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BACKGROUND: Food allergy (FA) is a common disease in children; thus, a high level of safety is required for its prevention and treatment. Colonic regulatory T cells (Tregs) have been suggested to attenuate FA. We investigated the Treg-inducing ability and anti-FA effects of carotenoids, a pigment contained in vegetables and fruits. METHODS: C57BL/6N mice were fed a diet containing 0.01% (w/w) of lycopene, ß-carotene, astaxanthin or lutein for 4 weeks, and the population of colonic Tregs was assessed. Subsequently, to evaluate the Treg-inducing ability of lycopene, splenic naïve CD4+ T cells from BALB/c mice were cultured with anti-CD3/CD28 antibody, TGF-ß and lycopene, and the frequencies of Tregs were examined. The effect of 0.1% (w/w) lycopene containing diet on FA was investigated in OVA-induced FA model BALB/c mice. RESULTS: In screening, only lycopene significantly increased the frequency and number of colonic Tregs. Lycopene also increased Treg differentiation in splenic naïve CD4+ T cells. In FA mice, lycopene feeding significantly increased the number of colonic Tregs and attenuated allergic symptoms. The expression levels of IL-4, IL-9 and IL-13 mRNA in colonic mucosa were also significantly reduced by lycopene. IL-9 is known to induce proliferation of mast cells, and we found that lycopene feeding significantly reduced the number of mast cells in the colonic mucosa of FA mice. CONCLUSION: Our results suggest that lycopene, a carotenoid present in many common foods on the market, may have the potential to induce colonic Tregs and suppress FA symptoms.
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Hipersensibilidade Alimentar , Linfócitos T Reguladores , Animais , Humanos , Licopeno/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BLRESUMO
BACKGROUND AND AIM: Mucosal healing is an important clinical goal in patients with inflammatory bowel disease. Recently, short-chain fatty acids (SCFAs) have been reported to have multifaceted effects to host. However, the effects of SCFAs on wound healing in intestinal epithelial cells are unclear. In the present study, we investigated the effects of acetate, one of the major SCFAs, on the wound healing of murine colonic epithelial cells. METHODS: Young adult mouse colonic epithelial cells were used to determine the effect of acetate using wound healing assay. Mitogen-activated protein kinase and Rho kinase inhibitor were used to elucidate intracellular signal of wound healing treated with acetate. Meanwhile, Rho activation assays were utilized to measure Rho activation levels. To assess in vivo effects, C57B6 mice with dextran sodium sulfate for 7 days were treated with enema administration of acetate for 7 days. Body weight, disease activity index, colon length, and mucosal break ratio in histology were examined. RESULTS: Acetate enhanced wound healing and fluorescence intensity of actin stress fiber compared with control. These effects were canceled with pretreatment of c-Jun N-terminal kinase (JNK) inhibitor or Rho kinase inhibitor. Furthermore, JNK inhibitor reduced the activation of Rho induced by acetate. In the dextran sodium sulfate-induced colitis model, the mice with enema treatment of acetate significantly exhibited recovery. CONCLUSIONS: In this study, we demonstrated that acetate promoted murine colonic epithelial cell wound healing via activation of JNK and Rho signaling pathways. These findings suggested that acetate could have applications as a therapeutic agent for patients with intestinal mucosal damage, such as inflammatory bowel disease.
