure for diffusion of gases across the gut–blood barrier, as well as for bacterial consumption and, hence, may influence intestinal gas volume, composition, and tolerance.

sume hydrogen and release very small amounts of sulfur- containing gases (hydrogen sulfide and methanethiol) that are highly odoriferous. Approximately 30% of the population also has a pool of methanogenic bacteria in the left colon that consume large quantities of hydrogen and release methane. 46,47,49 51 Because of the competi- tion for hydrogen of both bacterial pools, in these sub- jects sulfate-reducing bacteria are circumscribed to the right colon. 46 Intraluminal gases tend to equilibrate with the gases in venous blood, depending on 3 factors: the partial pressure of each gas at both sides of the gut-blood barrier, its diffusibility, and the time of exposure of the gas to the diffusible surface, that is, the speed of gas transit. 14,52,53 Hence, highly diffusible gases present in large quantities within the gut, such as carbon dioxide in the small bowel, are readily absorbed. Oxygen, coming from swallowed air, is also absorbed from the small intestine to equilibrate with its partial pressure in blood. The diffusibility of nitrogen is much lower, but still, a

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September 2005 Figure 3. The gas challenge test. To evaluate gut propulsion, gas is infused at

Figure 3. The gas challenge test. To evaluate gut propulsion, gas is infused at a constant rate in the jejunum while anal gas outflow is measured. Objective abdominal distention and subjective sensations are simultaneously measured.

large proportion of nitrogen in flatus may derive from blood. Part of the gases produced by colonic bacteria diffuse into the blood and are excreted by breath, where they can be detected by gas chromatography. 14 Indeed, approximately half of the hydrogen evacuated follows this pathway. 54,55 This is the basis for the hydrogen and methane breath tests. The remaining gases are elimi- nated by the anus. The composition of intraluminal gas varies greatly along the gut, and the composition of the anal outflow reflects the net balance of multiple processes within the gut lumen. 46 During basal conditions, nitro- gen accounts for most of the volume in flatus, but after consumption of meals rich in fermentable carbohydrates, hydrogen, carbon dioxide, and methane (in producers) markedly rise and predominate. The amount of oxygen, the other major component in flatus, is fairly low (ap- proximately 10%). Various other gases are also present in trace quantities. 14 It is important to remember that gas transit deter- mines the time of exposure for diffusion of intraluminal gases across the gut– blood barrier, as well as for bacterial consumption, and, hence, may influence not only the volume of gas in the gut, but also the final composition of gas in flatus. 56 Intestinal gas transit and tolerance have been measured by using a gas challenge test. The test consists of an infusion of a mixture of gases, in various proportions to minimize absorption, into the jejunum while anal gas output is quantified (Figure 3). A dose– response study showed that most healthy subjects propel and evacuate as much gas as is infused, up to 30 mL/min, without discomfort. 17 Hence, gas transit is finely adapted to a very broad range of intestinal gas loads, but the type

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of motor activity that determines gas transit is not

known. Gas infusion does not induce detectable changes

in small-bowel intestinal motility recorded by manom-

etry. 57 In contrast, preliminary experiments with the barostat suggest that gas infusion induces tonic changes:

a contraction orad to the infusion site and a relaxation distal to the collection site. 58 Conceivably, movement and displacement of large masses of low-resistance gas are produced by changes in tonic activity and capacitance of the gut. 59 Gas boluses infused into the left colon have been shown to elicit forceful peristaltic contractions pre- ceding small gas expulsion, 60 but this type of phasic event has not been recorded during continuous gas in- fusion with a barostat located inside the rectum. 58 Hence, these phasic events could be a response to focal distention produced by abrupt intraluminal gas delivery.

Do Patients With Bloating Produce More Intestinal Gas?

As described previously, gas production is deter- mined by 2 main factors: the amount of fermentable foodstuffs that escape small-bowel absorption and enter the colon and the composition of the colonic flora. Thus, bloating may be a clinical feature of malabsorption dis- orders in which excessive amounts of unabsorbed sub- strates are fermented in the colon. Under special circum- stances, such as bacterial overgrowth, abnormal fermentation of foodstuffs may take place within the small bowel. In both of these situations, intestinal mal- absorption and bacterial overgrowth, bloating, and other gas symptoms usually constitute a minor part of the clinical presentation and, hence, are of limited clinical relevance. The real challenge in clinical practice is indi- viduals who complain of gas symptoms without detect- able abnormalities by conventional testing, that is, pa- tients with functional gastrointestinal disorders or, more precisely, with disorders of gastrointestinal function. 3 Whether some degree of nutrient malabsorption plays

a role in patients with functional bloating remains doubtful. Some studies suggest that the absorption ca- pacity of certain substrates in the small bowel is reduced in IBS patients. 61 63 However, other studies did not replicate these results. 64,65 Furthermore, it has been shown that people with proven lactose malabsorption tolerate 250 mL of milk without symptoms because the colon is able to deal with a certain amount of unabsorbed substrates via fermentation and absorption of short-chain fatty acids and absorption/consumption of gases. 32 Be- cause the definition of malabsorption is somewhat am- biguous, some investigators have explored the effect of exclusion diets on bloating. Again, the results have been inconclusive. 66 Furthermore, potential beneficial effects

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Table 2. Do Patients With Bloating Produce More Intestinal Gas?

