Small intestinal bacterial overgrowth: diagnosis and treatment

Small intestinal bacterial overgrowth (SIBO) is a clinical condition characterized by a malabsorption syndrome due to an increase in microorganisms within the small intestine. The main mechanisms restricting bacterial colonization in the upper gut are the gastric acid barrier, mucosal and systemic immunity and intestinal clearance. When these mechanisms fail, bacterial overgrowth develops. Diarrhea, steatorrhea, chronic abdominal pain, bloating and flatulence are common symptoms and are similar to those observed in irritable bowel syndrome. Breath tests (glucose and/or lactulose breath tests) have been proposed as a sensitive and simple tool for the diagnosis of bacterial overgrowth, being non-invasive and inexpensive compared to the gold standard represented by the culture of intestinal aspirates. Antibiotic therapy is the cornerstone of SIBO treatment. Current SIBO treatment is based on empirical courses of broad-spectrum antibiotics since few controlled studies concerning the choice and duration of antibiotic therapy are available at present.     

Blähungen und Reizdarmsyndrom (RDS)

Complaints such as abdominal bloating and distension are frequent in patients with functional intestinal diseases, including irritable bowel syndrome (IBS). Bloating or meteorism is defined as the subjective perception of abdominal distension and does not necessarily accompany objective abdominal distension. Disturbances of intestinal gas dynamics with hypersensitivity has been detected as a significant cause of bloating in IBS patients. Abdominal distension with no increase in bowel contents (e. g., by abnormal relaxation of the anterior abdominal muscles or phrenic dysregulation) is another important mechanism of bloating. The multilayered problem of abdominal bloating and distension, especially in IBS patients, requires individual strategies and complex therapies with the goal of normalizing intestinal activity and patient perception.     

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.     

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.     

Intestinal microbiota in short bowel syndrome

Short bowel syndrome (SBS) is the main cause of intestinal failure especially in children. The colon is a crucial partner for small intestine adaptation and function in patients who have undergone extensive small bowel resection. However, SBS predisposes the patient to small intestine bacterial overgrowth (SIBO), explaining its high prevalence in patients with this disorder. SIBO may significantly compromise digestive and absorptive functions and may delay or prevent weaning from total parenteral nutrition (TPN). Moreover, SIBO may be one of the causes of intestinal failure-associated liver disease, requiring liver transplantation in some cases. Traditional tests for assessing SIBO may be unreliable in SBS patients. Management of SIBO with antibiotic therapy as a first-line approach remains a matter of debate, while other approaches, including probiotics, offer potential based on experimental evidence, though only few data from human studies are available.     

Irritable bowel syndrome and small intestinal bacterial overgrowth:Meaningful association or unnecessary hype

Irritable bowel syndrome(IBS)is a common condition characterized by abdominal pain or discomfort,bloating,and altered stool form and passage.Small intestinal bacterial overgrowth(SIBO)is a condition in which there is overgrowth of bacteria in small bowel in excess of 105colony forming units per milliliter on culture of the upper gut aspirate.Frequency of SIBO varied from 4%-78%among patients with IBS and from 1%-40%among controls.Higher frequency in some studies might be due to fallacious criteria[postlactulose breath-hydrogen rise 20 PPM above basal within 90 min(early-peak)].Glucose hydrogen breath test(GHBT)has a low sensitivity to diagnose SIBO.Hence,studies based on GHBT might have under-estimated frequency of SIBO.Therefore,it is important to analyze these studies carefully to evaluate whether the reported association between IBS and SIBO is over or under-projected.This review evaluates studies on association between SIBO and IBS,discordance between different studies,their strength and weakness including methodological issues and evidence on therapeutic manipulation of gut flora on symptoms of IBS.     

What are the effects of proton pump inhibitors on the small intestine?

