Role of colonic fermentation in the perception of colonic distention in irritable bowel syndrome and functional bloating.

BACKGROUND & AIMS: Bloating represents a frequent gastrointestinal symptom, but the pathophysiologic mechanism responsible for its onset is still largely unknown. Patients very frequently attribute the sensation of bloating to the presence of excessive bowel gas, but not all patients with gas-related symptoms exhibit increased intestinal production of gas. It is therefore possible that other still unrecognized mechanisms might contribute to its pathophysiology. Our aim was to evaluate whether a subgroup of patients affected by functional abdominal bloating presents hypersensitivity to colonic fermentation. METHODS: Sixty patients affected by functional gastrointestinal disorders (11 functional bloating, 36 constipation-predominant, and 13 diarrhea-predominant irritable bowel syndrome) and moderate to severe bloating took part in the study. Twenty sex- and age-matched healthy volunteers were enrolled as a control group. All the subjects underwent a preliminary evaluation of breath hydrogen excretion after oral lactulose. Then, on a separate day, an evaluation of sensitivity thresholds at rectal level was performed with a barostat before and after the induction of colonic fermentation with oral lactulose. A control test with electrolyte solution was also performed. RESULTS: Both breath hydrogen excretion and mouth-to-cecum transit time did not differ between the 4 groups studied. Neither electrolyte solution nor lactulose modified sensitivity thresholds in healthy volunteers. In low hydrogen producers, basal perception and discomfort thresholds were similar to high hydrogen producers, but after lactulose both perception and discomfort thresholds were significantly reduced only in low hydrogen producers. CONCLUSIONS: A subgroup of patients with functional gastrointestinal disorders and moderate to severe bloating might have hypersensitivity to products of colonic fermentation.     

Treatment of functional bowel disorders: is there room for antibiotics?

Small bowel bacterial overgrowth is a syndrome associated with a broad range of predisposing conditions, characterized by the presence of pathological amounts or types of bacteria at the level of the small bowel, clinically evident with a spectrum of symptoms such as diarrhea, flatulence, abdominal pain and bloating. Some of these symptoms are very common complaints in patients suffering from functional bowel disorders (FBDs). Although the pathophysiological mechanisms responsible for FBDs are certainly multifactorial and not yet completely understood, several pieces of evidence suggest that an increased metabolic activity of intestinal bacteria is responsible for gas-related intestinal symptoms in a large subgroup of patients. In addition, byproducts of colonic fermentation might be able to trigger symptoms in those patients displaying visceral hypersensitivity. Targeting enteric bacteria with antibiotics therefore represents a logical approach to FBDs. Although systemic antimicrobials have been mostly used in the past, the availability of poorly absorbed antibiotics like rifaximin, being safe and effective, has represented a step forward in the treatment of this challenging clinical condition.     

A randomized double-blind placebo-controlled trial of rifaximin in patients with abdominal bloating and flatulence

AIMS: To study the efficacy of rifaximin, a nonabsorbable antibiotic, in relieving chronic functional symptoms of bloating and flatulence. METHODS: Randomized double-blind placebo-controlled trial consisting of three 10-day phases: baseline (phase 1), treatment with rifaximin 400 mg b.i.d. or placebo (phase 2), and post-treatment period (phase 3). Primary efficacy variable was subjective global symptom relief at the end of each phase. A symptom score was calculated from a symptom diary. Lactulose H2-breath test (LHBT) was performed at baseline and end of study. RESULTS: One hundred and twenty-four patients were enrolled (63 rifaximin and 61 placebo). Baseline characteristics were comparable and none had an abnormal baseline LHBT. Rome II criteria were met in 58.7% and 54.1%, respectively. At the end of phase 2, there was a significant difference in global symptom relief with rifaximin versus placebo (41.3% vs 22.9%, p = 0.03). This improvement was maintained at the end of phase 3 (28.6% vs 11.5%, p = 0.02). Mean cumulative and bloating-specific scores dropped significantly in the rifaximin group (p < 0.05). Among patients with IBS, a favorable response to rifaximin was noted (40.5% vs 18.2%; p = 0.04) persisting by the end of phase 3 (27% vs 9.1%; p = 0.05). H2-breath excretion dropped significantly among rifaximin responders and correlated with improvement in bloating and overall symptom scores (p = 0.01). No adverse events were reported. CONCLUSIONS: Rifaximin is a safe and effective treatment for abdominal bloating and flatulence, including in IBS patients. Symptom improvement correlates with reduction in H2-breath excretion. Future trials are needed to examine the efficacy of long-term or cyclic rifaximin in functional colonic disorders.     