Study

Method

Result

Lasser 67,68

Washout

No

Haderstorfer 69

Breath test

No

King 54

Calorimetry

Yes a

Pimentel 70

Breath test

Yes

a Hydrogen production was larger, but total gas (hydrogen plus meth- ane) production was not different from that in controls.

of excluding offending foodstuffs may not necessarily imply excess fermentation, because other possible patho- physiological mechanisms, such as allergic or atopic re- actions, may be involved. In a brilliant series of studies in the 1970s, Levitt 38 measured intestinal gas production by using a washout technique. In these studies, gas was measured by infusing argon into the intestine at a relatively high flow rate (40 mL/min) and recovering rectal gas. During fasting, with no nutrients arriving into the colon, gas production was similar in healthy subjects and IBS patients 67 ( Table 2).

A single study, published only in abstract form, reported

on postprandial gas production and showed no differ- ences between patients with bloating and healthy con- trols. 68 Evaluation of intestinal gas production by breath tests has yielded conflicting results (Table 2). In one study, intestinal hydrogen production was measured during waking hours for 7 days in IBS patients with bloating and in a group of healthy controls. Breath hydrogen concentration was found to be similar in both groups, despite significantly higher rates of bloating in patients

during the test period. 69 Furthermore, breath hydrogen concentrations did not correlate with symptoms of bloat- ing. In contrast, another study measuring total excretion

(breath plus anal) by indirect calorimetry showed that on

a standard diet, IBS patients excreted more hydrogen

than healthy subjects. This suggests that patients might have a hyperactive gas-producing colonic flora. 54 How- ever, some subjects produced methane as well as hydro- gen, and when the total volume excreted (hydrogen plus methane) was measured, no difference was found between both groups. A third research line showed that the proportion of abnormal lactulose breath tests in IBS patients was higher than that in healthy controls; this was attributed to small-bowel bacterial overgrowth be- cause oral neomycin normalized the breath test and reduced IBS symptoms more than did placebo. 70 This interpretation has been questioned: it has been argued that the reliability of the lactulose breath test to diagnose small-bowel bacterial overgrowth is uncertain, that the reported symptom response to antibiotic therapy was

relatively poor, and that the placebo response was un- usually low compared with other studies. 71 In any event, it is important to point out that increased intestinal gas production (or reduced consumption), be it due to mal- absorption, hyperactive colonic flora, or bacterial over- growth, would likely result in flatulence, but not neces- sarily bloating, because most healthy subjects are able to propel and evacuate very large gas loads without percep- tion of abdominal distention. 17,32 Hence, other factors should be also operating to produce bloating.

Intraluminal gas volume. In their early studies

with the washout technique, Lasser et al 67,68 showed that the amount and composition of intestinal gas in IBS patients was similar to that of healthy subjects (Table 3). Using a similar technique, we did not find significant differences in intestinal gas volume among patients com- plaining of abdominal bloating and healthy controls. 18,39 Two separate studies using plain abdominal radio- graphs 72,73 concluded that intra-abdominal gas content was larger in IBS patients than in healthy subjects (by 54% and 118%, respectively), but no significant corre- lation between gas content and symptoms was found. The method was shown to be technically reproducible, but changes in body position from upright to supine increased the estimated gas content by 67%. 72 A multi- center study using abdominal plain x-ray films taken 1 to 2 hours after breakfast or lunch found a larger (approx- imately 28%) total gas area in patients with IBS com- plaining of visible abdominal distention as opposed to patients who did not. 20 However, the correlation be- tween the abdominal gas content and the usual intensity of distention was poor. It is interesting to note that no difference was found between patients with and without abdominal distention when their symptoms were more typical of functional dyspepsia than of bloating. Because the total intraluminal gas volume in IBS, measured by independent studies, is only 100 –300 mL, 18,39,67,68 the percentage differences reported by these 3 studies would account for a relatively small difference in absolute vol- ume. In fact, a computed tomography study of intestinal gas could not detect significant differences between con-

Table 3. Do Patients With Bloating Have More Gas Volume Within the Gut?

Study

Method

Result

Lasser 67,68

Washout Washout Washout X-ray film X-ray film X-ray film Computed tomographic scan

No

Serra 39

No

Caldarella 18

No

Chami 72

Yes

Koide 73

Yes

Poynard 20

Yes

Maxton 21

No

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September 2005 Figure 4. Severity of symptoms induced by infusion of gas into the jejunum of

Figure 4. Severity of symptoms induced by infusion of gas into the jejunum of healthy subjects and patients complaining of excessive gas, abdominal pain, and bloating (reprinted with permission 67 ).

trols and patients with significant daytime girth incre- ments and bloating. 21 These data suggest that clinical bloating may not be simply the result of too much intestinal gas, but rather that other factors, ie, abnormal gas handling and distribution within the gut, may be involved. Impaired gut handling. Conventional studies on gut motility and transit of chyme have failed to detect consistent abnormalities that could explain bloating. However, studies on intestinal gas transit and tolerance suggest that patients with bloating have impaired intes- tinal handling of gas loads. 18,19,39,67 These gas transit studies may be of particular relevance by disclosing gut propulsive abnormalities that, in conjunction with sen- sory abnormalities, probably constitute the pathophysi- ological basis of bloating. Only a very small proportion of healthy individuals (approximately 15%) show impaired handling and in- creased perception of intestinal gas. 17 If this fraction of the otherwise healthy population were to be challenged with a gas overload, they would experience abdominal symptoms. 17 Likewise, increased colonic gas formation, experimentally induced by direct infusion of starch into the colon, produces abdominal symptoms only in a small fraction of healthy subjects. 74 A similar effect can be observed in the case of experimental malabsorption in- duced by amylase inhibitors. 75 These findings suggest that some people are prone to bloating, but this symp- tom may develop only under special circumstances. In their seminal work with the washout technique, Lasser et al 67 noted that a proportion of patients with bloating and related symptoms did not tolerate the pro- cedure (Figure 4), and in some of them the infused gas refluxed into the stomach. This was interpreted as an indication of some kind of gut motor dysfunction. Using a gas challenge test, we later showed that bloating pa-

