Gene Kim’s research while affiliated with Cedars-Sinai Medical Center and other places

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Publications (31)


Figure 1. Shannon diversity indices for duodenal samples from IBS and healthy control subjects. The vertical axis represents the average diversity index from 1000 resampling trials, whereas the horizontal axis represents the number of sequences included in the calculation. The blue line represents healthy control communities, and the red line represents the IBS communities. The error bars represent the standard deviation of the measurements. p = 0.001953.  
Figure 2. Jackknifed hierarchical clustering between IBS (D) and healthy (H) subjects. The internal nodes are labeled by the p-Value, calculated from 1000 jackknifed replications, and are shown in red if the p < 0.05. The cluster indicates that IBS subjects are statistically significantly clustering together, separating from the healthy controls.  
Figure 5. Comparison of qPCR results in patients with diarrheapredominant irritable bowel syndrome (D-IBS) and patients with constipation-predominant or alternating IBS (C-/A-IBS): A) qPCR for Escherichia coli; and B) ratio of qPCR for E. coli to Aeromonas spp. p-Values indicate comparisons between D-IBS and C-/A-IBS.  
Molecular assessment of differences in the duodenal microbiome in subjects with irritable bowel syndrome
  • Article
  • Full-text available

April 2015

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575 Reads

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102 Citations

Scandinavian Journal of Gastroenterology

Evangelos Giamarellos-Bourboulis

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Breath testing and duodenal culture studies suggest that a significant proportion of irritable bowel syndrome (IBS) patients have small intestinal bacterial overgrowth. In this study, we extended these data through 16S rDNA amplicon sequencing and quantitative PCR (qPCR) analyses of duodenal aspirates from a large cohort of IBS, non-IBS and control subjects. Consecutive subjects presenting for esophagogastroduodenoscopy only and healthy controls were recruited. Exclusion criteria included recent antibiotic or probiotic use. Following extensive medical work-up, patients were evaluated for symptoms of IBS. DNAs were isolated from duodenal aspirates obtained during endoscopy. Microbial populations in a subset of IBS subjects and controls were compared by 16S profiling. Duodenal microbes were then quantitated in the entire cohort by qPCR and the results compared with quantitative live culture data. A total of 258 subjects were recruited (21 healthy, 163 non-healthy non-IBS, and 74 IBS). 16S profiling in five IBS and five control subjects revealed significantly lower microbial diversity in the duodenum in IBS, with significant alterations in 12 genera (false discovery rate < 0.15), including overrepresentation of Escherichia/Shigella (p = 0.005) and Aeromonas (p = 0.051) and underrepresentation of Acinetobacter (p = 0.024), Citrobacter (p = 0.031) and Microvirgula (p = 0.036). qPCR in all 258 subjects confirmed greater levels of Escherichia coli in IBS and also revealed increases in Klebsiella spp, which correlated strongly with quantitative culture data. 16S rDNA sequencing confirms microbial overgrowth in the small bowel in IBS, with a concomitant reduction in diversity. qPCR supports alterations in specific microbial populations in IBS.

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Methane-producing human subjects have higher serum glucose levels during oral glucose challenge than non-methane producers: A pilot study of the effects of enteric methanogens on glycemic regulation

January 2014

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381 Reads

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19 Citations

Research Journal of Endocrinology and Metabolism

Background: Recent studies support that intestinal microbes contribute to human disease, and enteric methanogens have been specifically linked to altered gut metabolism and weight gain. In this study, we tested








Citations (13)


... Uprkos nedostatku konsenzusa o razlikama u crevnom mikrobiomu između pacijenata sa IC i zdrave populacije, specifične mikrobne promene koreliraju sa ishodom bolesti i to je pokazano prethodnim molekularnim metodama koje opisuju obilje Gram-negativnih bakterija u mikrobiomu tankog creva pacijenata sa IC 34,35 . Studije koje su ispitivale fekalne uzorke potvrdile su smanjenje vrsta iz roda Bifidobacterium i Lactobacillus, a sa druge strane, povećano prisustvo Firmicutes/Bacteroidetes. ...

Reference:

The role of the connection between intestinal microbiota and brain in the pathogenesis of functional gastrointestinal disorders
267 The First Large Scale Deep Sequencing of the Duodenal Microbiome in Irritable Bowel Syndrome Reveals Striking Differences Compared to Healthy Controls

Gastroenterology

... 4,11 Increased understanding of the pathophysiology of IBS by the lead author and others has helped lead to the development of a novel IBS diagnostic blood panel (Commonwealth Laboratories, Inc, Salem, MA). [18][19][20][21][22][23][24] The biomarker consists of a simple blood test measurement of circulating antibodies to cytolethal distending toxin B (anti-CdtB) and vinculin (antivinculin). Studies in a postinfectious animal model have shown that an IBS-like phenotype was produced when host antibodies to CdtB cross-reacted with vinculin in the host gut. 25 This IBS diagnostic blood panel was recently validated in a large study that enrolled patients with IBS-D (n ¼ 2375), IBD (n ¼ 142), or celiac disease (n ¼ 121) and healthy control subjects (n ¼ 43). ...

