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3.
Am J Gastroenterol ; 96(2): 494-500, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11232696

ABSTRACT

OBJECTIVE: The aim of this study was to investigate the separate effects of indigenous oropharyngeal- and colonic-type flora on small intestinal mucosal immunity and morphometry in small intestinal bacterial overgrowth (SIBO). METHODS: A duodenal aspirate and random biopsies of underlying mucosa were obtained from 52 adult subjects (age range, 18-90 yr; median, 60 yr) without disorders that may otherwise disturb small intestinal histology or mucosal immunity. Villus height, crypt depth, villus/crypt ratios, counts of intraepithelial lymphocytes (IELs) and lamina propria total mononuclear cells, IgA, IgM, and IgG plasma cells, mast cells, and B and T lymphocytes were determined in relation to the presence or absence of SIBO and the nature of the overgrowth flora in all subjects. CD4+ve and CD8+ve T-cell counts were determined in 24 subjects. RESULTS: SIBO was present in 26 of 52 (50%) subjects. Overgrowth flora included colonic-type bacteria in 20 subjects and oropharyngeal-type flora alone in 6 subjects. Lamina propria IgA plasma cell counts were significantly increased in subjects with SIBO, irrespective of whether the overgrowth flora comprised oropharyngeal-type flora alone or included colonic-type bacteria. Neither villus height, crypt depth, villus/crypt ratios, nor total or other mononuclear cell counts in lamina propria differed significantly between subjects with and without SIBO, irrespective of the nature of the overgrowth flora. IEL counts were significantly higher than in culture-negative subjects only when the overgrowth flora included colonic-type bacteria. Even then, IEL counts were within a range currently considered normal. A significant, inverse correlation between advancing age and IEL counts became apparent after adjusting for the effect of SIBO of colonic-type flora. CONCLUSIONS: SIBO of oropharyngeal- and colonic-type flora are associated with differing disturbances of local duodenal mucosa. Nonetheless, these would not be readily apparent during routine histological assessment. Old age independently influences duodenal IEL counts.


Subject(s)
Bacterial Infections/immunology , Duodenal Diseases/microbiology , Duodenum/microbiology , Intestinal Mucosa/immunology , Bacterial Infections/pathology , Biopsy , Colon/microbiology , Duodenal Diseases/immunology , Duodenal Diseases/pathology , Duodenum/pathology , Humans , Immunity, Mucosal/immunology , Intestinal Mucosa/pathology , Lymphocyte Count , Middle Aged , Oropharynx/microbiology , Plasma Cells/pathology
4.
Am J Gastroenterol ; 95(10): 2858-64, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11051360

ABSTRACT

OBJECTIVES: The aims of this study were 1) to document the sensitivity, specificity, and predictive values of the rice breath hydrogen test for small intestinal bacterial overgrowth; 2) to determine the possible influence of concurrent gastric bacterial overgrowth and gastroduodenal pH on the efficacy of this test; and 3) to investigate whether reliability is limited by an inability of small intestinal luminal flora to ferment rice or its product of hydrolysis, maltose. METHODS: Twenty adult subjects were investigated with microbiological culture of proximal small intestinal aspirate and a 3-g/kg rice breath hydrogen test. Gastroduodenal pH, the presence or absence of gastric bacterial overgrowth, and the in vitro capability of small intestinal luminal flora to ferment rice and maltose, its product of hydrolysis, were determined. RESULTS: Sensitivity of the rice breath hydrogen test for small intestinal bacterial overgrowth was 33% and remained low even when subjects with small intestinal overgrowth with oropharyngeal-type (38%) and colonic-type flora (20%) and those with concurrent small intestinal and gastric bacterial overgrowth (40%) were considered separately. Sensitivity remained suboptimal despite favorable gastroduodenal luminal pH and documented ability of bacterial isolates to ferment rice and maltose in vitro. Specificity of the rice breath hydrogen test for small intestinal bacterial overgrowth was 91%. Positive predictive value, negative predictive value, and predictive accuracy were 75%, 63%, and 65%, respectively. CONCLUSIONS: Clinical value of the rice breath hydrogen test for detecting small intestinal bacterial overgrowth is limited. The rice breath hydrogen test is not a suitable alternative to small intestinal intubation and culture of secretions for the detection of small intestinal bacterial overgrowth.


