著者
Naofumi Yoshida Kengo Sasaki Daisuke Sasaki Tomoya Yamashita Hajime Fukuda Tomohiro Hayashi Tokiko Tabata Ro Osawa Ken-ichi Hirata Akihiko Kondo
出版者
Japan Atherosclerosis Society
雑誌
Journal of Atherosclerosis and Thrombosis (ISSN:13403478)
巻号頁・発行日
pp.47415, (Released:2018-12-27)
参考文献数
49
被引用文献数
24

Aim: Bacteroides vulgatus and B. dorei have a protective effect against atherosclerosis, suggesting that expansion of these species in the gut microbiota could help patients with coronary artery disease (CAD). This study aimed to investigate the effect of resistant starch (RS) on the gut microbiota and its metabolites in fecal sample cultures from patients with CAD and individuals without CAD, using a single-batch fermentation system.Methods: Fecal samples from 11 patients with CAD and 10 individuals without CAD were fermented for 30 h with or without RS in the Kobe University Human Intestinal Microbiota Model (KUHIMM). Gut microbiota and the abundance of B. vulgatus and B. dorei were analyzed using 16S ribosomal ribonucleic acid (rRNA) gene sequencing and the quantitative polymerase chain reaction. Short-chain fatty acids were analyzed using high-performance liquid chromatography.Results: Gut microbial analysis showed significantly lower levels of B. vulgatus and B. dorei in the original fecal samples from patients with CAD, which was simulated after 30 h of fermentation in the KUHIMM. Although RS significantly increased the absolute numbers of B. vulgatus and B. dorei, and butyrate levels in CAD fecal sample cultures, the numbers varied among each patient.Conclusions: The effect of RS on gut microbiota and its metabolites in the KUHIMM varied between CAD and non-CAD fecal sample cultures. The KUHIMM may be useful for preclinical evaluations of the effects of RS on the gut microbiota and its metabolites.
著者
Naofumi Yoshida Sachiyo Iwata Masato Ogawa Kazuhiro P. Izawa Shunsuke Kuroda Shun Kohsaka Taishi Yonetsu Takeshi Kitai Sho Torii Takahide Sano Yoshitada Sakai Tomoya Yamashita Ken-ichi Hirata Yuya Matsue Shingo Matsumoto Koichi Node
出版者
The Japanese Circulation Society
雑誌
Circulation Reports (ISSN:24340790)
巻号頁・発行日
vol.3, no.7, pp.375-380, 2021-07-09 (Released:2021-07-09)
参考文献数
18
被引用文献数
4

Background:The COVID-19 pandemic has challenged healthcare systems, at times overwhelming intensive care units (ICUs). We aimed to describe the length and rate of ICU admission, and explore the clinical variables influencing ICU use, for COVID-19 patients with known cardiovascular diseases or their risk factors (CVDRF).Methods and Results:A post hoc analysis was performed of 693 Japanese COVID-19 patients with CVDRF enrolled in the nationwide CLAVIS-COVID registration system between January and May 2020 (mean [±SD] age 68.3±14.9 years; 35% female); 199 patients (28.7%) required ICU management. The mean (±SD) ICU length of stay (LOS) was 19.3±18.5 days, and the rate of in-hospital death and hospital LOS were significantly higher (P<0.001) and longer (P<0.001), respectively, in the ICU than non-ICU group. Logistic regression analysis revealed that clinical variables reflecting impaired general condition (e.g., high C-reactive protein, low Glasgow Coma Scale score, SpO2, albumin level), male sex, and previous use of β-blockers) were associated with ICU admission (all P<0.001). Notably, age was inversely associated with ICU admission, and this was particularly prominent among elderly patients (OR 0.97, 95% confidence interval 0.95–0.99; P=0.0018).Conclusions:One-third of COVID patients with CVDRF required ICU care during the first phase of the pandemic in Japan. Other than anticipated clinical variables, such as hypoxia and altered mental status, age was inversely associated with the use of the ICU, warranting further investigation.
著者
Takuo Emoto Naoto Sasaki Tomoya Yamashita Kazuyuki Kasahara Keiko Yodoi Yoshihiro Sasaki Takuya Matsumoto Taiji Mizoguchi Ken-ichi Hirata
出版者
日本循環器学会
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
vol.78, no.12, pp.2935-2941, 2014-11-25 (Released:2014-11-25)
参考文献数
22
被引用文献数
9 40

