The Influence of Small Intestinal Bacterial Overgrowth in Digestive and Extra-Intestinal Disorders.

Small intestinal bacterial overgrowth (SIBO) is a condition hallmarked by an increase in the concentration of colonic-type bacteria in the small bowel. Watery diarrhea, bloating, abdominal pain and distension are the most common clinical manifestations. Additionally, malnutrition and vitamin (B12, D, A, and E) as well as minerals (iron and calcium) deficiency may be present. SIBO may mask or worsen the history of some diseases (celiac disease, irritable bowel disease), may be more common in some extra-intestinal disorders (scleroderma, obesity), or could even represent a pathogenetic link with some diseases, in which a perturbation of intestinal microbiota may be involved. On these bases, we performed a review to explore the multiple links between SIBO and digestive and extra-intestinal diseases.

Reduced interstitial cells of Cajal and increased intraepithelial lymphocytes are associated with development of small intestinal bacterial overgrowth in post-infectious IBS mouse model.

OBJECTIVE: Intestinal dysmotility and immune activation are likely involved in the pathogenesis of small intestinal bacteria overgrowth (SIBO) in irritable bowel syndrome (IBS). We aimed at investigating the role of interstitial cells of Cajal (ICC) and intestinal inflammation in the development of SIBO using a post-infectious IBS (PI-IBS) mouse model. MATERIALS AND METHODS: NIH mice were randomly infected with Trichinella spiralis. Visceral sensitivity and stool pattern were assessed at 8-weeks post-infection (PI). Intestinal bacteria counts from jejunum and ileum were measured by quantitative real-time PCR to evaluate the presence of SIBO. ICC density, intraepithelial lymphocytes (IELs) counts, and intestinal cytokine levels (IL1-ß, IL-6, toll-like receptor-4 (TLR-4), IL-10) in the ileum were examined. RESULTS: PI-IBS mice demonstrated increased visceral sensitivity compared with the control group. One-third of the PI-IBS mice developed SIBO (SIBO+/PI-IBS) and was more likely to have abnormal stool form compared with SIBO negative PI-IBS (SIBO-/PI-IBS) mice but without difference in visceral sensitivity. SIBO+/PI-IBS mice had decreased ICC density and increased IELs counts in the ileum compared with SIBO-/PI-IBS mice. No difference in inflammatory cytokine expression levels were detected among the groups except for increased TLR-4 in PI-IBS mice compared with the control group. CONCLUSIONS: Development of SIBO in PI-IBS mice was associated with reduced ICC density and increased IELs counts in the ileum. Our findings support the role of intestinal dysmotility and inflammation in the pathogenesis of SIBO in IBS and may provide potential therapeutic targets.

Prevalence of small intestinal bacterial overgrowth in Chinese patients with Parkinson's disease.

Parkinson's disease (PD) is associated with gastrointestinal motility abnormalities that could favor the occurrence of small intestinal bacterial overgrowth (SIBO). The aim of the study was to assess the prevalence of SIBO in Chinese patients with PD and the potential impact of SIBO on gastrointestinal symptoms and motor function. 182 consecutive Chinese patients with PD patients and 200 sex, age, and BMI-matched subjects without PD were included. All participants underwent the glucose breath test to assess SIBO. We examined the associations between factors and SIBO with logistic regression using SPSS. Fifty-five of the 182 PD patients were SIBO positive (30.2 %; 95 % CI 23.5-36.9 %) compared with 19 of 200 in the control group (9.5 %; 95 % CI 5.4-13.6 %); the difference was statistically significant (P < 0.0001; OR 4.13; 95 % CI 2.34-7.29). Motor fluctuations present was higher in the PD patients with SIBO than in the patients without SIBO (70.9 vs. 45.7 %; P = 0.002). Multivariate analysis showed that disease duration, Hoehn and Yahr stage, Unified PD Rating-III score, Unified PD Rating-IV score, and Non-Motor Symptoms Scale score were the factors associated with the SIBO-positive status in PD patients. SIBO was highly prevalent in PD, and nearly one-third was detected. SIBO was associated with worse gastrointestinal symptoms and worse motor function. Further studies are needed to specify the reasons underlying SIBO and worse motor function in PD.

Small Intestine Bacterial Overgrowth and Environmental Enteropathy in Bangladeshi Children.

