Small Intestinal Transit Time Is Delayed in Small Intestinal Bacterial Overgrowth.

BACKGROUND: Altered small intestinal motility is thought to contribute to the development of small intestinal bacterial overgrowth (SIBO). The clinical manifestations of SIBO and consequent malabsorption are wide ranging and include abdominal pain, bloating, diarrhea, weight loss, and nutritional deficiencies. However, due to the nonspecific nature of symptoms, the diagnosis may often be overlooked. To date, few studies have illustrated a direct relationship between impaired small intestinal motility and SIBO. In addition, further study has been limited by the technical challenges and lack of widespread availability of antroduodenal manometry. The development of a wireless motility capsule (WMC) (SmartPill) that evaluates pressure, pH, and temperature throughout the GI tract offers the potential to identify patients with small bowel transit delays who may be at risk for bacterial overgrowth. AIMS: The primary aims of this study were to: (1) characterize the relationship of prolonged small bowel transit time (SBTT) in patients undergoing WMC with SIBO as based on a positive lactulose breath testing (LBT); and (2) to assess the relationship of prolonged gastric, colonic, and whole gut transit times (WGTT) and additional motility parameters with SIBO (positive LBT). We also sought to evaluate the relationship of small bowel motility parameters (SB motility index, contractions per minute, and SB peak amplitudes) with LBT results. METHODS: We performed a retrospective study of consecutive patients who were referred for wireless motility testing at a single, tertiary care institution from April 2009 to December 2012. Of the 72 total patients identified, 34 underwent both WMC and LBT. Gastric, small bowel, colonic, WGTT, and SB motility parameters were measured and correlated with LBT results. Statistical methods utilized for data analysis include ANOVA, 2-sample t tests, nonparametric Kruskal Wallis test, Wilcoxon rank-sum test, and the Fisher exact test. RESULTS: Of the 37 patients who underwent both WMC and LBT, 24 (65%) were LBT positive. The mean SBTT among those who were LBT positive was 6.6 hours as compared with 4.2 hours in those who were LBT negative (P=0.04). Among patients who were LBT positive, 47.6% had prolonged SBTT (≥6 h), whereas only 7.7% of those who were LBT negative had a delay in their SBTT (P=0.01). In addition, patients who were LBT positive were more likely to have prolongation of both colonic and WGTT versus those who were LBT negative (CTT: positive LBT=64.4 h vs. negative LBT=35.5 h, P=0.02; WGTT: positive LBT=70.5 h vs. negative LBT=44.1 h, P=0.02). However, there were no statistical differences observed between the groups for gastric emptying times or other small intestinal motility parameters (SB motility index, contractions per minute, and peak amplitudes) between the 2 groups. CONCLUSIONS: Patients with underlying SIBO have significant delays in SBTT as compared with those without. The association between prolonged SBTT and positive LBT may be useful in identifying those patients with SIBO diagnosed by LBT and potentially target therapeutic options for those refractory to standard therapy. Interestingly, patients with positive LBT did not necessarily have a generalized gastrointestinal motility (similar GETs among groups), suggesting that small bowel transit specifically predisposes to the development of SIBO. Future, prospective studies are needed to further characterize intestinal dysmotility and other contributing pathophysiological mechanisms in SIBO and to investigate the potential benefits of prokinetics in this challenging patient population.

Detection of drug effects on gastric emptying and contractility using a wireless motility capsule.

BACKGROUND: A wireless motility capsule is a new method for ambulatory assessment of transit times and motility throughout the gastrointestinal tract. The objective of this study was to evaluate the ability of a wireless motility capsule to detect drug effects on gastric emptying time (GET) and gastric contractility. METHODS: 15 healthy adults were administered in random order saline, erythromycin IV 150 mg, or morphine IV 0.05 mg/kg BW. Subjects ate a standard meal after each infusion, and subsequently ingested the motility capsule. Data were recorded for 8 hours, and the results were analyzed using the manufacturer's software. RESULTS: GET was significantly faster after erythromycin than either saline or morphine. Morphine tended to delay emptying of the capsule compared to saline. There was a trend toward a greater frequency of gastric contractions with erythromycin and a reduced frequency of gastric contractions with morphine that did not reach statistical significance. CONCLUSIONS: A wireless motility capsule successfully detected acceleration of gastric emptying induced by erythromycin, and retardation of gastric motility caused by morphine. These results indicate that a wireless motility capsule is a promising technique to assess pharmacologic effects on gastric transit and contractility and aid in development of drugs for gastric motor disorders.

Low ileocecal valve pressure is significantly associated with small intestinal bacterial overgrowth (SIBO).