Background:The protective function of regulatory T cells (Treg) has been identified in experimental atherosclerosis, but the contribution of Tregto the pathogenesis of human coronary artery disease (CAD) remains poorly understood. We investigated Tregand regulatory T-cell/effector T-cell (Treg/Teff) ratio in peripheral blood samples from CAD patients using a new strategy for precise identification of Treg.Methods and Results:Peripheral blood samples were collected from 73 stable CAD patients (55 middle-aged CAD patients and 18 old CAD patients) and 64 controls (47 middle-aged controls and 17 young controls). CD3+CD4+FoxP3+T cells were divided into 3 fractions: CD45RA+FoxP3lowresting Treg(Fr1), CD45RA–FoxP3highactivated Treg(Fr2), and CD45RA–FoxP3lownon-Treg(Fr3). CAD patients had lower percentages of Fr1 and Fr2 and higher percentages of Fr3 and CD45RA–Foxp3–Teff(Fr4+5) within the CD3+CD4+T-cell population compared to age-matched controls. Treg/Teffratio (Fr1+2/Fr3+4+5) in CAD patients was also markedly lower than in controls (middle-aged control, 0.17±0.09 vs. middle-aged CAD, 0.10±0.05; P<0.001). The percentage of CD4+CD28nullT cells within the CD4+T-cell population was negatively correlated with Treg/Teffratio, excluding CD4+CD28nullT cells <0.3% (r=–0.27, P<0.05). High-sensitivity C-reactive protein was also negatively correlated with Treg/Teffratio (r=–0.22, P<0.05).Conclusions:CAD patients had reduced Tregand Treg/Teffratio compared to healthy controls. The present findings may be helpful when developing immunotherapy for the prevention of CAD. (Circ J 2014; 78: 2935–2941)
著者
Satoshi WATANABE Naofumi YOSHIDA Kairi BABA Hiroyuki YAMASAKI Natsuko O. SHINOZAKI Masato OGAWA Tomoya YAMASHITA Aya K. TAKEDA
出版者
BMFH Press
雑誌
Bioscience of Microbiota, Food and Health (ISSN:21863342)
巻号頁・発行日
pp.2022-047, (Released:2023-10-18)

Gut microbiota imbalance plays an important role in the pathogenesis of various diseases. Here, we determined microbe–microbe interactions and gut microbiome stability in a Japanese population with varying body mass indices (BMIs) and enterotypes. Using 16S ribosomal RNA gene sequencing, we analyzed gut microbial data from fecal samples obtained from 3,365 older Japanese individuals. The individuals were divided into lean, normal, and obese groups based on their BMIs. They were further categorized according to their gut microbiota enterotypes: Bacteroides (enterotype B), Prevotella (enterotype P), and Ruminococcus (enterotype R). We obtained data on different host factors, such as age, BMI, and disease status, using a survey questionnaire evaluated by the Mykinso gut microbiome testing service. Subsequently, we evaluated the co-occurrence network. Individual differences in BMI were associated with differences in co-occurrence networks. By exploring the network topology based on BMI status , we observed that the network density was lower in the lean group than that in the normal group. Furthermore, a simulation-based stability analysis revealed a lower resistance index in the lean group than those in the other two groups. Our results provide insights into various microbe–microbe interactions and gut microbial stability and could aid in developing appropriate therapeutic strategies targeting gut microbiota modulation to manage frailty.
著者
Naofumi YOSHIDA Satoshi WATANABE Hiroyuki YAMASAKI Hajime SAKUMA Aya K. TAKEDA Tomoya YAMASHITA Ken-ichi HIRATA
出版者
BMFH Press
雑誌
Bioscience of Microbiota, Food and Health (ISSN:21863342)
巻号頁・発行日
pp.2021-056, (Released:2021-12-07)
被引用文献数
13