UNLABELLED: Recent studies suggest small intestine bacterial overgrowth (SIBO) is common among developing world children. SIBO's pathogenesis and effect in the developing world are unclear. Our objective was to determine the prevalence of SIBO in Bangladeshi children and its association with malnutrition. Secondary objectives included determination of SIBO's association with sanitation, diarrheal disease, and environmental enteropathy. We performed a cross-sectional analysis of 90 Bangladeshi 2-year-olds monitored since birth from an impoverished neighborhood. SIBO was diagnosed via glucose hydrogen breath testing, with a cutoff of a 12-ppm increase over baseline used for SIBO positivity. Multivariable logistic regression was performed to investigate SIBO predictors. Differences in concomitant inflammation and permeability between SIBO-positive and -negative children were compared with multiple comparison adjustment. A total of 16.7% (15/90) of the children had SIBO. The strongest predictors of SIBO were decreased length-for-age Z score since birth (odds ratio [OR], 0.13; 95% confidence interval [CI], 0.03 to 0.60) and an open sewer outside the home (OR, 4.78; 95% CI, 1.06 to 21.62). Recent or frequent diarrheal disease did not predict SIBO. The markers of intestinal inflammation fecal Reg 1ß (116.8 versus 65.6 µg/ml; P = 0.02) and fecal calprotectin (1,834.6 versus 766.7 µg/g; P = 0.004) were elevated in SIBO-positive children. Measures of intestinal permeability and systemic inflammation did not differ between the groups. These findings suggest linear growth faltering and poor sanitation are associated with SIBO independently of recent or frequent diarrheal disease. SIBO is associated with intestinal inflammation but not increased permeability or systemic inflammation. IMPORTANCE: A total of 165 million children worldwide are considered stunted, which is associated with increased risk of death prior to age 5 years and cognitive disability. Stunting has, in part, been attributed to the presence of environmental enteropathy. Environmental enteropathy is a poorly understood condition leading to chronic intestinal inflammation. It has been postulated that small intestine bacterial overgrowth contributes to the pathogenesis of environmental enteropathy as overgrowth has been associated with intestinal inflammation and micronutrient malabsorption when it develops in other clinical contexts. This study confirms the finding that overgrowth occurs at high rates in the developing world. This is the first study to show that overgrowth is associated with intestinal inflammation and linear growth delay in this setting and is the first to examine why children with no known gastrointestinal dysfunction develop overgrowth from the developing world environment.

The biopsy pathology of non-coeliac enteropathy.

Tropical sprue (TS) is a malabsorption syndrome of presumed infectious aetiology that affects residents of (or visitors to) the tropics. The histological changes of TS are similar to those of coeliac disease, with increased intraepithelial lymphocytes being central to both. Unlike in coeliac disease, however, a completely flat small bowel biopsy is uncommon in TS. TS typically involves the terminal ileum, whereas coeliac disease does not. Small intestinal bacterial overgrowth (SIBO) has been defined as an increase in number and/or a change in the type of bacteria in the upper gut. Conditions that predispose to SIBO are largely those that decrease or interfere with small bowel motility. The mucosal histology is variable, and may include modest villous blunting accompanied by increased lamina propria and epithelial inflammation. Autoimmune enteropathy (AE) is a family of rare diseases that share common themes such as immunodeficiency states and autoantibodies. AE cases typically have marked villous atrophy similar to that in fully developed coeliac disease, but they lack the intense surface epithelial lymphocytosis. Apoptosis and lymphocyte infiltration at the base of the crypts, crypt abscesses and cryptitis are also seen. Patients with anti-goblet cell antibodies can have a lack of goblet cells, endocrine cells, and Paneth cells.

All that glitters is not always gold.

Biopsies from the second part of the duodenum are routinely performed in patients with unintentional weight loss. When villous atrophy and an increased intraepithelial lymphocytosis are detected, the commonest cause of it is coeliac disease. Severe villous atrophy with increased intraepithelial lymphocytosis (Marsh IIIc) is highly specific for coeliac disease. However, coeliac disease with this presentation is very rare. Milder abnormalities such as Marsh I-II (microscopic enteritis) and Marsh IIIa are not specific for coeliac disease and could occur in other conditions like those listed in the discussion. We present the case of a 74-year-old woman who, after being diagnosed with seronegative coeliac disease, failed to improve on a gluten-free diet. We discuss the differential diagnosis of coeliac disease and the possible alternative causes for villous blunting, paying particular attention to the diagnosis of small intestinal bacterial overgrowth.