BACKGROUND: Small intestinal bacterial overgrowth (SIBO) is a significant and increasingly recognized syndrome. While the development may be multifactorial, impairment of the ileocecal valve (ICV), small bowel motility, and gastric acid secretion have been hypothesized to be risk factors. ICV dysfunction remains largely unexplored using standard technology. The wireless motility capsule (WMC) that evaluates pressure, pH, and temperature throughout the GI tract provides the ability to assess these parameters. AIMS: The primary aims of this study were to assess the relationship of ICV pressures, small bowel transit time (SBTT) and intestinal pH with lactulose hydrogen breath testing (LBT) results in subjects with suspected SIBO. METHODS: We retrospectively studied consecutive patients referred to our institution for WMC and LBT from 2010-2012. Ileocecal junction pressures (IJP), as a surrogate for ICV pressures, were defined as the highest pressure over a 4-min window prior to the characteristic ileocecal pH drop. SBTT and pH were calculated and compared with LBT results. RESULTS: Twenty-three patients underwent both WMC and LBT, with positive results observed in 15 (65.2%). IJP were significantly higher in LBT(-) negative vs. LBT(+) (79.9 vs. 45.1, p < 0.01). SBTT was significantly longer in LBT(+) versus LBT(-) (5.82 vs. 3.81 h, p = 0.05). Among LBT(+) subjects, gastric pH was significantly higher versus LBT(-) subjects (2.76 vs. 1.63, p = 0.01). There was poor correlation between IJP and other parameters (SBTT, small bowel pH, and gastric pH). CONCLUSIONS: Low IJP is significantly associated with SIBO. While this is physiologically plausible, to our knowledge, this is the first study to make this connection. Prolonged SBTT and higher pH are also independently associated with SIBO. Our findings add value of the WMC test as a diagnostic tool in patients with functional gastrointestinal complaints and suggest re-focus of attention on the ileocecal valve as a prominent player in intestinal disorders.

Impact of acid suppression on upper gastrointestinal pH and motility.

BACKGROUND: Proton pump inhibitors (PPIs), widely prescribed to patients with upper gastrointestinal symptoms, alter intragastric pH, and may affect upper gastrointestinal transit and motility parameters in addition to affecting the ability to determine Wireless Motility Capsule (WMC) gastric emptying time. AIM: To assess PPI effect on motility parameters of the upper gastrointestinal tract and to determine if PPIs confound ability of WMC to measure gastric emptying time. METHODS: Twenty healthy subjects were treated with esomeprazole 40 mg bid for 1 week. Another 50 healthy subjects underwent evaluation in absence of PPIs. All subjects underwent WMC test after meal ingestion. After a rapid, sustained luminal pH rise ≥ 0.5 pH units, marking potential gastric emptying time of WMC, an abdominal X-ray (KUB) was taken for gastric emptying time confirmation. Mean pH, pressure and transit time were compared between PPI-treated and untreated groups. RESULTS: There was no difference in gastric emptying time, small bowel transit time (SBTT), or pressure profiles between the groups. The pH in all cases rose ≥ 0.5 pH units. Distal small bowel pH was significantly lower in subjects on PPIs. Gastric emptying time was identified in all subjects treated with PPIs. Pressure and slope criteria were developed to confirm the time of emptying. CONCLUSION: PPI therapy does not have a significant impact on upper gastrointestinal transit and motility but it does decrease distal small bowel pH. The medication reduced the magnitude of pH change at gastric emptying time but using additional criteria based on slope and contraction frequency, WMC was able to measure gastric emptying time in all patients treated with PPIs.

Heightened colon motor activity measured by a wireless capsule in patients with constipation: relation to colon transit and IBS.

Relationships of regional colonic motility to transit in health, constipation, and constipation-predominant irritable bowel syndrome (C-IBS) are poorly characterized. This study aimed to 1) characterize regional differences in colon pressure, 2) relate motor differences in constipation to colon transit, and 3) quantify the role of IBS in altered contractility with constipation. Colon pH and pressure were measured by wireless capsules in 53 healthy and 36 constipated subjects. Numbers of contractions >25 mmHg and areas under curves (AUC) were calculated for colon transit quartiles by time. Constipation was classified as normal transit (<59 h), moderate slow transit (STC) (59-100 h), and severe STC (>100 h). Twelve out of 36 constipated subjects had C-IBS; 24 had functional constipation. Numbers of contractions and AUCs increased from the first to the fourth quartile in health (P < 0.0001). Mean numbers of contractions in constipated subjects were similar to controls. Mean AUCs with normal transit (P = 0.01) and moderate STC (P = 0.004) but not severe STC (P = NS) were higher than healthy subjects. IBS was associated with greater mean numbers of contractions (P = 0.05) and AUCs (P = 0.0006) vs. controls independent of transit. Numbers of contractions increased from the first to fourth quartiles in moderate STC, C-IBS, and functional constipation; AUCs increased from the first to fourth quartiles in all groups (all P < 0.05). In conclusion, colon pressure activity is greater distally than proximally in health. Constipated patients with normal or moderately delayed transit show increased motor activity that is partly explained by IBS. These findings emphasize differential effects on transit and motility in different constipation subtypes.

