Research activity information

• Oct. 2008 消化器病学会, 優秀ポスター賞, 当院で経験した膵管内乳頭粘液性腫瘍(IPMN)の他臓器癌の合併についての検討

  Inoue Jun

  Japan society

• ADAMDEC1 is not a driver of intestinal fibrosis but a marker of the inflammation–stromal niche in Crohn's disease

  Hiroshi Tanabe, Daisuke Watanabe, Misaki Agawa, Hirotaka Nakamura, Tetsuya Yoshizaki, Jun Inoue, Shin Urai, Hironori Bando, Yuzo Kodama

  Elsevier BV, Jun. 2026, Biochemical and Biophysical Research Communications, 817, 153749 - 153749

  [Refereed]

  Scientific journal


• Impact of Enterococcus faecium 129 BIO 3B-R on Helicobacter pylori eradication therapy side effects in adult patients: a randomized, double-blind, placebo-controlled study

  Eri Tokunaga, Jun Inoue, Naoki Asaji, Katsuaki Oyama, Akihiro Soga, Yusaku Shimamoto, Masato Kinoshita, Takeshi Tanaka, Hiroki Hayashi, Takuya Ikegawa, Yuki Ito, Sayaka Ikeda, Norihiro Okamoto, Haruka Miyazaki, Yuna Ku, Daisuke Watanabe, Makoto Ooi, Namiko Hoshi, Hiroo Makimoto, Ikuko Yano, Eiji Umegaki, Yuzo Kodama

  Corresponding, Springer Science and Business Media LLC, Sep. 2025, Scientific Reports, 15(1) (1)

  [Refereed]

  Scientific journal


• Combination of probiotics enhancing butyrogenesis in colonic microbiota model of patients with ulcerative colitis

  Kentaro Inokuma, Daisuke Sasaki, Tomoya Shintani, Jun Inoue, Katsuaki Oyama, Yuta Noda, Takayuki Maeda, Ryouichi Yamada, Yasushi Matsuki, Yuzo Kodama, Akihiko Kondo

  Springer Science and Business Media LLC, May 2025, Applied Microbiology and Biotechnology, 109(1) (1)

  [Refereed]

  Scientific journal


• Impact of intratumoral microbiome on tumor immunity and prognosis in human pancreatic ductal adenocarcinoma

  Shohei Abe, Atsuhiro Masuda, Tomonori Matsumoto, Jun Inoue, Hirochika Toyama, Arata Sakai, Takashi Kobayashi, Takeshi Tanaka, Masahiro Tsujimae, Kohei Yamakawa, Masanori Gonda, Shigeto Masuda, Hisahiro Uemura, Shinya Kohashi, Noriko Inomata, Kae Nagao, Yoshiyuki Harada, Mika Miki, Yosuke Irie, Noriko Juri, Testuhisa Ko, Yusuke Yokotani, Yuki Oka, Shogo Ota, Maki Kanzawa, Tomoo Itoh, Toshio Imai, Takumi Fukumoto, Eiji Hara, Yuzo Kodama

  Abstract Background Recent evidence suggests that the presence of microbiome within human pancreatic ductal adenocarcinoma (PDAC) tissue potentially influences cancer progression and prognosis. However, the significance of tumor-resident microbiome remains unclear. We aimed to elucidate the impact of intratumoral bacteria on the pathophysiology and prognosis of human PDAC. Methods The presence of intratumoral bacteria was assessed in 162 surgically resected PDACs using quantitative polymerase chain reaction (qPCR) and in situ hybridization (ISH) targeting 16S rRNA. The intratumoral microbiome was explored by 16S metagenome sequencing using DNA extracted from formalin-fixed paraffin-embedded tissues. The profile of intratumoral bacteria was compared with clinical information, pathological findings including tumor-infiltrating T cells, tumor-associated macrophage, fibrosis, and alterations in four main driver genes (KRAS, TP53, CDKN2A/p16, SMAD4) in tumor genomes. Results The presence of intratumoral bacteria was confirmed in 52 tumors (32%) using both qPCR and ISH. The 16S metagenome sequencing revealed characteristic bacterial profiles within these tumors, including phyla such as Proteobacteria and Firmicutes. Comparison of bacterial profiles between cases with good and poor prognosis revealed a significant positive correlation between a shorter survival time and the presence of anaerobic bacteria such as Bacteroides, Lactobacillus, and Peptoniphilus. The abundance of these bacteria was correlated with a decrease in the number of tumor-infiltrating T cells positive for CD4, CD8, and CD45RO. Conclusions Intratumoral infection of anaerobic bacteria such as Bacteroides, Lactobacillus, and Peptoniphilus is correlated with the suppressed anti-PDAC immunity and poor prognosis.

  Springer Science and Business Media LLC, Jan. 2024, Journal of Gastroenterology, 59(3) (3), 250 - 262

  [Refereed]

  Scientific journal


• Metabolic Syndrome Accelerates the Age-Related Increase of Intraductal Papillary Mucinous Neoplasm of the Pancreas

  Shunta Tanaka, Masahiro Tsujimae, Atsuhiro Masuda, Jun Inoue, Noriko Inomata, Hisahiro Uemura, Shinya Kohashi, Kae Nagao, Shigeto Masuda, Shohei Abe, Masanori Gonda, Kohei Yamakawa, Shigeto Ashina, Ryota Nakano, Takeshi Tanaka, Yasutaka Yamada, Arata Sakai, Takashi Kobayashi, Hideyuki Shiomi, Koichi Fujita, Takahiro Anami, Tsuyoshi Fujita, Akihiko Watanabe, Yuzo Kodama

  Objectives Aging is associated with a high prevalence of pancreatic cysts and intraductal papillary mucinous neoplasms (IPMNs). Metabolic syndrome (MS) may increase the risk of neoplasms, including those that develop in the pancreas. However, the influence of factors associated with MS on the development of IPMN remains unclear. Methods A total of 9363 patients who underwent abdominal ultrasound examinations between April 2012 and May 2013 were included in this study. Multivariate logistic regression analysis was performed to identify factors associated with the presence of IPMN by age. Results Pancreatic cysts were detected in 198 of 9363 patients, of whom 129 were found to have IPMNs. The presence of IPMN significantly correlated with age (10-year increments; odds ratio, 2.73; 95% CI, 2.28–3.29; P < 0.001). High body mass index, history of smoking, hyperlipidemia, hypertension, and MS were associated with a higher prevalence of IPMN with advancing age. In multivariate analysis, the presence of IPMN was more frequent in elderly patients with MS (odds ratio, 3.14; 95% CI, 3.14–6.72; P = 0.003). Conclusions The present study suggests that the incidence of IPMN increases with age and is accelerated in the presence of MS.