Efficacy of rifaximin, a nonabsorbed oral antibiotic, in the treatment of small intestinal bacterial overgrowth

INTRODUCTION: Rifamixin is an orally administrated, nonabsorbed antibiotic whose utility in eradication of small intestinal bacterial overgrowth (SIBO) is currently being evaluated. PURPOSE: The aim of this study was to investigate efficacy and safety of rifaximin in relieving symptoms and normalizing the glucose breath test (GBT) in patients with SIBO. METHODS: Symptom score assessment, consisting of frequency and severity of bloating, gas, abdominal pain, and bowel movements and the GBT were performed before and after treatment with rifaximin 800 mg/d for 4 weeks. SUBJECTS: Twenty consecutive symptomatic patients (16 women and 4 men; mean age, 47.8 years; range, 19 to 85 years) who had a positive GBT were prospectively studied in an open-labeled fashion. Fourteen patients (70.0%) presented with diarrhea, 3 (15.0%) with bloating and gas, and 3 (15.0%) with constipation as the dominant symptom. RESULTS:: Eleven patients were hydrogen producers, 8 exclusively methane, and 1 patient produced both gases by the GBT. Among patients with diarrhea, 12 of 14 (85.7%) reported improvement in symptom scores of more than 50%; 1 between 25% and 50%, 1 had no response after 4 weeks of rifamixin. Among patients with bloating and gas or constipation as the main symptom: 2 of 6 (33.3%) had improvement between 50% and 75%; 3 (50%) had 25% to 50% improvement, and 1 (16.7%) had no response. Repeat GBT at the end of the 4 weeks showed that 54.5% of hydrogen formers and 50.0% of methane producers were eradicated, and there was a significant reduction (P <0.05) in the area under the concentration-time curve and peak values. No adverse effects were observed. CONCLUSIONS: Rifaximin in a dose of 800 mg per day for 4 weeks: 1) was safe and effective treatment in reducing symptoms in patients with SIBO of multiple etiologies, especially when diarrhea was the dominant symptom; and 2) normalized the GBT in approximately 50% of patients. Data support a future therapeutic role for rifaximin in SIBO.     

Microbiota and irritable bowel syndrome

Irritable bowel syndrome (IBS) is a multifactorial disease during which the pathophysiological role of the gut microbiota has been recently highlighted. In almost 20% of the patients, IBS is clearly a post-infectious IBS as a consequence of an acute bacterial gastroenteritis. Some papers have reported an abnormal colonic fermentation in IBS patients that could explain symptoms such as bloating and be one of the factors triggering visceral hypersensitivity. More recently, significant differences in the composition of both the luminal and mucosa-associated microbiota have been reported between both IBS patients and healthy controls and IBS subgroups while some arguments exist for a small intestinal overgrowth in a subset of IBS patients. All these arguments for a deleterious role of the gut microbiota lead to the actual discuss to consider new therapeutic options, including mainly pre- and probiotics and maybe antibiotics.     