Blunting of Colon Contractions in Diabetics with Gastroparesis Quantified by Wireless Motility Capsule Methods.

Generalized gut transit abnormalities are observed in some diabetics with gastroparesis. Relations of gastric emptying abnormalities to colon contractile dysfunction are poorly characterized. We measured colon transit and contractility using wireless motility capsules (WMC) in 41 healthy subjects, 12 diabetics with gastroparesis (defined by gastric retention >5 hours), and 8 diabetics with normal gastric emptying (≤5 hours). Overall numbers of colon contractions >25 mmHg were calculated in all subjects and were correlated with gastric emptying times for diabetics with gastroparesis. Colon transit periods were divided into quartiles by time and contraction numbers were calculated for each quartile to estimate regional colon contractility. Colon transit in diabetics with gastroparesis was prolonged vs. healthy subjects (P<0.0001). Overall numbers of colon contractions in gastroparetics were lower than controls (P = 0.02). Diabetics with normal emptying showed transit and contraction numbers similar to controls. Gastric emptying inversely correlated with overall contraction numbers in gastroparetics (r = -0.49). Numbers of contractions increased from the 1st to 4th colon transit quartile in controls and diabetics with normal emptying (P≤0.04), but not gastroparetics. Numbers of contractions in the 3rd and 4th quartiles were reduced in gastroparetics vs. healthy controls (P≤0.05) and in the 4th quartile vs. diabetics with normal emptying (P = 0.02). Numbers of contractions were greatest in the final 15 minutes of transit, but were reduced in gastroparetics vs. healthy controls and diabetics with normal emptying (P≤0.005). On multivariate analyses, differences in numbers of contractions were not explained by demographic or clinical variables. In conclusion, diabetics with gastroparesis exhibit delayed colon transit associated with reductions in contractions that are prominently blunted in latter transit phases and which correlate with delayed gastric emptying, while diabetics with normal emptying show no significant colonic impairments. These findings emphasize diabetic gastroparesis may be part of a generalized dysmotility syndrome.

Differences in intragastric pH in diabetic vs. idiopathic gastroparesis: relation to degree of gastric retention.

Evidence suggests that distinct mechanisms underlie diabetic and idiopathic gastroparesis. Differences in gastric acid in gastroparesis of different etiologies and varying degrees of gastric stasis are uninvestigated. We tested the hypotheses that 1) gastric pH profiles show differential alteration in diabetic vs. idiopathic gastroparesis and 2) abnormal pH profiles relate to the severity of gastric stasis. Sixty-four healthy control subjects and 44 gastroparesis patients (20 diabetic, 24 idiopathic) swallowed wireless transmitting capsules and then consumed (99m)Tc-sulfur colloid-labeled meals for gastric scintigraphy. Gastric pH from the capsule was recorded every 5 s. Basal pH was higher in diabetic (3.64 +/- 0.41) vs. control subjects (1.90 +/- 0.18) and idiopathic subjects (2.41 +/- 0.42; P < 0.05). Meals evoked initial pH increases that were greater in diabetic (4.98 +/- 0.32) than idiopathic patients (3.89 +/- 0.39; P = 0.03) but not control subjects (4.48 +/- 0.14). pH nadirs prior to gastric capsule evacuation were higher in diabetic patients (1.50 +/- 0.23) than control subjects (0.58 +/- 0.11; P = 0.003). Four-hour gastric retention was similar in diabetic (18.3 +/- 0.5%) and idiopathic (19.4 +/- 0.5%) patients but higher than control subjects (2.2 +/- 0.5%; P < 0.001). Compared with control subjects, those with moderate-severe stasis (>20% retention at 4 h) had higher basal (3.91 +/- 0.55) and nadir pH (2.23 +/- 0.42) values (P < 0.05). In subgroup analyses, both diabetic and idiopathic patients with moderate-severe gastroparesis exhibited increased pH parameters vs. those with mild gastroparesis. In conclusion, diabetic patients with gastroparesis exhibit reduced gastric acid, an effect more pronounced in those with severely delayed gastric emptying. Idiopathic gastroparetic subjects exhibit nearly normal acid profiles, although those with severely delayed emptying show reduced acid vs. those with mild delays. Thus both etiology and degree of gastric stasis determine gastric acidity in gastroparesis.