Generally, proton-pump inhibitors(PPIs) have great benefit for patients with acid related disease with less frequently occurring side effects. According to a recent report, PPIs provoke dysbiosis of the small intestinal bacterial flora, exacerbating nonsteroidal anti-inflammatory drug-induced small intestinal injury.Several meta-analyses and systematic reviews have reported that patients treated with PPIs, as well as post-gastrectomy patients, have a higher frequency of small intestinal bacterial overgrowth(SIBO) compared to patients who lack the aforementioned conditions.Furthermore, there is insufficient evidence that these conditions induce Clostridium difficile infection. At this time, PPI-induced dysbiosis is considered a type of SIBO. It now seems likely that intestinal bacterial flora influence many diseases, such as inflammatory bowel disease, diabetes mellitus, obesity, nonalcoholic fatty liver disease, and autoimmune diseases.When attempting to control intestinal bacterial flora with probiotics, prebiotics, and fecal microbiota transplantation, etc., the influence of acid suppression therapy, especially PPIs, should not be overlooked.     

Management of small intestinal bacterial overgrowth

Similar to that of all mammals, the human gastrointestinal tract is colonized by 100 trillion bacteria shortly after birth. Remarkably, in the open-tube arrangement of the intestine, this bacterial population is tightly compartmentalized to the distal gut. Contamination of the small intestine with colonic bacterial flora or small intestinal bacterial overgrowth (SIBO) has been understood previously as a complication of uncommon conditions associated with obvious intestinal stasis. However, SIBO has also been found in 78% to 84% of patients with the common condition of irritable bowel syndrome (IBS). In this paper, the diagnostic and treatment approaches to SIBO are reconsidered within the larger framework of the patient with IBS.     

Irritable bowel-type symptoms in spontaneous and induced constipation.

The prevalence and severity of irritable bowel symptoms was assessed by systematic questioning in 44 constipated volunteers, most of whom had documented slow intestinal transit. All but two had one or more of the following: passage of mucus, rectal dissatisfaction, bloating, and abdominal pain relieved by defecation. All the symptoms were more prevalent than in 17 normal volunteers or in 301 apparently healthy people studied previously. When 12 normal subjects were made constipated with loperamide all developed one or more irritable bowel symptoms. When 24 constipated subjects received effective laxative treatment the prevalence and severity of these symptoms fell markedly. The findings suggest that in some subjects the slowing down of intestinal transit is associated with irritable bowel symptoms.     

Anismus: a marker of multi-site functional disorders?

PURPOSE: This study was undertaken to assess the clinical significance of anismus in patients who complain of constipation. PATIENTS AND METHODS: Thirty control subjects and 93 consecutive patients complaining of functional constipation took part in the study. Colonic transit time study and anorectal manometry were performed. Questions about depression and urinary and sexual diseases were added to a questionnaire based on the Rome II criteria, and visual analog scales about four items (constipation, diarrhoea, abdominal bloating and abdominal pain). RESULTS: Constipated patients have lower threshold sensation volume, lower constant sensation volume, and lower maximum tolerable volume than controls. Thirty-seven patients (40%) were found to have anismus, based on anorectal manometry. No significant difference was found between constipated patients with anismus and constipated patients without anismus, using anorectal manometry. Constipated patients had longer colorectal transit time than controls, but neither total nor segmental colonic transit time was correlated with the presence or absence of anismus. In patients with anismus, a higher frequency of oesophageal symptoms, dysmotility-like dyspepsia, aerophagia, functional bowel disorders, functional abdominal pain, soiling, and dyschezia was found. In addition, a higher frequency of urinary complaints, sexual complaints, and depression was found. Anismus was associated with increased awareness of constipation, abdominal bloating, and abdominal pain, but not with diarrhoea.     

Impaired reflex control of intestinal gas transit in patients with abdominal bloating

