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Murine studies have demonstrated that the presence of indigenous gut flora is crucial for the induction of systemic immune hyporesponsiveness to antigens initially encountered within the gastrointestinal lumen. This study investigated whether increased titers of such flora, as occur in human small intestinal bacterial overgrowth, may be associated with increased suppression of systemic immune responsiveness and the possible relation between systemic and mucosal immunity in this setting. Serum total immunoglobulin (Ig), immunoglobulin subclass, and soluble interleukin-2 receptor levels and lamina propria IgA plasma cell counts were determined in 50 consecutive subjects with (N = 30) and without (N = 20) small intestinal bacterial overgrowth. Luminal IgA levels were measured in 35 of these subjects. Serum concentrations of IgG3, but not of other immunoglobulin isotypes or soluble interleukin-2 receptors, were significantly reduced in subjects with bacterial overgrowth (P0.0005). Small intestinal lamina propria IgA plasma cell counts (P0.0005) and luminal IgA concentrations (P = 0.001) were significantly increased in this group. Serum IgG3 levels were significantly inversely correlated with luminal IgA levels (P0.01) and fell below the lower limit of normal (0.41 g/liter) in 17/30 (56.7%) subjects with bacterial overgrowth compared to 1/20 (5.0%) subjects without (P0.0005). These findings document an association between small intestinal bacterial overgrowth with indigenous gut flora and reduced serum IgG3 reactivity in humans, possibly via an interaction with mucosa-related immunoregulatory mechanisms. The possibility of underlying small intestinal bacterial overgrowth should be considered in patients with serum IgG3 deficiency, especially those with compatible symptoms and/or known predisposition.

Our aim was to determine the relationships between interleukin-6 and immunoglobulin levels within small intestinal luminal secretions. Twenty adult subjects with small intestinal bacterial overgrowth (N = 13), irritable bowel syndrome (N = 4), and nonulcer dyspepsia (N = 3) underwent endoscopic aspiration of secretions from the small intestinal mucosal surface for assessment of IL-6, IgA1, IgA2, IgM, IgG1, IgG2, IgG3, and IgG4 concentrations. Serum immunoglobulin concentrations and small intestinal histology were also determined. IgA2 and IgG3 were the predominant IgA and IgG subclasses in luminal secretions in 19/20 (95%) and 20/20 (100%) subjects, respectively. IgA1 and IgG1 predominated in serum in all subjects. No subject had villous atrophy. Luminal IL-6 concentrations correlated significantly with luminal IgA2, IgM, and IgG3 concentrations but not with IgA1 or any other IgG subclass levels. Conversely, luminal IL-6 or immunoglobulin concentrations did not correlate significantly with levels of any immunoglobulin isotype in serum. These observations suggest that important relationships exist between local IL-6 and IgA2, IgM, and IgG3 responses in human small intestinal luminal secretions. Local investigation is mandatory when assessing intestinal immune activity.

Elevated antigliadin antibody levels in small intestinal luminal secretions of subjects with normal or only mildly abnormal small intestinal histology are considered indicative of "latent" or "potential" celiac disease. The purpose of this study was to determine whether small intestinal bacterial overgrowth (SIBO) might provide an alternative explanation for positive luminal antigliadin antibodies in such subjects.Twenty-six adult subjects without predisposition to disturbed mucosal immunity were investigated with culture of small intestinal luminal secretions. Luminal total IgA and IgA-antigliadin antibody concentrations were measured by radial immunodiffusion and indirect enzyme immunoassay, respectively. Local mucosal counts of IgA-plasma cells were determined by immunohistochemistry. Small intestinal histology and intraepithelial lymphocyte counts were assessed by light microscopy. Corresponding serum antigliadin antibody concentrations were determined.SIBO was present in 17/26 (65.4%) subjects. No subject with SIBO had villous atrophy. Luminal total IgA concentrations (p0.0005), mucosal IgA-plasma cell counts (p0.01), and intraepithelial lymphocyte counts (p0.01) were significantly increased in subjects with SIBO. Luminal IgA-antigliadin antibodies were detected in 6/17 (35.3%) subjects with SIBO and 0/9 (0%) subjects without SIBO. Luminal IgA-antigliadin antibody concentrations correlated significantly with luminal total IgA levels (p0.01) but not with serum values (p0.1). Serum IgG-antigliadin antibody concentrations were elevated in 2/6 (33.3%) subjects with SIBO and positive luminal antigliadin antibodies.SIBO may be an alternative explanation to "latent" or "potential" celiac disease for positive luminal antigliadin antibodies in subjects with either normal or only mildly abnormal small intestinal histology, even when serum antigliadin antibody concentrations are elevated. Positive luminal antigliadin antibodies in SIBO probably occur as epiphenomena in the context of a graded mucosal immune response to local bacterial antigens.

