Junki Miyamoto
@tuat.ac.jp
Tokyo University of Agriculture and Technology
Scopus Publications
Scopus Publications
Hiroaki Takeda, Yuki Matsuzawa, Manami Takeuchi, Mikiko Takahashi, Kozo Nishida, Takeshi Harayama, Yoshimasa Todoroki, Kuniyoshi Shimizu, Nami Sakamoto, Takaki Oka,et al.
Springer Science and Business Media LLC
AbstractLipidomics and metabolomics communities comprise various informatics tools; however, software programs handling multimodal mass spectrometry (MS) data with structural annotations guided by the Lipidomics Standards Initiative are limited. Here, we provide MS-DIAL 5 for in-depth lipidome structural elucidation through electron-activated dissociation (EAD)-based tandem MS and determining their molecular localization through MS imaging (MSI) data using a species/tissue-specific lipidome database containing the predicted collision-cross section values. With the optimized EAD settings using 14 eV kinetic energy, the program correctly delineated lipid structures for 96.4% of authentic standards, among which 78.0% had the sn-, OH-, and/or C = C positions correctly assigned at concentrations exceeding 1 μM. We showcased our workflow by annotating the sn- and double-bond positions of eye-specific phosphatidylcholines containing very-long-chain polyunsaturated fatty acids (VLC-PUFAs), characterized as PC n-3-VLC-PUFA/FA. Using MSI data from the eye and n-3-VLC-PUFA-supplemented HeLa cells, we identified glycerol 3-phosphate acyltransferase as an enzyme candidate responsible for incorporating n-3 VLC-PUFAs into the sn1 position of phospholipids in mammalian cells, which was confirmed using EAD-MS/MS and recombinant proteins in a cell-free system. Therefore, the MS-DIAL 5 environment, combined with optimized MS data acquisition methods, facilitates a better understanding of lipid structures and their localization, offering insights into lipid biology.
Hiroaki Takeda, Manami Takeuchi, Mayu Hasegawa, Junki Miyamoto, and Hiroshi Tsugawa
American Chemical Society (ACS)
Shinsuke Inuki, Junki Miyamoto, Naoki Hashimoto, Hidenori Shimizu, Hitomi Tabuchi, Atsuko Kawai, Luca C. Greiner, Ikuo Kimura, and Hiroaki Ohno
Elsevier BV
Junki Miyamoto, Yuna Ando, Akari Nishida, Mayu Yamano, Shunsuke Suzuki, Hiromi Takada, and Ikuo Kimura
Wiley
ScopeObesity and metabolic diseases are closely associated, and individuals who become obese are also prone to type 2 diabetes and cardiovascular disorders. Gut microbiota is mediated by diet and can influence host metabolism and the incidence of metabolic disorders. Recent studies have suggested that improving gut microbiota through a fructooligosaccharide (FOS)‐supplemented diet may ameliorate obesity and other metabolic disorders. Although accumulating evidence supports the notion of the developmental origins of health and disease, the underlying mechanisms remain obscure.Methods and resultsICR mice are fed AIN‐93G formula‐based cellulose –, FOS–, acetate–, or propionate‐supplemented diets during pregnancy. Offspring are reared by conventional ICR foster mothers for 4 weeks; weaned mice are fed high fat diet for 12 weeks and housed individually. The FOS and propionate offspring contribute to suppressing obesity and improving glucose intolerance. Gut microbial compositions in FOS‐fed mothers and their offspring are markedly changed. However, the beneficial effect of FOS diet on the offspring is abolished when antibiotics are administered to pregnant mice.ConclusionThe findings highlight the link between the maternal gut environment and the developmental origin of metabolic syndrome in offspring. These results open novel research avenues into preemptive therapies for metabolic disorders by targeting the maternal gut microbiota.
