Naotaka Ogasawara

Aichi Medical University, Касугай, Aichi, Japan

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Publications (81)270.87 Total impact

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    ABSTRACT: Bleeding remains a serious complication after endoscopic submucosal dissection (ESD). Second-look endoscopy for hemostasis helps prevent post-ESD bleeding. We investigated the relationships between patient characteristics, tumor characteristics, and the Forrest classification for exposed vessels on artificial ulcers after ESD and evaluated whether hemostasis during second-look endoscopy was useful for preventing post-ESD bleeding. We analyzed 250 patients (265 lesions) who underwent ESD for gastric neoplasms. Vessels classified by Forrest classifications during scheduled second-look endoscopy were analyzed for associations with patient characteristics, tumor characteristics, and recurrent bleeding. Two of 250 patients (0.8%) underwent emergency hemostatic endoscopy before scheduled second-look endoscopy. The remaining 248 patients (99.2%) underwent scheduled second-look endoscopy on the day after ESD. Patients with Forrest classification Ia, Ib, or IIa vessels had a significantly higher risk for recurrent bleeding after scheduled second-look endoscopy compared with patients with IIb or III vessels according to univariate analysis (P<0.05) and multivariate logistic regression analysis (odds ratio: 3.45; 95% confidence interval: 1.04-11.41; P=0.042). Univariate analysis indicated that hemodialysis correlated significantly with the presence of Ia, Ib, or IIa vessels compared with that of IIb or III vessels found during second-look endoscopy (P<0.05). Multivariate analysis indicated a significant relationship between hemodialysis and recurrent bleeding after second-look endoscopy (odds ratio: 10.05; 95% confidence interval: 1.97-51.26; P=0.006). Hemodialysis is a risk factor for post-ESD bleeding. Proper classification of exposed vessels within post-ESD ulcers according to the Forrest classification using second-look endoscopy might help predict or prevent recurrent bleeding.
    European journal of gastroenterology & hepatology 06/2015; DOI:10.1097/MEG.0000000000000419
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    ABSTRACT: Helicobacter heilmannii-like organisms (HHLOs) are associated with mucosa-associated lym-phoid tissue lymphoma and peptic ulcer. However, the sensitivity of diagnostic tests for HHLOs, such as rapid urease test (RUT), urea breath test (UBT) and blood antibody, is not high. Tightly coiled spiral microorganisms were found in the gastric mucosal biopsy specimen of a 48-year-old asymptomatic woman. Her findings were positive for RUT and UBT, but negative for blood antibody and stool antigen against H. pylori. A 7-day course of esomepra-zole, amoxicillin and clarithromycin was administered, resulting in the successful eradication of the HHLOs. Analysis of the 16S rRNA and urease genes suggested a diagnosis of the HHLO H. suis. The sensitivity results of RUT, UBT, culture, blood antibody, immunohistochem-istry and stool antigen were 40.0, 14.8, 0, 23.1, 40.0 and 0%, respectively. We report asymp-tomatic nodular gastritis due to an HHLO. Histological techniques, most likely with smears, are expected to be the most effective method for diagnosing infections by HHLOs, and genetic diagnosis by polymerase chain reaction can be very useful to identify the species of HHLOs.
    Case Reports in Gastroenterology 05/2015; 9(2):179-187. DOI:10.1159/000431169
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    ABSTRACT: To investigate the pathophysiology of functional heartburn (FH) in Japanese patients. A total of 111 patients with proton pump inhibitor (PPI)-refractory non-erosive gastroesophageal reflux disease underwent intraesophageal pressure testing and 24-h multichannel intraluminal impedance-pH (24MII-pH) testing. The patients also completed several questionnaires while they were receiving the PPI treatment, including the questionnaire for the diagnosis of reflux disease (QUEST), the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG), the gastrointestinal symptoms rating scale (GSRS), SF-36, and the Cornell Medical Index (CMI). The subjects were classified into FH and endoscopy-negative reflux disease (ENRD) groups based on the Rome III criteria. Thirty-three patients with esophageal motility disorder were excluded from this study, while 22 patients with abnormal esophageal acid exposure time (pH-POS) and 34 with hypersensitive esophagus (HE) were included in the ENRD group. The FH group included 22 patients with no reflux involvement. Sex, age, and body mass index did not differ significantly between the groups. The mean SF-36 values were < 50 (normal) for all scales in these groups, with no significant differences. The GSRS scores in these groups were not different and showed overlap with other gastrointestinal symptoms. The QUEST and the FSSG scores did not differ significantly between the groups. Neuroticism was diagnosed using the CMI questionnaire in 17 of the 78 included subjects within the pH-POS (n = 4), HE (n = 8), and FH (n = 5) groups, with no significant differences. Clinical characteristics of the FH and PPI-refractory ENRD groups were similar. Therefore, esophageal function should be examined via manometry and 24MII-pH testing to differentiate between them.