  Ovid Technologies (Wolters Kluwer Health), Oct. 2023, Pancreas, 53(1) (1), e9 - e15

  [Refereed]

  Scientific journal


• A comprehensive analysis of tumor-stromal collagen in relation to pathological, molecular, and immune characteristics and patient survival in pancreatic ductal adenocarcinoma

  Shigeto Ashina, Atsuhiro Masuda, Kohei Yamakawa, Tsuyoshi Hamada, Masahiro Tsujimae, Takeshi Tanaka, Hirochika Toyama, Keitaro Sofue, Hideyuki Shiomi, Arata Sakai, Takashi Kobayashi, Shohei Abe, Masanori Gonda, Shigeto Masuda, Noriko Inomata, Hisahiro Uemura, Shinya Kohashi, Kae Nagao, Yoshiyuki Harada, Mika Miki, Noriko Juri, Yosuke Irie, Maki Kanzawa, Tomoo Itoh, Jun Inoue, Toshio Imai, Takumi Fukumoto, Yuzo Kodama

  Abstract Background Abundant collagen deposition is a hallmark of pancreatic ductal adenocarcinomas (PDACs). This study clarified the interactive relationship between tumor-stromal collagen, molecular and immune characteristics, and tumor pr ogression in human PDAC. Methods We performed a comprehensive examination using an integrative molecular pathological epidemiology database on 169 cases with resected PDAC . The amount of tumor-stromal collagen was quantified through digital imaging analysis for Elastica van Gieson-stained whole-section tumor slides. We analyzed the association of tumor-stromal collagen with gene alterations (KRAS, TP53, CDKN2A/p16, and SMAD4), immune parameters (CD4⁺ tumor-infiltrating lymphocytes [TILs], CD8⁺ TILs, FOXP3⁺ TILs, and tertiary lymphoid structures), and patient prognosis. Results Low amounts of tumor-stromal collagen were associated with poor differentiation (multivariable OR = 3.82, 95%CI = 1.41–12.2, P = 0.008) and CDKN2A/p16 alteration (OR [95%CI] = 2.06 [1.08–4.02], P = 0.03). Tumors with low collagen levels had shorter overall survival (HR [95%CI] = 2.38 [1.59–3.56], P < 0.0001). In the S-1 and gemcitabine (GEM) treatment groups, low tumor-stromal collagen was linked to poor prognosis of patients with PDAC (S-1 group: multivariable HR [95%CI] = 2.76 [1.36–5.79], P = 0.005; GEM group: multivariate HR [95%CI] = 2.91 [1.34–6.71], P = 0.007). Additionally, low amounts of tumor-stromal collagen were also linked to low levels of CD4⁺ TILs (P = 0.046), CD8⁺ TILs (P = 0.09), and tertiary lymphoid structures (P = 0.001). Conclusions Tumor-stromal collagen deposition may play a crucial role in modulating tumor-immune microenvironment and determining response to adjuvant chemotherapy and patient survival outcomes.

  Springer Science and Business Media LLC, Jul. 2023, Journal of Gastroenterology, 58(10) (10), 1055 - 1067

  [Refereed]

  Scientific journal


• Integrated analysis of tertiary lymphoid structures in relation to tumor-infiltrating lymphocytes and patient survival in pancreatic ductal adenocarcinoma

  Takeshi Tanaka, Atsuhiro Masuda, Jun Inoue, Tsuyoshi Hamada, Takuya Ikegawa, Hirochika Toyama, Keitaro Sofue, Hideyuki Shiomi, Arata Sakai, Takashi Kobayashi, Shunta Tanaka, Ryota Nakano, Yasutaka Yamada, Shigeto Ashina, Masahiro Tsujimae, Kohei Yamakawa, Shohei Abe, Masanori Gonda, Shigeto Masuda, Noriko Inomata, Hisahiro Uemura, Shinya Kohashi, Kae Nagao, Maki Kanzawa, Tomoo Itoh, Yoshihide Ueda, Takumi Fukumoto, Yuzo Kodama

  Springer Science and Business Media LLC, Jan. 2023, Journal of Gastroenterology, 58(3) (3), 277 - 291

  [Refereed]

  Scientific journal


• Predicting Inadequate Bowel Preparation When Using Sodium Picosulfate plus Magnesium Citrate for Colonoscopy: Development and Validation of a Prediction Score

  Norihiro Okamoto, Shinwa Tanaka, Hirohumi Abe, Haruka Miyazaki, Tastuya Nakai, Kazunori Tsuda, Hiroya Sakaguchi, Tetsuya Yoshizaki, Nobuaki Ikezawa, Jun Inoue, Makoto Ooi, Yuzo Kodama

  <b><i>Introduction:</i></b> Sodium picosulfate plus magnesium citrate is a bowel preparation agent with high patient acceptability. However, it is unclear which patients are more likely to have inadequate bowel preparation when using this agent. This study aimed to identify the risk factors for inadequate bowel preparation when using sodium picosulfate plus magnesium citrate for colonoscopy and to develop a scoring model to predict which patients will have inadequate bowel preparation. <b><i>Methods:</i></b> A total of 350 Japanese patients were enrolled from June 2021 to April 2022. Data on patient background, details of colonoscopy, and satisfaction assessment questionnaire results were prospectively collected. The scoring model for inadequate bowel preparation was developed based on multiple logistic regression analyses, and its performance was internally validated using bootstrapping. <b><i>Results:</i></b> Adequate bowel preparation was obtained in 295 patients (84.3%); 335 (95.7%) were able to ingest the drug without difficulty. The scoring model consisted of five independent risk factors and points of risk scores were assigned to each one as follows: American Society of Anesthesiologists physical status III (1 point), diabetes comorbidities (5 points), use of laxatives (4 points), no defecation once in a day (2 points), and drug use for mental disorder (6 points). The C-statistics of the scoring system for inadequate bowel preparation was 0.75. <b><i>Discussion:</i></b> We identified five risk factors for inadequate bowel preparation when using sodium picosulfate plus magnesium citrate regimen and developed a scoring model for inadequate bowel preparation with satisfactory discrimination and calibration.

  S. Karger AG, Nov. 2022, Digestion, 103(6) (6), 462 - 469

  [Refereed]

  Scientific journal


• Constitution of mucosa‐associated microbiota in the lower digestive tract does not change in early stage of non‐alcoholic fatty liver disease with fecal dysbiosis

  Naoki Asaji, Jun Inoue, Hiroki Hayashi, Eri Tokunaga, Yusaku Shimamoto, Masato Kinoshita, Takeshi Tanaka, Arata Sakai, Yoshihiko Yano, Yoshihide Ueda, Yuzo Kodama