Yuri Haneishi, Lucia Treppiccione, Francesco Maurano, Diomira Luongo, Junki Miyamoto, and Mauro Rossi
Wiley
AbstractThe intestinal immune system plays a crucial role in obesity and insulin resistance. An altered intestinal immunity is associated with changes to the gut microbiota, barrier function, and tolerance to luminal antigens. Lipid metabolism and its unbalance can also contribute to acute and chronic inflammation in different conditions. In celiac disease (CD), the serum phospholipid profile in infants who developed CD is dramatically different when compared to that of infants at risk of CD not developing the disease. In a mouse model of gluten sensitivity, oral wheat gliadin challenge in connection with inhibition of the metabolism of arachidonic acid, an omega‐6 polyunsaturated fatty acid, specifically induces the enteropathy. Recent evidence suggests that gluten may play a role also for development of life‐style related diseases in populations on a high fat diet (HFD). However, the mechanisms behind these effects are not yet understood. Exploratory studies in mice feed HFD show that wheat gliadin consumption affects glucose and lipid metabolic homeostasis, alters the gut microbiota, and the immune cell profile in liver.
Kanako Tokiyoshi, Yuki Matsuzawa, Mikiko Takahashi, Hiroaki Takeda, Mayu Hasegawa, Junki Miyamoto, and Hiroshi Tsugawa
American Chemical Society (ACS)
Shiro Otake, Shotaro Chubachi, Junki Miyamoto, Yuri Haneishi, Tetsuya Arai, Hideto Iizuka, Takashi Shimada, Kaori Sakurai, Shinichi Okuzumi, Hiroki Kabata,et al.
Elsevier BV
Yuri HANEISHI, Saya WATANABE, Ayana OKADA, Hitoshi TAKEMAE, Deborah BASTONI, Lucia TREPPICCIONE, Anella SAGGESE, Tetsuya MIZUTANI, Mauro ROSSI, and Junki MIYAMOTO
Center for Academic Publications Japan
The composition of gut microbiota is determined not only by genetic factors but also by environmental factors, such as diet, exercise, and disease conditions. Among these factors, diet is crucial in changing the gut microbial composition. Dietary lipids composed of different fatty acids not only alter host metabolism but also have a significant impact on the composition of gut microbiota. However, the molecular mechanisms underlying the relationship between these host effects and their impact on gut microbiota remain unclear. Here, we demonstrated that intake of different dietary lipids improved glucose tolerance by modulating gut microbiota. The results of our analysis show that the taxa of bacteria that increase in number as a result of dietary lipid intake play an important role in glucose metabolism. Thus, we have identified a new mechanism underlying the function of dietary lipids in regulating glucose homeostasis. Our findings contribute to possible new methods to prevent and treat metabolic disorders by modifying the composition of gut microbiota.
Yuri Haneishi, Yuma Furuya, Mayu Hasegawa, Hitoshi Takemae, Yuri Tanioka, Tetsuya Mizutani, Mauro Rossi, and Junki Miyamoto
Springer Science and Business Media LLC
AbstractDiet is the primary factor affecting host nutrition and metabolism, with excess food intake, especially high-calorie diets, such as high-fat and high-sugar diets, causing an increased risk of obesity and related disorders. Obesity alters the gut microbial composition and reduces microbial diversity and causes changes in specific bacterial taxa. Dietary lipids can alter the gut microbial composition in obese mice. However, the regulation of gut microbiota and host energy homeostasis by different polyunsaturated fatty acids (PUFAs) in dietary lipids remains unknown. Here, we demonstrated that different PUFAs in dietary lipids improved host metabolism in high-fat diet (HFD)-induced obesity in mice. The intake of the different PUFA-enriched dietary lipids improved metabolism in HFD-induced obesity by regulating glucose tolerance and inhibiting colonic inflammation. Moreover, the gut microbial compositions were different among HFD and modified PUFA-enriched HFD-fed mice. Thus, we have identified a new mechanism underlying the function of different PUFAs in dietary lipids in regulating host energy homeostasis in obese conditions. Our findings shed light on the prevention and treatment of metabolic disorders by targeting the gut microbiota.