It is unknown whether bacteriolysis due to luminal complement activation contributes to local defense mechanisms against small intestinal bacterial overgrowth, particularly with gram-negative bacteria. This study addressed this issue. Thirty adult subjects were investigated with culture of luminal secretions adherent to proximal small intestinal mucosa. Luminal and plasma concentrations of C3 and C3d and C3d/C3 ratios were determined. Activated terminal complement complex was sought in surface epithelium to which aspirated secretions had been adherent. Small intestinal bacterial overgrowth with gram-negative bacteria was present in 12/30 (40.0%) subjects. C3, C3d, and C3d/C3 profile indicated that increased local but not systemic C3 activation occurs in this group. Conversely, no activation of terminal complement complex was evident in this circumstance. Thus, complement-mediated bacteriolysis is unlike to contribute to local defense mechanisms against small intestinal bacterial overgrowth, even when overgrowth flora includes gram-negative bacteria. Factors preventing full local activation of the complement cascade in this circumstance require investigation.

1) To determine the prevalence of small intestinal overgrowth with colonic-type bacteria in symptomatic elderly subjects, particularly those without important "clues" such as clinically apparent predisposition or vitamin B12 deficiency, and 2) to investigate defense mechanisms such as gastric acidity, small intestinal motility, and luminal IgA in this setting.Fifty-two symptomatic subjects without vitamin B12 deficiency or clinically apparent predisposition to bacterial overgrowth or disturbed mucosal immunity, including 22 subjectsor = 75 yr old, underwent culture of small intestinal luminal secretions. Indicator paper was used to measure fasting gastric pH. The presence of bacteria of confirmed nonsalivary origin in small intestinal secretions served as an index of small intestinal dysmotility. Small intestinal luminal IgA concentrations were measured by radial immunodiffusion.Small intestinal overgrowth with colonic-type flora was not present in any subject investigated for dyspepsia, irrespective of age. In subjects with chronic diarrhea, anorexia, or nausea, overgrowth with colonic-type flora (Enterobacteriaceae) was present in 0/12 (0%), 1/10 (10.0%), and 9/14 (64.3%) subjects aged50 yr, 50-74 yr, andor = 75 yr, respectively. Enterobacteriaceae were not concurrently recovered from saliva of any subjector = 75 yr old with small intestinal overgrowth with these bacteria. Fasting hypochlorhydria was present in only 1/9 (11.1%) such subjects. Luminal IgA concentrations were significantly greater in subjectsor = 75 yr old with bacterial overgrowth than in culture-negative subjects (por = 0.003).Small intestinal overgrowth with colonic-type bacterial should be considered in subjectsor = 75 yr old with chronic diarrhea, anorexia, or nausea, even in the absence of clues such as clinically apparent predisposition or vitamin B12 deficiency. Small intestinal dysmotility, rather than fasting hypochlorhydria or mucosal immunosenescence, probably is responsible for the prevalence of bacterial overgrowth in this group.

Small intestinal hypomotility is an important cause of small intestinal bacterial overgrowth, yet assessment of small intestinal motility in this setting is problematic. This study was performed to investigate the validity of a bacteriological method for detecting small intestinal hypomotility.Twenty-five subjects without previous gastric surgery were studied with (i) concurrent bacteriological analyses of fasting saliva and gastric and proximal small intestinal aspirates, (ii) measurement of gastric pH, and (iii) scintigraphic assessment of small intestinal transit rates of a liquid test meal. The reproducibility of bacteriological analyses of saliva and small intestinal secretions was determined in 12 subjects.Serial bacteriological analyses of saliva and proximal small intestinal secretions yielded reproducible results over time periods of up to 1 month. Eleven subjects were deemed to harbor Enterobacteriaceae of nonsalivary origin in proximal small intestinal secretions. Orocaecal transit, but not gastric emptying, of a liquid test meal was significantly delayed in this group (p = 0.002 and p = 0.84, respectively), suggesting the presence of small intestinal hypomotility. Impaired gastric acidity unlikely confounded assessment of the origin of small intestinal Enterobacteriaceae in any instance.The presence of Enterobacteriaceae of nonsalivary origin in proximal small intestinal secretions may be taken to reflect the presence of small intestinal hypomotility. The presence of impaired gastric acidity does not confound this approach. Because small intestinal intubation and culture of aspirate are required anyway to accurately diagnose small intestinal bacterial overgrowth, the simple addition of concurrent bacteriological analysis of saliva may allow small intestinal hypomotility to be detected at the same time as the presence or absence of small intestinal bacterial overgrowth itself is established, thus streamlining the investigation of subjects for this disorder and its possible causes.