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Acetatos/farmacologia , Acetatos/uso terapêutico , Colo/citologia , Células Epiteliais/patologia , Ácidos Graxos Voláteis/farmacologia , Ácidos Graxos Voláteis/uso terapêutico , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Cicatrização/genética , Quinases Associadas a rho/metabolismo , Acetatos/administração & dosagem , Animais , Células Cultivadas , Colite/tratamento farmacológico , Modelos Animais de Doenças , Sistema de Sinalização das MAP Quinases/genética , Masculino , Camundongos Endogâmicos C57BLRESUMO
BACKGROUND: Constipation is one of the most common gastrointestinal complaints. Although the causes of constipation are varied, dietary habits have a significant influence. Excessive fat intake is suggested as one of the main causes of constipation; however, the exact mechanism is unknown. AIMS: To investigate whether a high-fat diet (HFD) causes constipation in mice and to clarify the underlying mechanism, focusing on the amount of colonic mucus. METHODS: Six-week-old male C57BL/6 mice were randomly divided into two groups: mice fed with HFD and those with normal chow diet (NCD). Fecal weight, water content, total gastrointestinal transit time, and colon transit time were measured to determine whether the mice were constipated. The colonic mucus was evaluated by immunostaining and quantified by spectrometry. Malondialdehyde (MDA) was measured using the thiobarbituric acid (TBA) test as a marker for oxidative stress. RESULTS: Compared to the NCD group, the weight of feces was less in the HFD group. In the functional experiment, the total gastrointestinal transit time and colon transit time were longer in the HFD group. Furthermore, HFD significantly reduced the amount of colonic mucus. In addition, the reduction in colonic mucus caused by surfactant resulted in constipation in the NCD group. CONCLUSIONS: HFD causes constipation with delayed colon transit time possibly via the reduction in colonic mucus in mice.
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Colo/metabolismo , Constipação Intestinal/etiologia , Dieta Hiperlipídica/efeitos adversos , Muco/metabolismo , Animais , Constipação Intestinal/metabolismo , Trânsito Gastrointestinal , Masculino , Malondialdeído/metabolismo , Camundongos Endogâmicos C57BL , Distribuição AleatóriaRESUMO
The spectrum of non-alcoholic fatty liver disease (NAFLD) ranges from simple hepatic steatosis commonly associated with obesity, to non-alcoholic steatohepatitis, which can progress to fibrosis, cirrhosis and hepatocellular carcinoma. Recent reports have indicated the crucial role of gut microbiota and their metabolites in the progression of NAFLD. In the present review, we demonstrated the influence of oral administration of (-)-epigallocatechin-3-gallate (EGCG) on the gut microbiota, serum bile acid profile, and gene expression in the liver in mice fed a high-fat diet (HFD). EGCG significantly inhibited the increase in histological fatty deposit and triglyceride accumulation in the liver induced by HFD, and improved intestinal dysbiosis. One of important findings is that the abundance of Proteobacteria and Defferibacteres phylums increased markedly in the HFD group, and this increase was significantly suppressed in the EGCG group. Interestingly, taurine-conjugated cholic acid (TCA) increased in the HFD group, like the mirror image against a marked decrease in the cholic acid (CA) value, and this increase was markedly inhibited in the EGCG group. TCA is not a simple serum biomarker for liver injury but TCA may be a causal factor to disturb lipid metabolism. The distribution of correlation coefficients by Heatmap analysis showed that the abundance of Akkermansia and Parabacteroides genus showed a positive correlation with CA and a negative correlation with TCA, and significantly increased in the EGCG group as compared with the HFD group. In addition, nutrigenomics approaches demonstrated that sirtuin signaling, EIF2 pathway and circadian clock are involved in the anti-steatotic effects of EGCG. In the present paper, we summarized recent update data of EGCG function focusing on intestinal microbiota and their interaction with host cells.
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BACKGROUND AND AIM: Daikenchuto, a traditional Japanese herbal medicine, has been reported to exhibit anti-inflammatory effects against intestinal inflammation. However, whether daikenchuto has a therapeutic effect against intestinal mucosal injuries remains unclear. Thus, the aim of this study was to determine the effect of daikenchuto on intestinal mucosal healing. METHODS: Colitis was induced in male Wistar rats by using trinitrobenzenesulfonic acid. Daikenchuto (900 mg/kg/day) was administered for 7 days after the induction of colitis. Thereafter, intestinal mucosal injuries were evaluated by determining the colonic epithelial regeneration ratio ([area of epithelial regeneration/area of ulcer] × 100). Restoration of rat intestinal epithelial cells treated with daikenchuto and its constituent herbs (Zanthoxylum fruit, processed ginger, and ginseng) and ginsenoside Rb1, which is a ginseng ingredient, was evaluated using a wound-healing assay. RESULTS: The colon epithelial regeneration ratio in the daikenchuto-treated rats was significantly higher than that in the control rats. Daikenchuto, ginseng, and ginsenoside Rb1 enhanced wound healing, and the ginsenoside Rb1-induced enhancement was inhibited by extracellular signal-regulated kinase and Rho inhibitors. CONCLUSIONS: Daikenchuto and its constituent, ginsenoside Rb1, promoted wound healing. Because mucosal healing is one of the most important therapeutic targets in patients with inflammatory bowel disease, ginsenoside Rb1 may be a novel therapeutic agent against intestinal mucosal damage such as that occurring in intestinal bowel disease.