Yudai Uehira, Hiroaki Ueno, Junki Miyamoto, Ikuo Kimura, Yohei Ishizawa, Hiroshi Iijima, Shota Muroga, Toru Fujita, Soichi Sakai, Yoshishige Samukawa,et al.
Elsevier BV
Yuri Haneishi, Yuma Furuya, Mayu Hasegawa, Antonio Picarelli, Mauro Rossi, and Junki Miyamoto
MDPI AG
Inflammatory bowel disease (IBD) is an inflammatory disease of the gastrointestinal tract, the incidence of which has rapidly increased worldwide, especially in developing and Western countries. Recent research has suggested that genetic factors, the environment, microbiota, and immune responses are involved in the pathogenesis; however, the underlying causes of IBD are unclear. Recently, gut microbiota dysbiosis, especially a decrease in the abundance and diversity of specific genera, has been suggested as a trigger for IBD-initiating events. Improving the gut microbiota and identifying the specific bacterial species in IBD are essential for understanding the pathogenesis and treatment of IBD and autoimmune diseases. Here, we review the different aspects of the role played by gut microbiota in the pathogenesis of IBD and provide a theoretical basis for modulating gut microbiota through probiotics, fecal microbiota transplantation, and microbial metabolites.
Satoshi Wanezaki, Takumi Taniwaki, Junki Miyamoto, and Masashi Hosokawa
Japan Oil Chemists' Society
Dietary fish oil containing n-3 polyunsaturated fatty acids provides health benefits by lowering lipid levels in the liver and serum. β-Conglycinin (βCG) is a major constituent protein in soybean with many physiological effects, such as lowering blood triglyceride levels, preventing obesity and diabetes, and improving hepatic lipid metabolism. However, the combined effects of fish oil and βCG remain unclear. Here, we investigated the effects of a dietary combination of fish oil and βCG on lipid and glucose parameters in diabetic/obese KK-A y mice. KK-A y mice were divided into three groups: control, fish oil, and fish oil + βCG; these groups were fed a casein-based diet containing 7% (w/w) soybean oil, a casein-based diet containing 2% (w/w) soybean oil and 5% (w/w) fish oil, and a βCG-based diet containing 2% (w/w) soybean oil and 5% (w/w) fish oil, respectively. The effects of the dietary combination of fish oil and βCG on blood biochemical parameters, adipose tissue weight, expression levels of fat- and glucose metabolism-related genes, and cecal microbiome composition were evaluated. The total white adipose tissue weight (p < 0.05), levels of total serum cholesterol (p < 0.01), triglyceride (p < 0.01), and blood glucose (p < 0.05), and expression levels of fatty acid synthesis-related genes (including Fasn (p < 0.05) and Acc (p < 0.05)), and glucose metabolism-related genes (such as Pepck (p < 0.05)) were lower in the fish oil and fish oil + βCG groups than in the control group. Furthermore, the relative abundance of Bacteroidaceae and Coriobacteriaceae differed significantly between the fish oil + βCG and control groups. These findings suggest that dietary intake of fish oil + βCG may prevent obesity and diabetes, alleviate lipid abnormalities, and alter the gut microbiome composition in diabetic/obese KK-A y mice. Further research is needed to build on this study to evaluate the health benefits of major components of Japanese food.
Junki Miyamoto, Hidenori Shimizu, Keiko Hisa, Chiaki Matsuzaki, Shinsuke Inuki, Yuna Ando, Akari Nishida, Ayano Izumi, Mayu Yamano, Chihiro Ushiroda,et al.