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tients who met Rome II criteria for either IBS or func- tional bloating diagnoses had impaired transit and tol- erance of intestinal gas. 18,19,39 These patients retained gas and/or experienced abdominal discomfort in response to intestinal gas loads that are well tolerated by most healthy individuals (Figure 5). Furthermore, the gas challenge reproduced their customary symptoms. In these experiments, patients also developed objective ab- dominal distention that correlated with the volume of gas retained in their guts.

Mechanisms

of

impaired

gas

handling. The

mechanism of gas retention in such patients remains unknown. However, in healthy subjects, 2 mechanisms have been experimentally shown to be involved in intes- tinal gas retention: increased resistance to gas flow, mod- eled by self-restraint anal gas evacuation; and impaired intestinal propulsion, produced by glucagon-induced motor inhibition 76 ( Figure 6). By using the gas challenge test, it was shown that gas retention produced by im- paired propulsion induced objective abdominal disten- tion, which was well tolerated. However, when gas re- tention and objective distention were produced by increased resistance to flow, subjective abdominal com- plaints were much higher than when gas retention was induced by pharmacological inhibition of propulsion. Hence, abdominal distention depends largely on the volume of gas retained, but abdominal discomfort likely relates more directly to uncoordinated intestinal motility rather than to weak propulsion. Conceivably, small gas

rather than to weak propulsion. Conceivably, small gas Figure 5. Individual responses (perception and gas

Figure 5. Individual responses (perception and gas retention) to a gas challenge test (12 mL/min jejunal gas plus 0.5 kcal/min duode- nal lipids for 120 minutes). Healthy subjects tolerated the challenge test with low perception and retention. In contrast, patients who complained of bloating had impaired gut handling and fell outside the normal ranges. Reprinted with permission. 18

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AZPIROZ AND MALAGELADA GASTROENTEROLOGY Vol. 129, No. 3 Figure 6. Mechanisms of gut retention and intraluminal

Figure 6. Mechanisms of gut retention and intraluminal pooling. Re- tention can be due to a high-resistance barrier obstructing flow or to impaired propulsion. Symptom perception depends on the mecha- nism of retention: at the same volumes, flow obstruction produces more symptoms than impaired propulsion, but objective abdominal distention is similar.

bubbles pushed against high-resistance barriers may in- crease intestinal wall tension and produce symptoms. Furthermore, if several bubbles are trapped at different levels, perception would increase by spatial summation phenomena. 77 In healthy subjects, voluntary anal contraction has been shown to effectively retain gas. 76 In most bloated patients, gas retention and symptoms during the gas challenge test were similar whether gas was collected by an external cannula or by an intrarectal cannula that bypassed the anal gate. 39 Nevertheless, in clinical prac- tice, there are patients in whom the anus probably con- tributes to gas retention, either because of poor anal relaxation (functional outlet obstruction; see below) or voluntary inhibition of anal flatus as a result of social or psychological interferences. Reflex control. Further data suggest that im- paired gas transit in patients with unexplained bloating is the result of abnormal reflex control. Gas transit is regulated by viscerovisceral reflexes that operate along the gastrointestinal tract. 58,78 Intraluminal lipids dose- dependently delay gas transit and induce retention of exogenous gas loads. 19 Lipids seem more effective when infused into the ileum than into the duodenum, in consonance with the activation of the ileal brake mech- anism that regulates the transit of solid/liquid chyme. 79 By contrast, other reflexes speed gas transit. For instance, gastric distention produces an immediate evacuation of the endogenous gas present in the gut and accelerates the transit of exogenous gas loads, thus suggesting the re- lease of gastrocolic reflexes. 78 However, the gastrocolic reflex seems to be part of a more generalized reflex phenomenon, because distention performed at various levels of the gut, such as the duodenum or the rectum,

produces the same stimulatory effect. 58,78 Furthermore, focal gut distention antagonizes the inhibitory effect of lipids. 58,78 It has been shown that intestinal gas clearance is enhanced in the erect position 80 and during mild physical activity 81 ; this suggests that somatovisceral re- flexes may also participate in the regulation of intestinal gas transit. Conceivably, under physiological conditions, different types of reflexes interact to produce a net final effect. It has been shown that the slowing effect of lipids is up-regulated in patients with bloating, 19 whereas the accelerating effect of distention is markedly impaired. 82 Indeed, the gas challenge test, in conjunction with in- traluminal lipid infusion, provides a clear-cut distinction between IBS/bloated patients and healthy subjects: pa- tients retain large volumes of gas and or report symp- toms, thus indicating that gas propulsion may be inef- fective or symptomatic. 19

Which Area of the Gut Gives Rise to Bloating?