Subject(s)
Breath Tests , Diarrhea/microbiology , Enterobacteriaceae/pathogenicity , Hydrogen/analysis , Intestine, Small/microbiology , Malabsorption Syndromes/microbiology , Oryza , Adolescent , Adult , Aged , Aged, 80 and over , Colony Count, Microbial , Female , Fermentation , Gastric Mucosa/microbiology , Humans , Male , Middle Aged , Predictive Value of Tests
5.
Dig Dis Sci ; 44(5): 939-44, 1999 May.
Article in English | MEDLINE | ID: mdl-10235601

ABSTRACT

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 (P < 0.0005). Small intestinal lamina propria IgA plasma cell counts (P < 0.0005) and luminal IgA concentrations (P = 0.001) were significantly increased in this group. Serum IgG3 levels were significantly inversely correlated with luminal IgA levels (P < 0.01) 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 (P < 0.0005). 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.


Subject(s)
Immunoglobulins/blood , Intestine, Small/microbiology , Receptors, Interleukin-2/analysis , Adolescent , Adult , Aged , Aged, 80 and over , Humans , Immunoglobulin A/blood , Immunoglobulin G/blood , Middle Aged
6.
Dig Dis Sci ; 43(2): 442-5, 1998 Feb.
Article in English | MEDLINE | ID: mdl-9512143

ABSTRACT

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.


Subject(s)
Immunoglobulins/analysis , Interleukin-6/analysis , Intestinal Diseases/immunology , Intestine, Small/immunology , Adult , Aged , Aged, 80 and over , Colonic Diseases, Functional/immunology , Diarrhea/immunology , Dyspepsia/immunology , Humans , Intestinal Mucosa/immunology , Linear Models , Middle Aged
7.
Am J Gastroenterol ; 92(8): 1335-8, 1997 Aug.
Article in English | MEDLINE | ID: mdl-9260801

ABSTRACT

OBJECTIVE: 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. METHODS: 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. RESULTS: SIBO was present in 17/26 (65.4%) subjects. No subject with SIBO had villous atrophy. Luminal total IgA concentrations (p < 0.0005), mucosal IgA-plasma cell counts (p < 0.01), and intraepithelial lymphocyte counts (p < 0.01) 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 (p < 0.01) but not with serum values (p < 0.1). Serum IgG-antigliadin antibody concentrations were elevated in 2/6 (33.3%) subjects with SIBO and positive luminal antigliadin antibodies. CONCLUSIONS: 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.


Subject(s)
Antibodies, Anti-Idiotypic/analysis , Bacteria/isolation & purification , Gliadin/immunology , Immunoglobulin A , Intestine, Small/immunology , Intestine, Small/microbiology , Adult , Aged , Aged, 80 and over , Antigens, Bacterial/immunology , Bacteria/immunology , Humans , Intestine, Small/metabolism , Middle Aged
8.
Dig Dis Sci ; 42(6): 1128-36, 1997 Jun.
Article in English | MEDLINE | ID: mdl-9201072

ABSTRACT

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.


Subject(s)
Complement Activation , Complement C3/immunology , Complement C3d/immunology , Gram-Negative Bacterial Infections/immunology , Gram-Positive Bacterial Infections/immunology , Intestinal Diseases/immunology , Intestine, Small/microbiology , Adult , Aged , Aged, 80 and over , Case-Control Studies , Causality , Gram-Negative Bacterial Infections/microbiology , Gram-Positive Bacterial Infections/microbiology , Humans , Intestinal Diseases/microbiology , Intestinal Mucosa/immunology , Intestinal Mucosa/microbiology , Intestinal Secretions/immunology , Intestinal Secretions/microbiology , Intestine, Small/immunology , Middle Aged
9.
Scand J Gastroenterol ; 32(6): 556-63, 1997 Jun.
Article in English | MEDLINE | ID: mdl-9200287