  Abstract Background and Aim Regarding the gut–liver axis, fecal dysbiosis is implicated in the pathogenesis of non‐alcoholic fatty liver disease (NAFLD). The significance of mucosa‐associated microbiota (MAM, which is present in the mucin layer covering the intestinal mucosa) has not been well explored. We aimed to clarify the characteristics of MAM in patients with NAFLD. Methods MAM were obtained from seven patients with early‐stage NAFLD and seven controls by colonoscopy in five locations (terminal ileum, cecum, ascending and sigmoid colon, and rectum) using mucosal brushes. The microbial 16S rDNA profiles of the MAM and fecal microbiota of patients in the NAFLD and control groups were analyzed. Results α‐diversities of fecal microbiota were decreased in patients with NAFLD (observed species, Shannon index, and Chao1: 174.57 vs 134.86, 5.51 vs 4.65, and 206.34 vs 167.91; P = 0.048, 0.067, and 0.087, respectively), and microbial composition analyses by principal coordinate analysis differed between the fecal microbiota of patients with NAFLD and those of controls (permutational analysis of variance [PERMANOVA] of weighted and unweighted: Pseud‐F: 1.4179/P‐value: 0.05 and Pseud‐F: 2.1497/P‐value: 0.049, respectively). However, α‐diversities or microbial composition of MAM in most parts of the intestine did not differ significantly between the NAFLD and control groups. Unclassified Rikenellaceae, Oscillospira, Odoribacter, unclassified clostridiales, and Holdemania were decreased in the feces of patients with NAFLD (determined by linear discriminant analysis effect size), but five (except Holdemania) of the six genera were not decreased in the MAM of these patients. Conclusion In early‐stage NAFLD, MAM was uniform and relatively stable throughout the intestine, even when fecal dysbiosis appeared.

  Corresponding, Wiley, Aug. 2022, JGH Open, 6(10) (10), 677 - 684

  [Refereed]

  Scientific journal


• ASO Visual Abstract: Comprehensive Analysis of Molecular Biological Characteristics of Pancreatic Ductal Adenocarcinoma Concomitant with Intraductal Papillary Mucinous Neoplasm.

  Masahiro Tsujimae, Atsuhiro Masuda, Takuya Ikegawa, Takeshi Tanaka, Jun Inoue, Hirochika Toyama, Keitaro Sofue, Hisahiro Uemura, Shinya Kohashi, Noriko Inomata, Kae Nagao, Shigeto Masuda, Shohei Abe, Masanori Gonda, Kohei Yamakawa, Shigeto Ashina, Yasutaka Yamada, Shunta Tanaka, Ryota Nakano, Arata Sakai, Takashi Kobayashi, Hideyuki Shiomi, Maki Kanzawa, Tomoo Itoh, Takumi Fukumoto, Yoshihide Ueda, Yuzo Kodama

  May 2022, Annals of surgical oncology, English, International magazine

  [Refereed]

  Scientific journal


• The Kobe University Human Intestinal Microbiota Model for gut intervention studies

  Namiko Hoshi, Jun Inoue, Daisuke Sasaki, Kengo Sasaki

  Springer Science and Business Media LLC, Apr. 2021, Applied Microbiology and Biotechnology, 105(7) (7), 2625 - 2632

  [Invited]

  Scientific journal


• W27 IgA suppresses growth of Escherichia in an in vitro model of the human intestinal microbiota

  Kengo Sasaki, Tomoyuki Mori, Namiko Hoshi, Daisuke Sasaki, Jun Inoue, Reiko Shinkura, Akihiko Kondo

  W27 monoclonal immunoglobulin A (IgA) suppresses pathogenic Escherichia coli cell growth; however its effect on the human intestine remains unclear. We thus aimed to determine how W27 IgA affects the human colonic microbiota using the in vitro microbiota model. This model was established using fecal samples collected from 12 healthy volunteers; after anaerobic cultivation, each model was found to retain the genera found in the original human fecal samples. After pre-incubating W27 IgA with the respective fecal sample in aerobic condition, the mixture of W27 IgA (final concentration, 0.5 µg/mL) and each fecal sample was added to the in vitro microbiota model and cultured under anaerobic condition,. Next-generation sequencing of the bacterial 16S rRNA gene revealed that W27 IgA addition significantly decreased the relative abundance of bacteria related to the genus Escherichia in the model. Additionally, at a final concentration of 5 µg/mL, W27 IgA delayed growth in pure culture of Escherichia coli isolated from human fecal samples. Our study thus revealed the suppressive effect of W27 IgA on the genus Escherichia at relatively low-concentrations and the usefulness of an in vitro microbiota model to evaluate the effect of IgA as a gut microbiota regulator.

  Research Square, Mar. 2021

  [Refereed]


• Effect of Daikenchuto On Spontaneous Intestinal Tumors in ApcMin/+ Mice.

  Lingling Kong, Namiko Hoshi, Daisuke Watanabe, Yasutaka Yamada, Eiichiro Yasutomi, Soichiro Adachi, Makoto Ooi, Yunlong Sui, Ryutaro Yoshida, Ryohei Sekimoto, Eri Tokunaga, Haruka Miyazaki, Yuna Ku, Haruka Takenaka, Tadao Kunihiro, Jun Inoue, Zibin Tian, Yuzo Kodama

  Daikenchuto (TU-100) is herbal medicine which predominantly contains ginger, Japanese pepper, and ginseng. We investigated whether TU-100 can affect the composition of gut flora and intestinal tumor development using ApcMin/+ mice, a murine model of intestinal tumor. Bacterial 16S rRNA sequencing and short-chain fatty acid analysis were performed on faecal samples. Tumor number and size were analysed. Any change in gene expression of the tumor tissues was assessed by real-time PCR. Principal coordinate analysis (PCoA) showed that the faecal microbiota cluster of TU-100-fed mice was different from the microbiota of control mice. However, no significant difference was observed in the concentration of short-chain fatty acids, tumor number, and gene expression levels between the two groups. Our data showed that TU-100 can affect the intestinal environment; however, it does not contribute in tumor progression or inhibition in our setting.

  Jan. 2021, The Kobe journal of medical sciences, 66(4) (4), E139-E148, English, Domestic magazine

  [Refereed]

  Scientific journal


• Adrenic acid induces oxidative stress in hepatocytes.

  Jing Zhao, Shin Nishiumi, Ryoma Tagawa, Yoshihiko Yano, Jun Inoue, Namiko Hoshi, Masaru Yoshida, Yuzo Kodama

  Adrenic acid (ADA), which is an endogenously synthesized polyunsaturated free fatty acid, was significantly increased in nonalcoholic fatty liver disease (NAFLD) patients and NAFLD-model mice compared with the corresponding controls in our previous study. To elucidate the involvement of ADA in NAFLD and nonalcoholic steatohepatitis (NASH), we examined ADA-induced lipotoxicity in human hepatocarcinoma HepG2 cells. The ROS production in HepG2 cells was increased by exposure to ADA. It was also shown that the treatment with ADA decreased cell viability in a dose-dependent manner. The N-Acetyl-L-Cysteine pretreatment counteracted this ADA-induced ROS production and cell death. Furthermore, ADA modulated the expressions of SOD2, HO-1 and Gpx1 as antioxidant enzymes. These findings suggest that ADA could induce oxidative stress accompanied by cell death, providing new insights into lipotoxicity that is involved in the pathogenesis of NAFLD and NASH.