BACKGROUND: Patients with abdominal bloating and distension exhibit impaired transit of intestinal gas which may lead to excessive gas retention and symptoms. Furthermore, we have previously shown that intestinal gas transit is normally accelerated by rectal distension. We hypothesise that in patients with functional bloating this modulatory mechanism fails and impairs gas transit. METHODS: In 12 healthy subjects and eight patients with abdominal bloating we compared, by paired studies, the effect of rectal versus sham distension on intestinal gas transit. Gas was infused into the jejunum (12 ml/min) for three hours with simultaneous perfusion of lipids into the duodenum (Intralipid 1 kcal/min) while measuring evacuation of gas per rectum. RESULTS: In healthy subjects, duodenal lipid infusion produced gas retention (409 (68) ml) which was prevented by rectal distension (90 (90) ml; p<0.05 v sham distension). In contrast, rectal distension in patients with abdominal bloating failed to reduce lipid induced gas retention (771 (217) ml retention during rectal distension v 730 (183) ml during sham distension; NS; p<0.05 v healthy controls for both). CONCLUSION: Failure of distension related reflexes impairs intestinal gas propulsion and clearance in patients with abdominal bloating.     

小肠细菌过度生长和胃食管反流病

胃食管反流病（GERD）患者多伴有其它功能性胃肠病症状。特别是与肠易激综合征（IBS）和小肠细菌过度生长（SIBO）的症状存在高度的重叠性。胃食管反流病患者中小肠细菌过度生长的发病率明显高于对照组,反之,小肠细菌过度生长患者中胃食管反流病的发病率也明显高于对照组。小肠细菌过度生长的一个明显特点是在小肠过度增生的细菌酵解碳水化合物产生氢气和二氧化碳,在有产甲烷菌存在的情况下还会产生甲烷。过量的气体会通过三种机制导致胃食管反流：1.导致腹胀和腹内压增加,压迫胃内容物逆行进入食管;2.部分气体在压力作用下上行,通过胃和食管溢出;3.引起反射性下食管括约肌松弛。了解胃食管反流病和小肠细菌过度生长的关系有助于为寻找胃食管反流病的致病原因,制定合理的治疗胃食管反流病提供新的方向。     

Prokinetic effects in patients with intestinal gas retention

BACKGROUND & AIMS: We have previously shown that patients with irritable bowel syndrome (IBS) have impaired transit of intestinal gas loads. Because abnormal gas retention can be experimentally reproduced in healthy subjects by pharmacological inhibition of gut motility, we hypothesized that impaired gas transit and retention can be reciprocally corrected by pharmacologically stimulating intestinal propulsion. METHODS: In 28 patients with abdominal bloating (14 IBS, 14 functional bloating) and in 14 healthy subjects, gas evacuation and perception of jejunal gas infusion (12 mL/min) were measured. After 2 hours, in 20 patients we tested the effect of intravenous neostigmine (0.5 mg) vs. intravenous saline administered blindly and randomly at a 1-hour interval. RESULTS: After 2 hours of gas infusion, patients with IBS and functional bloating alike exhibited significant gas retention (418 +/- 86 mL), abdominal symptoms (2.7 +/- 0.5 score), and objective distention (8 +/- 2 mm girth increment), in contrast to healthy controls, who experienced none (46 +/- 102 mL retention, 0.4 +/- 0.3 symptom score, and 3 +/- 1 mm distention; P < 0.05 for all). Neostigmine produced immediate clearance of gas retained within the gut (603 +/- 53 mL/30 minutes vs. 273 +/- 59 mL/30 minutes after saline; P < 0.05) and by 1 hour reduced gas retention (by 373 +/- 57 mL), abdominal symptoms (by 1.1 +/- 0.5 score), and distention (by 6 +/- 1 mm; P < 0.05 for all), whereas intravenous saline produced no effects. CONCLUSIONS: In patients with intestinal gas retention, pharmacological stimulation of intestinal propulsion improves gas transit, abdominal symptoms, and distention.     

Relationship of Bloating to Other GI and Menstrual Symptoms in Women with Irritable Bowel Syndrome

This report examines the relationships between bloating and other symptoms in young women with irritable bowel syndrome (IBS), using both retrospective and daily diary measures of symptoms. Of the 195 IBS women, 147 (75%) reported retrospectively that they often feel bloated and distended. Across-women analyses of both retrospective and daily diary data show that bloating is most strongly associated with constipation, abdominal pain, and intestinal gas. Within-woman analyses of daily symptoms also show a strong association of bloating with abdominal pain and intestinal gas (i.e., abdominal pain and intestinal gas are higher on days when bloating is higher) but only a weak association with constipation. Bloating is strongly associated with uterine cramping and breast tenderness, but only when perimenses days are included in the analysis. In conclusion, bloating is a very common symptom in women with IBS that is most strongly related to abdominal pain and intestinal gas but may be confounded with menses-associated symptoms.     

