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Biomedical subjects

Mark Pimentel

Publications and source records attributed to Mark Pimentel.

15 recordsLinked to original sources
PubMed2026

Do Multi-Omics Approaches Improve the Diagnosis of Microbial Overgrowth Syndromes?

PURPOSE OF REVIEW: This review investigates how advances in breath testing (BT), small bowel (SB) culture, metagenomics, metatranscriptomics, transcriptomics and proteomics are reshaping the definition and diagnosis of small intestinal bacterial overgrowth (SIBO). It also discusses whether SIBO should be redefined as part of a larger group of microbial overgrowth syndromes. RECENT FINDINGS: Recent studies identify distinct hydrogen-, methane-, and hydrogen sulfide-associated overgrowth phenotypes, termed SIBO, intestinal methanogen overgrowth (IMO), and intestinal sulfide overproduction (ISO). SB sampling shows that these conditions involve different microbial patterns and functional activity, symptoms, and host responses. Quantitative shotgun metagenomics provides greater taxonomic and functional resolution than culture, while metatranscriptomics reveals active microbial pathways. On top of that, host transcriptomics and proteomics contribute to the better understanding of the predominant microbial effects in host cellular mechanisms in each of the distinct small bowel overgrowth types. SIBO has been increasingly identified as a disorder of microbial ecology and function rather than bacterial quantity alone. Integrating BT with SB sampling and multi-omics approaches may improve classification, clarify symptom mechanisms, and support a more individualized treatment, although standardized methods and further clinical validation remain necessary.

Humans↗
PubMed2006

Studying the overlap between IBS and GERD: a systematic review of the literature.

Evidence points to a significant overlap between irritable bowel syndrome (IBS) and gastroesophageal reflux disease (GERD). In this study, we evaluate this overlap by conducting a systematic review of the literature. Six electronic databases from 1966 through January 2005 were screened by multiple search terms to identify all epidmiological evidence linking IBS and GERD. In addition, AGA meeting abstracts for 2003 and 2004 were also screened. All studies were validated by the authors and data extracted according to predefined criteria. As a separate search strategy, studies evaluating the prevalence of IBS and GERD in the general population were sought. These articles were obtained to compare the prevalence of IBS and GERD in the community to the degree of overlap. The search identified 997 original titles with 15 publications that fulfilled our eligibility criteria. Among the 15 studies, 7 determined the GERD maximum mean prevalence in patients already diagnosed with IBS to be 39.3% and the weighted mean 30.3%. The other 7 studies examined the prevalence of IBS in patients already diagnosed with GERD. The maximum mean prevalence of IBS in subjects with known GERD was 48.8% and the weighted mean 60.5%. Based on the prevalence of IBS (12.1%) and GERD (19.4%) in the community, the rate of IBS in the non-GERD community was calculated to be only 5.1%. There is a strong overlap between GERD and IBS that exceeds the individual presence of each condition. In the absence of GERD, IBS is relatively uncommon.

Databases as Topic↗
PubMed2006

The effect of a nonabsorbed oral antibiotic (rifaximin) on the symptoms of the irritable bowel syndrome: a randomized trial.

BACKGROUND: Alterations in gut flora may be important in the pathophysiology of the irritable bowel syndrome (IBS). OBJECTIVE: To determine whether the nonabsorbed antibiotic rifaximin is more effective than placebo in reducing symptoms in adults with IBS. DESIGN: Double-blind, randomized, placebo-controlled study. SETTING: 2 tertiary care medical centers. PARTICIPANTS: 87 patients who met Rome I criteria for IBS and were enrolled from December 2003 to March 2005. INTERVENTIONS: Participants who met enrollment criteria were randomly assigned to receive 400 mg of rifaximin 3 times daily for 10 days (n = 43) or placebo (n = 44). Eighty participants completed rifaximin therapy or placebo, and follow-up data were available for at least 34 participants per study group at any time point thereafter. MEASUREMENTS: A questionnaire was administered before treatment and 7 days after treatment. The primary outcome was global improvement in IBS. Patients were then asked to keep a weekly symptom diary for 10 weeks. RESULTS: Over the 10 weeks of follow-up, rifaximin resulted in greater improvement in IBS symptoms (P = 0.020). In addition, rifaximin recipients had a lower bloating score after treatment. LIMITATIONS: The major limitations of the study were its modest sample size and short duration and that most patients were from 1 center. CONCLUSIONS: Rifaximin improves IBS symptoms for up to 10 weeks after the discontinuation of therapy.