Tu2029 Deep Sequencing Reveals That the Microbiome of the Human Duodenum Is Unique and Unrelated to Stool Bacterial Profiling
  • Citing Conference Paper
  • May 2013

Gastroenterology

... Further, rats which gained most weight were those with the most bowel segments colonized with M. smithii, irrespective of whether or not they were on high-fat chow (23). An important aspect of this study was that it demonstrated M. smithii colonization throught the small intestine, a finding we later confirmed in human duodenal samples (25). This was significant as M. smithii had previously been thought to only colonize the large intestine, weakening the likelihood that it could play a significant role in caloric harvest and weight gain. ...

Tu2030 Quantitation of Bacteria in Duodenal Aspirates by qPCR Appears to Identify Viable Organisms in IBS
  • Citing Article
  • May 2013

Gastroenterology

... Treatment with lovastatin lactone resulted in a significant reduction in M. smithii levels in the distal small bowel (ileum), and treatment with lovastatin hydroxyacid resulted in looser stools, when compared to rats maintained on the HFD, indicating that inhibiting methanogens resulted in normalization of % wet weights away from the constipation-like phenotype. Of note, while methanogens are typically most abundant in the colon in humans, we have previously demonstrated high abundance of methanogens in the small intestine, both in rats [12] and in some human subjects [27]. These findings suggest that increased levels of methanogens, particularly M. smithii, directly contribute to a constipation phenotype in subjects with IBS-C. ...

439 Methanobrevibacter Smithii is Found in Human Duodenum and is Associated With Altered Luminal Cytokines
  • Citing Article
  • May 2012

Gastroenterology

... 8,10 Furthermore, the development of antibodies to CdtB was associated with altering gut microbiota associated with reducing specific interstitial cells of Cajal (ICC). 11,12 These findings are possibly due to the ability of anti-CdtB to cross-react with the host cell adhesion protein vinculin present in interstitial cells of Cajal and the myenteric ganglia that control the normal activity of the intestinal tract, including phase III of inter-digestive motor activity. 13 Absence or decrease in phase III contractions results in small intestinal bacterial overgrowth in animal models and human patients with IBS. ...

Tu2110 Circulating Antibodies to Cytolethal Distending Toxin B Correlate With the Development of Small Intestinal Bacterial Overgrowth in a Rat Model of Post-Infectious IBS
  • Citing Article
  • May 2013

Gastroenterology

... Following from this, methane producers also had worse glucose tolerance compared to nonmethane producers 83 , and pharmacologically reducing breath methane (through antibiotic use) in obese patients improved glucose tolerance 84 . Patients who were positive for both methane and hydrogen also displayed reduced (prorated) percentage changes in BMI following bariatric surgery 85 . ...

Methane-producing human subjects have higher serum glucose levels during oral glucose challenge than non-methane producers: A pilot study of the effects of enteric methanogens on glycemic regulation

Research Journal of Endocrinology and Metabolism

... A recent study showed that using a single--lumen catheter to aspirate small bowel fluid resulted in a 19.6% contamination rate (25) . Furthermore, only 40% of the total gut flora can be identified using conventional culture methods (26) . Not all hydrogen-producing bacteria are culturable, and some microbiology laboratories are not able to culture methanogenic archaea (27) . ...

Molecular assessment of differences in the duodenal microbiome in subjects with irritable bowel syndrome

Scandinavian Journal of Gastroenterology

... Among adults only, methane excretion was significantly associated with constipation (OR = 3.47; 95% CI, 1.84-6.54). As shown by Kim et al, 85 the responsible strain in these patients was the M. smithii. The combination of rifaximin plus neomycin proved to be effective in these cases. ...

T1832 Methanobrevibacter Smithii is Prominent in Stool of Subjects With Constipation Predominant IBS and Methane on Lactulose Breath Test
  • Citing Article
  • May 2010

Gastroenterology

... Some evidence supports that methanogens have an impact on host metabolism in mouse models [11]. For example, mice inoculated with methanogens showed increased weight and adiposity despite consuming the same amount of food as controls [21,22]. However, the role of methanogens in human metabolism is complicated and controversial. ...

Intestinal Methanobrevibacter smithii but Not Total Bacteria Is Related to Diet-Induced Weight Gain in Rats
  • Citing Article
  • April 2013

Obesity

... The research results of Lauritano et al. showed that the overall incidence of adverse events of rifaximin was significantly lower than that of metronidazole group, showing that the side effects of non-absorbable antibiotics were less [154]. The results of a drug resistance study showed that the concentration of stool Staphylococcus spp and stool Coliforms would be temporarily reduced during the treatment of rifaximin [155]. Xu et al. showed that rifaximin changed the bacterial population in the ileum of rats, increasing the relative abundance of Lactobacillus, and preventing mucosal inflammation and impaired intestinal barrier [156]. ...

The Effect of Rifaximin on Gut Flora and Staphylococcus Resistance

Digestive Diseases and Sciences