    04/2015; 21(16):5009-16. DOI:10.3748/wjg.v21.i16.5009
  • Gastroenterology 04/2015; 148(4):S-541. DOI:10.1016/S0016-5085(15)31813-8
  • Digestion 01/2015; 91(1):93-93.
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    ABSTRACT: The number of reported cases of alpha-fetoprotein (AFP)-producing gastric cancer has gradually increased, with a reported prevalence of 1.3-1.5% of all gastric cancer cases. However, reports of gastric cancer accompanied by elevated serum levels of both AFP and protein induced by vitamin K antagonist-II (PIVKA-II) are rare. The prognosis of AFP- and PIVKA-II-producing gastric cancer has been reported to be very poor because the tumor cells were considered to have a high malignant potential and the cancer progressed rapidly. We described a case of gastric cancer producing AFP and PIVKA-II in which chemotherapy was effective and resulted in prolonged survival, and these two tumor markers were useful for monitoring the treatment response. Routine health screening using upper abdominal ultrasonography revealed hepatic tumors in an apparently healthy 65-year-old man. Whole-body computed tomography (CT) revealed multiple hepatic tumors, and an esophagogastroduodenoscopy (EGD) revealed a Bormann type 3 tumor in the lower stomach. A biopsy specimen confirmed that the tumor was immunohistochemically positive for AFP, PIVKA-II, and human epidermal growth factor receptor 2. After chemotherapy, the gastric tumor appeared as a small elevated lesion on EGD, and CT revealed a remarkable reduction in the size of the metastatic liver tumors. The patient is still alive, 35 months after the initial chemotherapy.
    Case Reports in Gastroenterology 01/2015; 9(1):113-9. DOI:10.1159/000382072
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    ABSTRACT: A 47-year-old man was found to have a 3-cm epiphrenic esophageal diverticulum on an upper gastrointestinal (UGI) barium study. He developed the symptoms of heartburn approximately 12 months later. UGI endoscopy indicated non-erosive gastroesophageal reflux disease (NERD) and an epiphrenic esophageal diverticulum. A proton pump inhibitor (PPI) did not relieve the symptoms. An UGI barium study at that time showed that the epiphrenic esophageal diverticulum had enlarged to 7 cm, and esophageal manometry showed findings of achalasia and diffuse esophageal spasm (DES), thus vigorous achalasia was diagnosed. Resection of the epiphrenic esophageal diverticulum, myotomy, and fundoplication (the Heller-Dor procedure) were successfully performed and no postoperative symptoms were encountered.
    Internal Medicine 01/2015; 54(13):1609-12. DOI:10.2169/internalmedicine.54.4506
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    ABSTRACT: Helicobacter heilmannii-like organisms (HHLOs) are associated with mucosa-associated lym-phoid tissue lymphoma and peptic ulcer. However, the sensitivity of diagnostic tests for HHLOs, such as rapid urease test (RUT), urea breath test (UBT) and blood antibody, is not high. Tightly coiled spiral microorganisms were found in the gastric mucosal biopsy specimen of a 48-year-old asymptomatic woman. Her findings were positive for RUT and UBT, but negative for blood antibody and stool antigen against H. pylori. A 7-day course of esomepra-zole, amoxicillin and clarithromycin was administered, resulting in the successful eradication of the HHLOs. Analysis of the 16S rRNA and urease genes suggested a diagnosis of the HHLO H. suis. The sensitivity results of RUT, UBT, culture, blood antibody, immunohistochem-istry and stool antigen were 40.0, 14.8, 0, 23.1, 40.0 and 0%, respectively. We report asymp-tomatic nodular gastritis due to an HHLO. Histological techniques, most likely with smears, are expected to be the most effective method for diagnosing infections by HHLOs, and genetic diagnosis by polymerase chain reaction can be very useful to identify the species of HHLOs.