Adolescent↗
PubMed2006

Neomycin improves constipation-predominant irritable bowel syndrome in a fashion that is dependent on the presence of methane gas: subanalysis of a double-blind randomized controlled study.

Recent studies have shown that normalization of the lactulose breath test (LBT) with neomycin leads to a significant reduction in irritable bowel syndrome (IBS) symptoms. This subanalysis was done on the constipation-predominant IBS subgroup of patients (C-IBS) to test the ability of neomycin to improve constipation and its correlation with the elimination of methane on breath test. IBS subjects underwent LBT in a blinded fashion. They were then randomly allocated to neomycin or placebo groups. For the purpose of this analysis, only the C-IBS subjects were identified. They were then evaluated for global improvement, abdominal pain, and constipation severity. The ability of neomycin to eliminate methane and its associated improvement in constipation was also determined. One hundred eleven subjects meeting Rome I criteria for IBS were included in the study. Thirty-nine of these had C-IBS. Of these, 20 received placebo and 19 received neomycin. With neomycin, a global improvement of 36.7+/-7.9% was seen, compared to 5.0+/-3.2% for placebo (P < .001) in the intention-to-treat analysis. Constipation was improved by 32.6+/-9.9% with neomycin compared to 18.7+/-7.2% for placebo (P=.26). Of the original 111 subjects, 12 demonstrated methane on breath test. All 12 of these patients were constipation predominant. In the methane producers receiving neomycin or placebo, improvement in constipation was significantly greater in those receiving neomycin (44.0+/-12.3%) compared to placebo (5.0+/-5.1%) (P < .05). Treatment with neomycin improves constipation in C-IBS. This improvement depends on the presence and elimination of methane on breath test.

Adult↗
PubMed2006

Bacteria and irritable bowel syndrome: the evidence for small intestinal bacterial overgrowth.

Irritable bowel syndrome (IBS) is a complex, yet common diagnosis in gastroenterology. Recent data suggest the increasing importance of bacteria in the pathophysiology of IBS. Some studies have shown that IBS can be precipitated by an acute case of gastroenteritis. These pathogenic organisms may contribute to long-term gut dysfunction. In another line of effort, a growing body of evidence links IBS to the presence of excessive bacteria in the small bowel, called bacterial overgrowth. Although the means by which this is determined have been indirect, studies demonstrating the benefit of unabsorbed antibiotics suggest that reduction in gut flora is important. Further work has also examined bacterial overgrowth in the context of the various symptoms of patients with IBS. These symptom complexes include constipation, diarrhea, and alternating forms of the condition. Although this idea seems initially counterintuitive, it has been demonstrated that the fermentation of methane in the gut is associated with and can result in the slowing of intestinal transit, resulting in constipation. In this review, these topics are discussed and outlined.

Bacteria↗
PubMed2005

Methane, a gas produced by enteric bacteria, slows intestinal transit and augments small intestinal contractile activity.

The presence of methane on lactulose breath test among irritable bowel syndrome (IBS) subjects is highly associated with the constipation-predominant form. Therefore, we set out to determine whether methane gas can alter small intestinal motor function. In dogs, small intestinal fistulae were created to permit measurement of intestinal transit. Using a radiolabel, we evaluated transit during infusion of room air and subsequently methane. In this model, small intestinal infusion of methane produced a slowing of transit in all dogs by an average of 59%. In a second experiment, guinea pig ileum was pinned into an organ bath for the study of contractile activity in response to brush strokes applied to the mucosa. The force of contraction was measured both orad and aborad to the stimulus. The experiment was repeated while the bath was gassed with methane. Contractile activities orad and aborad to the stimulus were significantly augmented by methane compared with room air (P < 0.05). In a third experiment, humans with IBS who had undergone a small bowel motility study were compared such that subjects who produced methane on lactulose breath test were compared with those producing hydrogen. The motility index was significantly higher in methane-producing IBS patients (1,851 +/- 861) compared with hydrogen producers (1,199 +/- 301) (P < 0.05). Therefore, methane, a gaseous by-product of intestinal bacteria, slows small intestinal transit and appears to do so by augmenting small bowel contractile activity.