肠易激综合征患者结肠黏膜辣椒素受体、P物质和肥大细胞变化的研究

背景:腹痛是一般人群中最常见的肠道症状,肠易激综合征(IBS)患者的腹痛症状更为严重、频繁,然而其发生机制尚不明确。目的:分析IBS患者结肠黏膜中与痛觉和内脏高敏感相关的辣椒素受体VR1、P物质(SP)和肥大细胞(MC)的变化,探讨IBS患者内脏高敏感和腹痛的发生机制。方法:39例IBS患者[腹泻型IBS(IBS-D)21例,便秘型IBS(IBS-C)18例]和18名健康人纳入研究。受检者于结肠镜检查时在回盲部和乙状结肠取活检,行VR1、SP免疫组化染色和MC改良甲苯胺蓝染色。结肠镜检查前采用视觉模拟评分法行疼痛评分。结果:IBS患者乙状结肠VR1、回盲部和乙状结肠SP免疫反应阳性细胞以及回盲部MC数量显著多于正常对照组(P0.01),IBS-D与IBS-C组间则无明显差异。IBS-D和IBS-C患者的腹痛评分均与VR1呈正相关(r=0.553,P=0.009;r=0.592,P=0.010)。结论:IBS患者结肠黏膜中VR1、SP免疫反应阳性细胞和MC数量显著增多,VR1与腹痛评分呈正相关,三者可能参与了IBS患者内脏高敏感和腹痛的发生机制。     

Bloating and intestinal gas

Opinion statement The most common symptoms associated with intestinal gas are eructation, flatulence, abdominal bloating, and distention. Aerophagia is an uncommon cause of eructation in which repetitive air swallowing results in belching, abdominal distention, and increased flatus. Few therapies have been shown to be effective in treating these symptoms. Eructation can be treated by decreasing excessive air swallowing. Occasionally, behavioral therapy and psychotherapy are employed. Bloating, distention, and other gas-related symptoms are common in functional gastrointestinal disorders; however, their pathophysiology is poorly understood. Additionally, evidence supporting the use of various available therapies in treating gas-related symptoms is either absent or poor. Dietary therapy may be effective in patients with excessive gas production. Excessive gas production, identified by increased flatus, may benefit from a low-carbohydrate diet. Many patients with gas-related symptoms have normal gas production but may have either impaired gas transport or transit through the gut or visceral hypersensitivity. Few studies have addressed the treatment of impaired gas transport.     

Sensation of bloating and visible abdominal distension in patients with irritable bowel syndrome

OBJECTIVES: Abdominal bloating and distension are common symptoms of irritable bowel syndrome (IBS). The postulated pathophysiological mechanisms underlying these symptoms include increased production, retention, or perception of gas or luminal contents. The aims of this study were to prospectively compare the prevalence of, and clinical factors related to, bloating and distension in an IBS patient population. METHODS: A total of 714 consecutive patients who met Rome I criteria for IBS were prospectively surveyed, and were classified as having bloating alone (B) or bloating and distension (B+D) based on a comprehensive bowel symptom questionnaire. GI, extraintestinal, and psychological symptoms, as well as health-related quality of life measures were also assessed using validated survey instruments. RESULTS: A total of 542 IBS patients (76%) who reported abdominal bloating were studied. Of these, 132 patients fulfilled criteria for the B group, whereas 410 patients fulfilled criteria for the B+D group. There was a significantly different gender distribution in the B and B+D groups (female:male ratios, 1.4:1 and 2.8:1, respectively p < 0.02). There was also a significantly different bowel habit subgroup distribution, with a greater predominance of constipation in B+D group and of diarrhea in the B group (p < 0.03). Both groups were similar in other clinical parameters, including progressive worsening of symptoms during the day, and relief by passing stool or gas. Both bloating and distension worsened when other abdominal symptoms worsened. Abdominal distension was associated with greater symptom severity and less diurnal variation in symptoms, and was less often perceived as associated with food intake. CONCLUSIONS: Bloating and visible abdominal distension may arise from two distinct but interrelated physiological processes. Although the sensation of bloating may be related to enhanced sensitivity to visceral afferent stimulation, abdominal distension in more severely affected patients may be related to triggering of a visceromotor reflex affecting the tone of abdominal wall muscles.     