Informa UK Limited
ABSTRACT Fermented foods demonstrate remarkable health benefits owing to probiotic bacteria or microproducts produced via bacterial fermentation. Fermented foods are produced by the fermentative action of several lactic acid bacteria, including Leuconostoc mesenteroides; however, the exact mechanism of action of these foods remains unclear. Here, we observed that prebiotics associated with L. mesenteroides-produced exopolysaccharides (EPS) demonstrate substantial host metabolic benefits. L. mesenteroides-produced EPS is an indigestible α-glucan, and intake of the purified form of EPS improved glucose metabolism and energy homeostasis through EPS-derived gut microbial short-chain fatty acids, and changed gut microbial composition. Our findings reveal an important mechanism that accounts for the effects of diet, prebiotics, and probiotics on energy homeostasis and suggests an approach for preventing lifestyle-related diseases by targeting bacterial EPS.
Yujie Ma, Eunyoung Lee, Hayato Yoshikawa, Tomoe Noda, Junki Miyamoto, Ikuo Kimura, Ryo Hatano, and Takashi Miki
Elsevier BV
Akari Nishida, Yuna Ando, Ikuo Kimura, and Junki Miyamoto
MDPI AG
Due to the excess energy intake, which is a result of a high fat and high carbohydrate diet, dysfunction of energy balance leads to metabolic disorders such as obesity and type II diabetes mellitus (T2DM). Since obesity can be a risk factor for various diseases, including T2DM, hypertension, hyperlipidemia, and metabolic syndrome, novel prevention and treatment are expected. Moreover, host diseases linked to metabolic disorders are associated with changes in gut microbiota profile. Gut microbiota is affected by diet, and nutrients are used as substrates by gut microbiota for produced metabolites, such as short-chain and long-chain fatty acids, that may modulate host energy homeostasis. These free fatty acids are not only essential energy sources but also signaling molecules via G-protein coupled receptors (GPCRs). Some GPCRs are critical for metabolic functions, such as hormone secretion and immune function in various types of cells and tissues and contribute to energy homeostasis. The current studies have shown that GPCRs for gut microbial metabolites improved host energy homeostasis and systemic metabolic disorders. Here, we will review the association between diet, gut microbiota, and host energy homeostasis.
Eunyoung Lee, Xilin Zhang, Tomoe Noda, Junki Miyamoto, Ikuo Kimura, Tomoaki Tanaka, Kenichi Sakurai, Ryo Hatano, and Takashi Miki
MDPI AG
Background: α-cyclodextrin (α-CD) is one of the dietary fibers that may have a beneficial effect on cholesterol and/or glucose metabolism, but its efficacy and mode of action remain unclear. Methods: In the present study, we examined the anti-hyperglycemic effect of α-CD after oral loading of glucose and liquid meal in mice. Results: Administration of 2 g/kg α-CD suppressed hyperglycemia after glucose loading, which was associated with increased glucagon-like peptide 1 (GLP-1) secretion and enhanced hepatic glucose sequestration. By contrast, 1 g/kg α-CD similarly suppressed hyperglycemia, but without increasing secretions of GLP-1 and insulin. Furthermore, oral α-CD administration disrupts lipid micelle formation through its inclusion of lecithin in the gut luminal fluid. Importantly, prior inclusion of α-CD with lecithin in vitro nullified the anti-hyperglycemic effect of α-CD in vivo, which was associated with increased intestinal mRNA expressions of SREBP2-target genes (Ldlr, Hmgcr, Pcsk9, and Srebp2). Conclusions: α-CD elicits its anti-hyperglycemic effect after glucose loading by inducing lecithin inclusion in the gut lumen and activating SREBP2, which is known to induce cholecystokinin secretion to suppress hepatic glucose production via a gut/brain/liver axis.