    Case Reports in Gastroenterology 01/2015; 9:179-187.
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    ABSTRACT: Abstract Background: We reported that deficiency of the eNOS protein exacerbates colitis induced by dextran sodium sulfate (DSS-induced colitis) [1]. However, the role of eNOS in colitis remains controversial. Therefore, we studied how over-expression of eNOS affected this inflammatory condition, using vascular endothelial cells and mice as in vitro and in vivo models, respectively. Furthermore, we investigated the influence of a polymorphism in the eNOS gene on the clinical features of ulcerative colitis (UC). Methods: We examined the effect of eNOS overexpression on the expression of adhesion molecules in the endothelium, and assessed the degree of DSS-induced colitis in eNOS transgenic (eNOS-Tg) mice. We also investigated the relationship between a polymorphism in the eNOS gene and clinical features of patients with UC. Results: The expression of adhesion molecules, under inflammatory conditions, was attenuated in eNOS gene-transfected vascular endothelial cells, as measured by western blot analysis. Symptoms of DSS-induced colitis were likewise attenuated in eNOS-Tg mice, which exhibited lower weight loss, mortality, histological damage (by inflammation score and crypt damage score), and colonic myeloperoxidase activity, TNF-α expression, and MAdCAM-1 expression than in wild-type mice. Furthermore, there was a significant relationship between intractable cases of UC and a polymorphism in the eNOS gene promoter (c.-786 T>C), that decreases eNOS expression. Conclusion: The eNOS gene plays an important role in the regulation of colonic inflammation. The level of eNOS expression may be a predictive marker for prognosis of UC, and eNOS expression may be a novel therapeutic target.
    Free Radical Research 10/2014; DOI:10.3109/10715762.2014.977788
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    ABSTRACT: A 53-year-old man was admitted to our hospital with anterior chest pain and difficulty swallowing. Computed tomography revealed significant esophageal wall thickening. Esophageal intraluminal manometry revealed uncoordinated contraction and strong peristaltic pressure associated with the chest pain. The patient was subsequently diagnosed with diffuse esophageal spasm (DES). His serum immunoglobulin E level was high, and peripheral blood eosinophilia was observed. No eosinophilic infiltration was detected in the esophageal mucosa on endoscopic biopsy. It was presumed that this case of DES was induced by allergic disease. Treatment with 30 mg of oral prednisolone led to a prompt resolution of symptoms;the thickness of the esophageal wall decreased, and the simultaneous contractions disappeared. However, given the presence of a strong peristaltic wave, nutcracker esophagus (NE) was also suspected. This was a rare case of atypical DES induced by allergic disease and associated with NE.
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    ABSTRACT: Esophageal carcinosarcoma is a rare malignant neoplasm consisting of both carcinomatous and sarcomatous components. It is generally treated by surgery, radiotherapy and chemotherapy according to the protocols used for other esophageal cancers. However, the treatment of esophageal carcinosarcoma by radiotherapy alone before surgery has not been previously described. We report a patient with a rapidly growing esophageal carcinosarcoma that was efficiently reduced by neoadjuvant radiotherapy alone. A previously healthy 69-year-old man was admitted with dysphagia. Initial esophagogastroduodenoscopy (EGD) revealed a small nodular polypoid lesion of about 10 mm in the middle esophagus. A second EGD 1 month later showed that the tumor had expanded into a huge mass. A biopsy specimen revealed that the tumor comprised squamous cell carcinoma with spindle cell components, and the tumor was diagnosed as carcinosarcoma which was diagnosed as stage I (T1bN0M0). Due to renal dysfunction, the patient was treated with neoadjuvant radiotherapy (40 Gy) without chemotherapy. A third EGD 1 month later revealed remarkable tumor reduction. He then underwent total esophagectomy with regional lymph node dissection (pStage 0, pT1aN0M0). After surgical operation, the patient was followed up without adjuvant therapy. Whole body computed tomography revealed lung metastasis 14 months after surgery, and the patient died 2 months later. The neoadjuvant radiotherapy for esophageal carcinosarcoma was considered to have contributed to the subsequent surgery and his prolonged survival time. Thus, radiotherapy alone might be a suitable neoadjuvant therapy for esophageal carcinosarcomas.