Effect of tegaserod on recto-sigmoid tonic and phasic activity in constipation-predominant irritable bowel syndrome

OBJECTIVES: In irritable bowel syndrome (IBS), the modulation of neural pathways may be altered and we have recently shown that postprandial recto-sigmoid tone modification is impaired. On pathophysiological grounds, we do not know whether this alteration may have a role in symptom onset and, in particular, whether an effective drug, such as tegaserod, can improve this response together with symptom severity. METHODS: Twenty-two female patients with constipation-predominant IBS (IBS-C), diagnosed according to Rome II criteria, were studied. All subjects underwent an evaluation of the presence and severity of IBS symptoms and the recto-sigmoid barostat test to measure fasting and postprandial recto-sigmoid tone and phasic contractility. They were then randomly assigned to receive either tegaserod 6 mg b.i.d (12 patients) or placebo tablets (10 patients) for 4 wk, according to a double-blind protocol. Symptom assessment and recto-sigmoid tone and contractility were re-evaluated at the end of the treatment. RESULTS: Both symptom severity and postprandial modification of recto-sigmoid tone improved only in the tegaserod group and a significant correlation was evident between the improvement of bloating and the improvement of postprandial recto-sigmoid tone modification. No effect of tegaserod on recto-sigmoid motility index or correlation between motility index and symptom improvement was evident. CONCLUSIONS: In IBS-C female patients, the administration of tegaserod improves symptom severity and is accompanied by an improvement of recto-sigmoid tone response to a meal.     

Irritable bowel syndrome: focus on otilonium bromide

Irritable bowel syndrome is a prevalent and chronic disorder, characterized by recurrent abdominal pain/discomfort, bloating and altered bowel habits. This condition affects an estimated 10–15% of the population worldwide and impacts heavily on a patient's daily life and ability to work, as well as healthcare resource utilization. Drug therapy aimed at correcting the primary symptoms of diarrhea/constipation/bloating may have little effect on abdominal pain, which results from visceral hypersensitivity. Smooth muscle relaxants or antispasmodics decrease the tone and contractility of intestinal smooth muscle, effectively managing abdominal pain. Otilonium bromide has been widely used worldwide and has been found to be safe and well tolerated, and superior to placebo for the reduction of symptoms and the prevention of symptom relapse in patients with irritable bowel syndrome.     

Antibiotic Treatment of Constipation-Predominant Irritable Bowel Syndrome

Background

The antibiotic rifaximin is used to treat non-constipated irritable bowel syndrome (IBS). Methane production is associated with constipation and its severity in constipation-predominant IBS (C-IBS). A previous retrospective study suggested that rifaximin and neomycin was superior to neomycin alone in improving symptoms in methane-positive subjects.

Aims

To determine the effectiveness of neomycin alone or with rifaximin in improving symptoms in methane-positive C-IBS subjects.

Methods

A double-blind, randomized, placebo-controlled trial was performed from 2010 to 2013 at three tertiary care centers. Subjects aged 18–65 with C-IBS (Rome II criteria) and breath methane (>3 ppm) meeting the inclusion and exclusion criteria were recruited. Subjects completed a baseline symptom questionnaire rating the severity of abdominal and bowel symptoms on a visual analog scale and were randomized to receive neomycin and placebo or neomycin and rifaximin for 14 days. Symptom severity was assessed by weekly questionnaire for 2 weeks of therapy and 4 additional weeks of follow-up.

Results

Thirty-one subjects (16 neomycin and placebo, 15 neomycin and rifaximin) were included in the intention-to-treat analysis. Constipation severity was significantly lower in the neomycin and rifaximin group (28.6 ± 30.8) compared to neomycin alone (61.2 ± 24.1) (P = 0.0042), with greater improvement in constipation (P = 0.007), straining (P = 0.017) and bloating (P = 0.020), but not abdominal pain. In the neomycin and rifaximin group, subjects with methane <3 ppm after treatment reported significantly lower constipation severity (30.5 ± 21.8) than subjects with persistent methane (67.2 ± 32.1) (P = 0.020).