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Proliferação de Células/efeitos dos fármacos , Colite/tratamento farmacológico , Colo/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Ginsenosídeos/farmacologia , Mucosa Intestinal/efeitos dos fármacos , Extratos Vegetais/farmacologia , Cicatrização/efeitos dos fármacos , Proteínas rho de Ligação ao GTP/metabolismo , Animais , Linhagem Celular , Colite/induzido quimicamente , Colite/enzimologia , Colite/patologia , Colo/enzimologia , Colo/patologia , Modelos Animais de Doenças , Mucosa Intestinal/enzimologia , Mucosa Intestinal/patologia , Masculino , Panax , Ratos Wistar , Transdução de Sinais , Ácido Trinitrobenzenossulfônico , Zanthoxylum , ZingiberaceaeRESUMO
Gut microbiota have profound effects on bile acid metabolism by promoting deconjugation, dehydrogenation, and dehydroxylation of primary bile acids in the distal small intestine and colon. High-fat diet-induced dysbiosis of gut microbiota and bile acid dysregulation may be involved in the pathology of steatosis in patients with non-alcoholic fatty liver disease. Epigallocatechin-3-gallate (EGCG), the most abundant polyphenolic catechin in green tea, has been widely investigated for its inhibitory or preventive effects against fatty liver. The aim of the present study was to investigate the effects of EGCG on the abundance of gut microbiota and the composition of serum bile acids in high-fat diet-fed mice and determine the specific bacterial genera that can improve the serum bile acid dysregulation associated with EGCG anti-hepatic steatosis action. Male C57BL/6N mice were fed with the control diet, high-fat diet, or high-fat diet + EGCG at a concentration of 0.32% for 8 weeks. EGCG significantly inhibited the increases in weight, the area of fatty lesions, and the triglyceride content in the liver induced by the high-fat diet. Principal coordinate analysis revealed significant differences in microbial structure among the groups. At the genus level, EGCG induced changes in the microbiota composition in high-fat diet-fed mice, showing a significantly higher abundance of Adlercreutzia, Akkermansia, Allobaculum and a significantly lower abundance of Desulfovibrionaceae. EGCG significantly reversed the decreased population of serum primary cholic acid and ß-muricholic acid as well as the increased population of taurine-conjugated cholic acid, ß-muricholic acid and deoxycholic acid in high-fat diet-fed mice. Finally, the correlation analysis between bile acid profiles and gut microbiota demonstrated the contribution of Akkermansia and Desulfovibrionaceae in the improvement of bile acid dysregulation in high-fat diet-fed mice by treatment with EGCG. In conclusion, the present study suggests that EGCG could alter bile acid metabolism, especially taurine deconjugation, and suppress fatty liver disease by improving the intestinal luminal environment.
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BACKGROUND: Acetyl salicylic acid (ASA) is a useful drug for the secondary prevention of cerebro-cardiovascular diseases, but it has adverse effects on the small intestinal mucosa. The pathogenesis and prophylaxis of ASA-induced small intestinal injury remain unclear. In this study, we focused on the intestinal mucus, as the gastrointestinal tract is covered by mucus, which exhibits protective effects against various gastrointestinal diseases. MATERIALS AND METHODS: ASA was injected into the duodenum of rats, and small intestinal mucosal injury was evaluated using Evans blue dye. To investigate the importance of mucus, Polysorbate 80 (P80), an emulsifier, was used before ASA injection. In addition, rebamipide, a mucus secretion inducer in the small intestine, was used to suppress mucus reduction in the small intestine of P80-administered rats. RESULTS: The addition of P80 reduced the mucus and exacerbated the ASA-induced small intestinal mucosal injury. Rebamipide significantly suppressed P80-reduced small intestinal mucus and P80-increased intestinal mucosal lesions in ASA-injected rats, demonstrating that mucus is important for the protection against ASA-induced small intestinal mucosal injury. These results provide new insight into the mechanism of ASA-induced small intestinal mucosal injury. CONCLUSION: Mucus secretion-increasing therapy might be useful in preventing ASA-induced small intestinal mucosal injury.
