المؤلفون: Felix Salim, Sayaka Mizutani, Satoshi Shiba, Hiroyuki Takamaru, Masayoshi Yamada, Takeshi Nakajima, Tatsuo Yachida, Tomoyoshi Soga, Yutaka Saito, Shinji Fukuda, Shinichi Yachida, Takuji Yamada

المصدر: iScience, Vol 27, Iss 7, Pp 110181- (2024)

مصطلحات موضوعية: Health sciences, Microbiome, Bioinformatics, Metabolomics, Cancer, Science

الوصف: Summary: Accumulating evidence demonstrates clear correlation between the gut microbiota and sporadic colorectal cancer (CRC). Despite this, there is limited understanding of the association between the gut microbiota and CRC in Lynch Syndrome (LS), a hereditary type of CRC. Here, we analyzed fecal shotgun metagenomic and targeted metabolomic of 71 Japanese LS subjects. A previously published Japanese sporadic CRC cohort, which includes non-LS controls, was utilized as a non-LS cohort (n = 437). LS subjects exhibited reduced microbial diversity and low-Faecalibacterium enterotypes compared to non-LS. Patients with LS-CRC had higher levels of Fusobacterium nucleatum and fap2. Differential fecal metabolites and functional genes suggest heightened degradation of lysine and arginine in LS-CRC. A comparison between LS and non-LS subjects prior to adenoma formation revealed distinct fecal metabolites of LS subjects. These findings suggest that the gut microbiota plays a more responsive role in CRC tumorigenesis in patients with LS than those without LS.

وصف الملف: electronic resource

Relation: http://www.sciencedirect.com/science/article/pii/S2589004224014068; https://doaj.org/toc/2589-0042

URL الوصول: https://doaj.org/article/228eafe334a64bd291bfc67044002e84

المؤلفون: Miyuki Nomura, Mai Ohuchi, Yoshimi Sakamoto, Kei Kudo, Keisuke Yaku, Tomoyoshi Soga, Yuki Sugiura, Mami Morita, Kayoko Hayashi, Shuko Miyahara, Taku Sato, Yoji Yamashita, Shigemi Ito, Naohiko Kikuchi, Ikuro Sato, Rintaro Saito, Nobuo Yaegashi, Tatsuro Fukuhara, Hidekazu Yamada, Hiroshi Shima, Keiichi I. Nakayama, Atsushi Hirao, Kenta Kawasaki, Yoichi Arai, Shusuke Akamatsu, Sei-ichi Tanuma, Toshiro Sato, Takashi Nakagawa, Nobuhiro Tanuma

المصدر: Nature Communications, Vol 14, Iss 1, Pp 1-15 (2023)

مصطلحات موضوعية: Science

الوصف: Abstract Nicotinamide phosphoribosyltransferase (NAMPT) plays a major role in NAD biosynthesis in many cancers and is an attractive potential cancer target. However, factors dictating therapeutic efficacy of NAMPT inhibitors (NAMPTi) are unclear. We report that neuroendocrine phenotypes predict lung and prostate carcinoma vulnerability to NAMPTi, and that NAMPTi therapy against those cancers is enhanced by dietary modification. Neuroendocrine differentiation of tumor cells is associated with down-regulation of genes relevant to quinolinate phosphoribosyltransferase-dependent de novo NAD synthesis, promoting NAMPTi susceptibility in vitro. We also report that circulating nicotinic acid riboside (NAR), a non-canonical niacin absent in culture media, antagonizes NAMPTi efficacy as it fuels NAMPT-independent but nicotinamide riboside kinase 1-dependent NAD synthesis in tumors. In mouse transplantation models, depleting blood NAR by nutritional or genetic manipulations is synthetic lethal to tumors when combined with NAMPTi. Our findings provide a rationale for simultaneous targeting of NAR metabolism and NAMPT therapeutically in neuroendocrine carcinoma.