Akari Nishida, Junki Miyamoto, Hidenori Shimizu, and Ikuo Kimura
Elsevier BV
Olfactory receptor 78 (Olfr78), which is also known as a receptor for short-chain fatty acids (SCFAs) produced via gut microbial fermentation from indigestible polysaccharides such as dietary fibers, is expressed in the enteroendocrine cells of the colon. However, the role of Olfr78 in gut hormone secretion remains unknown. Here, we aimed to investigate the function and mechanism of action of Olfr78 in vivo and in vitro. Toward this, we assessed the expression of Olfr78 in several tissues, affinity of Olfr78 to various monocarboxylates, and the secretion of anorexigenic gut hormone peptide YY (PYY) via Olfr78 using various molecular and biochemical techniques. Olfr78 was abundantly expressed in the colon and mouse enteroendocrine cell line STC-1 and showed specific affinity to SCFAs such as acetate and propionate, but not butyrate, in a monocarboxylate ligand screening assay using a heterologous expression system. Acetate promoted PYY secretion in STC-1 cells via Olfr78-protein kinase A signaling, whereas the effects were abolished by Olfr78 RNA interference. Colonic SCFAs production via oral administration of fructo-oligosaccharide significantly increased plasma PYY levels, whereas this effect was abolished in Olfr78-deficient and germ-free mice. These results suggested that the SCFA receptor Olfr78 is important for anti-obesity and anorexigenic effects of the gut microbiota and dietary fibers.
Kiyotaka Uchiyama, Shu Wakino, Junichiro Irie, Junki Miyamoto, Ayumi Matsui, Takaya Tajima, Tomoaki Itoh, Yoichi Oshima, Ayumi Yoshifuji, Ikuo Kimura,et al.
Oxford University Press (OUP)
Abstract Background Chronic kidney disease (CKD) leads to insulin resistance (IR) and sarcopenia, which are associated with a high mortality risk in CKD patients; however, their pathophysiologies remain unclear. Recently, alterations in gut microbiota have been reported to be associated with CKD. We aimed to determine whether uremic dysbiosis contributes to CKD-associated IR and sarcopenia. Methods CKD was induced in specific pathogen-free mice via an adenine-containing diet; control animals were fed a normal diet. Fecal microbiota transplantation (FMT) was performed by oral gavage in healthy germ-free mice using cecal bacterial samples obtained from either control mice (control-FMT) or CKD mice (CKD-FMT). Vehicle mice were gavaged with sterile phosphate-buffered saline. Two weeks after inoculation, mice phenotypes, including IR and sarcopenia, were evaluated. Results IR and sarcopenia were evident in CKD mice compared with control mice. These features were reproduced in CKD-FMT mice compared with control-FMT and vehicle mice with attenuated insulin-induced signal transduction and mitochondrial dysfunction in skeletal muscles. Intestinal tight junction protein expression and adipocyte sizes were lower in CKD-FMT mice than in control-FMT mice. Furthermore, CKD-FMT mice showed systemic microinflammation, increased concentrations of serum uremic solutes, fecal bacterial fermentation products and elevated lipid content in skeletal muscle. The differences in gut microbiota between CKD and control mice were mostly consistent between CKD-FMT and control-FMT mice. Conclusions Uremic dysbiosis induces IR and sarcopenia, leaky gut and lipodystrophy.
Ikuo Kimura, Junki Miyamoto, Ryuji Ohue-Kitano, Keita Watanabe, Takahiro Yamada, Masayoshi Onuki, Ryo Aoki, Yosuke Isobe, Daiji Kashihara, Daisuke Inoue,et al.
American Association for the Advancement of Science (AAAS)
Antibiotics and dietary habits can affect the gut microbial community, thus influencing disease susceptibility. Although the effect of microbiota on the postnatal environment has been well documented, much less is known regarding the impact of gut microbiota at the embryonic stage. Here we show that maternal microbiota shapes the metabolic system of offspring in mice. During pregnancy, short-chain fatty acids produced by the maternal microbiota dictate the differentiation of neural, intestinal, and pancreatic cells through embryonic GPR41 and GPR43. This developmental process helps maintain postnatal energy homeostasis, as evidenced by the fact that offspring from germ-free mothers are highly susceptible to metabolic syndrome, even when reared under conventional conditions. Thus, our findings elaborate on a link between the maternal gut environment and the developmental origin of metabolic syndrome.
Junki Miyamoto, Miki Igarashi, Keita Watanabe, Shin-ichiro Karaki, Hiromi Mukouyama, Shigenobu Kishino, Xuan Li, Atsuhiko Ichimura, Junichiro Irie, Yukihiko Sugimoto,et al.