High prevalence of small intestinal bacterial overgrowth in patients with morbid obesity: a contributor to severe hepatic steatosis.

BACKGROUND: With the increasing prevalence of obesity, non-alcoholic fatty liver disease (NAFLD) has become a major cause of liver diseases. Small intestinal bacterial overgrowth (SIBO) could be related to NAFLD. Our aim was to determine the prevalence of SIBO and its relationship with liver lesions in morbidly obese patients. METHODS: A glucose hydrogen (H(2)) breath test (positive if fasting breath H(2) concentration > 20 ppm and/or an increase of > 10 ppm over baseline within the first 2 h) was performed in obese patients referred for bariatric surgery (body mass index [BMI] > 40 kg/m(2) or > 35 in association with comorbidities) and in healthy non-obese subjects. In obese patients, a surgical liver biopsy was performed. RESULTS: One hundred and forty-six patients (129 women, age [mean+/-SE]: 40.7 +/- 11.4 years) were prospectively included in the study. The mean BMI was 46.1+/-6.4 kg/m(2). A liver biopsy was available in 137 patients and a breath test in 136. The frequency of positive breath tests was higher in obese patients (24/136, 17.1%) than in healthy subjects (1/40, 2.5%; P=0.031). In the univariate analysis, SIBO was not associated with clinical variables, but tended to be associated with more frequent severe hepatic steatosis (26.3 vs. 10.3%, P=0.127), whereas the frequency of sinusoidal or portal fibrosis, lobular necrosis and non-alcoholic steatohepatitis (NASH) were not different. In the multivariate analysis, SIBO (P=0.005) and the presence of a metabolic syndrome (P=0.006) were independent factors of severe hepatic steatosis. CONCLUSION: In morbidly obese patients, bacterial overgrowth prevalence is higher than in healthy subjects and is associated with severe hepatic steatosis.

[20-year old woman with diarrhea of unknown etiology]. / Unklare persistierende Diarrhö bei einer 20-jährigen Patientin : Protrahierte infektiöse Duodenitis als sehr seltene Differenzialdiagnose.

We report on a 20-year old woman who suffered from watery diarrhea. The results of the histology and the serology as well as clinical symptoms lead us to the diagnosis of sprue. Under specific gluten-free diet the diarrhea frequency was reduced. After a few weeks the patient returned to hospital again because of watery diarrhea. Histological examination of duodenal biopsy specimen showed a protracted infectious duodenitis and a secondary villous flattening of the small bowel. This diagnosis was a life-threatening illness that needed antibiotic treatment. These patients receive parenteral nutrition as long as the villous have not been recovered from the flattening. Additionally octreotid can be given to reduce the frequency of the diarrhea.

[Chronic diarrhea in adults: diagnostic strategies]. / Stratégies diagnostiques des diarrhées chroniques de l'adulte.

The presence of chronic diarrhea requires a prompt diagnostic strategy in order to avoid risks of malnutrition and electrolytic disturbances. Two different clinical situations, i.e. collagen colitis and secretory diarrhea, exemplify the diagnostic evaluation of a single symptom. This non exhaustive review should lead to a diagnostic strategy of chronic diarrhea.

Uréter con terminación ciega frente a divertículo ureteral / Blind-ending ureter versus ureteral diverticulum

Pretendemos establecer que el uréter con terminación ciega y los divertículos ureterales son dos manifestaciones diferentes de una misma entidad, pues su origen embriológico, su composición tisular y la patología que desarrollan es la misma, variando únicamente en su morfología digitiforme u ovoidea, respectivamente. Aportamos la novedad de la descripción ecográfica del uréter en terminación ciega, completándose, en nuestro caso, el estudio de imagen con urografía intravenosa. (AU)

[Formation of a blind loop: an unusual bleeding site in chronic intestinal hemorrhage]. / Blindsackbildung: eine aussergewöhnliche Blutungsquelle bei chronischer Darmblutung.