ABSTRACT

BACKGROUND: The influence of luminal bacteria on small-intestinal permeability has not been fully assessed. This study addressed this issue. METHODS: Thirty-four subjects (mean age 64 years; range 22-95 years) were investigated for possible small-intestinal bacterial overgrowth (SIBO) with culture of a small-intestinal aspirate. A lactulose/mannitol small-intestinal permeability test was performed, small-intestinal histology assessed and serum vitamin B12 concentrations measured in all subjects. Permeability was also assessed in a control group of 34 asymptomatic volunteers. RESULTS: Urinary lactulose/mannitol ratios were significantly increased in subjects with SIBO with colonic-type flora (P < 0.0005), even in the absence of villous atrophy. Urinary lactulose/mannitol ratios were increased in this group due to significantly increased urinary lactulose concentrations (P < 0.0005) rather than reduced urinary mannitol levels, after correcting for inter-subject variations in renal function. Counts of intraepithelial lymphocytes of CD8 phenotype were significantly increased in this group (P = 0.003). Although a significant correlation was found between intraepithelial lymphocyte counts and small-intestinal permeability overall (P < 0.002), these counts were not significantly different in subjects with SIBO with colonic-type flora whose permeability values were < or = > 0.028, the upper limit of normal in asymptomatic controls. Serum vitamin B12 concentrations did not differ significantly between groups (P > 0.5). Ageing did not independently influence small-intestinal permeability (P > 0.5). CONCLUSIONS: Small-intestinal permeability is increased in subjects with SIBO with colonic-type bacteria. This effect is independent of ageing and not mediated by vitamin B12 deficiency. Although counts of intraepithelial lymphocytes of CD8 phenotype are increased in this disorder, it is also unlikely that these cells play an important causative role in this process. Routine light microscopic assessment underestimates the prevalence of small-intestinal functional disturbance in this disorder.


Subject(s)
Bacterial Infections/physiopathology , Intestinal Absorption , Intestine, Small/microbiology , Bacterial Infections/diagnosis , Case-Control Studies , Humans , Intestinal Secretions/microbiology , Intestine, Small/metabolism , Lactulose , Mannitol , Middle Aged , Permeability , Vitamin B 12/blood , Vitamin B 12 Deficiency/diagnosis
10.
Am J Gastroenterol ; 92(1): 47-51, 1997 Jan.
Article in English | MEDLINE | ID: mdl-8995936

ABSTRACT

OBJECTIVE: 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. METHODS: Fifty-two symptomatic subjects without vitamin B12 deficiency or clinically apparent predisposition to bacterial overgrowth or disturbed mucosal immunity, including 22 subjects > or = 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. RESULTS: 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 aged < 50 yr, 50-74 yr, and > or = 75 yr, respectively. Enterobacteriaceae were not concurrently recovered from saliva of any subject > or = 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 subjects > or = 75 yr old with bacterial overgrowth than in culture-negative subjects (p < or = 0.003). CONCLUSIONS: Small intestinal overgrowth with colonic-type bacterial should be considered in subjects > or = 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.


Subject(s)
Bacterial Infections/diagnosis , Intestinal Diseases/diagnosis , Intestine, Small/microbiology , Aged , Anorexia/etiology , Bacterial Infections/complications , Chronic Disease , Diarrhea/microbiology , Enterobacteriaceae/isolation & purification , Gastric Acidity Determination , Gastrointestinal Motility/physiology , Humans , Immunoglobulin A/analysis , Intestinal Diseases/complications , Intestine, Small/immunology , Middle Aged , Saliva/microbiology
11.
Am J Gastroenterol ; 91(11): 2399-405, 1996 Nov.
Article in English | MEDLINE | ID: mdl-8931425

ABSTRACT

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.