وصف الملف: electronic resource

Relation: https://doaj.org/toc/2041-1723

URL الوصول: https://doaj.org/article/84428954a433469dabdd48178f38d87e

المؤلفون: Tomoya Tsukimi, Nozomu Obana, Suguru Shigemori, Kazuharu Arakawa, Eiji Miyauchi, Jiayue Yang, Isaiah Song, Yujin Ashino, Masataka Wakayama, Tomoyoshi Soga, Masaru Tomita, Hiroshi Ohno, Hirotada Mori, Shinji Fukuda

المصدر: mSystems, Vol 9, Iss 2 (2024)

مصطلحات موضوعية: gut microbiota, Escherichia coli, genetic mutation, intestinal colonization, intestinal nutrient, Microbiology, QR1-502

الوصف: ABSTRACTMammalian gut microbes colonize the intestinal tract of their host and adapt to establish a microbial ecosystem. The host diet changes the nutrient profile of the intestine and has a high impact on microbiota composition. Genetic mutations in Escherichia coli, a prevalent species in the human gut, allow for adaptation to the mammalian intestine, as reported in previous studies. However, the extent of colonization fitness in the intestine elevated by genetic mutation and the effects of diet change on these mutations in E. coli are still poorly known. Here, we show that notable mutations in sugar metabolism-related genes (gatC, araC, and malI) were detected in the E. coli K-12 genome just 2 weeks after colonization in the germ-free mouse intestine. In addition to elevated fitness by deletion of gatC, as previously reported, deletion of araC and malI also elevated E. coli fitness in the murine intestine in a host diet-dependent manner. In vitro cultures of medium containing nutrients abundant in the intestine (e.g., galactose, N-acetylglucosamine, and asparagine) also showed increased E. coli fitness after deletion of the genes-of-interest associated with their metabolism. Furthermore, the host diet was found to influence the developmental trajectory of gene mutations in E. coli. Taken together, we suggest that genetic mutations in E. coli are selected in response to the intestinal environment, which facilitates efficient utilization of nutrients abundant in the intestine under laboratory conditions. Our study offers some insight into the possible adaptation mechanisms of gut microbes.IMPORTANCEThe gut microbiota is closely associated with human health and is greatly impacted by the host diet. Bacteria such as Escherichia coli live in the gut all throughout the life of a human host and adapt to the intestinal environment. Adaptive mutations in E. coli are reported to enhance fitness in the mammalian intestine, but to what extent is still poorly known. It is also unknown whether the host diet affects what genes are mutated and to what extent fitness is affected. This study suggests that genetic mutations in the E. coli K-12 strain are selected in response to the intestinal environment and facilitate efficient utilization of abundant nutrients in the germ-free mouse intestine. Our study provides a better understanding of these intestinal adaptation mechanisms of gut microbes.

وصف الملف: electronic resource

Relation: https://doaj.org/toc/2379-5077

URL الوصول: https://doaj.org/article/6c21002eaf084c9dbfa695248a4bc888

المؤلفون: Yasushi Kojima, Emi Mishiro-Sato, Teruaki Fujishita, Kiyotoshi Satoh, Rie Kajino-Sakamoto, Isao Oze, Kazuki Nozawa, Yukiya Narita, Takatsugu Ogata, Keitaro Matsuo, Kei Muro, Makoto Mark Taketo, Tomoyoshi Soga, Masahiro Aoki

المصدر: Nature Communications, Vol 14, Iss 1, Pp 1-23 (2023)

مصطلحات موضوعية: Science

الوصف: Abstract Cancer cachexia is a complex metabolic disorder accounting for ~20% of cancer-related deaths, yet its metabolic landscape remains unexplored. Here, we report a decrease in B vitamin-related liver enzymes as a hallmark of systemic metabolic changes occurring in cancer cachexia. Metabolomics of multiple mouse models highlights cachexia-associated reductions of niacin, vitamin B6, and a glycine-related subset of one-carbon (C1) metabolites in the liver. Integration of proteomics and metabolomics reveals that liver enzymes related to niacin, vitamin B6, and glycine-related C1 enzymes dependent on B vitamins decrease linearly with their associated metabolites, likely reflecting stoichiometric cofactor-enzyme interactions. The decrease of B vitamin-related enzymes is also found to depend on protein abundance and cofactor subtype. These metabolic/proteomic changes and decreased protein malonylation, another cachexia feature identified by protein post-translational modification analysis, are reflected in blood samples from mouse models and gastric cancer patients with cachexia, underscoring the clinical relevance of our findings.