The prevalence of small intestinal bacterial overgrowth in non-surgical patients with chronic pancreatitis and pancreatic exocrine insufficiency (PEI)

Background

Small intestinal bacterial overgrowth (SIBO) is a condition characterised by symptoms similar to pancreatic exocrine insufficiency (PEI) in chronic pancreatitis patients. SIBO is thought to complicate chronic pancreatitis in up to 92% of cases; however, studies are heterogeneous and protocols non-standardised. SIBO may be determined by measuring lung air-expiration of either hydrogen or methane which are by-products of small bowel bacterial fermentation of intraluminal substrates such as carbohydrates. We evaluated the prevalence of SIBO among a defined cohort of non-surgical chronic pancreatitics with mild to severe PEI compared with matched healthy controls.

Bloating and functional gastro-intestinal disorders: Where are we and where are we going?

Bloating is one of the most common and bothersome symptoms complained by a large proportion of patients. This symptom has been described with various definitions, such as sensation of a distended abdomen or an abdominal tension or even excessive gas in the abdomen, although bloating should probably be defined as the feeling (e.g. a subjective sensation) of increased pressure within the abdomen. It is usually associated with functional gastrointestinal disorders, like irritable bowel syndrome, but when bloating is not part of another functional bowel or gastrointestinal disorder it is included as an independent entity in Rome III criteria named functional bloating. In terms of diagnosis, major difficulties are due to the lack of measurable parameters to assess and grade this symptom. In addition, it is still unclear to what extent the individual patient complaint of subjective bloating correlates with the objective evidence of abdominal distension. In fact, despite its clinical, social and economic relevance, bloating lacks a clear pathophysiology explanation, and an effective management endorsement, turning this common symptom into a true challenge for both patients and clinicians. Different theories on bloating etiology call into questions an increased luminal contents (gas, stools, liquid or fat) and/or an impaired abdominal empting and/or an altered intra-abdominal volume displacement (abdomino-phrenic theory) and/or an increased perception of intestinal stimuli with a subsequent use of empirical treatments (diet modifications, antibiotics and/or probiotics, prokinetic drugs, antispasmodics, gas reducing agents and tricyclic antidepressants). In this review, our aim was to review the latest knowledge on bloating physiopathology and therapeutic options trying to shed lights on those processes where a clinician could intervene to modify disease course.     

Intestinal Involvement in Systemic Sclerosis: A Clinical Review

Systemic sclerosis (SSc) is a chronic systemic disease characterized by microvasculopathy, autoantibodies, and extensive fibrosis. Intestinal involvement is frequent in SSc and represents a significant cause of morbidity. The pathogenesis of intestinal involvement includes vascular damage, nerve dysfunction, smooth muscle atrophy, and fibrosis, causing hypomotility, which leads to small intestinal bacterial overgrowth (SIBO), malabsorption, malnutrition, diarrhea, pseudo-obstruction, constipation, pneumatosis intestinalis, and fecal incontinence. Manifestations are often troublesome and reduce quality of life and life expectancy. Assessment of intestinal involvement includes screening for small intestine hypomotility, malnutrition, SIBO, and anorectal dysfunction. Current management of intestinal manifestations is largely inadequate. Patients with diarrhea are managed with low-fat diet, medium-chain triglycerides, avoidance of lactulose and fructose, and control of bacterial overgrowth with antibiotics for SIBO. In diarrhea/malabsorption, bile acid sequestrant and pancreatic enzyme supplementation may help, and nutritional support is needed. General measures are applied for constipation, and intestine rest plus antibiotics for pseudo-obstruction. Fecal incontinence is managed with measures for associated SIBO, or constipation, and with behavioral therapies. Pneumatosis intestinalis is usually an incidental finding that does not require any specific treatment. Immunomoduation should be considered early in intestinal involvement. Multidisciplinary approach of intestinal manifestations in SSc by gastroenterologists and rheumatologists is required for optimum management.     