In healthy subjects, gas tolerance depends on the site of retention. In a model of gas retention modeled by infusion during blocked anal gas outflow, it was shown that similar volumes of gas retention produced signifi- cantly more abdominal symptoms with jejunal than with rectal gas infusion, whereas abdominal distention was similar. 83 Scintigraphic imaging using xenon 133 to label gas showed that gas infused into the jejunum predominantly accumulated in the small bowel and prox- imal colon, whereas gas infused per rectum largely accu- mulated in the distal colon. 83 These data indicate that gas-related symptoms are determined by intestinal gas distribution, whereas abdominal distention depends on the total volume of gas retained in the gut. Xenon-133 scintigraphy has been also used to inves- tigate segmental gas transit. In healthy individuals, total gut transit of gas was expeditious, and, interestingly, small-intestinal transit time was similar to colonic tran- sit time. Hence, in contrast to solids and liquids, the speed of intestinal gas clearance is equally determined by the passage time through the small-intestinal and colonic compartments. Using the gas challenge technique, we have shown that in patients with bloating, intestinal gas clearance is delayed because of impaired small-intestinal propulsion, whereas colonic transit is normal. 84 These data were confirmed by measuring the responses to gas directly infused at different levels of the gut via an intraluminal catheter. These responses showed that pa- tients retained gas infused into the jejunum, but not infused into the ileum or cecum. 84 Hence, the ileocolonic junction does not seem to be responsible for gas reten- tion, and, altogether, these data point toward the prox-

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imal small bowel, rather than the colon, as the source of symptoms in patients complaining of abdominal bloat- ing. Indeed, large amounts of carbon dioxide are physi- ologically produced from neutralization of acids in the proximal small bowel. 14,41 Carbon dioxide is rapidly absorbed into the bloodstream, but the luminal fraction may still overflow an incompetent intestine and produce symptoms. At the same time, it would seem reasonable to contem- plate other possibilities. For instance, patients with in- creased gas production who are unwilling or unable to expel excess gas may accumulate gas in the colon. Conceivably, the area of the gut in which bloating originates also depends on the clinical features. Indeed, postprandial bloating in dyspeptic patients may originate in the stomach. 36,37 Nor- mally, a meal largely accommodates in the proximal stom- ach, partly because antral filling induces a fundic relaxatory reflex. Additionally, when gastric emptying starts, intesti- nal nutrients induce enterofundic relaxatory reflexes that control the accommodation process over the postprandial period. Dyspeptic patients show impaired enterofundic and antrofundic relaxatory reflexes, and this may result in de- fective fundic accommodation, with distal displacement of intragastric contents and antral overload. 37 Furthermore, these patients show increased gastric perception, which also affects the antrum. 37 The mixed sensory motor dysfunction, leading to overdistention of a hypersensitive antrum, may explain the genesis of dyspeptic bloating independently of gas transit in the bowel.

Gas or No Gas: Which Is the Key Offending Element?

Gas transit studies in patients with unexplained bloating have evidenced a failure of gut propulsive mo- tility associated with increased perception, which, in some way, seems to play a pathophysiological role in their abdominal symptoms. However, the triggering fac- tor of bloating may not be invariably gas, but other element(s) of gut content. Bloating may be a prominent feature in the absence of increased gas production. Levitt et al 85 nicely showed the disparities between bloating and flatulence by observing the responses of healthy subjects to oral loads of either lactulose or 2 types of fiber (psyllium and methylcellu- lose). Lactulose, which is not absorbed in the small intestine and is fermented in the colon, releasing hydro- gen, induced flatulence, a sensation of rectal gas, and bloating. It is interesting to note that neither ferment- able (psyllium) nor nonfermentable (methylcellulose) fi- ber produced hydrogen release detectable by the breath test and did not induce flatulence or rectal gas sensation but still induced the sensation of abdominal bloating.

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The authors concluded that bloating associated with experimental fiber overload presumably reflects an in- creased intraluminal mass. Increased intestinal fluid content may also be an im- portant cause of bloating under some circumstances, for instance, in acute diarrheal conditions and perhaps in some instances of postprandial bloating. However, data on the transit of chyme in the small bowel in relation to bloating are inconsistent and show both accelerated 86 and delayed 87 transit. It has been hypothesized that the terminal ileum and the ileocolonic junction play a special role in the regulation of chyme transit. However, specific studies on ileocecal transit have also yielded contradic- tory results, 88,89 although chyme arrival to the cecum seems temporarily related to symptoms. 87 In some pa- tients, intestinal infusion of nutrients reproduces cus- tomary postprandial bloating and visible abdominal dis- tention. They may constitute a specific subset of patients, different from typical dyspepsia and IBS, but data avail- able on this condition are too scanty to allow even speculative conclusions. Abdominal bloating and distention may also derive from an expansion in extraluminal water content in the abdominal cavity. Vascular ingurgitation and visceral edema, conceivably under neurohormonal influences, could be involved in some forms (for instance, menstrual bloating), but this possibility has not been explored and stands only on a theoretical basis.

An Integrative Overview

Bloating may be produced by different mecha- nisms. The pathophysiology of bloating may be evident, for instance, in case of intra-abdominal volume incre- ment, but in most patients, the dysfunction that leads to bloating is more subtle and difficult to detect by con- ventional methods. Gas transit studies have evidenced that patients with bloating have impaired reflex control of gut handling of contents (Figure 7). Segmental pool- ing, either of gas or of solid/liquid components, may induce a bloating sensation, particularly in patients with altered gut perception. Gut stimuli induce visceroso- matic reflexes to adapt the abdominal wall to its content, and some data indicate that patients with bloating also have affected viscerosomatic reflexes that lead to abdom- inal wall dystony and abnormal protrusion (Figure 7).