Conclusions

Rifaximin plus neomycin is superior to neomycin alone in improving multiple C-IBS symptoms. This effect is predicted by a reduction in breath methane.     

Does oral α-galactosidase relieve irritable bowel symptoms?

Objective. Abdominal bloating is reported by a majority of irritable bowel syndrome (IBS) patients. Excess colonic fermentation may cause gaseous symptoms. Several foodstuffs contain oligosaccharides with an α-galactosidic linkage that is resistant to mammalian hydrolases. Assisted hydrolysis by exogenous α-galactosidase enzyme (AG) could offer a way of controlling IBS symptoms by reducing colonic fermentation and gas production. The aim of this study was to assess the effect of AG on symptom severity and quality of life in IBS patients with abdominal bloating or flatulence. Methods. A total of 125 subjects with IBS received AG or placebo at meals for 12 weeks. IBS-Symptom Severity Score (IBS-SSS) and quality of life (QoL) were assessed at baseline, during the treatment and at 4-week follow-up. Results. AG showed a trend toward a more prominent decrease in IBS-SSS. The responder rate at week 16 was higher for the AG group. No difference was detected in QoL between AG and placebo groups. A total of 25 patients (18 in AG group and 7 in placebo group, p = 0.016) withdrew from the study. Abdominal pain and diarrhea were more often reported as reason for withdrawal in AG group. Conclusions. We found no evidence to support the use of AG routinely in IBS patients. Improvement of clinical response at 4-week follow-up may suggest a long-term effect of unknown mechanism, but could also be attributed to non-responder drop out. Gastrointestinal (GI) side effects may be a coincidence in this study, but irritation of GI tract by AG administration cannot be excluded.     

New insights into visceral hypersensitivity--clinical implications in IBS

A subset of patients with IBS have visceral hypersensitivity and/or somatic hypersensitivity. Visceral hypersensitivity might have use as a clinical marker of IBS and could account for symptoms of urgency for bowel movements, bloating and abdominal pain. The mechanisms that lead to chronic visceral hypersensitivity in patients who have IBS are unclear. However, several working models may be considered, including: nociceptive input from the colon that leads to hypersensitivity; increased intestinal permeability that induces a visceral nociceptive drive; and alterations in the expression of microRNAs in gastrointestinal tissue that might be delivered via blood microvesicles to other target organs, such as the peripheral and/or central nervous system. As such, the chronic visceral hypersensitivity that is present in a subset of patients with IBS might be maintained by both peripheral and central phenomena. The theories underlying the development of chronic visceral hypersensitivity in patients with IBS are supported by findings from new animal models in which hypersensitivity follows transient inflammation of the colon. The presence of somatic hypersensitivity and an alteration in the neuroendocrine system in some patients who have IBS suggests that multisystemic factors are involved in the overall disorder. Thus, IBS is similar to other chronic pain disorders, such as fibromyalgia, chronic regional pain disorder and temporomandibular joint disorder, as chronic nociceptive mechanisms are activated in all of these disorders.     

Origin of gas retention and symptoms in patients with bloating

BACKGROUND & AIMS: Patients reporting abdominal bloating exhibit impaired tolerance to intestinal gas loads. The aim of this study was to identify the gut compartment responsible for gas retention. METHODS: In 30 patients predominantly reporting abdominal bloating (24 with irritable bowel syndrome and 6 with functional bloating) and 22 healthy subjects, gas (nitrogen, carbon dioxide, and oxygen) was infused into the intestine for 2 hours while measuring rectal gas outflow. First, in 12 patients and 10 healthy subjects, gas transit (24 mL/min jejunal infusion labeled with 74 MBq bolus of 133 Xe) was measured by scintigraphy. Second, in groups of patients and healthy subjects, the effects of gas infusion (12 mL/min) in the jejunum versus ileum, jejunum versus cecum, and jejunum versus sham infusion (n=6 each) were compared by paired tests. RESULTS: In patients, total gut transit of gas was delayed (50% clearance time, 33 +/- 4 min vs 23 +/- 4 min in healthy subjects; P <.05) owing to impaired small bowel transit (50% clearance time, 20 +/- 2 min vs 12 +/- 3 min in healthy subjects; P <.05), whereas colonic transit was normal (50% clearance time, 13 +/- 2 min vs 11 +/- 2 min in healthy subjects; not significant). Furthermore, jejunal gas infusion in patients was associated with gas retention (329 +/- 81 mL vs 88 +/- 79 mL in healthy subjects; P <.05), whereas direct ileal or colonic infusion was not (61 +/- 103 mL and -143 +/- 87 mL retention, respectively). CONCLUSIONS: In patients reporting bloating, the small bowel is the gut region responsible for ineffective gas propulsion.     