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Aspirina/farmacologia , Mucosa Intestinal/lesões , Intestino Delgado/lesões , Muco/metabolismo , Alanina/análogos & derivados , Alanina/farmacologia , Animais , Mucosa Intestinal/patologia , Intestino Delgado/patologia , Masculino , Muco/efeitos dos fármacos , Polissorbatos/administração & dosagem , Polissorbatos/farmacologia , Substâncias Protetoras/farmacologia , Quinolonas/farmacologia , Ratos Sprague-DawleyRESUMO
BACKGROUND AND AIM: Secreted protein acidic and rich in cysteine (SPARC) is a matricellular glycol that regulates cell proliferation, tissue repair, and tumorigenesis. Despite evidence linking SPARC to inflammation, the mechanisms are unclear. Accordingly, the role of SPARC in intestinal inflammation was investigated. METHODS: Colitis was induced in wild-type (WT) and SPARC knockout (KO) mice using trinitrobenzene sulfonic acid (TNBS). Colons were assessed for damage; leukocyte infiltration; Tnf, Ifng, Il17a, and Il10 mRNA expression; and histology. Cytokine profiling of colonic lamina propria mononuclear cells (LPMCs) was performed by flow cytometry. Naïve CD4+ T cells were isolated from WT and SPARC KO mouse spleens, and the effect of SPARC on Th17 cell differentiation was examined. Recombination activating gene 1 knockout (RAG1 KO) mice reconstituted with T cells from either WT or SPARC KO mice were investigated. RESULTS: Trinitrobenzene sulfonic acid exposure significantly reduced bodyweight and increased mucosal inflammation, leukocyte infiltration, and Il17a mRNA expression in WT relative to SPARC KO mice. The percentage of IL17A-producing CD4+ T cells among LPMCs from KO mice was lower than that in WT mice when both groups were exposed to TNBS. Th17 cell differentiation was suppressed in cells from SPARC KO mice. In the T cell transfer colitis model, RAG1 KO mice receiving T cells from WT mice were more severely affected than those reconstituted with cells from SPARC KO mice. CONCLUSIONS: Secreted protein acidic and rich in cysteine accelerates colonic mucosal inflammation via modulation of IL17A-producing CD4+ T cells. SPARC is a potential therapeutic target for conditions involving intestinal inflammation.
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Linfócitos T CD4-Positivos/patologia , Colite/etiologia , Colite/patologia , Interleucina-17/metabolismo , Osteonectina/fisiologia , Animais , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Diferenciação Celular/genética , Células Cultivadas , Colite/tratamento farmacológico , Feminino , Expressão Gênica , Interleucina-17/genética , Mucosa Intestinal/imunologia , Mucosa Intestinal/patologia , Leucócitos/patologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Terapia de Alvo Molecular , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Células Th17RESUMO
High-fat diet (HFD)-induced alteration in the gut microbial composition, known as dysbiosis, is increasingly recognized as a major risk factor for various diseases, including colon cancer. This report describes a comprehensive investigation of the effect of agaro-oligosaccharides (AGO) on HFD-induced gut dysbiosis, including alterations in short-chain fatty acid contents and bile acid metabolism in mice. C57BL/6N mice were fed a control diet or HFD, with or without AGO. Terminal restriction fragment-length polymorphism (T-RFLP) analysis produced their fecal microbiota profiles. Profiles of cecal organic acids and serum bile acids were determined, respectively, using HPLC and liquid chromatography-tandem mass spectrometry systems. T-RFLP analyses showed that an HFD changed the gut microbiota significantly. Changes in the microbiota composition induced by an HFD were characterized by a decrease in the order Lactobacillales and by an increase in the Clostridium subcluster XIVa. These changes of the microbiota community generated by HFD treatment were suppressed by AGO supplementation. As supported by the data of the proportion of Lactobacillales order, the concentration of lactic acid increased in the HFD + AGO group. Data from the serum bile acid profile showed that the level of deoxycholic acid, a carcinogenic secondary bile acid produced by gut bacteria, was increased in HFD-receiving mice. The upregulation tended to be suppressed by AGO supplementation. Finally, results show that AGO supplementation suppressed the azoxymethane-induced generation of aberrant crypt foci in the colon derived from HFD-treated mice. Our results suggest that oral intake of AGO prevents HFD-induced gut dysbiosis, thereby inhibiting colon carcinogenesis.