    Case Reports in Gastroenterology 05/2014; 8(2):227-34. DOI:10.1159/000365320
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    ABSTRACT: Despite improvements in endoscopic hemostasis and pharmacological therapies, upper gastrointestinal (UGI) ulcers repeatedly bleed in 10% to 20% of patients, and those without early endoscopic reintervention or definitive surgery might be at a high risk for mortality. This study aimed to identify the risk factors for intractability to initial endoscopic hemostasis. We analyzed intractability among 428 patients who underwent emergency endoscopy for bleeding UGI ulcers within 24 hours of arrival at the hospital. Durable hemostasis was achieved in 354 patients by using initial endoscopic procedures. Sixty-nine patients with Forrest types Ia, Ib, IIa, and IIb at the second-look endoscopy were considered intractable to the initial endoscopic hemostasis. Multivariate analysis indicated that age ≥70 years (odds ratio [OR], 2.06; 95% confidence interval [CI], 1.07 to 4.03), shock on admission (OR, 5.26; 95% CI, 2.43 to 11.6), hemoglobin <8.0 mg/dL (OR, 2.80; 95% CI, 1.39 to 5.91), serum albumin <3.3 g/dL (OR, 2.23; 95% CI, 1.07 to 4.89), exposed vessels with a diameter of ≥2 mm on the bottom of ulcers (OR, 4.38; 95% CI, 1.25 to 7.01), and Forrest type Ia and Ib (OR, 2.21; 95% CI, 1.33 to 3.00) predicted intractable endoscopic hemostasis. Various factors contribute to intractable endoscopic hemostasis. Careful observation after endoscopic hemostasis is important for patients at a high risk for incomplete hemostasis.
    03/2014; 47(2):162-73. DOI:10.5946/ce.2014.47.2.162
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    ABSTRACT: Background: The symptom improvement rate is low with proton pump inhibitors (PPIs) in nonerosive reflux disease (NERD). The underlying pathogenic mechanism is complex. Esophageal motility disorders (EMDs) are thought to be a factor, but their prevalence, type, symptoms and the role played by gastroesophageal reflux (GER) in symptom onset have not been fully investigated. Aim: To investigate the role of GER in symptom onset in PPI-refractory NERD patients with EMDs. Methods: This study comprised 76 patients with PPI-refractory NERD. Manometry was performed during PPI treatment and patients were divided into an EMD group and normal motility (non-EMD) group. Then, multichannel intraluminal impedance-pH monitoring was performed and medical interviews were conducted. Results: Nineteen patients (25%) had an EMD. Data were compared between 17 patients, excluding 2 with achalasia and 57 non-EMD patients. No significant differences were observed between groups in 24-hour intraesophageal pH <4 holding time (HT), mean number of GER episodes or mean number of proximal reflux episodes. The reflux-related symptom index (≥50%) showed a relationship between reflux and symptoms in 70.5% of EMD patients and 75% of non-EMD patients. In the EMD group, the score for FSSG (Frequency Scale for the Symptoms of GERD) question (Q)10 was significantly correlated with the number of GER episodes (r = 0.58, p = 0.02) and the number of proximal reflux episodes (r = 0.63, p = 0.02). In addition, the score for Q9 tended to be correlated with the number of GER episodes (r = 0.44, p = 0.06). Conclusion: Our results suggest that some PPI-refractory NERD patients have EMDs, and that GER plays a role in symptom onset. © 2014 S. Karger AG, Basel.