Subject(s)
Bacterial Infections/diagnosis , Gastrointestinal Motility/physiology , Intestinal Secretions/microbiology , Intestine, Small/physiopathology , Saliva/microbiology , Bacterial Infections/etiology , Enterobacteriaceae/isolation & purification , Gastric Emptying/physiology , Gastric Juice/microbiology , Gastrointestinal Transit/physiology , Humans , Hydrogen-Ion Concentration , Intestine, Small/diagnostic imaging , Intestine, Small/microbiology , Middle Aged , Radionuclide Imaging , Reproducibility of Results , Streptococcus/isolation & purification , Technetium Tc 99m Sulfur Colloid
12.
Scand J Gastroenterol ; 31(11): 1098-102, 1996 Nov.
Article in English | MEDLINE | ID: mdl-8938903

ABSTRACT

BACKGROUND: Factors regulating proximal small-intestinal luminal concentrations of IgG3, the predominant IgG subclass at this site, are unclear. This study determined whether luminal IgG3 concentrations are related to those of complement protein 4 (C4), an acute-phase reactant predominantly derived from local mucosa. METHODS: Proximal small-intestinal luminal and peripheral blood IgG subclass and C4 concentrations were measured by radial immunodiffusion in 30 adult subjects without predisposition to disturbed mucosal immunity. Mucosal C4 immunoreactivity and the presence or absence of small-intestinal bacterial overgrowth were determined in all subjects. Caecal luminal concentrations of IgG3 and C4 were measured in a separate cohort of eight asymptomatic subjects. RESULTS: Proximal small-intestinal luminal C4 and IgG subclass concentrations were not significantly influenced by the presence of absence of small-intestinal bacterial overgrowth (P > 0.2). Nor did plasma C4 levels significantly influence C4 concentrations in small-intestinal luminal secretions (P > 0.2). Mucosal immunoreactivity for C4 was present in every subject. A significant correlation was found between C4 and IgG3 concentrations in proximal small-intestinal luminal secretions (P < 0.0005) and also in caecal secretions (P < 0.05) but not in peripheral blood (P > 0.1). CONCLUSIONS: Common factors, not including the presence or absence of small-intestinal bacterial overgrowth, regulate luminal concentrations of C4 and IgG3. Local investigation is mandatory when assessing mucosal immune mechanisms.


Subject(s)
Complement C4/metabolism , Immunoglobulin G/metabolism , Intestinal Secretions/metabolism , Intestine, Small/metabolism , Cecum/immunology , Cecum/metabolism , Humans , Intestinal Mucosa/immunology , Intestinal Mucosa/metabolism , Intestinal Secretions/immunology , Intestine, Small/immunology , Intestine, Small/microbiology , Middle Aged
13.
Scand J Gastroenterol ; 31(11): 1103-9, 1996 Nov.
Article in English | MEDLINE | ID: mdl-8938904

ABSTRACT

BACKGROUND: The independent influences of small-intestinal bacterial overgrowth and old age on mucosal immunoglobulin production and secretion have not been assessed. This is an important issue, since luminal IgA deficiency may exacerbate small-intestinal bacterial overgrowth, the prevalence of which is high in selected elderly populations. METHODS: Proximal small-intestinal aspirates were obtained from 33 subjects for bacteriologic analysis and measurement of total IgA, IgM, total IgG. IgG subclass, and IgD concentrations. IgA subclasses were measured in 24 unselected subjects. Serum immunoglobulin and salivary IgA concentrations were measured in all subjects. RESULTS: IgA2 and IgG3 were predominant IgA and IgG subclasses in proximal small-intestinal luminal secretions. Luminal concentrations of IgA2 and IgM, but not IgG3 or any other IgG subclass, were significantly increased in small-intestinal bacterial overgrowth, which was present in 19 of 33 (57.6%) subjects. Old age did not influence these levels. Luminal immunoglobulin concentrations did not correlate significantly with either serum or salivary values. IgD was not measureable in proximal small-intestinal secretions. CONCLUSIONS: Increased luminal concentrations of the secretory immunoglobulins, IgA2 and IgM, occur in small-intestinal bacterial overgrowth. Local investigation is mandatory when assessing the mucosal immunopathology of this disorder. Luminal IgG3 is unlikely to be predominantly derived from serum. Old age does not independently influence luminal immunity.