Clinical Presentation

General Clinical Features

Abdominal bloating presents some characteristic and well-recognized features, but given the scarcity of

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AZPIROZ AND MALAGELADA GASTROENTEROLOGY Vol. 129, No. 3 Figure 7. Pathophysiology of bloating. Bloating may be

Figure 7. Pathophysiology of bloating. Bloating may be produced by intra-abdominal volume increment, but in most cases the dysfunction is more subtle and multifactorial. Impaired reflex control of gut han- dling of contents may result in segmental pooling and bloating sen- sations, particularly in patients with altered gut perception. Impaired viscerosomatic reflexes may lead to abdominal wall dystony and distention, even without major increments in intra-abdominal volume.

systematic investigations, data are mostly based on phy- sicians’ impressions. Recently, Whitehead’s group (per- sonal communication, December 2003) has initiated a large-scale study to characterize the diverse clinical pre- sentations of bloating; this study may yield useful infor- mation. Bloating, as with most functional gastrointestinal symptoms, is much more frequent in women than in men. 1,4 The severity of bloating may vary from very mild to severe and uncomfortable. 4 An important aspect of the anamnesis is to discriminate whether bloating is uncom- fortable/painful or whether the patient has associated but separate abdominal discomfort or pain. 7,8 It is also im- portant to record the patient’s own impression about the presence and severity of objective abdominal distention. 1 Bloating may be localized in the upper abdomen (some- times associated with dyspeptic symptoms) or in the lower abdomen, as part of IBS or related syndromes. Of course, a large overlap exists, and many patients describe bloating of the entire abdomen. 1,28 Bloating may be related to food intake. A substantial number of patients with bloating, up to 82%, describe that it develops or worsens in the early postprandial

period. 28 Some patients complain of even being unable to complete a full meal because of bloating. This effect is more pronounced when eating large and specially fatty meals. Postprandial bloating is a characteristic feature in specific subgroups of patients, such as those with dys- pepsia and binge eaters (see below). Some patients claim specific food intolerances in connection with bloating, 1 but the putative mechanism of the intolerance, or even whether this is real or imaginary, remains unclear. High- fiber foods or fiber supplements are frequently reported to worsen bloating, in consonance with the experimental findings of Levitt et al 86 described previously. Dairy products are frequently reported as deleterious, but only an undetermined fraction of these cases are due to gen- uine lactose intolerance, particularly when intolerance occurs in response to low quantities of dietary lactose. 32 Fatty foods and carbonated drinks are also frequently reported as offending. Both of these possibilities are supported by some experimental evidence, as described previously, but in some patients the relation may actu- ally be based on imaginary assumptions. Food intoler- ances may be related to atopic phenomena, but most likely this is an uncommon occurrence. Circadian variations are a common feature of bloat- ing. 1,21,28 In most patients, bloating progressively devel- ops during daily activity and tends to diminish or dis- appear after night rest. This probably has a physiological basis, because continuous measurement of girth in healthy subjects has shown that girth progressively in- creases during the day and returns to basal at night. 24,25 Meals are another factor that has been shown to increase girth in healthy subjects. 24 Girth is also larger in the upright position than in the supine position, 24 and like- wise, bloating tends to be alleviated by lying down, 28 which may point to a contribution from the abdominal musculature. Stress is reported by some patients (approx- imately one third in one study) to worsen bloating, 28 and patients tend to feel better when relaxed. 1 In some patients, bloating is associated with tiredness and diffi- culties sleeping, and these symptoms altogether impair quality of life. No clear mechanism has been elucidated. Some patients characteristically describe a rapid onset of bloating after a precipitating event: 60 seconds in 35% and 10 minutes in another 26%. 28 Such abrupt devel- opment would fit with either a vascular or muscular mechanism of bloating, but this remains purely specu- lative. Abdominal rumbling is a frequent associated fea- ture, but passing flatus or stool does not necessarily alleviate bloating. 1,28 In up to 40% of women, bloating gets worse before and during the menstrual period. 1,90 Furthermore, bloat- ing is one of the most frequent menstrual symptoms. 91

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Neurohormonal factors have been implicated, but the prevalence of bloating is the same in premenopausal and postmenopausal women. 1 Furthermore, some recent data indicate that in healthy women during the menstrual period, bloating may progressively increase during the day but is not paralleled by objective girth increments. 92

Clinical Conditions Associated With Bloating

Abdominal bloating in patients has various forms of clinical presentation, and conversely, in different clin- ical syndromes, bloating may be a prominent feature or even the primary complaint. Constipation. A considerable proportion of pa- tients who complain of bloating acknowledge that their abdominal symptom is related to bowel habit: bloating develops as days go by without a bowel movement and resolves with evacuation. Conversely, the incidence of bloating in constipated patients is very high— up to 80% in some studies. 10,11 Furthermore, when 12 healthy subjects were made constipated with loperamide, there was a significant increase in abdominal bloating, similar to that reported by constipated patients. 10 Reciprocally, effective laxative treatment in 24 constipated subjects markedly alleviated the prevalence and severity of their bloating. 10 In contrast to these symptomatic patients, in other cases, such as encopresis, fecal retention is well tolerated even for prolonged periods of time without any abdominal complaints. Plausibly, constipated patients with significant abdominal symptoms, including bloat- ing, have an irritable bowel with poor tolerance of the overload. Most of these constipation-predominant IBS patients with bloating have visible abdominal distention. 1 Diarrhea. In some patients, bloating is associated with loose stools, increased frequency of stools, or ur- gency. This subgroup would fall within the definition of diarrhea-predominant IBS, and in approximately one third of them, bloating is not associated with visible abdominal distention. 1 Patients with both bloating and diarrhea should be evaluated for possible lactose or fruc- tose intolerance. In this particular group, weight loss or nutritional deficiency should alert physicians to the pos- sibility of malabsorption or maldigestion. Indeed, ab- dominal bloating is a common clinical feature of organic diarrhea, such as malabsorptive diarrhea, infectious diar- rhea, and other types. Mechanisms involved—ie, inflam- mation, fluid or gas pooling, motor/sensory disturbances, carbohydrate fermentation, and so on—may not be sin- gularly involved in each condition but, rather, are mixed in various proportions. Unfortunately, clinicopatho-