  Nov. 2020, Biochemical and biophysical research communications, 532(4) (4), 620 - 625, English, International magazine

  [Refereed]

  Scientific journal


• Detection of Novel Amino Acid Polymorphisms in the East Asian CagA of Helicobacter Pylori with Full Sequencing Data.

  Hiroki Hayashi, Jun Inoue, Katsuaki Oyama, Koki Matsuoka, Shin Nishiumi, Masaru Yoshida, Yoshihiko Yano, Yuzo Kodama

  Cytotoxin-associated gene A (CagA) is generally accepted to be the most important virulence factor of Helicobacter pylori and increases the risk of developing gastric cancer. East Asian CagA, which includes the EPIYA-D segment at the C-terminal region, has a significantly higher gastric carcinogenic rate than Western CagA including the EPIYA-C segment. Although the amino acid polymorphism surrounding the EPIYA motif in the C-terminal region has been examined in detail, limited information is currently available on the amino acid polymorphism of the N-terminal region of East Asian CagA. In the present study, we analyzed the sequencing data of East Asian CagA that we obtained previously to detect amino acid changes (AACs) in the N-terminal region of East Asian CagA. Four highly frequent AACs in the N-terminal region of East Asian CagA were detected in our datasets, two of which (V356A, Y677F) exhibited reproducible specificity using a validation dataset from the NCBI database, which are candidate AACs related to the pathogenic function of CagA. We examined whether these AACs affect the functions of CagA in silico model. The computational docking simulation model showed that binding affinity between CagA and phosphatidylserine remained unchanged in the model of mutant CagA reflecting both AAC, whereas that between CagA and α5β1 integrin significantly increased. Based on whole genome sequencing data we herein identified novel specific AACs in the N-terminal regions of EPIYA-D that have the potential to change the function of CagA.

  Corresponding, Jun. 2020, The Kobe journal of medical sciences, 66(1) (1), E22-E31, English, Domestic magazine

  [Refereed]

  Scientific journal


• Bacillus coagulans SANK 70258 suppresses Enterobacteriaceae in the microbiota of ulcerative colitis in vitro and enhances butyrogenesis in healthy microbiota.

  Kengo Sasaki, Daisuke Sasaki, Jun Inoue, Namiko Hoshi, Takayuki Maeda, Ryouichi Yamada, Akihiko Kondo

  The aim of this study was to clarify the effect of the spore-forming and lactic acid-producing probiotic strain, Bacillus coagulans SANK 70258, on human colonic microbiota of healthy subjects and ulcerative colitis patients. A model culture system was employed to construct the in vitro human colonic microbiota, to retain the bacterial species richness and simulate the patient's disordered composition, from the fecal inoculum. Bacterial 16S rRNA gene sequencing confirmed that administration of B. coagulans SANK 70258 (at an initial concentration of 4 × 107-total cells/mL) suppressed bacteria related to the family Enterobacteriaceae in the microbiota models for both healthy subjects (P = 0.016) and ulcerative colitis patients (P = 0.023). In addition, administration of B. coagulans SANK 70258 increased bacteria related to the family Lachnospiraceae (P = 0.031), thereby enhancing butyrate production (P = 0.031) in the microbiota models of healthy subjects. However, these changes were not observed in the microbiota models of ulcerative colitis patients, likely owing to the low abundance of Lachnospiraceae species. This study demonstrates the potential of B. coagulans SANK 70258 to exhibit antimicrobial activity against harmful organisms in patients with ulcerative colitis, while improving the intestinal microenvironment by increasing butyrogenesis in healthy persons. KEY POINTS: • B. coagulans SANK 70258 treatment reduced colonic Enterobacteriaceae species. • B. coagulans SANK 70258 treatment enhanced butyrogenesis in healthy individuals. • B. coagulans SANK 70258 treatment increased Lachnospiraceae in healthy persons. • B. coagulans SANK 70258 improves the colonic microenvironment in ulcerative colitis.

  Mar. 2020, Applied microbiology and biotechnology, English, International magazine

  [Refereed]


• Butyryl-CoA:acetate CoA-transferase gene associated with the genus Roseburia is decreased in the gut microbiota of Japanese patients with ulcerative colitis

  Ryohei Shinohara, Kengo Sasaki, Jun Inoue, Namiko Hoshi, Itsuko Fukuda, Daisuke Sasaki, Akihiko Kondo, Ro Osawa

  Oct. 2019, Bioscience of Microbiota, Food and Health, 38(4) (4), 159 - 163, English

  [Refereed]

  Scientific journal


• Construction of a Model Culture System of Human Colonic Microbiota to Detect Decreased Lachnospiraceae Abundance and Butyrogenesis in the Feces of Ulcerative Colitis Patients

  Sasaki K, Inoue Jun, Sasaki D, Hoshi Namiko, Shirai T, Fukuda I, Azuma T, Kondo A, Osawa R

  Lead, Feb. 2019, Biotechnol J, English

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Construction of a model culture system of human colonic microbiota to detect decreased Lachnospiraceae abundance and butyrogenesis in the feces of ulcerative colitis patients

  SASAKI KENGO, INOUE JUN, SASAKI DAISUKE, HOSHI NAMIKO, SHIRAI TOMOKAZU, FUKUDA ITSUKO, AZUMA TAKESHI, KONDO AKIHIKO, OSAWA RO

  Compositional alteration of the gut microbiota is associated with ulcerative colitis (UC). Here, a model culture system is established for the in vitro human colonic microbiota of UC, which will be helpful for determining medical interventions. 16S ribosomal RNA sequencing confirms that UC models are successfully developed from fecal inoculum and retain the bacterial species biodiversity of UC feces. The UC models closely reproduce the microbial components and successfully preserve distinct clusters from the healthy subjects (HS), as observed in the feces. The relative abundance of bacteria belonging to the family Lachnospiraceae significantly decreases in the UC models compared to that in HS, as observed in the feces. The system detects significantly lower butyrogenesis in the UC models than that in HS, correlating with the decreased abundance of Lachnospiraceae. Interestingly, the relative abundance of Lachnospiraceae does not correlate with disease activity (defined as partial Mayo score), suggesting that Lachnospiraceae persists in UC patients at a decreased level, irrespective of the alteration in disease activity. Moreover, the system shows that administration of Clostridium butyricum MIYAIRI restores butyrogenesis in the UC model. Hence, the model detects deregulation in the intestinal environment in UC patients and may be useful for simulating the effect of probiotics.

  Lead, 2019, Biotechnology Journal, 14(5) (5), e1800555, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Proton Pump Inhibitors Increase the Susceptibility of Mice to Oral Infection with Enteropathogenic Bacteria.