    Digestion 01/2014; 89(1):61-7. DOI:10.1159/000356222
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    ABSTRACT: Gastritis cystica profunda (GCP) consists of hyperplasia and cystic dilatation of the gastric glands extending into the submucosa. It occurs in the residual stomach post surgery and in the unoperated stomach. GCP is considered a benign lesion, but there is controversy about its malignant potential. We report a case of early gastric cancer arising from GCP treated by endoscopic submucosal dissection (ESD) in a 55-year-old unoperated man. Upper gastrointestinal endoscopy revealed a 15-mm diameter submucosal tumor (SMT) in the upper corpus of the stomach. The surface had angiotelectasia and slight depression covered with normal mucosa. Neither ulceration nor erosion was seen. Narrow-band imaging endoscopy showed no abnormalities suggesting gastric cancer. Endoscopic ultrasonography visualized the internally low-echoic SMT, harboring tiny cystic lesions, mainly within the second and third layers of the gastric wall. The SMT was removed by ESD to avoid retention and allow for comprehensive diagnosis. It was diagnosed as GCP with partial well-differentiated adenocarcinoma without involvement of the lateral and deep margins, lymphatic invasion, vascular invasion and perineural invasion. The gastric epithelium comprised normal mucosa without dysplasia. ESD seems to be useful for the diagnosis of SMT, including GCP harboring gastric cancer, and avoids unnecessary surgical procedures.
    Case Reports in Gastroenterology 01/2014; 8(3):270-275. DOI:10.1159/000368076
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    ABSTRACT: Long-term administration of low-dose aspirin (LDA) is associated with a greater risk of adverse events, including gastroduodenal ulcers. The purpose of this study was to identify the risk factors for and assess the role of medication use in the development of peptic ulcer disease in Japanese patients with no history of peptic ulcers. Consecutive outpatients receiving LDA (75 mg/day) who underwent esophagogastroduodenoscopy between January and December 2010 were enrolled. Clinical parameters, peptic ulcer history, concomitant drugs, the presence of Helicobacter pylori infection, reason for endoscopy, and endoscopic findings were analysed. Of 226 total patients, 14 (6.2%) were endoscopically diagnosed with peptic ulcer. Age, sex, current smoking status, current alcohol consumption, endoscopic gastric mucosal atrophy, and abdominal symptoms were not significantly associated with peptic ulcers. Diabetes mellitus was more frequent (42.9% vs. 16.5%; P = 0.024) in patients with peptic ulcers than in those without peptic ulcers. Using multiple logistic regression analysis, co-treatment with anticoagulants or proton pump inhibitors (PPIs) was significantly associated with increased and decreased risk for peptic ulcer, respectively (odds ratio [OR], 5.88; 95% confidence interval [CI], 1.19 - 28.99; P = 0.03 and OR, 0.13; 95% CI, 0.02 - 0.73; P = 0.02, respectively). Co-treatment with additional antiplatelet agents, H2-receptor antagonists, angiotensin II Type 1 receptor blockers, angiotensin-converting enzyme inhibitor, 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor, or nonsteroidal anti-inflammatory drugs was not associated with peptic ulcer development. The use of PPIs reduces the risk of developing gastric or duodenal ulcers in Japanese patients taking LDA without pre-existing gastroduodenal ulcers. However, this risk is significantly increased in both patients ingesting anticoagulants and patients with diabetes. These results may help identify patients who require intensive prophylaxis against aspirin-induced peptic ulcers.
    BMC Research Notes 11/2013; 6(1):455. DOI:10.1186/1756-0500-6-455
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    ABSTRACT: Short-chain fatty acids (SCFAs), which are produced by the fermentation of dietary fiber by intestinal microbiota, may positively influence immune responses and protect against gut inflammation. SCFAs bind to G protein-coupled receptor 43 (GPR43). Here, we show that SCFA-GPR43 interactions profoundly affect the gut inflammatory response. Colitis was induced by adding dextran sulfate sodium to the drinking water of GPR43 knockout (-/-) and wild-type mice. Dextran sulfate sodium-treated GPR43 mice exhibited weight loss, increased disease activity index (a combined measure of weight loss, rectal bleeding, and stool consistency), decreased hematocrit, and colon shortening, resulting in significantly worse colonic inflammation than in wild-type mice. Tumor necrosis factor alpha and interleukin 17 protein levels in the colonic mucosa of GPR43 mice were significantly higher than in wild-type mice. Treatment of wild-type mice with 150 mM acetate in their drinking water markedly improved these disease indices, with an increase in colon length and decrease in the disease activity index; however, it had no effect on GPR43 mice. Mononuclear cell production of tumor necrosis factor alpha after lipopolysaccharide stimulation was suppressed by acetate. This effect was inhibited by anti-GPR43 antibody. SCFA-GPR43 interactions modulate colitis by regulating inflammatory cytokine production in mononuclear cells.