Rifaximin for the treatment of diarrhea-predominant irritable bowel syndrome

Irritable bowel syndrome (IBS) is a chronic, functional bowel disorder characterized by abdominal pain or discomfort and altered bowel habit. The pathophysiology is unclear, but may include altered gut motility, visceral hypersensitivity, abnormal central pain processing, chronic low-grade intestinal inflammation, or disturbances in the gut microbiome. These etiological mechanisms, alongside environmental factors such as stress and anxiety, vary between individuals and represent potential targets for treatment. Rifaximin is a poorly absorbed oral antibiotic proposed to act on the gut microenvironment, used in the treatment of travelers’ diarrhea and hepatic encephalopathy. Clinical trials suggest the drug can reduce global IBS symptoms and improve bloating, abdominal pain, and stool consistency in some patients with non-constipated IBS, leading to Food and Drug Administration approval in the United States. This article considers the pharmacology of rifaximin, the evidence for its use in IBS, and the safety and tolerability of the drug.     

Intestinal gas and bloating: effect of prokinetic stimulation

BACKGROUND:  It is unknown if abdominal bloating is attributable to excess abdominal gas or improved by a prokinetic agent.
AIMS:  To assess abdominal gas content in functional abdominal bloating and to ascertain the effect of a prokinetic agent on intestinal gas symptoms in these patients.
METHODS:  In 20 patients, intra-abdominal gas content and symptoms were quantified before and during treatment with pyridostigmine (30 mg/8 hp. o) in this randomized, placebo-controlled, double-blind study. Daily symptoms were quantified for 5 days before and 10 days during treatment, and abdominal gas volume was quantified by CT imaging before and at the fourth day of treatment. A CT scan was also obtained in 10 healthy subjects.
RESULTS:  Before treatment, the total volume of intestinal gas was similar in patients (112 ± 18 mL) and in healthy controls (116 ± 20 mL). The treatment-induced change in total and regional intestinal gas volume was not significantly different between pyridostigmine (−4 ± 18 mL; mean ± SEM) and placebo (0 ± 15 mL). However, pyridostigmine reduced the severity of bloating from 3.3 ± 0.3 to 2.6 ± 0.4 ( P < 0.05), whereas placebo did not (3.2 ± 0.3 vs 3.0 ± 0.4), although the change did not reach statistical difference across groups.
CONCLUSION:  In patients complaining of functional bloating, the volume and distribution of intestinal gas, measured on nonselected days, is comparable to asymptomatic subjects. Prokinetic stimulation improves bloating sensation without detectable changes in gas content.     