Subject(s)
Bacterial Infections/immunology , Immunity, Mucosal/immunology , Immunoglobulins/immunology , Intestinal Diseases/immunology , Age Factors , Aged , Aged, 80 and over , Case-Control Studies , Humans , Immunoglobulins/metabolism , Intestinal Diseases/microbiology , Intestinal Mucosa/immunology , Intestine, Small/immunology , Intestine, Small/microbiology , Middle Aged
14.
Scand J Gastroenterol ; 31(10): 977-84, 1996 Oct.
Article in English | MEDLINE | ID: mdl-8898418

ABSTRACT

BACKGROUND: Mucosal production of interferon-gamma, interleukin-6, and tumour necrosis factor-alpha is increased in inflammatory bowel disease and parallels disease activity. Interferon-gamma production is also increased in coeliac disease. Conversely, local cytokine profiles have not been investigated in small-intestinal bacterial overgrowth. This study addressed this issue. METHODS: Eighteen adult subjects were studies with culture of proximal small-intestinal luminal secretion and measurement of luminal interferon-gamma, interleukin-6, and tumour necrosis factor-alpha concentrations by enzyme-linked immunosorbent assay. Small-intestinal histology was assessed by light microscopy. RESULTS: Interferon-gamma, interleukin-6, and tumour necrosis factor-alpha were measurable in proximal small-intestinal luminal secretions of all subjects, even in the absence of light microscopic evidence of enteropathy. Small-intestinal bacterial overgrowth was present in 12 of 18 (66.7%) subjects. Luminal concentrations of neither interferon-gamma nor tumour necrosis factor-alpha differed significantly in subjects with and without small-intestinal bacterial overgrowth (P + 0.06 and P = 1.0, respectively). Conversely, luminal interleukin-6 concentrations were significantly increased in subjects with this disorder (P = 0.02). Multivariate linear regression analysis suggested that colonic-type rather than salivary-type flora mediated this increased interleukin-6 response (P = 0.02 and P = 0.64, respectively). No correlation was found between luminal interleukin-6 and tumour necrosis factor-alpha concentrations, even after the confounding influence of colonic-type bacteria was excluded (P = 0.60). CONCLUSIONS: These findings suggest that increased mucosal production of interleukin-6 occurs in small-intestinal bacterial overgrowth, particularly when the overgrowth flora includes colonic-type bacteria. Conversely, luminal levels of neither interferon-gamma nor tumour necrosis factor-alpha are increased in the circumstance, distinguishing the local cytokine profile in this disorder from those that occur in coeliac disease and inflammatory bowel disease.


Subject(s)
Interferon-gamma/metabolism , Interleukin-6/metabolism , Intestinal Mucosa/metabolism , Intestine, Small/microbiology , Tumor Necrosis Factor-alpha/metabolism , Adult , Aged , Aged, 80 and over , Colony Count, Microbial , Cytokines/analysis , Cytokines/metabolism , Endoscopy, Gastrointestinal , Enzyme-Linked Immunosorbent Assay , Humans , Interferon-gamma/analysis , Interleukin-6/analysis , Intestinal Diseases/metabolism , Intestinal Diseases/physiopathology , Intestinal Mucosa/microbiology , Intestinal Mucosa/pathology , Intestine, Small/metabolism , Intestine, Small/pathology , Linear Models , Middle Aged , Multivariate Analysis , Regression Analysis , Tumor Necrosis Factor-alpha/analysis
15.
Am J Gastroenterol ; 91(9): 1795-803, 1996 Sep.
Article in English | MEDLINE | ID: mdl-8792701

ABSTRACT

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.