Animals↗
PubMed2005

Measurement of gastrointestinal transit.

An abnormality in transit is commonly considered to account for unexplained gastrointestinal (GI) symptoms. Since the symptoms of delayed transit overlap with those of accelerated transit, direct measurement of GI transit is needed to establish an accurate diagnosis. Similarly, since symptoms originating from one part of the gut may overlap with symptoms from another, localizing transit abnormality to one organ vs. another using direct measurement is an important part of diagnostic evaluations. Consequently, noninvasive tests of GI transit should be done early in the evaluation to guide therapy. We now have tools to measure transit accurately; results of transit tests often depend on the conditions selected for the test, so test results will match clinical expectations most closely when test conditions are selected to reproduce the circumstances for symptom production. This review describes the most commonly used methods for the measurement of GI transit including the gastric emptying test for some dyspeptic symptoms, small bowel transit test for dyspeptic symptoms and diarrhea, colonic transit test for constipation, and factors that influence the result of these studies. As we make progress in our understanding of the pathophysiology of transit disorders, the clinical usefulness of these diagnostic tests will be further enhanced.

Breath Tests↗
PubMed2004

A 14-day elemental diet is highly effective in normalizing the lactulose breath test.

Treatment of small intestinal bacterial overgrowth is frustrated by the low efficacy of antibiotics. Elemental diets have been shown to reduce enteric flora. In this study, we evaluate the ability of an elemental diet to normalize the lactulose breath test (LBT) in IBS subjects with abnormal breath test findings. Consecutive subjects with IBS and abnormal LBT suggesting the presence of bacterial overgrowth underwent a 2-week exclusive elemental diet. The diet consisted of Vivonex Plus (Novartis Nutrition Corp., Minneapolis, MN) in a quantity based on individual caloric requirement. On day 15 (prior to solid food), subjects returned for a follow-up breath test and those with an abnormal LBT were continued on the diet for an additional 7 days. The ability of an elemental diet to normalize the LBT was determined for days 15 and 21. A chart review was then conducted to evaluate any clinical benefit 1 month later. Of the 93 subjects available for analysis, 74 (80%) had a normal LBT on day 15 of the elemental diet. When those who continued to day 21 were included, five additional patients normalized the breath test (85%). On chart review, subjects who successfully normalized their breath test had a 66.4 +/- 36.1% improvement in bowel symptoms, compared to 11.9 +/- 22.0% in those who failed to normalize (P < 0.001). An elemental diet is highly effective in normalizing an abnormal LBT in IBS subjects, with a concomitant improvement in clinical symptoms.

Breath Tests↗
PubMed2004

IBS subjects with methane on lactulose breath test have lower postprandial serotonin levels than subjects with hydrogen.

We have previously shown that methane on lactulose breath test (LBT) is highly associated with constipation in IBS and that methane gas itself slows small bowel transit in dogs. Previous studies suggest that serotonin may have a role in the control of transit in IBS. In this study, we aim to evaluate the role of serotonin in methane producing IBS subjects. Rome I-positive IBS subjects were recruited into the study after exclusion criteria were met. A fasting LBT was performed after subjects filled out a questionnaire rating the degree of constipation and diarrhea. Within 7 days of this test, subjects returned fasting for determination of serotonin before and after a 75-g oral glucose meal. The serotonin response was compared between hydrogen and methane producing IBS subjects. After 2 subjects were excluded for inadequate blood samples, 18 subjects completed the study. Four of 18 subjects produced methane. The postprandial serotonin level in methane producing IBS subjects was lower than in hydrogen producers (P < 0.05). Methane producers had a reduction in serotonin after glucose. Methane producing IBS subjects have reduced postprandial serotonin. Whether methane is a surrogate marker of constipation or contributing to the reduced serotonin remains to be determined.

Adolescent↗
PubMed2003

Methane production during lactulose breath test is associated with gastrointestinal disease presentation.