وصف الملف: electronic resource

Relation: https://doaj.org/toc/2041-1723

URL الوصول: https://doaj.org/article/1ee9040a74a0436c807b06119e134c56

المؤلفون: Yoshiki Ishibashi, Sei Harada, Yoko Eitaki, Ayako Kurihara, Suzuka Kato, Kazuyo Kuwabara, Miho Iida, Aya Hirata, Mizuki Sata, Minako Matsumoto, Takuma Shibuki, Tomonori Okamura, Daisuke Sugiyama, Asako Sato, Kaori Amano, Akiyoshi Hirayama, Masahiro Sugimoto, Tomoyoshi Soga, Masaru Tomita, Toru Takebayashi

المصدر: Environmental Health and Preventive Medicine, Vol 29, Pp 22-22 (2024)

مصطلحات موضوعية: metabolomics, cadmium, urine, plasma, multivariable regression model, Public aspects of medicine, RA1-1270

الوصف: Background: The application of metabolomics-based profiles in environmental epidemiological studies is a promising approach to refine the process of health risk assessment. We aimed to identify potential metabolomics-based profiles in urine and plasma for the detection of relatively low-level cadmium (Cd) exposure in large population-based studies. Method: We analyzed 123 urinary metabolites and 94 plasma metabolites detected in fasting urine and plasma samples collected from 1,412 men and 2,022 women involved in the Tsuruoka Metabolomics Cohort Study. Regression analysis was performed for urinary N-acetyl-beta-D-glucosaminidase (NAG), plasma, and urinary metabolites as dependent variables, and urinary Cd (U-Cd, quartile) as an independent variable. The multivariable regression model included age, gender, systolic blood pressure, smoking, rice intake, BMI, glycated hemoglobin, low-density lipoprotein cholesterol, alcohol consumption, physical activity, educational history, dietary energy intake, urinary Na/K ratio, and uric acid. Pathway-network analysis was carried out to visualize the metabolite networks linked to Cd exposure. Result: Urinary NAG was positively associated with U-Cd, but not at lower concentrations (Q2). Among urinary metabolites in the total population, 45 metabolites showed associations with U-Cd in the unadjusted and adjusted models after adjusting for the multiplicity of comparison with FDR. There were 12 urinary metabolites which showed consistent associations between Cd exposure from Q2 to Q4. Among plasma metabolites, six cations and one anion were positively associated with U-Cd, whereas alanine, creatinine, and isoleucine were negatively associated with U-Cd. Our results were robust by statistical adjustment of various confounders. Pathway-network analysis revealed metabolites and upstream regulator changes associated with mitochondria (ACACB, UCP2, and metabolites related to the TCA cycle). Conclusion: These results suggested that U-Cd was associated with metabolites related to upstream mitochondrial dysfunction in a dose-dependent manner. Our data will help develop environmental Cd exposure profiles for human populations.

وصف الملف: electronic resource

Relation: https://www.jstage.jst.go.jp/article/ehpm/29/0/29_23-00218/_html/-char/en; https://doaj.org/toc/1342-078X; https://doaj.org/toc/1347-4715

URL الوصول: https://doaj.org/article/b8ffeb5611d34e488d0f972ee8e867d0

المؤلفون: Yuki Ito, Shinsuke Uda, Toshiya Kokaji, Akiyoshi Hirayama, Tomoyoshi Soga, Yutaka Suzuki, Shinya Kuroda, Hiroyuki Kubota

المصدر: Scientific Reports, Vol 13, Iss 1, Pp 1-17 (2023)

مصطلحات موضوعية: Medicine, Science

الوصف: Abstract Interactions between various molecular species in biological phenomena give rise to numerous networks. The investigation of these networks, including their statistical and biochemical interactions, supports a deeper understanding of biological phenomena. The clustering of nodes associated with molecular species and enrichment analysis is frequently applied to examine the biological significance of such network structures. However, these methods focus on delineating the function of a node. As such, in-depth investigations of the edges, which are the connections between the nodes, are rarely explored. In the current study, we aimed to investigate the functions of the edges rather than the nodes. To accomplish this, for each network, we categorized the edges and defined the edge type based on their biological annotations. Subsequently, we used the edge type to compare the network structures of the metabolome and transcriptome in the livers of healthy (wild-type) and obese (ob/ob) mice following oral glucose administration (OGTT). The findings demonstrate that the edge type can facilitate the characterization of the state of a network structure, thereby reducing the information available through datasets containing the OGTT response in the metabolome and transcriptome.