Subject(s)
Bacterial Infections/diagnosis , Breath Tests , Intestine, Small/microbiology , Bacterial Infections/diagnostic imaging , Fermentation , Humans , Hydrogen/analysis , Hydrogen-Ion Concentration , Lactulose/metabolism , Middle Aged , Radionuclide Imaging , Reproducibility of Results , Sensitivity and Specificity , Stomach/microbiology
16.
J Pediatr Gastroenterol Nutr ; 22(2): 144-7, 1996 Feb.
Article in English | MEDLINE | ID: mdl-8642485

ABSTRACT

Rice carbohydrate malabsorption is common in Burmese village children and adults and may contribute to diminished growth. Its diagnosis depends on a rice breath hydrogen test, which has limitations. Almost 20% of Burmese children under age 5 produce methane, compared with less than 7% of children in Africa and Hong Kong. If an increased carbohydrate load in the colon due to rice malabsorption provides increased substrate for methanogenic bacteria in the left colon, higher fasting breath methane concentrations might be a simpler method of diagnosing rice malabsorption. We tested breath hydrogen and methane over a 4-h period and did anthropometric measurements in 142 subjects, 79 children, and 63 adults. Seventy percent of children were rice-malabsorbers. Methane production occurred in 20% of children under 5 years of age and increased to 60% of adults. There is an association of rice malabsorption with reduced length. There was not correlation between rice malabsorption and breath methane, and the concentration of breath methane does not, therefore, indicate rice absorption status and cannot replace rice breath hydrogen tests.


Subject(s)
Dietary Carbohydrates/pharmacokinetics , Hydrogen/metabolism , Malabsorption Syndromes/metabolism , Methane/metabolism , Oryza/metabolism , Adult , Aging/metabolism , Aging/physiology , Anthropometry , Body Height , Breath Tests , Child , Child, Preschool , Colon/metabolism , Colon/microbiology , Dietary Carbohydrates/analysis , Dietary Carbohydrates/metabolism , Female , Humans , Infant , Malabsorption Syndromes/diagnosis , Malabsorption Syndromes/epidemiology , Male , Middle Aged , Myanmar/epidemiology , Nutritional Status , Oryza/chemistry , Prevalence
17.
J Gastroenterol Hepatol ; 11(1): 71-6, 1996 Jan.
Article in English | MEDLINE | ID: mdl-8672746

ABSTRACT

While up to 50% of Western populations produce methane, this is less than that of rural black Africans and there is no information on methane production in populations from Asian developing countries. Females consistently produce methane more commonly than males, and methane production in children under the age of five years, except in Nigeria, is unusual. Breath methane was sampled in 1426 subjects from Myanmar ranging in age from 1 month to 88 years, with a mean age of 26.2 years. Half (49.8%) of the Myanmar population produced methane, this figure comprising 53% of females and 46% of males sampled. Methane production increases with age and reaches adult levels after 10 years of age. A high prevalence of methane production was found in children under 3 years of age (15.8%). Methane production was absent in 13 solely breast-fed children and increased as other food was introduced into the diet. There was an association of methane production within families and with smoking. The prevalence of methane production increased in male and female smokers, with 75% of smokers producing methane. Methane production was not associated with occupation, education, income, water source, latrine type, previous diarrhoea, antibiotic usage or socio-economic status.


Subject(s)
Methane/metabolism , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Breath Tests , Child , Child, Preschool , Cross-Sectional Studies , Diet , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Myanmar , Sex Factors , Smoking/epidemiology , Socioeconomic Factors
18.
Am J Gastroenterol ; 90(9): 1455-60, 1995 Sep.
Article in English | MEDLINE | ID: mdl-7661169