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physiological relations have not been deeply investi- gated, and only conjectural conclusions are possible.

Irritable bowel syndrome. A series of studies in

the past few years have clearly shown the importance of bloating among the symptom spectrum of IBS. 1,7,11 In- deed, IBS is the clinical group in which the incidence and implications of bloating have been best established. Bloating-type symptoms are the most common abdom- inal complaint in patients with IBS and are reported by up to 96% of them. 7 Furthermore, 60% of IBS patients consider bloating their most bothersome abdominal complaint, even more so than abdominal pain, which is listed by only 29% of the patients. 7 Bloating also has a major effect on quality of life and impairs it more than does abdominal pain. 8,9 From a different perspective, it can be stated that a considerable proportion of patients with bloating fulfill IBS criteria. That is, bloating is a part (even the most apparent and bothersome part) of IBS, which by defini- tion is associated with disturbed bowel habits. Hence, in these patients, bloating may be associated with consti- pation, diarrhea, or both, thus sharing the characteristics of the groups described previously. Dyspepsia. Bloating is one of the integral symp- toms of dysmotility-like dyspepsia, and, indeed, a very large proportion of dyspeptic patients (54%–57%) re- ported they frequently felt “blown up.” 5 Visible abdom- inal distention has also been reported by 36% of patients with dyspepsia, vs 7% of healthy subjects. 6 In dyspepsia, bloating is often located in the upper abdomen, al- though, not surprisingly, given the common association between dyspepsia and IBS, it may also be diffuse. Stom- ach rumbling may be an associated symptom. Bloating in patients with dyspepsia tends to be precipitated by meals, 37 and some patients may even occasionally refrain from eating to prevent bloating. It is unclear whether these patients constitute a distinctive subgroup of dys- pepsia or whether they just use the term bloating to mean an imprecise sensation that could also be described as abdominal fullness, tension, pressure, or another similar term.

Eating disorders and obesity. Bloating is a fre-

quent clinical feature of eating disorders, such as binge eating 93,94 and anorexia, 95 and it is also related to body mass index and obesity. 93,96,97 Although healthy individ- uals may get bloated on occasion after overindulging in a large meal or in association with an overload of fer- mentable foodstuffs, such bloating tends to be relatively short, lasting a maximum of a few hours. Self-induced bloating is rarely a cause for concern or medical consul- tation, because the individual easily connects the bloat- ing sensation to excess feeding and subsequent sponta-

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neous relief. Important exceptions, however, are individuals who are so annoyed by postprandial bloating or who have such unrealistic expectations of overload tolerance that they may consult, not out of true concern about the significance of their symptom, but to obtain some form of preventive relief to allow them to overin- dulge without feeling uncomfortable. Aerophagia. Some patients complain of upper abdominal bloating that is alleviated by belching. The problem here is that during repetitive attempted belch- ing, the patient swallows air, thereby increasing the discomfort. When belching finally occurs, the sensation of bloating diminishes, leading the patient to errone- ously conclude that there is excess gas production in the stomach. 14,98 Frequently the underlying sensation of ab- dominal bloating/fullness in these patients is just a dys- peptic symptom that they misinterpret as gas, thus trig- gering the aerophagia/belching vicious circle. Flatulence. Some patients complain of excessive and/or odoriferous gas evacuation, which may become socially disabling. However, flatulence is neither neces- sarily nor frequently associated with bloating. The latter may occur only in response to increased gas production in susceptible individuals, who, as explained earlier in this review, manifest either impaired gas handling or in- creased visceral sensation, because the normal gut is extremely efficient in disposing of even extremely large gas loads. 17 An increased volume of flatus may be exceptionally related to air swallowing 99 and could theoretically also be related to impaired gas absorption or even diffusion from blood. However, by and large, both excessive and odor- iferous gas evacuation depend on the fermentation of undigested substrates by microflora in the colon. Odor is produced by trace elements, such as sulfur-containing gases and other yet-unidentified components. 46,100 Exces- sive volume may result from either increased production or impaired consumption by colonic bacteria. 14 It has been shown that some food components in the normal diet are incompletely absorbed in the small bowel and enter the colon, where they undergo fermentation by colonic bacteria and release gas. 101103 Incompletely ab- sorbed gas-producing food components include ferment- able dietary fiber, such as xylan and pectin 104,105 ; some types of dietary starch, for instance, in macaroni and white wheat bread 101 ; some oligosaccharides, such as raffinose and stachyose 106 108 ; and some sugars, such as sorbitol and fructose. 109,110 Other components of normal meals interfere with absorption of nutrients: for instance, fiber increases starch malabsorption, 111 and a pancreatic amylase inhibitor in beans antagonizes carbohydrate di- gestion and absorption. 75,112114 Mucoproteins of endog-