وصف الملف: electronic resource

Relation: https://doaj.org/toc/2045-2322

URL الوصول: https://doaj.org/article/d49e627e1b084f6791576e488423b87c

المؤلفون: Tomohiro Yabushita, Takumi Chinen, Atsuya Nishiyama, Shuhei Asada, Keita Yamamoto, Naru Sato, Yutaka Enomoto, Keiko Katoh, Kaori Saitoh, Takamasa Ishikawa, Tomoyoshi Soga, Yasuhito Nannya, Makoto Nakanishi, Daiju Kitagawa, Toshio Kitamura, Susumu Goyama

المصدر: HemaSphere, Vol 7, p e20270ec (2023)

مصطلحات موضوعية: Diseases of the blood and blood-forming organs, RC633-647.5

وصف الملف: electronic resource

Relation: http://journals.lww.com/10.1097/01.HS9.0000968536.20270.ec; https://doaj.org/toc/2572-9241

URL الوصول: https://doaj.org/article/f87f3d9fc84c4f848d07dfb6e3f8b97e

المؤلفون: Atsuko Miyake, Sei Harada, Daisuke Sugiyama, Minako Matsumoto, Aya Hirata, Naoko Miyagawa, Ryota Toki, Shun Edagawa, Kazuyo Kuwabara, Tomonori Okamura, Asako Sato, Kaori Amano, Akiyoshi Hirayama, Masahiro Sugimoto, Tomoyoshi Soga, Masaru Tomita, Kazuharu Arakawa, Toru Takebayashi, Miho Iida

المصدر: Metabolites, Vol 14, Iss 1, p 77 (2024)

مصطلحات موضوعية: metabolomics, capillary electrophoresis–mass spectrometry, reliability, time-series data, repeated measurements, longitudinal data, Microbiology, QR1-502

الوصف: Studies examining long-term longitudinal metabolomic data and their reliability in large-scale populations are limited. Therefore, we aimed to evaluate the reliability of repeated measurements of plasma metabolites in a prospective cohort setting and to explore intra-individual concentration changes at three time points over a 6-year period. The study participants included 2999 individuals (1317 men and 1682 women) from the Tsuruoka Metabolomics Cohort Study, who participated in all three surveys—at baseline, 3 years, and 6 years. In each survey, 94 plasma metabolites were quantified for each individual and quality control (QC) sample. The coefficients of variation of QC, intraclass correlation coefficients, and change rates of QC were calculated for each metabolite, and their reliability was classified into three categories: excellent, fair to good, and poor. Seventy-six percent (71/94) of metabolites were classified as fair to good or better. Of the 39 metabolites grouped as excellent, 29 (74%) in men and 26 (67%) in women showed significant intra-individual changes over 6 years. Overall, our study demonstrated a high degree of reliability for repeated metabolome measurements. Many highly reliable metabolites showed significant changes over the 6-year period, suggesting that repeated longitudinal metabolome measurements are useful for epidemiological studies.

وصف الملف: electronic resource

Relation: https://www.mdpi.com/2218-1989/14/1/77; https://doaj.org/toc/2218-1989

URL الوصول: https://doaj.org/article/680b3b7ff89145978db4ca6311e1cfaa

المؤلفون: Yohko Yoshida, Ippei Shimizu, Atsuhiro Shimada, Keita Nakahara, Sachiko Yanagisawa, Minoru Kubo, Shinji Fukuda, Chiharu Ishii, Hiromitsu Yamamoto, Takamasa Ishikawa, Kuniyuki Kano, Junken Aoki, Goro Katsuumi, Masayoshi Suda, Kazuyuki Ozaki, Yutaka Yoshida, Shujiro Okuda, Shigeo Ohta, Shiki Okamoto, Yasuhiko Minokoshi, Kanako Oda, Toshikuni Sasaoka, Manabu Abe, Kenji Sakimura, Yoshiaki Kubota, Norihiko Yoshimura, Shingo Kajimura, Maria Zuriaga, Kenneth Walsh, Tomoyoshi Soga, Tohru Minamino