ABSTRACT

OBJECTIVES: To document the sensitivity of the 1-g 14C-D-xylose breath test for bacterial overgrowth and to investigate luminal and nonluminal factors that may influence breath 14CO2 levels and impact on the clinical utility of this test. METHODS: Thirty-five adult subjects were investigated for bacterial overgrowth by culture of gastric and small intestinal aspirates and by a 1-g 14C-D-xylose breath test. Body weight, gastroduodenal pH and the in vitro capability of overgrowth flora to ferment D-xylose were assessed. Serial breath 14CO2 levels were also recorded before and after the resolution of malabsorption in a subject with celiac disease to determine the importance of postabsorptive metabolism of this substrate. RESULTS: Gastric and small intestinal bacterial overgrowth were present in 19/35 (54.3%) and 21/35 (60.0%) subjects, respectively. The positivity rate of culture of aspirate exceeded that of the 1-g 14C-D-xylose breath test. Endogenous CO2 production independently influenced breath 14CO2 levels. After excluding this influence, sensitivity of the 1-g 14C-D-xylose breath test for gastric bacterial overgrowth or small intestinal bacterial overgrowth was poor, even when overgrowth with specific "marker organisms" was considered. Poor sensitivity could not be explained by unfavorable luminal pH. Overgrowth flora were proven capable of in vitro D-xylose fermentation in 81.8% of subjects. Systemic and/or colonic metabolism of 1-g 14C-D-xylose appear to be important factors influencing results of the 1-g 14C-D-xylose breath test, especially in partial gastrectomy subjects. CONCLUSIONS: The 1-g 14C-D-xylose breath test is not a suitable alternative to culture of aspirate for the investigation of subjects for bacterial overgrowth.


Subject(s)
Bacterial Infections/diagnosis , Breath Tests , Intestine, Small/microbiology , Stomach/microbiology , Xylose , Aged , Bacteria/growth & development , Bacteria/metabolism , Bacterial Infections/epidemiology , Carbon Radioisotopes , Colon/metabolism , Female , Fermentation , Gastrectomy , Humans , Hydrogen-Ion Concentration , Male , Sensitivity and Specificity , Xylose/metabolism
19.
Scand J Gastroenterol ; 30(7): 681-5, 1995 Jul.
Article in English | MEDLINE | ID: mdl-7481532

ABSTRACT

BACKGROUND: Although culture of luminal secretions is regarded as the most accurate diagnostic test for small-intestinal bacterial overgrowth, obtaining an aspirate is often difficult owing to the sparseness of luminal secretions present at the time of aspiration. Obtaining a mucosal biopsy specimen for bacteriologic analysis would overcome this problem. METHODS: Culture of small-intestinal and gastric aspirates and unwashed small-intestinal mucosal specimens was performed in 51 adult subjects investigated for small-intestinal overgrowth. RESULTS: Highly significant (r = 0.85-0.90; p < 0.0005) correlations were found between viable bacterial counts in small-intestinal luminal secretions and biopsy specimens. Small-intestinal bacterial overgrowth was present in 60.8% of subjects. When specimens weighing 4.0-84.0 mg were suspended in diluent, total aerobic and/or anaerobic bacterial counts > or = 10(2) CFU/ml were found to have 90.3% sensitivity and 100% specificity for small-intestinal bacterial overgrowth. CONCLUSION: Culture of an unwashed small-intestinal mucosal biopsy specimen is a useful alternative to culture of a small-intestinal aspirate for detecting subjects with small-intestinal bacterial overgrowth, especially when luminal secretions are scanty at the time of aspiration.


Subject(s)
Bacteria, Aerobic/growth & development , Bacteria, Anaerobic/growth & development , Gastric Mucosa/microbiology , Intestinal Mucosa/microbiology , Adult , Aged , Aged, 80 and over , Biopsy , Colony Count, Microbial , Culture Media , Gastric Mucosa/pathology , Humans , Intestinal Mucosa/pathology , Intestine, Small/microbiology , Middle Aged , Sensitivity and Specificity
20.
J Trop Med Hyg ; 98(2): 117-20, 1995 Apr.
Article in English | MEDLINE | ID: mdl-7714934

ABSTRACT

The efficacy of a string test for the detection of small bowel bacterial overgrowth (SBBO) was determined by comparison with a sterile endoscopic method for sampling small bowel secretions in 15 subjects investigated for SBBO. Clinical value was found to be limited by poor sensitivity, specificity and positive predictive value. The string test is not an adequate substitute for oro-duodenal intubation for the detection of SBBO.


Subject(s)
Endoscopy, Gastrointestinal/methods , Intestinal Secretions/microbiology , Intestine, Small/microbiology , Microbiological Techniques , Adult , Colony Count, Microbial , Humans , Predictive Value of Tests , Sensitivity and Specificity , Suction
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