  Eiichiro Yasutomi, Namiko Hoshi, Soichiro Adachi, Takafumi Otsuka, Lingling Kong, Yuna Ku, Haruka Yamairi, Jun Inoue, Tsukasa Ishida, Daisuke Watanabe, Makoto Ooi, Masaru Yoshida, Tomoya Tsukimi, Shinji Fukuda, Takeshi Azuma

  BACKGROUND AND AIMS: Proton pump inhibitors (PPIs) are among the most frequently prescribed medications. Side effects including an increased risk of intestinal infections have been reported. It is assumed that PPIs can increase susceptibility to enteropathogens; however, the underlying mechanisms are unknown. Here in this study, we explored whether Lansoprazole (Laz), one of the PPIs, increases the susceptibility to enteropathogens, and further investigated the mechanism of it. METHODS: Mice were administered Laz intraperitoneally once daily and orally infected with Citrobacter rodentium (C. rodentium). The establishment of intestinal infection was assessed by histology and inflammatory cytokine expression levels measured by quantitative PCR. To test whether Laz changes the intestinal environment to influence the susceptibility, intestinal pH, microbiota, metabolites and immune cell distributions were evaluated via pH measurement, 16S rRNA gene sequencing, metabolome, and flow cytometry analyses after Laz administration. RESULTS: Colitis was induced with less C. rodentium in Laz-treated mice as compared with the controls. We found that increased numbers of C. rodentium could reach the cecum following Laz administration. Laz increased pH in the stomach but not in the intestines. It induced dysbiosis and changed the metabolite content of the small intestine. However, these changes did not lead to alterations of immune cell distribution. CONCLUSIONS: Laz raised susceptibility to C. rodentium as increased numbers of the pathogen reach the site of infection. Our results suggest that it was due to increased stomach pH which allowed more peroral enteropathogens to pass the stomach, but not because of changes of intestinal environment.

  Apr. 2018, Digestive diseases and sciences, 63(4) (4), 881 - 889, English, International magazine

  [Refereed]

  Scientific journal


• Indigo Naturalis Ameliorates Oxazolone-Induced Dermatitis but Aggravates Colitis by Changing the Composition of Gut Microflora

  Soichiro Adachi, Namiko Hoshi, Jun Inoue, Eiichiro Yasutomi, Takafumi Otsuka, Ramesh Dhakhwa, Zi Wang, Yuna Koo, Toshihiro Takamatsu, Yuriko Matsumura, Haruka Yamairi, Daisuke Watanabe, Makoto Ooi, Toshihito Tanahashi, Shin Nishiumi, Masaru Yoshida, Takeshi Azuma

  2017, INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY, 173(1) (1), 23 - 33, English

  [Refereed]

  Scientific journal


• Cisplatin resistance in human lung cancer cells is linked with dysregulation of cell cycle associated proteins

  Sayo Horibe, Akira Matsuda, Toshihito Tanahashi, Jun Inoue, Shoji Kawauchi, Shigeto Mizuno, Masaki Ueno, Kyohei Takahashi, Yusaku Maeda, Tatsuya Maegouchi, Yoshiki Murakami, Ryoko Yumoto, Junya Nagai, Mikihisa Takano

  Mar. 2015, LIFE SCIENCES, 124, 31 - 40, English

  [Refereed]

  Scientific journal


• Downregulation of CYP3A and P-Glycoprotein in the Secondary Inflammatory Response of Mice With Dextran Sulfate Sodium Induced Colitis and Its Contribution to Cyclosporine A Blood Concentrations

  Shoji Kawauchi, Tsutomu Nakamura, Ikuya Miki, Jun Inoue, Tsuneo Hamaguchi, Toshihito Tanahashi, Shigeto Mizuno

  Feb. 2014, JOURNAL OF PHARMACOLOGICAL SCIENCES, 124(2) (2), 180 - 191, English

  [Refereed]

  Scientific journal


• The influences of pepsin concentrations and pH levels on the disinfective activity of ozone nanobubble water against helicobacter pylori

  Takenaka Mamoru, Hoshi Namiko, Masuda Atsuhiro, Nishiumi Sin, Azuma Takeshi

  2014, Digestion, 90(1) (1), 10 - 7, English

  [Refereed]

  Scientific journal


• Intestinal and Hepatic Expression of Cytochrome P450s and mdr1a in Rats with Indomethacin-Induced Small Intestinal Ulcers

  Shoji Kawauchi, Tsutomu Nakamura, Hiroyuki Yasui, Chikako Nishikawa, Ikuya Miki, Jun Inoue, Sayo Horibe, Tsuneo Hamaguchi, Toshihito Tanahashi, Shigeto Mizuno

  2014, INTERNATIONAL JOURNAL OF MEDICAL SCIENCES, 11(12) (12), 1208 - 1217, English

  [Refereed]

  Scientific journal


• Effect of 18β-glycyrrhetinic acid and hydroxypropyl γcyclodextrin complex on indomethacin-induced small intestinal injury in mice.

  Tsukasa Ishida, Ikuya Miki, Toshihito Tanahashi, Saori Yagi, Yasuyuki Kondo, Jun Inoue, Shoji Kawauchi, Sin Nishiumi, Masaru Yoshida, Hideko Maeda, Chisato Tode, Atsuko Takeuchi, Hirokazu Nakayama, Takeshi Azuma, Shigeto Mizuno

  Non-steroidal anti-inflammatory drugs (NSAIDs)-induced small intestinal injury is a serious clinical event with recent advances of diagnostic technologies, but a successful therapeutic method to treat such injuries is still lacking. Licorice, a traditional herbal medicine, and its derivatives have been widely used for the treatment of a variety of diseases due to their extensive biological actions. However, it is unknown whether these derivatives have an effect on NSAIDs-induced small intestinal damage. Previously, the anti-inflammatory effects of three compounds extracted from the licorice root, glycyrrhizin, 18β-glycyrrhetinic acid, and dipotassium glycyrrhizinate, were compared in vitro cell culture. The most prominent inhibitory effect on the tumor necrosis factor-α (TNF-α) production was observed with the administration of 18β-glycyrrhetinic acid as an active metabolite of glycyrrhizin. In this study, a complex compound of 18β-glycyrrhetinic acid and hydroxypropyl γcyclodextrin was examined to improve the oral bioavailability. After administration of this complex to indomethacin treated mice, a significantly high plasma concentration of 18β-glycyrrhetinic acid was detected using the tandem mass spectrometry coupled with the HPLC. Furthermore, the complex form of 18β-glycyrrhetinic acid and hydroxypropyl γcyclodextrin reduced mRNA expressions of TNF-α, interleukin (IL)-1β, and IL-6, which was histologically confirmed in the improvement of indomethacin-induced small intestinal damage. These results suggest that the complex of 18β-glycyrrhetinic acid and hydroxypropyl γcyclodextrin has the potential therapeutic value for preventing the adverse effects of indomethacin-induced small intestinal injury.

  Aug. 2013, European journal of pharmacology, 714(1-3) (1-3), 125 - 31, English, International magazine

  [Refereed]

  Scientific journal


• Linoleoyl ethanolamide reduces lipopolysaccharide-induced inflammation in macrophages and ameliorates 2,4-dinitrofluorobenzene-induced contact dermatitis in mice.