Springer Science and Business Media LLC
Gut microbiota mediates the effects of diet, thereby modifying host metabolism and the incidence of metabolic disorders. Increased consumption of omega-6 polyunsaturated fatty acid (PUFA) that is abundant in Western diet contributes to obesity and related diseases. Although gut-microbiota-related metabolic pathways of dietary PUFAs were recently elucidated, the effects on host physiological function remain unclear. Here, we demonstrate that gut microbiota confers host resistance to high-fat diet (HFD)-induced obesity by modulating dietary PUFAs metabolism. Supplementation of 10-hydroxy-cis-12-octadecenoic acid (HYA), an initial linoleic acid-related gut-microbial metabolite, attenuates HFD-induced obesity in mice without eliciting arachidonic acid-mediated adipose inflammation and by improving metabolic condition via free fatty acid receptors. Moreover, Lactobacillus-colonized mice show similar effects with elevated HYA levels. Our findings illustrate the interplay between gut microbiota and host energy metabolism via the metabolites of dietary omega-6-FAs thereby shedding light on the prevention and treatment of metabolic disorders by targeting gut microbial metabolites. The gut microbiome is an important regulator of metabolic health. Here the authors show that intestinal bacteria metabolize dietary linoleic acid to 10-hydroxy-cis-12-octadecenoic acid (HYA) which confers host resistance to high fat diet-induced obesity in mice.
Eunyoung Lee, Emily L. Miedzybrodzka, Xilin Zhang, Ryo Hatano, Junki Miyamoto, Ikuo Kimura, Kosuke Fujimoto, Satoshi Uematsu, Sergio Rodriguez-Cuenca, Antonio Vidal-Puig,et al.
MDPI AG
As glucose-dependent insulinotropic polypeptide (GIP) possesses pro-adipogenic action, the suppression of the GIP hypersecretion seen in obesity might represent a novel therapeutic approach to the treatment of obesity. However, the mechanism of GIP hypersecretion remains largely unknown. In the present study, we investigated GIP secretion in two mouse models of obesity: High-fat diet-induced obese (DIO) mice and leptin-deficient Lepob/ob mice. In DIO mice, plasma GIP was increased along with an increase in GIP mRNA expression in the lower small intestine. Despite the robust alteration in the gut microbiome in DIO mice, co-administration of maltose and the α-glucosidase inhibitor (α-GI) miglitol induced the microbiome-mediated suppression of GIP secretion. The plasma GIP levels of Lepob/ob mice were also elevated and were suppressed by fat transplantation. The GIP mRNA expression in fat tissue was not increased in Lepob/ob mice, while the expression of an interleukin-1 receptor antagonist (IL-1Ra) was increased. Fat transplantation suppressed the expression of IL-1Ra. The plasma IL-1Ra levels were positively correlated with the plasma GIP levels. Accordingly, although circulating GIP levels are increased in both DIO and Lepob/ob mice, the underlying mechanisms differ, and the anti-obesity actions of α-GIs and leptin sensitizers may be mediated partly by the suppression of GIP secretion.