The blind-pouch-syndrome may display a variety of symptoms. But it rarely causes intestinal bleeding. In a patient suffering from anemia of chronic intestinal hemorrhage, a blind-pouch was diagnosed through the search for colon polyps. A hemicolectomy with a side-to-side ileocolic anastomosis was performed 30 years ago, but there were no symptoms of maldigestion or malabsorption. The explorative laparotomy revealed an anastomotic stricture with a lot of coproliths in the ileum-blind-pouch. The histological examination of the resected anastomosis showed an unspecific inflammation of the mucosa. Excluding other potential causes of intestinal hemorrhage, this mucosal irritation was presumed to be the bleeding site.

Blind loop syndrome: multiple ileal ulcers following side-to-side anastomosis.

A 59 yr old woman who had multiple ileal ulcers following side-to-side anastomosis without bowel resection is reported. She had a surgical history of adhesive ileus 15 yrs earlier, and was admitted with a complaint of lower abdominal pain. A barium meal study showed a stagnant and dilated distal ileum. At laparotomy, a previously performed side-to-side ileal anastomosis was encountered, and a markedly dilated bypassed loop was recognized. The affected intestine was resected revealing multiple longitudinal ulcers and small shallow ulcers mostly located on the mesenteric side. This feature is similar to that of ischemic enteritis. This case further supports the fact that when side-to-side anastomosis is performed as a bypass operation, multiple ulcers may develop in a bypassed loop after a long period of time.

[Blind loop of the large intestine--bypass enteropathy or diversion colitis?]. / Der Dickdarm-Blindsack--Bypassenteropathie oder Diversionskolitis?

Investigating three patients with longstanding diarrhoea, severe abdominal bloating and cramps revealed an exclusion of the right hemicolon in all patients and additionally of the terminal ileum in one of them. The anastomosis of the ileo-colic bypass, performed decades ago due to complicated appendicitis, was stenotic in two of them. Because a classical blind-loop-syndrome could not be proven, the functional disorder is described as a clinical entity characterized by signs of bypass-enteropathy and diversion-colitis. The importance of the radiological examination for diagnosis and therapy-planing is emphasized, because endoscopically and histologically Crohn's disease might be suspected. The surgical reintegration of the bowel into the orthograde continuity of the intestinal tract is recommended as the causative treatment. Symptoms disappear completely and patients win normal health even after some decades, because the morphological signs of inflammation are reversible and bowel function is not lost during the exclusion.

Tight junction regulation during impaired ion transport in blind loops of rat jejunum.

Epithelial cell tight junction structure in self-filling blind loops of rat jejunum, a model for blind loop syndrome in humans, was analyzed morphometrically along the crypt-villus axis. In control jejunum, the number of strands and junctional depth, including meshwork depth, decreased from crypt to villus tip. In the blind loop, aberrant strands appeared below the meshwork, particularly in crypt cells. Consequently, total junctional depth was greater than in controls. Furthermore, strand number and junctional meshwork depth were increased in blind loops at the villus tip. It is that site along the crypt-villus axis which showed the most shallow junction in control jejunum. This structural change is paralleled by a three-fold increase in epithelial resistance as previously measured by alternating current impedance analysis. Relative Na over Cl permeability (PNa:Cl) was obtained from dilution potential measurements. PNa:Cl was 1.50:1 in control jejunum and 1.35:1 in the blind loop (n.s.). Considering the cation selectivity of the tight junction, the increase in epithelial resistance in blind loops cannot be attributed to a collapse of the lateral intercellular space but is due to changes in tight junctional permeability resulting from structural alteration. The blind loop syndrome represents a further example of diminished epithelial ion transport and concomitant decrease in tight junction permeability, thus supporting the general concept of regulation of the tight junction in response to active transport activity.

Multiple malignant lymphoma within an ileal blind loop--report of a case.

A 55-year-old woman presented to our hospital with abdominal fullness and edema of both legs. She had undergone a bypass operation by an ileotransversostomy for adhesive ileus following a drainage operation for acute appendicitis 35 years previously. We diagnosed the patient as having blind loop syndrome as a consequence of the side-to-side ileotransversostomy, and performed a right hemicolectomy and intestinal resection. The resected specimen of dilated ileal blind loop contained 15 crater-like lesions, proven histologically to be nodular proliferation of atypical lymphocytes. Lymph follicles had also proliferated in the mucosa of the blind loop and the histologically confirmed diagnosis of non-Hodgkins lymphoma of the diffuse medium-sized cell type was thus made. The etiology of such tumors is probably related to the alteration in intestinal environment caused by conditions such as fecal stasis, bacterial overgrowth, and bacterial toxins in the blind loop.