It has recently been determined that there is an increased prevalence of bacterial overgrowth in IBS. Since there are two gases (hydrogen and methane) measured on lactulose breath testing, we evaluated whether the different gas patterns on lactulose breath testing coincide with diarrhea and constipation symptoms in IBS and IBD. Consecutive patients referred to the gastrointestinal motility program at Cedars-Sinai Medical Center for lactulose breath testing were given a questionnaire to evaluate their gastrointestinal symptoms. Symptoms were graded on a scale of 0-5. Upon completion of the breath test, the results were divided into normal, hydrogen only, hydrogen and methane, and methane only positive breath tests. A comparison of all subjects and IBS subjects was undertaken to evaluate diarrhea and constipation with regards to the presence or absence of methane. This was further contrasted to Crohn's and ulcerative colitis (UC) patients in the database. After exclusion criteria, 551 subjects from the database were available for comparison. Of the 551 subjects (P < 0.05, one-way ANOVA) and in a subgroup of 296 IBS subjects (P < 0.05, one-way ANOVA), there was a significant association between the severity of reported constipation and the presence of methane. The opposite was true for diarrhea (P < 0.001). If a breath test was methane positive, this was 100% associated with constipation predominant IBS. Furthermore, IBS had a greater prevalence of methane production than Crohn's or UC. In fact, methane was almost nonexistent in the predominantly diarrheal conditions of Crohn's and UC. In conclusion, a methane positive breath test is associated with constipation as a symptom.

Breath Tests↗
PubMed2003

Normalization of lactulose breath testing correlates with symptom improvement in irritable bowel syndrome. a double-blind, randomized, placebo-controlled study.

OBJECTIVE: We have recently found an association between abnormal lactulose breath test (LBT) findings and irritable bowel syndrome (IBS). The current study was designed to test the effect of antibiotic treatment for IBS in a double-blind fashion. METHODS: Consecutive IBS subjects underwent an LBT with the results blinded. All subjects were subsequently randomized into two treatment groups (neomycin or placebo). The prevalence of abnormal LBT was compared with a gender-matched control group. Seven days after completion of treatment, subjects returned for repeat LBT. A symptom questionnaire was administered on both days. RESULTS: After exclusion criteria were met, 111 IBS subjects (55 neomycin, 56 placebo) entered the study, with 84% having an abnormal LBT, compared with 20% in healthy controls (p < 0.01). In an intention-to-treat analysis of all 111 subjects, neomycin resulted in a 35.0% improvement in a composite score, compared with 11.4% for placebo (p < 0.05). Additionally, patients reported a percent bowel normalization of 35.3% after neomycin, compared with 13.9% for placebo (p < 0.001). There was a graded response to treatment, such that the best outcome was observed if neomycin was successful in normalizing the LBT (75% improvement) (one-way ANOVA, p < 0.0001). LBT gas production was associated with IBS subgroup, such that methane excretion was 100% associated with constipation-predominant IBS. Methane excretors had a mean constipation severity of 4.1, compared with 2.3 in all other subjects (p < 0.001). CONCLUSIONS: An abnormal LBT is common in subjects with IBS. Normalization of LBT with neomycin leads to a significant reduction in IBS symptoms. The type of gas seen on LBT is also associated with IBS subgroup.

Adult↗
PubMed2003

Breath testing to evaluate lactose intolerance in irritable bowel syndrome correlates with lactulose testing and may not reflect true lactose malabsorption.