enous origin may also be fermented, and this would account for exaggerated gas evacuation during fasting in some patients. 115 In some patients, flatulence may be the consequence of a malabsorption disorder with an excess load of undi- gested substrates into the colon, but in such cases other manifestations of the primary disorder are usually appar- ent. Isolated flatulence is a more challenging clinical problem. It is known that gas evacuation in healthy subjects maintained on a similar diet may differ substan- tially depending on the composition of their colonic microflora. However, within subjects, gas output varies in relation to the diet and the amount of undigested residues arriving into the colon that serve as a gas- producing substrate to the colonic flora. 106,116 It has been shown that healthy subjects on a normal diet containing 200 g of beans evacuated 705 mL of gas per 24 hours, whereas with a fiber-free diet, gas evacuation was 214 mL. 117 In healthy subjects, the frequency of gas evacua- tion is variable (usually approximately 10 evacuations per day). 118 Flatulence is manifested by an increased number of evacuations, and objective recording in a diary may help to clarify the diagnosis in some cases. Organic diseases. Acute diarrheal diseases caused by salmonella and other enteropathogenic infections may be associated with severe bloating in the early stages of the clinical picture, even before the onset of diarrhea. Under these circumstances, the patient may experience sudden bloating, but the origin of the problem becomes quickly evident. Malabsorptive conditions, chiefly celiac disease and other mucosal small-bowel enteropathies, may produce significant bloating, with or without asso- ciated flatulence, and in that instance, the diagnosis may not be as readily apparent. Acute or subacute bowel ischemia from low-output cardiac failure or mesenteric insufficiency is a clinically important cause of bloating that is often associated with visible abdominal distention caused by dilated air-filled bowel loops. However, isch- emic bloating tends to be seen in hospitalized patients or in the context of major cardiovascular deficits. Bloating may also be a clinical complaint in patients with ascitis. Rarely, episodic abdominal bloating, pain, and disten- tion may be a feature of angioedema affecting the gut.

Management

As described previously, abdominal bloating is a multifactorial and multimorphic clinical condition. The management of these patients is mostly unclear, but in some subgroups, specific recommendations can be made.

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Aerophagia

Some patients with aerophagia can be retrained to control air swallowing, and even a clear pathophysiolog- ical explanation may suffice. However, when aerophagia and bloating are part of a dyspeptic syndrome, the ther- apeutic outcome may be poor, because the associated dyspeptic symptoms may not resolve after retraining.

Flatulence

Patients complaining of odoriferous and/or exces- sive gas evacuation usually benefit from a regimen that excludes gas-producing foodstuffs. Unfortunately, reli- able scientific information about diet-related gas metab- olism and evacuation is surprisingly scarce. Based on systematic and methodical observations of a patient who passed large amounts of flatus, a classification of food- stuffs depending on their gas-producing capacity was elaborated. 119 Very few controlled studies on specific foodstuffs have been later added to complement this information. 104,107,120 Extremely flatulogenic foodstuffs include beans, brussels sprouts, onions, celery, carrots, raisins, bananas, prune juice, apricots, wheat germ, and bagels. Moderately flatulogenic foodstuffs include pota- toes, eggplant, citrus fruit, apples, pastries, and bread. Low flatulogenic foodstuffs include meat, fowl, fish, eggs, some vegetables (lettuce, tomato, avocado, broccoli, cau- liflower, and asparagus), some fruits (cherries, grapes, and cantaloupe), rice, corn chips, popcorn, nuts, and choco- late. After 1 week on a “gas-free” diet, patients usually experience frank symptom relief. Orderly reintroduction of other foodstuffs helps the patient learn to identify the offending meal components and avoid them to prevent recurrence of the flatulence. Basically, these patients need to decide the “flatus price” they have to pay for each type of meal and whether it is worth it. Theoretically, a change in the composition of the colonic bacteria, reducing the activity of gas-producing flora and/or increasing the gas-consuming pool, should also help to reduce excess gas production. In practice, however, this approach has been generally unsuccessful. Recent attempts with antibiotics, prebiotics, and probi- otics have not produced satisfactory clinical results so far, particularly with respect to bloating. 121,122

Difficult Gas Evacuation With or Without Constipation

Rectal evacuation is physiologically achieved by a mild abdominal compression coupled with anal relax- ation. In case of abdominoperineal dyssynergia, inade- quate anal relaxation during straining is associated with impaired evacuation. 123,124 Functional outlet obstruction

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may produce a sensation of difficult gas evacuation, con- stipation, or both, but some patients also complain of bloating and other IBS-type abdominal symptoms. Prob- able pathophysiological mechanisms of bloating include fecal retention, increased time for fermentation, and pos- sibly impaired gas evacuation. Anal uncoordination can be resolved with biofeedback treatment, 123,124 and in some patients the abdominal symptoms fade when co- lonic retention is corrected. In some patients, constipa- tion is associated with upper abdominal bloating, which is aggravated by meals, thus mimicking a dyspeptic syndrome, and these symptoms may also improve if constipation resolves.