Ryuji Ohue-Kitano, Satsuki Taira, Keita Watanabe, Yuki Masujima, Toru Kuboshima, Junki Miyamoto, Yosuke Nishitani, Hideaki Kawakami, Hiroshige Kuwahara, and Ikuo Kimura
MDPI AG
4-Hydroxy-3-methoxycinnamic acid (HMCA), a hydroxycinnamic acid derivative, is abundant in fruits and vegetables, including oranges, carrots, rice bran, and coffee beans. Several beneficial effects of HMCA have been reported, including improvement of metabolic abnormalities in animal models and human studies. However, its mitigating effects on high-fat diet (HFD)-induced obesity, and the mechanism underlying these effects, remain to be elucidated. In this study, we demonstrated that dietary HMCA was efficacious against HFD-induced weight gain and hepatic steatosis, and that it improved insulin sensitivity. These metabolic benefits of HMCA were ascribable to 3-(4-hydroxy-3-methoxyphenyl)propionic acid (HMPA) produced by gut microbiota. Moreover, conversion of HMCA into HMPA was attributable to a wide variety of microbes belonging to the phylum Bacteroidetes. We further showed that HMPA modulated gut microbes associated with host metabolic homeostasis by increasing the abundance of organisms belonging to the phylum Bacteroidetes and reducing the abundance of the phylum Firmicutes. Collectively, these results suggest that HMPA derived from HMCA is metabolically beneficial, and regulates hepatic lipid metabolism, insulin sensitivity, and the gut microbial community. Our results provide insights for the development of functional foods and preventive medicines, based on the microbiota of the intestinal environment, for the prevention of metabolic disorders.
Junki Miyamoto, Ryuji Ohue-Kitano, Hiromi Mukouyama, Akari Nishida, Keita Watanabe, Miki Igarashi, Junichiro Irie, Gozoh Tsujimoto, Noriko Satoh-Asahara, Hiroshi Itoh,et al.
Proceedings of the National Academy of Sciences
Ketone bodies, including β-hydroxybutyrate and acetoacetate, are important alternative energy sources during energy shortage. β-Hydroxybutyrate also acts as a signaling molecule via specific G protein-coupled receptors (GPCRs); however, the specific associated GPCRs and physiological functions of acetoacetate remain unknown. Here we identified acetoacetate as an endogenous agonist for short-chain fatty acid (SCFA) receptor GPR43 by ligand screening in a heterologous expression system. Under ketogenic conditions, such as starvation and low-carbohydrate diets, plasma acetoacetate levels increased markedly, whereas plasma and cecal SCFA levels decreased dramatically, along with an altered gut microbiota composition. In addition, Gpr43-deficient mice showed reduced weight loss and suppressed plasma lipoprotein lipase activity during fasting and eucaloric ketogenic diet feeding. Moreover, Gpr43-deficient mice exhibited minimal weight decrease after intermittent fasting. These observations provide insight into the role of ketone bodies in energy metabolism under shifts in nutrition and may contribute to the development of preventive medicine via diet and foods.
T. Ogita, J. Miyamoto, Y. Hirabayashi, M. Rossi, G. Mazzarella, I. Takahashi, S. Tanabe, and T. Suzuki
Wageningen Academic Publishers
The aim of this study was to analyse hypoxia-associated dendritic cells (DCs) in colitic mice and the effects of probiotics on interleukin (IL)-10 production in inflammatory DCs under hypoxic conditions. Extensive hypoxia was observed in the colonic mucosa of dextran sodium sulphate-induced colitic mice. Flow cytometric analysis demonstrated that hypoxia-inducible factor-1α+ DCs in colonic lamina propria (CLP) lymphocytes and mesenteric lymph nodes (MLN) were more abundant in colitic mice than those in controls. Among three subsets of DCs, i.e. plasmacytoid DCs, conventional DCs (cDCs), and monocyte-derived DCs (mDCs), cDCs and mDCs were more abundant in CLP of colitic mice. Bone marrow-derived Flt-3L-induced DCs (Flt-DCs) but not bone marrow-derived GM-CSF-induced DCs (GM-DCs), incubated with 1% O2 exhibited an inflammatory phenotype, with higher CD86, IL-6, and tumour necrosis factor-α expression, and lower IL-10 levels than those in Flt-DCs incubated with 21% O2. The hypoxia-induced decrease in IL-10 expression in Flt-DCs was restored by Bifidobacterium bifidum JCM 1255T promoted IL-10 expression through the p38 pathway under normoxic conditions. The anti-inflammatory effects of B. bifidum JCM 1255T in Flt-DCs were mediated through different cellular mechanisms under hypoxic and normoxic conditions. B. bifidum JCM 1255T could be used therapeutically for its anti-inflammatory effects.