Imbalance of the gut microbiota plays an important role in the pathogenesis of various diseases. Although many clinical studies have analyzed the gut microbiota, the definition of normal gut microbiota remains unclear. In this study, we aim to establish the average gut microbiota in the healthy Japanese population. Using 16S ribosomal RNA gene sequencing, we analyzed gut microbial data from fecal samples obtained from 6,101 healthy Japanese individuals. Based on their ages, the individuals were divided into three groups: young, middle-age, and old. Individuals were further categorized according to body mass index (BMI) into lean, normal, and obese groups. The α and β diversities in the old group were significantly higher than those in the young and middle-age groups. The Firmicutes/Bacteroidetes ratio of subjects in the obese category was significantly lower compared with those of subjects in the lean and normal categories in the young and middle-age groups. Genus Bacteroides was the dominant gut microbiota across all the BMI categories in all the age groups. Among the top ten genera, the abundances of Bacteroides, Bifidobacterium, Anaerostipes, Blautia, Dorea, Fusicatenibacter, Lachnoclostridium, and Parabacteroides were significantly lower in the old group than in the young and middle-age groups. The correlation network at the genus level revealed different microbe-microbe interactions associated with age and BMI. We determined the average Japanese gut microbiota, and this information could be used as a reference. The gut microbiota greatly differs based on the life stage and metabolic status of the host, and this gives rise to a variety of host–gut microbe interactions that can lead to an increased susceptibility to disease.
著者
Tomohiro Hayashi Tomoya Yamashita Hikaru Watanabe Kenjiro Kami Naofumi Yoshida Tokiko Tabata Takuo Emoto Naoto Sasaki Taiji Mizoguchi Yasuhiro Irino Ryuji Toh Masakazu Shinohara Yuko Okada Wataru Ogawa Takuji Yamada Ken-ichi Hirata
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
vol.83, no.1, pp.182-192, 2018-12-25 (Released:2018-12-25)
参考文献数
44
被引用文献数
79

Background: Gut microbiome composition or circulating microbiome-related metabolites in patients with heart failure (HF) have not been investigated at different time points (i.e., in the decompensated (Decomp) and compensated (Comp) phases). Methods and Results: We prospectively enrolled 22 patients admitted for HF and 11 age-, sex-, and comorbidity-matched hospitalized control subjects without a history of HF. Gut flora and plasma microbiome-related metabolites were evaluated by amplicon sequencing of the bacterial 16S ribosomal RNA gene and capillary electrophoresis time-of-flight mass spectrometry, respectively. HF patients were evaluated in both the Decomp and Comp phases during hospitalization. The phylum Actinobacteria was enriched in HF patients compared with control subjects. At the genus level, Bifiodobacterium was abundant while Megamonas was depleted in HF patients. Meanwhile, plasma concentration of trimethylamine N-oxide (TMAO), a gut microbiome-derived metabolite, was increased in HF patients (Decomp HF vs. control, P=0.003; Comp HF vs. control, P=0.004). A correlation analysis revealed positive correlations between the abundance of the genus Escherichia/Shigella and levels of TMAO and indoxyl sulfate (IS, a microbe-dependent uremic toxin) in Comp HF (TMAO: r=0.62, P=0.002; IS: r=0.63, P=0.002). Escherichia/Shigella was more abundant in Decomp than in Comp HF (P=0.030). Conclusions: Our results suggest that gut microbiome composition and microbiome-related metabolites are altered in HF patients.
著者
Tomoya Yamashita
出版者
一般社団法人 日本動脈硬化学会
雑誌
Journal of Atherosclerosis and Thrombosis (ISSN:13403478)
巻号頁・発行日
pp.38265, (Released:2016-12-07)
参考文献数
42
被引用文献数
36

Atherosclerosis is a chronic inflammatory disease. Interventions targeting the inflammatory process could provide new strategies for preventing atherosclerotic cardiovascular diseases (CVD). Previously, we have reported that oral administration of anti-CD3 antibodies, or active vitamin D3, reduced atherosclerosis in mice via recruiting regulatory T cells and tolerogenic dendritic cells to the gut-associated lymphoid tissues. From this, it is reasonable to propose that the intestine could be a novel therapeutic target for prevention of atherosclerotic CVD. Recently, the association between cardio-metabolic diseases and gut microbiota has attracted increased attention. Gut microbiota, reported to be highly associated with intestinal immunity and metabolism, were shown to aggravate CVD by contributing to the production of trimethylamine-N-oxide (TMAO), a pro-atherogenic compound. We have also previously investigated the relationship between patient susceptibility to coronary artery disease (CAD) and gut microbiota. We found that the order Lactobacillales was significantly increased and the phylum Bacteroidetes was decreased in CAD patients compared with control patients. In this review article, we discuss the evidence for the relationship between the gut microbiota and cardio-metabolic diseases, and consider the gut microbiota as new potential diagnostic and therapeutic tool for treating CVD.
著者
Tomoya Yamashita Takuo Emoto Naoto Sasaki Ken-ichi Hirata
出版者
一般社団法人 インターナショナル・ハート・ジャーナル刊行会
雑誌
International Heart Journal (ISSN:13492365)
巻号頁・発行日
pp.16-414, (Released:2016-11-04)
被引用文献数
52