Pseudoobstruction With or Without Abdominal Pain

In some patients, bloating is very severe and mimics the clinical presentation of chronic or subacute intestinal pseudoobstruction when distention is promi- nent or of functional abdominal pain when the bloating sensation is intense and becomes painful. These rare patients require further evaluation, including intestinal manometry, to rule out intestinal neuropathy. 125

General Measures

The role of diet when bloating is not associated with flatulence remains unsettled. Fiber overload is now- adays a common occurrence in bloated patients. Fiber has been shown to worsen IBS symptoms; this phenomenon may be directly related to gas production or to the intraluminal overload. 126 Such patients usually benefit from removal of the extra fiber load. Except in docu- mented cases of malabsorption, there is no strong evi- dence to support the use of exclusion diets. Even patients with lactose malabsorption may tolerate normal amounts of dairy products in their diet. 32 Artificial sweeteners are incompletely absorbed in the small bowel and subse- quently fermented in the colon. Hence, excessive con- sumption of sugar-free candies and diet soft drinks could contribute to bloating, but this possibility has not been experimentally tested. In patients with a fatty, promi- nent abdomen, particularly if associated with recent weight gain, a low-calorie diet and weight reduction may improve the symptoms, although some patients are re- luctant to accept this solution. It is important to be aware that bloating may be due not only to gas, but also to solid and fluid intraluminal content, as well as to extraluminal fluid, for instance, in case of ascitis. Some experimental data have shown that exercise improves intestinal gas clearance in healthy subjects, 81 but its therapeutic value in patients with bloating has not been tested yet. Likewise, intestinal gas transit is

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more rapid in the upright position than in the supine position, 80 and this could play a potential role in the pathophysiology and management of immobilized pa- tients. Hypnosis has been shown to improve bloating in patients with IBS. 127 The rapid effect of hypnotic induction on objective abdominal distention suggests that this option may be particularly effective in pa- tients with bloating related to abdominal wall dystony. Nevertheless, hypnosis has been also shown to exert sensory motor influences on the gut. 127,128

Putative Pharmacological Therapies

Current treatment options have been recently reviewed elsewhere. 13 In some patients, bloating is just a feature of specific functional gastrointestinal disorders, particularly IBS and dyspepsia, and the treatment recommendations for these conditions would also apply here. Antidepressants seem effective in these disorders and may also improve bloating. 129

Prokinetics Versus Spasmolytics

Prokinetics and spasmolytics have been tradi- tionally used in the treatment of bloating. Both mod- ify the gut accommodation/propulsion balance, and it is not clear to what extent by enhancing one factor the other may be hampered, that is, whether the effects on gas clearance and abdominal symptoms may antago- nize. Experimental data in healthy subjects using the gas challenge test showed that intestinal gas retention produced fewer abdominal symptoms when glucagon, a potent relaxatory drug, was concomitantly adminis- tered, but the same objective abdominal distention remained. 76 Conversely, the administration of neostig- mine, a potent prokinetic drug, produced gas clear- ance in patients with intestinal gas retention, and this was followed by improvement of both abdominal symptoms and objective distention 18 ( Figure 8 ). The results with these drugs, used as a proof of concept, indicate that prokinetic and spasmolytic activity could have a role in the treatment of abdominal bloating. However, the experience with currently available drugs is not definitive. 130 Nevertheless, these data open the possibility that new compounds, particularly those with prokinetic activity, could be an effective treatment option. 131 Peppermint oil has been pro- posed to antagonize the bad odor of flatus, but its active principal ingredient, menthol, seems to act as a spasmolytic rather than a deodorant because of cal- cium channel blocker activity, with controversial ef- fects on bloating and flatulence. 132,133

ef- fects on bloating and flatulence. 1 3 2 , 1 3 3 Figure 8. Prokinetic

Figure 8. Prokinetic effects on intestinal gas retention, abdominal symptoms, and distention. Neostigmine administration during intestinal gas infusion in patients significantly reduced gas retention, abdominal symptoms, and distention as compared with saline administration (* P .05 for all). Reprinted with permis- sion. 18

Gas-Reducing Substances

Silicone derivates with surfactant properties have been postulated as antifoaming agents to improve gas absorption and evacuation from the gut, but their efficacy seems questionable. 134,135 Oral activated char- coal can adsorb and inactivate poisons in the gut, but it seems ineffective in reducing either the total gas volume or the fraction of odoriferous trace elements in flatus. 136 Enzymatic preparations are a popular therapy for gas symptoms and bloating, but effectivity data are scarce. 137,138

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Conclusion

Bloating is being increasingly recognized as an important clinical problem. Predictably, in the next few years this condition will elicit a concerted effort to understand its pathogenetic mechanisms and to develop effective therapy. In this review, we have proposed a framework for the investigation of bloating, taking into account both the clinical and the laboratory perspectives. Given the paucity of prior solid information on bloating, rather than providing answers, we aimed at formulating a comprehensive series of questions pertinent to its pathophysiology and polymorphic clinical presentation. We hope that this approach will stimulate the develop- ment of specific studies and, ultimately, make bloating a treatable condition.

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Received August 5, 2004. Accepted November 24, 2004. Address requests for reprints to: Fernando Azpiroz, MD, Digestive System Research Unit, Hospital General Vall d’Hebron, 08035 Barce- lona, Spain. e-mail: fernando.azpiroz@wol.es; fax: (34) 93-489-44-56. Supported in part by the National Institutes of Health (grant DK57064), the Spanish Ministry of Education (grant BFI 2002-03413), and the Instituto Carlos III (grant C03/02). The authors thank Gloria Santaliestra for secretarial assistance.