  Tsukasa Ishida, Shin Nishiumi, Toshihito Tanahashi, Akifumi Yamasaki, Asahi Yamazaki, Takahiro Akashi, Ikuya Miki, Yasuyuki Kondo, Jun Inoue, Shoji Kawauchi, Takeshi Azuma, Masaru Yoshida, Shigeto Mizuno

  In our previous study, it was found that linoleoyl ethanolamide (LE) is present in sake lees, which are produced as a byproduct during the making of Japanese sake. LE is a fatty acid ethanolamide, which have been demonstrated to exert a variety of biological functions, and in this study, the anti-inflammatory effects of LE were examined using in vitro cell culture and in vivo animal experiments. In mouse RAW264.7 macrophages, LE suppressed the lipopolysaccharide (LPS)-induced expression of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6. In addition, LE inhibited LPS-induced increases in the levels of cyclooxygenase enzyme-2 and prostaglandin E(2), which are indicators of inflammation. The inhibitory effect of LE on the release of TNF-α was stronger than that of dipotassium glycyrrhizinate, which is widely used in external human skin care treatments. LE also suppressed the LPS-induced activation of Toll-like receptor 4 signaling and nuclear translocation of nuclear factor-κB (NF-κB) p65. In a contact dermatitis animal model, applying LE to affected ear skin ameliorated 2,4-dinitrofluorobenzene-induced contact dermatitis and pro-inflammatory cytokine expression at inflamed sites. These results indicate that LE exerts anti-inflammatory effects by inhibiting NF-κB signaling, and LE is proposed to be a useful therapeutic agent against contact dermatitis.

  Jan. 2013, European journal of pharmacology, 699(1-3) (1-3), 6 - 13, English, International magazine

  [Refereed]

  Scientific journal


• Regulation of the metabolite profile by an APC gene mutation in colorectal cancer

  Tomoo Yoshie, Shin Nishiumi, Yoshihiro Izumi, Aya Sakai, Jun Inoue, Takeshi Azuma, Masaru Yoshida

  Jun. 2012, CANCER SCIENCE, 103(6) (6), 1010 - 1021, English, International magazine

  [Refereed]

  Scientific journal


• Autophagy in the intestinal epithelium is not involved in the pathogenesis of intestinal tumors.

  Shin Nishiumi, Yoshimi Fujishima, Jun Inoue, Atsuhiro Masuda, Takeshi Azuma, Masaru Yoshida

  Autophagy has been demonstrated to be associated with the pathogenesis of cancer, but no consensus has been reached about its precise role. Therefore, we investigated whether autophagy in the intestinal epithelium is involved in the pathogenesis of intestinal tumors. To evaluate the relationship between autophagy and intestinal tumors, GFP-LC3-APC(min/+) mice were generated by mating GFP-LC3 transgenic mice with APC(min/+) mice. Autophagy was weakly induced in the intestinal polyp regions of the mice in comparison to their non-polyp regions. Under starved conditions, autophagy was not induced in the polyp regions, whereas it was observed in the non-polyp regions. Then, to examine whether a lack of autophagy in the intestinal epithelium enhances the induction of intestinal tumor, Atg7flox/flox:vil-cre-APC(min/+) mice, in which Atg7 had been conditionally deleted in the intestinal epithelium, were generated by mating Atg7flox/flox:vil-cre mice with APC(min/+) mice. However, there was no significant difference in the number of intestinal polyps between the Atg7flox/flox:vil-cre-APC(min/+) and the corresponding control Atg7flox/flox-APC(min/+) mice. These results indicate that autophagy in the intestinal epithelium is not involved in the pathogenesis of intestinal tumors, and future research should focus on regulating autophagy as a form of cancer therapy.

  May 2012, Biochemical and biophysical research communications, 421(4) (4), 768 - 72, English, International magazine

  [Refereed]

  Scientific journal


• Autophagy in the intestinal epithelium regulates Citrobacter rodentium infection

  Jun Inoue, Shin Nishiumi, Yoshimi Fujishima, Atsuhiro Masuda, Hideyuki Shiomi, Koji Yamamoto, Masayuki Nishida, Takeshi Azuma, Masaru Yoshida

  Lead, Elsevier BV, May 2012, Archives of Biochemistry and Biophysics, 521(1-2) (1-2), 95 - 101

  [Refereed]

  Scientific journal


• Mitochondria Determine the Efficacy of Anticancer Agents that Interact with DNA but Not the Cytoskeleton

  Kenjirou Hara, Emiko Kasahara, Nozomi Takahashi, Masami Konishi, June Inoue, Mika Jikumaru, Shuji Kubo, Haruki Okamura, Eisuke Sato, Masayasu Inoue

  Jun. 2011, JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 337(3) (3), 838 - 845, English

  [Refereed]

  Scientific journal


• [Two cases of localized autoimmune pancreatitis that relapsed after surgical treatment].

  Inoue J, Masuda A, Saito M, Onoyama M, Shiomi H, Toyama H, Shinzeki R, Matsumoto I, Hayashi Y, Makino T, Tada H, Kutsumi H, Ku Y, Azuma T

  Since the revision of Clinical Diagnostic Criteria for Autoimmune Pancreatitis (AIP) 2006, many cases of localized AIP have been reported. Localized AIP is often difficult to preoperatively differentiate from pancreatic carcinoma. We present two cases of localized AIP that developing relapse after surgical treatment. Swollen hilar lymph nodes of lung was detected on CT in both two cases. Recently, AIP is thought to be the pancreatic manifestation of an IgG4 related systemic disease, which has been associated with many extrapancreatic lesions. Response to steroid treatment and the detection of extrapancreatic lesions may contribute to provide adequate diagnosis thereby avoiding unnecessary surgery.
  

  Lead, The Japanese Society of Gastroenterology, Apr. 2011, Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology, 108(4) (4), 640 - 649, Japanese

  [Refereed]

  Scientific journal


• Flush knifeを用いた乳頭プレカット手技

  佐貫 毅, 豊永 高史, 家本 孝雄, 小林 隆, 角山 沙織, 南 晶洋, 松木 信之, 井上 潤, 坂井 文, 竹中 完, 古松 恵介, 三村 卓也, 塩見 英之, 吉田 志栄, 増田 充弘, 杉本 真樹, 早雲 孝信, 久津見 弘, 東 健

  (一社)日本消化器内視鏡学会, Mar. 2011, Gastroenterological Endoscopy, 53(Suppl.1) (Suppl.1), 924 - 924, Japanese


• Autophagy in the intestinal epithelium reduces endotoxin-induced inflammatory responses by inhibiting NF-κB activation.