To i) document the sensitivity and specificity of a combined scintigraphic/lactulose breath hydrogen test for small intestinal bacterial overgrowth and ii) investigate the validity of currently accepted definitions of an abnormal lactulose breath hydrogen test based on "double peaks" in breath hydrogen concentrations.Twenty-eight subjects were investigated with culture of proximal small intestinal aspirate and a 10-g lactulose breath hydrogen test combined with scintigraphy. Gastroduodenal pH, the presence or absence of gastric bacterial overgrowth, and the in vitro capability of overgrowth flora to ferment lactulose were determined.Sensitivity (16.7%) and specificity (70.0%) of the lactulose breath hydrogen test alone for small intestinal bacterial overgrowth were poor. Combination with scintigraphy resulted in 100% specificity, because double peaks in serial breath hydrogen concentrations may occur as a result of lactulose fermentation by cecal bacteria. Sensitivity increased to 38.9% with scintigraphy, because a single rise in breath hydrogen concentrations, commencing before the test meal reaches the cecum, may occur in this disorder. Sensitivity remained suboptimal irrespective of the definition of small intestinal bacterial overgrowth used, the nature of the overgrowth flora, favorable luminal pH, the presence of concurrent gastric bacterial overgrowth, or the in vitro ability of the overgrowth flora to ferment lactulose.Definitions of an abnormal lactulose breath hydrogen test based on the occurrence of double peaks in breath hydrogen concentrations are inappropriate. Not even the addition of scintigraphy renders this test a clinically useful alternative to culture of aspirate for diagnosing small intestinal bacterial overgrowth.

Twenty patients with persistent diarrhoea participated in a randomised, double-blind trial of oral sodium cromoglycate and placebo. Eight patients noted significant improvement in their diarrhoea while taking sodium cromoglycate and this did not correlate with the presence of other atopic diseases, a history of food intolerance, or the presence of lactase deficiency. The results suggest that some patients with diarrhoea of unknown cause may have food allergy as a major contributing cause for their diarrhoea.

A method has been developed to record directly myoelectrical activity from the smooth muscle of the colon of intact subjects using pairs of intramuscular wires. Discrete bursts of myoelectrical activity occurred at 4–20 per min. A small interelectrode distance in this method allows contamination of colonic myoelectrical activity by the electromyogram of skeletal muscle to be excluded. This artefact has not been considered in previous recordings of ‘colonic’ activity.

A Sengstaken-Blakemore tube was unable to be withdrawn 14 h after its initial insertion. Despite a number of recognized maneuvers, both gastric and esophageal balloons remained inflated leading to impaction of the tube. This uncommon complication along with other complications peculiar to the Sengstaken-Blakemore tube are described.

The group of conditions variously termed biliary dyskinesia, acalculous cholecystitis, biliary pain without stones, or functional disorders of the biliary tract, is poorly defined clinically, and no consistent pathological abnormalities have been previously described in patients with this diagnosis. In this paper we report histological abnormalities encountered in operative liver biopsies in such patients. The criteria for the diagnosis of a functional biliary tract disorders were: pain typical of biliary pain, negative results of investigations for organic biliary tract or other gastrointestinal disease, and reproduction of the patient's symptoms by cholecystokinin, or morphine, or both. Twenty of 45 patients with a presumptive diagnosis satisfied these criteria, and had a wedge liver biopsy at the time of operation. The 20 liver biopsy specimens were compared in a blind fashion with similar ones taken from patients having diagnostic laparotomies: patients with stones confined to the gallbladder; patients with gallstone pancreatitis; and patients with proven common bile duct stones. The biopsy findings were found to be similar to those in the latter two groups. Thus the abnormalities were similar to those found in partial or intermittent biliary obstruction, and it is suggested that they may be due to intermittent increases in biliary pressure.