المصدر: Scientific Reports, Vol 12, Iss 1, Pp 1-15 (2022)

مصطلحات موضوعية: Medicine, Science

الوصف: Abstract Low body temperature predicts a poor outcome in patients with heart failure, but the underlying pathological mechanisms and implications are largely unknown. Brown adipose tissue (BAT) was initially characterised as a thermogenic organ, and recent studies have suggested it plays a crucial role in maintaining systemic metabolic health. While these reports suggest a potential link between BAT and heart failure, the potential role of BAT dysfunction in heart failure has not been investigated. Here, we demonstrate that alteration of BAT function contributes to development of heart failure through disorientation in choline metabolism. Thoracic aortic constriction (TAC) or myocardial infarction (MI) reduced the thermogenic capacity of BAT in mice, leading to significant reduction of body temperature with cold exposure. BAT became hypoxic with TAC or MI, and hypoxic stress induced apoptosis of brown adipocytes. Enhancement of BAT function improved thermogenesis and cardiac function in TAC mice. Conversely, systolic function was impaired in a mouse model of genetic BAT dysfunction, in association with a low survival rate after TAC. Metabolomic analysis showed that reduced BAT thermogenesis was associated with elevation of plasma trimethylamine N-oxide (TMAO) levels. Administration of TMAO to mice led to significant reduction of phosphocreatine and ATP levels in cardiac tissue via suppression of mitochondrial complex IV activity. Genetic or pharmacological inhibition of flavin-containing monooxygenase reduced the plasma TMAO level in mice, and improved cardiac dysfunction in animals with left ventricular pressure overload. In patients with dilated cardiomyopathy, body temperature was low along with elevation of plasma choline and TMAO levels. These results suggest that maintenance of BAT homeostasis and reducing TMAO production could be potential next-generation therapies for heart failure.

وصف الملف: electronic resource

Relation: https://doaj.org/toc/2045-2322

URL الوصول: https://doaj.org/article/47e7cf28377a4d3a94aefb37d6721e18

المؤلفون: Toshiya Kokaji, Miki Eto, Atsushi Hatano, Katsuyuki Yugi, Keigo Morita, Satoshi Ohno, Masashi Fujii, Ken-ichi Hironaka, Yuki Ito, Riku Egami, Saori Uematsu, Akira Terakawa, Yifei Pan, Hideki Maehara, Dongzi Li, Yunfan Bai, Takaho Tsuchiya, Haruka Ozaki, Hiroshi Inoue, Hiroyuki Kubota, Yutaka Suzuki, Akiyoshi Hirayama, Tomoyoshi Soga, Shinya Kuroda

المصدر: Scientific Reports, Vol 12, Iss 1, Pp 1-19 (2022)

مصطلحات موضوعية: Medicine, Science

الوصف: Abstract Metabolic regulation in skeletal muscle is essential for blood glucose homeostasis. Obesity causes insulin resistance in skeletal muscle, leading to hyperglycemia and type 2 diabetes. In this study, we performed multiomic analysis of the skeletal muscle of wild-type (WT) and leptin-deficient obese (ob/ob) mice, and constructed regulatory transomic networks for metabolism after oral glucose administration. Our network revealed that metabolic regulation by glucose-responsive metabolites had a major effect on WT mice, especially carbohydrate metabolic pathways. By contrast, in ob/ob mice, much of the metabolic regulation by glucose-responsive metabolites was lost and metabolic regulation by glucose-responsive genes was largely increased, especially in carbohydrate and lipid metabolic pathways. We present some characteristic metabolic regulatory pathways found in central carbon, branched amino acids, and ketone body metabolism. Our transomic analysis will provide insights into how skeletal muscle responds to changes in blood glucose and how it fails to respond in obesity.

وصف الملف: electronic resource

Relation: https://doaj.org/toc/2045-2322

URL الوصول: https://doaj.org/article/dd5db8b9f47843dbacf9bbaaf001a016