Gut microbiota have been attracting increased attention in many fields of medicine recently. We can perform a comprehensive analysis of gut microbiota using next-generation sequencing techniques together with bioinformatics technology, which expands our knowledge of a large ecosystem consisting of a host and gut microbiota. We summarize some reports about the correlations between gut microbiota and metabolic disorders, particularly atherosclerosis, and discuss future directions for the diagnostic or therapeutic potential of gut microbiota. To take simple examples, we demonstrated that the order Lactobacillales was significantly increased; while the phylum Bacteroidetes was significantly decreased in coronary artery disease (CAD) patients compared with controls or healthy volunteers. The characteristics of gut microbiota in type 2 diabetes and dyslipidemia have been reported. However, these studies have limitations, and the biological significance of gut microbiota and the causal relationships are still controversial. We hope the reports listed in this review article might lead to the development of a novel therapy to prevent CAD via modulating gut microbiota or their metabolites.
著者
Tomoya Yamashita Kazuyuki Kasahara Takuo Emoto Takuya Matsumoto Taiji Mizoguchi Naoki Kitano Naoto Sasaki Ken-ichi Hirata
出版者
日本循環器学会
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
vol.79, no.9, pp.1882-1890, 2015-08-25 (Released:2015-08-25)
参考文献数
48
被引用文献数
4 49

Atherosclerosis is considered a chronic inflammatory disease and an intervention targeting the inflammatory process could be a new therapeutic strategy for preventing atherosclerotic cardiovascular diseases (CVD). We hypothesized that the intestine, which is considered the biggest immune organ in the human body, could be a therapeutic target for preventing CVD. We demonstrated that oral administration of anti-CD3 antibody or an active form of vitamin D3reduced atherosclerosis in mice via induction of regulatory T cells and tolerogenic dendritic cells in the gut-associated lymphoid tissues. Similar to regulatory immune responses achieved by oral tolerance, our method had systemic effects that ultimately contributed towards atherosclerosis reduction. Recently, we have been interested in the gut microbiota, which have been reported as highly associated with intestinal immunity and systemic metabolic disorders, including obesity and diabetes. Notably, the guts of obese individuals are predominantly colonized byFirmicutesoverBacteroidetes. The association between atherosclerosis and microbiota has been attracting increased attention, and gut microbiota have been shown to participate in the metabolism of a proatherogenic compound called trimethylamine-N-oxide (TMAO) and aggravate CVD. Our investigation of the relationship between susceptibility to CVD and the gut microbiota revealed a characteristic flora type. Here, we discuss the evidence for the relationship between the gut microbiota and cardiometabolic diseases, and consider the gut microbiota as new potential therapeutic targets for treating CVD. (Circ J 2015; 79: 1882–1890)
著者
Takuo Emoto Naoto Sasaki Tomoya Yamashita Kazuyuki Kasahara Keiko Yodoi Yoshihiro Sasaki Takuya Matsumoto Taiji Mizoguchi Ken-ichi Hirata
出版者
日本循環器学会
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
pp.CJ-14-0644, (Released:2014-10-18)
参考文献数
22
被引用文献数
9 40

Background:The protective function of regulatory T cells (Treg) has been identified in experimental atherosclerosis, but the contribution of Tregto the pathogenesis of human coronary artery disease (CAD) remains poorly understood. We investigated Tregand regulatory T-cell/effector T-cell (Treg/Teff) ratio in peripheral blood samples from CAD patients using a new strategy for precise identification of Treg.Methods and Results:Peripheral blood samples were collected from 73 stable CAD patients (55 middle-aged CAD patients and 18 old CAD patients) and 64 controls (47 middle-aged controls and 17 young controls). CD3+CD4+FoxP3+T cells were divided into 3 fractions: CD45RA+FoxP3lowresting Treg(Fr1), CD45RA–FoxP3highactivated Treg(Fr2), and CD45RA–FoxP3lownon-Treg(Fr3). CAD patients had lower percentages of Fr1 and Fr2 and higher percentages of Fr3 and CD45RA–Foxp3–Teff(Fr4+5) within the CD3+CD4+T-cell population compared to age-matched controls. Treg/Teffratio (Fr1+2/Fr3+4+5) in CAD patients was also markedly lower than in controls (middle-aged control, 0.17±0.09 vs. middle-aged CAD, 0.10±0.05; P<0.001). The percentage of CD4+CD28nullT cells within the CD4+T-cell population was negatively correlated with Treg/Teffratio, excluding CD4+CD28nullT cells <0.3% (r=–0.27, P<0.05). High-sensitivity C-reactive protein was also negatively correlated with Treg/Teffratio (r=–0.22, P<0.05).Conclusions:CAD patients had reduced Tregand Treg/Teffratio compared to healthy controls. The present findings may be helpful when developing immunotherapy for the prevention of CAD.