  Yoshimi Fujishima, Shin Nishiumi, Atsuhiro Masuda, Jun Inoue, Ngoc Mai Thin Nguyen, Yasuhiro Irino, Masaaki Komatsu, Keiji Tanaka, Hiromu Kutsumi, Takeshi Azuma, Masaru Yoshida

  Autophagy is a lysosomal degradation pathway that is essential for survival, differentiation, development and homeostasis. There is growing evidence that impaired autophagy leads to the pathogenesis of diverse diseases. However, the role of autophagy in intestinal epithelium is not clearly understood, although previous studies have pointed out the possibility for the relationships of autophagy with bowel inflammation. In this study, we investigated the involvement of autophagy in intestinal epithelium with inflammatory responses. We generated the mice with a conditional deletion of Atg7, which is one of the autophagy regulated gene, in intestinal epithelium. In Atg7-deficient small intestinal epithelium, LPS-induced production of TNF-α and IL-1β mRNA was enhanced in comparison to the control small intestinal tissues. In addition, the degree of LPS-induced activation of NF-κB was promoted in Atg7-deficient intestinal epithelium. These results demonstrate that autophagy can attenuate endotoxin-induced inflammatory responses in intestinal epithelium resulting in the maintenance of intestinal homeostasis.

  Feb. 2011, Archives of biochemistry and biophysics, 506(2) (2), 223 - 35, English, International magazine

  [Refereed]

  Scientific journal


• Oxidative stress and renal pathophysiology.

  KasaharaE, Inoue Jun, JikumaruM, SatoE, InoueM

  2011, Rinsho Byori, 48(6) (6), 187 - 188, Japanese

  [Refereed]

  Scientific journal


• Ultraviolet-A Irradiation to the Eye Modulates Intestinal Mucosal Functions and Properties of Mast Cells in the Mouse

  Yurika Yamate, Keiichi Hiramoto, Emiko Kasahara, Mika Jikumaru, Eisuke F. Sato, June Inoue, Masayasu Inoue

  Jan. 2011, PHOTOCHEMISTRY AND PHOTOBIOLOGY, 87(1) (1), 191 - 198, English

  [Refereed]

  Scientific journal


• Role of Hydrogen Generation by Klebsiella pneumoniae in the Oral Cavity

  Tomoko Kanazuru, Eisuke F. Sato, Kumiko Nagata, Hiroshi Matsui, Kunihiko Watanabe, Emiko Kasahara, Mika Jikumaru, June Inoue, Masayasu Inoue

  Dec. 2010, JOURNAL OF MICROBIOLOGY, 48(6) (6), 778 - 783, English

  [Refereed]

  Scientific journal


• 当院における食道表在癌の内視鏡的治療について

  Morita Yoshinori, Toyonaga Takashi, Azuma Takeshi

  (一社)日本消化器内視鏡学会, Sep. 2008, Gastroenterological Endoscopy, 50(Suppl.2) (Suppl.2), 2254 - 2254, Japanese

  International conference proceedings


• 当院で経験した膵管内乳頭粘液性腫瘍(IPMN)の他臓器癌の合併についての検討

  Morita Yoshinori, Seo Yasushi, Toyonaga Takashi, Ku Yonson, Azuma Takeshi

  (一財)日本消化器病学会, Sep. 2008, 日本消化器病学会雑誌, 105(臨増大会) (臨増大会), A899 - A899, Japanese

  International conference proceedings


• 当院で経験した中・下咽頭微小癌の検討

  Morita Yoshinori, Toyonaga Takashi, Azuma Takeshi

  (一社)日本消化器内視鏡学会, Apr. 2008, Gastroenterological Endoscopy, 50(Suppl.1) (Suppl.1), 919 - 919, Japanese

  International conference proceedings

• 日本人潰瘍性大腸炎患者の腸内細菌叢における2種の酪酸産生遺伝子の定量

  篠原 涼平, 佐々木 建吾, 井上 潤, 星 奈美子, 福田 伊津子, 佐々木 大介, 近藤 昭彦, 大澤 朗

  (公財)日本ビフィズス菌センター, Apr. 2019, 腸内細菌学雑誌, 33(2) (2), 105 - 105, Japanese


• 【腎不全・透析患者さんのよろず健康相談-ビタミン、ミネラル、サプリメントと漢方薬】腸内細菌叢と尿毒症物質

  井上 潤, 星 奈美子, 児玉 裕三

  (株)東京医学社, Nov. 2018, 腎と透析, 85(5) (5), 629 - 634, Japanese


• Cell type-specific role of autophagy against Citrobacter rodentium infectious colitis

  Jun Inoue, Namiko Hoshi, Shin Nishiumi, Yoshimi Fujishima, Atsuhiro Masuda, Hideyuki Shiomi, Masaru Yoshida, Takeshi Azuma

  May 2013, JOURNAL OF IMMUNOLOGY, 190, English

  Summary international conference

• 腎と透析 / 腸内細菌叢と尿毒症物質

  Inoue Jun, 星奈美子, 児玉裕三

  Others, 東京医学社, 2018, Japanese

  Scholarly book


• メタゲノム解析技術の最前線 / 疾患とメタゲノム

  山本幸司, 吉田優, Inoue Jun, 大井充, 吉江智郎, 東健

  Others, シーエムシー, 2010, Japanese

  Scholarly book

• In vitro培養系ヒト腸内細菌叢モデルによる潰瘍性大腸炎患者の代謝プロファイル異常の検出

  SASAKI KENGO, INOUE JUN, HOSHI NAMIKO, SASAKI DAISUKE, FUKUDA ITSUKO, KONDO AKIHIKO, OSAWA RO

  第70回日本生物工学会大会, Sep. 2018, Japanese, 関西大学 千里山キャンパス, Domestic conference

  Poster presentation


• Successful detection of dysbiosis and altered short-chain-fatty acids levels in in vitro colonic microbiota culture system using faecal samples of ulcerative colitis

  Inoue Jun, 佐々木 建吾, Hoshi Namiko, 佐々木 大介, 近藤 昭彦, 大澤 朗

  European Crohn's and Colitis Organisation, Feb. 2018, English, オーストリア, ウィーン, International conference

  Poster presentation


• 複数の腸炎モデルマウスに対する漢方薬青黛の効果の検討

  足立 聡一郎, Hoshi Namiko, Inoue Jun, 安冨 栄一郎, 大塚 崇史, Ramesh Dhakhwa, 王 梓, 孔 玲玲, 渡邉 大輔, Ooi Makoto, Yoshida Masaru

  The 8th Annual Meeting of Japanese Society for Inflammatory Bowel disease, Dec. 2017, Japanese, Japanese Society for Inflammatory Boewel Disease, 東京, Domestic conference

  Poster presentation


• Increased susceptibility to enteropathogenic bacteria by proton pump inhibitors in the murine model of food poisoning

  安冨 栄一郎, Inoue Jun, 足立 聡一郎, 大塚 崇史, 渡邉 大輔, 具 潤亜, 山入 春香, Ooi Makoto, Hoshi Namiko, 福田 真嗣, Yoshida Masaru, Azuma Takeshi