Abdominal pain impacts quality of life in women with irritable bowel syndrome

OBJECTIVES: Patients with irritable bowel syndrome (IBS) report lower health-related quality of life (QoL) as compared to healthy controls. The aims of this analysis were to describe which IBS symptoms were rated on a daily diary as most distressing/severe by IBS women, and determine which IBS symptoms were most predictive of lower QoL and have the greatest impact on daily life. METHODS: This report is a secondary analysis of prospective and retrospective symptom severity and impact data, collected on 242 women with IBS, aged 18-48, who were studied between 1997 and 2004. RESULTS: On the daily diary, intestinal gas was the most frequent IBS symptom with subjects reporting at least minimal intestinal gas on 74% of days and moderate or worse severity on 27% of days. Abdominal pain occurred at least minimally on 62% of days. Diarrhea was the least common. Across women, abdominal pain was most strongly related to life impact variables and QoL, followed by intestinal gas and bloating. Analysis of day-to-day variation within women showed that abdominal pain was most strongly correlated with daily life impact variables and constipation had the weakest correlation. While diarrhea had a lower correlation with life impact, this was due to the low prevalence of diarrhea. When it occurs, diarrhea has a large impact. Partial correlation analysis showed that the impact of diarrhea is independent of abdominal pain. CONCLUSION: Abdominal pain is the most disruptive IBS symptom. Diarrhea also has an independent and significant impact when it occurs, especially in those with diarrhea-predominant IBS.     

Treatment of excessive intestinal gas

Opinion statement Symptoms of excessive intestinal gas may be related to eructation, excessive or odoriferous gas evacuation, and/or abdominal symptom attributed to gas retention. Patients with aerophagia and excessive eructation can be usually retrained to control air swallowing, but if present, basal dyspeptic symptoms may remain. Patients with excessive or odoriferous gas evacuation may benefit from a low-flatulogenic diet. In patients with gas retention due to impaired anal evacuation, anal incoordination can be resolved by biofeedback treatment, which also improves fecal retention, and thereby reduces the time for fermentation. Other patients complaining of abdominal symptoms that they attribute to intestinal gas, probably have irritable bowel syndrome or functional bloating, and their treatment options specifically targeting gas-related symptoms basically include prokinetics and spasmolytics. There is no consistent evidence to support the use of gas-reducing substances, such as charcoal or simethicone.     

Bacterial concepts in irritable bowel syndrome

An overlap of symptoms in irritable bowel syndrome (IBS) exists across subtype groups. Symptoms include intestinal gas, diarrhea, dyspepsia, bloating, abdominal pain, and constipation. The unifying symptom may be excessive intestinal gas as a by-product of intestinal microbial fermentation. Abnormal fermentation of food takes place when gut microbes expand proximally into the small intestine instead of being confined predominantly to the colon. Such proximal expansion of indigenous gut microbes or small intestinal bacterial overgrowth (SIBO) may lead to activation of host mucosal immunity and an increase in intestinal permeability to result in flu-like extra-intestinal symptoms that accompany the classic IBS symptoms of altered bowels. The presence of methane on lactulose breath testing is associated with constipation-predominant IBS. Antibiotic therapy may be appropriate to treat underlying SIBO in IBS patients. Seventy-five percent improvement of IBS symptoms was reported in a double-blind, placebo-controlled study once antibiotics succeeded in treating bacterial overgrowth. Once a good clinical response and normalization of the lactulose breath test are achieved, a prokinetic agent may be used to stimulate phase III of interdigestive motility to delay relapse of bacterial overgrowth.     

Intestinal Gas Production from Bacterial Fermentation of Undigested Carbohydrate in Irritable Bowel Syndrome

The relationship between abdominal pain and bowel gas from bacterial fermentation of undigested carbohydrate was investigated in nine patients with irritable bowel syndrome (IBS), six lactose malabsorbers, and 11 asymptomatic controls. All subjects took breath samples and marked analog scales for abdominal pain, bloating, and psychological stress hourly during all waking hours for 7 days. Breath samples were analyzed for hydrogen concentration within 3 days, and the concentration was corrected for storage time. Symptoms of pain and bloating were significantly more common in IBS patients than in lactose malabsorbers or normal controls, and pain was significantly correlated with bloating in IBS patients. Breath hydrogen concentration was similar in all three groups, and breath hydrogen was not correlated with pain ratings in IBS patients. Thus, abdominal pain may be related to bloating from gastrointestinal gas, but bacterial fermentation cannot be the cause of such gas. The most likely source is swallowed air. This study also demonstrates the feasibility of monitoring hydrogen production in the bowel in field studies by having subjects collect hourly breath samples.