Adaptation of the jejunal mucosa in the experimental blind loop syndrome: changes in paracellular conductance and tight junction structure.

Self-filling blind loops of rat jejunum exhibit hyperregenerative transformation of the mucosa. We used this experimental model to characterise mechanisms, which may occur under similar conditions in man (stagnant loop syndrome). Epithelial and subepithelial resistance were measured in the Ussing-chamber by voltage divider ratio measurements after positioning a microelectrode between epithelium and subepithelial tissue layers. In the blind loop, epithelial resistance increased from 8 +/- 1 to 23 +/- 1 omega cm2 and subepithelial resistance from 39 +/- 4 to 86 +/- 8 omega cm2 as compared with control jejunum. The increase in the subepithelial resistance was paralleled anatomically by an increase in the thickness of the subepithelial tissue layers from 63 +/- 4 microns to 177 +/- 19 microns. Ultrastructural analysis of the tight junction area by freeze fracture electron microscopy revealed an increase in the total junctional 'depth' in the crypts from 243 +/- 9 nm in control jejunum to 396 +/- 17 nm in the blind loop, while the number of horizontally oriented 'strands' remained unchanged. Villus tight junctions did not differ between blind loop and control. We interpret the alterations in the self-filling blind loop as an adaptive response of the epithelium which reduces backleakage of already absorbed electrolytes across the tight junction into the intestinal lumen. This mechanism is suitable to support the intestine in maintaining body electrolyte and water contents during cellular electrolyte malabsorption.

Pathogenesis of the mucosal hyperplasia in self-filling blind loops of rat jejunum: a morphometric study in germ free animals.

Bacterial overgrowth and high intraluminal concentrations of deconjugated bile acids are thought to be responsible for mucosal hyperplasia in self-filling blind loops of rat jejunum. To investigate this hypothesis further we have assessed the three dimensional architecture of these loops created in germ free animals without or with di- or mono-association of different bacterial species. It was found that mucosal hyperplasia develops in the absence of any bacterial contamination and that bacterial association does not lead to a more pronounced mucosal proliferation. This implies that other mechanisms provoke this morphological phenomenon. Increased bulk contents in these loops or immunological events are probably the most likely explanation.

Component quantitation of rat ileum.

Precise and accurate light microscopic morphometric analyses of biological tissue can be achieved utilizing component quantitative techniques. Component quantitation refers to measurements of the relative volumes of components in tissue sections. Such an assessment is predicated upon the mathematically verifiable assumption that direct quantitative relationships exist between an aggregate of profiles of a component contained per unit area in multiple sections and an aggregate of profiles contained per unit volume. A linear scanning device (micrometer component quantitator) was initially employed for quantitative analyses of pancreas. This quantitative technique has subsequently been applied to normal rat ileum conventionally processed for light microscopy, and the requisite sampling parameters have been defined. An identical technique was then applied to physiologically manipulated rat ileum--a gnotobiotic group, a group with ileal self-filling blind loops, and a group with ileal Thiry-Vella loops. The results observed support the following conclusions. The volume percentage of the various components of the rat ileal wall of control animals was defined utilizing the micrometer component quantitator. Hypertrophy of the ileal muscularis externa within the ileal self-filling blind loops was observed, probably secondary to mechanical obstruction. Atrophy of the ileal epithelium within the gnotobiotic group and within the Thiry-Vella loops was observed, possibly secondary to an altered endogenous microbial flora. Recognition of quantitative variations among the histological components of the intestinal wall in association with physiological manipulations or pathologic states was (is) feasible by utilization of this component quantitative technique.

[Significance of deficient bacterial colonization in the pathogenesis of mucosal lesions in experimental blind loop syndrome]. / Untersuchungen zur Bedeutung der bakteriellen Fehlbesiedlung in der Pathogenese der Schleimhautschädigung beim experimentellen Blindsacksyndrom.

A complete evaluation of the bacterial flora in jejunal self-filling blind loops was performed. The results show a significant increase in bacteria of the genera E. coli, Streptococcus and Bacteroides. In further experiments, jejunal self-filling blind loops were created in germ-free animals. In spite of the germ-free state the mucosa displayed marked hyperplasia. The same was true when the blind loops had been contaminated with aerobic bacteria. These results demonstrate that other factors in addition to bacterial overgrowth contribute to the mucosal damage observed in self-filling blind loops.