  25th United European Gastroenterology Week, Oct. 2017, English, United European Gastroenterology, バルセロナ, スペイン, International conference

  Poster presentation

• 潰瘍性大腸炎の腸内細菌による粘膜上皮障害を介した病態の解明

  井上 潤, 佐々木 大介, 渡邉 大輔, 遠藤 光晴

  日本学術振興会, 科学研究費助成事業, 基盤研究(C), 神戸大学, Apr. 2025 - Mar. 2028


• 過敏性腸症候群の腸管透過性の亢進を制御する腸内細菌および宿主の病態解析

  井上 潤, 木下 雅登

  日本学術振興会, 科学研究費助成事業, 基盤研究(C), 神戸大学, 01 Apr. 2022 - 31 Mar. 2025


• 自己免疫性膵炎の病態形成における腸内細菌の役割

  井上 潤, 酒井 新, 児玉 裕三

  日本学術振興会, 科学研究費助成事業, 基盤研究(C), 神戸大学, 01 Apr. 2019 - 31 Mar. 2023

  自己免疫性膵炎（AIP）は血清IgG4高値とIgG4陽性形質細胞の浸潤を特徴とする機序不明の膵炎で、わが国で報告され現在IgG4関連疾患の一つとして難病指定されている。ステロイドの反応性から自己免疫的機序によるものと推察されているが、特異的治療がなく再燃率も高く問題となっている。申請者のグループは腸内細菌に対する抗体などの免疫反応が膵臓の炎症を惹起し疾患発症に関与しているのではないかという仮説を立案し研究を行っている。 これまでに、AIP患者の腸管において分泌されている免疫グロブリンの組成が健常者と異なることを明らかとした。腸管に分泌される免疫グロブリンの各種アイソタイプと結合する菌をMACSおよびFACAにより分離し次世代シーケンサーにより菌の構成を解析した。AIP患者の免疫ブロブリンIgG4と結合している菌を解析し、AIPの腸管免疫に特異的に関わっている可能性のある菌の候補の絞り込みを行い、4菌種が抽出され、今後、それらの菌がどのようにAIPの病態に関わっているか、また腸内細菌が疾患マーカーになりうるかを解析する。さらに、AIP患者が腸管内容物の抗原に対して特異的に反応しているものをWestern blot法および質量分析法でタンパクのアミノ酸配列の同定を行った。解析したタンパクの中で細菌由来のタンパクの同定には至っていないが、AIP患者の血清の免疫グロブリンは便中のヒト膵臓由来のあるタンパクとの強く結合していることを見出した。今後、AIP患者の血清中免疫グロブリンと反応するタンパクの同定の条件検討を進め、免疫沈降法などを用いて特異的なタンパクの濃縮方法など条件検討を試みる。AIP患者の免疫グロブリンと結合する腸内細菌をMACS法およびFACS法で分離後の次世代シーケンサーによる菌叢解析の条件検討も行う。引き続きAIPに特異的な自己抗体候補の検索を行っていく。


• 非アルコール性脂肪肝炎への進展に関わる腸管粘膜表層細菌の解析

  酒井 新, 井上 潤, 矢野 嘉彦

  日本学術振興会, 科学研究費助成事業, 基盤研究(C), 神戸大学, 01 Apr. 2019 - 31 Mar. 2023

  非アルコール性脂肪性肝炎（NASH）は脂肪肝を背景とする肝炎である。さらにBMI正常であるにもかかわらず、膵切除後や消化管術後など腸内細菌変化が起こる患者でNASHを発症する患者が存在する。NASHは、健常人と比べ糞便中の腸内細菌叢構成の違いが指摘されているが、腸管粘膜上皮により近い上皮表面のムチン層内の細菌叢の違いとその病態への影響については不明な点が多い。当研究の目的は患者の腸管粘膜上皮表面の細菌叢に疾患特有性や病勢との関連があるかを明らかにすることである。 これまでの研究で、下部消化管内視鏡による粘膜上皮表面のムチン層に存在する細菌叢の採取方法およびDNA抽出方法、シーケンスライブラリー作成方法などの条件検討を行った。NASH患者15名と非NASH患者10名づつのサンプルを集積し、次世代シーケンサーを用いて、粘液表層細菌、唾液、糞便の腸内細菌解析を行い、NASH患者の粘膜表層細菌と健常者の菌叢との差異を解析した。NASH患者および健常者ともに、同一個人でも粘液中の細菌叢構成は糞便中のものと大きく違う一方で、健常人とNASH患者ともに同一個人内では粘膜表層の細菌は回腸末端や大腸の各場所の部位によらず似通っていることが、条件検討と同様の結果であることを明らかとした。今後NASH患者と健常者の腸内細菌の統計的な比較解析、さらにはNASHの病態に関わる腸内細菌の機能変化の解析を進め成果報告を行う。


• Tumor microenvironment and gut microbiota in pancreatic cancer

  Masuda Atsuhiro

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Kobe University, 01 Apr. 2019 - 31 Mar. 2022

  In recent years, it has become clear that bacterial infection is locally observed in pancreatic cancer, suggesting that it plays an important role in pancreatic carcinogenesis and its progression. However, there are still unclear what and how bacterial species are involved in pancreatic carcinogenesis and progression. In this study, we investigated the relationship between the microbiota profile of cancer and the pathological and clinical features using the histopathology of human pancreatic cancer. Compared with normal pancreatic tissue, pancreatic cancer showed a high amplification reaction of 16S rDNA, and analysis by the next-generation sequencer could identify the same bacteria as previously reported. Furthermore, immunostaining of LPS revealed that LPS-positive pancreatic cancer had a poor prognosis and that tumor immunity was suppressed. Currently, we are considering adding in situ hybridization.


• 過敏性腸症候群における腸管粘膜上皮表層細菌叢と病勢との相関解析

  井上 潤

  学術研究助成基金助成金／若手研究(B), Apr. 2017 - Mar. 2019, Principal investigator

  Competitive research funding


• Cell type-specific role of Autophagy against intestinal inflammation

  INOUE Jun

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Young Scientists (B), Kobe Pharmaceutical University, 01 Apr. 2013 - 31 Mar. 2015

  Genome-wide association studies identified autophagy gene as a Crohn’s disease susceptibility gene. However it is unclear how autophagy regulates the inflammation in the intestine. The purpose of this study is to clarify the mechanism of autophagy to regulate the intestinal inflammation. We generated the organs specific autophagy deficient mouse, then the involvement of autophagy in intestinal inflammation was examined. Secretion of IL-1β in the macrophages harvested from peritoneal cavity of the mice in which Atg7 had been conditionally deleted from the lysozyme cells was higher than that of control mice after infection with Citrobacter Rodentium, a pathogen used in the murine model of infectious enteritis. And more infected knockout mice exhibited greater clinical evidence of disease and higher expression levels of IL-1β mRNA in the large intestine. These results indicated that autophagy in the lysozyme cells have important role in the regulation of intestinal inflammation.