OBJECTIVES: An increased prevalence of lactose intolerance is seen in irritable bowel syndrome (IBS). Recently, we demonstrated a high prevalence of abnormal lactulose breath test results in IBS suggesting bacterial overgrowth. Because symptoms of lactose intolerance result from bacterial fermentation, the purpose of this study was to determine whether an abnormal lactose breath test is reflective of malabsorption or early presentation to bacteria. METHODS: Subjects with diarrhea-predominant IBS were enrolled. On day 1, subjects underwent a lactulose breath test after an overnight fast. Within 1 wk, subjects returned after fasting for a lactose breath test with simultaneous blood glucose measurements every 15 min to complete a lactose tolerance test (LTT). Symptoms were evaluated 3 h after lactose administration. RESULTS: Twenty subjects completed the study. One subject inadvertently received dextrose through the intravenous and was excluded. Of the remaining 19 subjects, three (16%) had an abnormal LTT suggesting malabsorption. In all, 10 subjects (53%) had an abnormal lactose breath test, 14 (74%) had an abnormal lactulose breath test, and 11 (58%) had symptoms after lactose administration. The agreement with symptoms was moderate (kappa = 0.47) and fair (kappa = 0.24) when compared to the lactose breath test and LTT, respectively. There was a fair correlation between lactose breath test and LTT (kappa = 0.29). However, lactose breath test hydrogen levels >166 ppm were universally predictive of abnormal LTT. Finally, a significant correlation was seen between the hydrogen production on lactose and lactulose breath test (r = 0.56, p = 0.01). CONCLUSIONS: Lactose breath testing in IBS subjects does not seem to reflect malabsorption; it may be an indicator of abnormal lactulose breath test, suggesting bacterial overgrowth.

Adult↗
PubMed2002

Lower frequency of MMC is found in IBS subjects with abnormal lactulose breath test, suggesting bacterial overgrowth.

We have recently described an association between irritable bowel syndrome (IBS) and abnormal lactulose breath test, suggesting small intestinal bacterial overgrowth (SIBO). However, the mechanism by which SIBO develops in IBS is unknown. In this case-control study we evaluate the role of small intestinal motility in subjects with IBS and SIBO. Small intestinal motility was studied in consecutive IBS subjects with SIBO on lactulose breath test. After fluoroscopic placement of an eight-channel water-perfused manometry catheter, 4-hr fasting recordings were obtained. Based on this, the number and duration of phase III was compared to 30 control subjects. To test whether there was a relationship between the motility abnormalities seen and the SIBO status of the patient at the time of the motility, subjects with a breath test within 5 days of the antroduodenal manometry were also compared. Sixty-eight subjects with IBS and SIBO were compared to controls. The number of phase III events was 0.7 +/- 0.8 in IBS subjects and 2.2 +/- 1.0 in controls (P < 0.000001). The duration of phase III was 305 +/- 123 sec in IBS subjects and 428 +/- 173 in controls (P < 0.001). Subjects whose SIBO was still present at the time of manometry had less frequent phase III events than subjects with eradicated overgrowth (P < 0.05). In conclusion, phase III is reduced in subjects with IBS and SIBO. Eradication of bacterial overgrowth seems to result in some normalization of motility.

Adult↗
PubMed2002

Increased prevalence of irritable bowel syndrome in patients with gastroesophageal reflux.

GOALS: To determine the prevalence of irritable bowel syndrome (IBS) in subjects with gastroesophageal reflux disease (GERD) compared with non-GERD controls. STUDY: Two hundred subjects were identified from a list of Cedars-Sinai Medical Foundation patients and gastroenterology motility practice subjects with and without a potential diagnosis of GERD. All subjects were then evaluated independently by two blinded physicians who were asked to identify subjects with GERD based on taking a history (gold standard). A follow-up questionnaire was later mailed to patients. This questionnaire included Rome I criteria for IBS. The prevalence of IBS was compared between GERD and non-GERD subjects. Finally, to further strengthen the method, a retrospective review of all subjects' charts was conducted to identify patients who had had 24-hour pH tests, and the prevalence of IBS was determined in this subgroup. RESULTS: Of the 200 subjects, 90 (45%) patients returned the questionnaire. After excluding subjects with IBD and incomplete questionnaires, there were 84 subjects (35 with GERD) included in the analysis. Of the 35 GERD subjects, 25 (71%) were Rome I criteria positive for IBS, whereas only 17 of the 49 (35%) non-GERD subjects had IBS (odds ratio = 54.7, CI = 1.7-13.5, p < 0.01). In 11 of the GERD subjects a 24-hour pH study was available and confirmed GERD. Of these 11 subjects, 7 (64%) met Rome I criteria for IBS. CONCLUSION: There is a higher prevalence of IBS in subjects with GERD compared with subjects without GERD.

Colonic Diseases, Functional↗