    Inflammatory Bowel Diseases 10/2013; 19(13). DOI:10.1097/01.MIB.0000435444.14860.ea
  • Digestive Diseases and Sciences 09/2013; 58(9):2435-2435.
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    ABSTRACT: Background The incidence of upper gastrointestinal injury by low-dose aspirin (LDA) has increased.
    08/2013; 1(4):259-264. DOI:10.1177/2050640613491254
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    ABSTRACT: Permeation of the small intestinal mucosa is a key mechanism in the induction of enteropathy. We investigated the effect of rebamipide in healthy subjects with diclofenac-induced small intestinal damage and permeability. In this crossover study, each treatment period was 1 week with a 4-week washout period. Diclofenac (75 mg/day) and omeprazole (20 mg/day) plus rebamipide (300 mg/day) or placebo were administered. Capsule endoscopy and a sugar permeability test were performed on days 1 and 7 in each period. Ten healthy subjects were enrolled. Small intestinal injuries were observed on day 7 in 6 of 10 subjects in both groups. Urinary excretion of administered lactulose increased from 0.30% to 0.50% of the initial dose during the first treatment period in the placebo group, and from 0.13% to 0.33% in the rebamipide group. Despite recovery from small-intestinal mucosal damage, the increased permeability in both groups resulted in sustained high levels of lactulose (0.50% to 1.06% in the placebo group and 0.33% to 1.12% in the rebamipide group) through the 4-week washout period. Diclofenac administration induced enteropathy and hyperpermeability of the small intestine. The sustained hyperpermeability during the washout period may indicate the presence of invisible fragility.
    Journal of Clinical Biochemistry and Nutrition 07/2013; 53(1):55-9. DOI:10.3164/jcbn.12-116
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    ABSTRACT: Background Recently, the relationship between gut microbiota and obesity has been highlighted. The present randomized, double-blind, placebo-controlled study aimed to evaluate the efficacy of transglucosidase (TGD) in modulating blood glucose levels and body weight gain in patients with type 2 diabetes mellitus (T2DM) and to clarify the underlying mechanism by analyzing the gut microbiota of T2DM patients. Methods This study included 60 patients who received placebo or TGD orally (300 or 900 mg/day) for 12 weeks, and blood and fecal samples were collected before and after 12 weeks. Comparisons of fecal bacterial communities were performed before and after the TGD treatment and were performed between T2DM patients and 10 healthy individuals, using the terminal-restriction fragment length polymorphism analysis. Results The Clostridium cluster IV and subcluster XIVa components were significantly decreased, whereas the Lactobacillales and Bifidobacterium populations significantly increased in the T2DM patients compared with the healthy individuals. By dendrogram analysis, most of the healthy individuals (6/10) and T2DM patients (45/60) were classified into cluster I, indicating no significant difference in fecal bacterial communities between the healthy individuals and the T2DM patients. In the placebo and TGD groups, the bacterial communities were generally similar before and after the treatment. However, after 12 weeks of TGD therapy, the Bacteroidetes-to-Firmicutes ratio in the TGD groups significantly increased and was significantly higher compared with that in the placebo group, indicating that TGD improved the growth of the fecal bacterial communities in the T2DM patients. Conclusions Therefore, TGD treatment decreased blood glucose levels and prevented body weight gain in the T2DM patients by inducing the production of oligosaccharides in the alimentary tract and modulating gut microbiota composition. Trial registration UMIN-CTR UMIN000010318
    BMC Gastroenterology 05/2013; 13(1):81. DOI:10.1186/1471-230X-13-81

Publication Stats

574 Citations
270.87 Total Impact Points

Institutions

  • 2009–2015
    • Aichi Medical University
      • • Department of Gastroenterology
      • • Division of Internal Medicine
      Касугай, Aichi, Japan
  • 2008–2009
    • Nagoya City University
      Nagoya, Aichi, Japan
  • 2003–2009
    • Aichi Cancer Center
      Ōsaka, Ōsaka, Japan