Small intestine bacterial overgrowth and irritable bowel syndrome-related symptoms： Experience with Rifaximin

AIM： TO estimate the prevalence of small intestinal bacterial overgrowth （SIBO） in our geographical area （Western Sicily, Italy） by means of an observational study, and to gather information on the use of locally active, non-absorbable antibiotics for treatment of SIBO.
METHODS： Our survey included 115 patients fulfilling the Rome II criteria for diagnosis of irritable bowel syndrome （IBS）; a total of 97 patients accepted to perform a breath test with lactulose （BTLact）, and those who had a positive test, received Rifaximin （Normix , Alfa Wassermann） 1200 mg/d for 7 d; 3 wk after the end of treatment, the BTLact was repeated.
RESULTS： Based on the BTLact results, SIBO was present in about 56% of IBS patients, and it was responsible for some IBS-related symptoms, such as abdominal bloating and discomfort, and diarrhoea. 1-wk treatment with Rifaximin turned the BTLact to negative in about 50% of patients and significantly reduced the symptoms, especially in those patients with an alternated constipation/diarrhoea-variant IBS.
CONCLUSION： SIBO should be always suspected in patients with IBS, and a differential diagnosis is done by means of a ＂breath test＂. Rifaximin may represent a valid approach to the treatment of SIBO.     

The role of fermentable carbohydrates and beverages in the symptomatology of functional gastrointestinal disease

Objectives: The pathophysiology behind functional gastrointestinal disease (FGID) has not been defined, but an intestinal accumulation of fermentable short-chain carbohydrates (FODMAPs) is thought to be involved. A restricted coffee intake is recommended. The aim was to investigate if symptoms of FGID were associated with intake of certain foods (including FODMAPs), as well as beverages (including coffee and tea).

Method and materials: Data were used from participants, age range 45–75 years, who had answered the EpiHealth questionnaire about their background factors, health status and intake of food and beverages. After exclusion of organic bowel diseases, 16,840 participants remained. The impact of food and beverages on functional abdominal pain, functional bloating, functional constipation and functional diarrhea were examined by adjusted binary logistic regression.

Results: Wholemeal bread (Swedish cracker) (OR: 1.361; 95% CI: 1.001–1.851) and white bread (low fiber content) (OR: 1.527; 95% CI: 1.075–2.169) were associated with constipation, whereas soft wholemeal bread (high fiber content) was associated with diarrhea (OR: 1.601; 95% CI: 1.040–2.463). Cheese was associated with bloating (OR: 1.460; 95% CI: 1.004–2.123). A high tea intake was associated with abdominal pain (p for trend?=.003), bloating (p for trend?=?.039) and diarrhea (p for trend <.001), whereas coffee intake was associated with a decreased risk of abdominal pain (p for trend =?.002) and bloating (p for trend?=?.007). High soda intake associated with abdominal pain and bloating and juice with diarrhea.

Conclusion: There are weak associations between intake of grain and dairy products and FGID symptoms. Tea is associated with increased risks, whereas coffee is associated with lower risks, of FGID symptoms.     

Irritable bowel syndrome and bloating

Gaseous symptoms in irritable bowel syndrome (IBS) including eructation, flatulence, and bloating occur as a consequence of excess gas production, altered gas transit, abnormal perception of normal amounts of gas within the gastrointestinal tract, or dysfunctional somatic muscle activity in the abdominal wall. Because of the prominence of gaseous complaints in IBS, recent investigations have focussed on new insights into pathogenesis and novel therapies of bloating. The evaluation of the IBS patient with unexplained gas and bloating relies on careful exclusion of organic disease with further characterisation of the underlying condition with directed functional testing. Treatment of gaseous symptomatology in IBS should be targeted to pathophysiologic defects whenever possible. Available therapies include lifestyle alterations, dietary modifications, enzyme preparations, adsorbents and agents which reduce surface tension, treatments that alter gut flora, and drugs that modulate gut transit.