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Neoplasias do Colo/microbiologia , Dieta Hiperlipídica/efeitos adversos , Disbiose/microbiologia , Oligossacarídeos/farmacologia , Sefarose/farmacologia , Animais , Ácidos e Sais Biliares/metabolismo , Clostridium , Fibras na Dieta , Disbiose/induzido quimicamente , Endotoxinas/sangue , Ácidos Graxos/metabolismo , Fezes/microbiologia , Lactobacillales , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microbiota , Obesidade/prevenção & controle , Oligossacarídeos/química , Sefarose/químicaRESUMO
Partially hydrolysed guar gum (PHGG), a water-soluble dietary fibre produced by the controlled partial enzymatic hydrolysis of guar gum beans, has various physiological roles. This study aimed to elucidate the beneficial effects of PHGG on colonic mucosal damage in a murine 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model. Acute colitis was induced in male C57BL/6 mice with TNBS after 2 weeks of pre-feeding with PHGG (5 %). The colonic mucosal inflammation was evaluated using macroscopic damage scores, and neutrophil infiltration was assessed by measuring tissue-associated myeloperoxidase (MPO) activity in the colonic mucosa. TNF-α expression in the colonic mucosa was measured by ELISA and real-time PCR. Moreover, the intestinal microbiota and production of SCFA were assessed by real-time PCR and HPLC, respectively. Colonic damage due to TNBS administration was significantly ameliorated by PHGG treatment. Furthermore, PHGG significantly inhibited increases in MPO activity and TNF-α protein and mRNA expression in the colonic mucosa in TNBS-induced colitis. On analysis of intestinal microbiota, we found that the concentration of the Clostridium coccoides group (Clostridium cluster XIVa), the Clostridium leptum subgroup (Clostridium cluster IV) and the Bacteroides fragilis group had significantly increased in PHGG-fed mice. On analysis of SCFA, we found that the caecal content of acetic acid, propionic acid and butyric acid had significantly increased in PHGG-fed mice. Together, these results suggest that chronic ingestion of PHGG prevents the development of TNBS-induced colitis in mice by modulating the intestinal microbiota and SCFA, which may be significant in the development of therapeutics for inflammatory bowel disease.
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Colite/tratamento farmacológico , Colite/microbiologia , Ácidos Graxos Voláteis/metabolismo , Galactanos/administração & dosagem , Microbioma Gastrointestinal/efeitos dos fármacos , Mananas/administração & dosagem , Gomas Vegetais/administração & dosagem , Ácido Trinitrobenzenossulfônico , Animais , Colite/induzido quimicamente , Colo/enzimologia , Modelos Animais de Doenças , Ácidos Graxos Voláteis/análise , Hidrólise , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/microbiologia , Mucosa Intestinal/enzimologia , Intestinos/química , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Peroxidase/metabolismo , RNA Mensageiro/análise , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/genéticaRESUMO
In Japan, nutritional guidance based on food-recording apps and food frequency questionnaires (FFQs) is becoming popular. However, it is not always recognized that different dietary assessment methods have different nutritional values. Here, we compared the compatibility of dietary intake data obtained from an app with those obtained from FFQs in 59 healthy individuals who recorded information regarding their diet for at least 7 days per month using an app developed by Asken (Tokyo, Japan). The diurnal coefficient of variation in total energy and protein intake was 20%, but those for vitamins B12 and D were >80%, reflecting the importance of 7 days of recording rather than a single day of recording for dietary intake analyses. Then, we compared the results of two FFQs-one based on food groups and one based on a brief self-administered diet history questionnaire-for 7 days, as recorded by the app. There was a correlation coefficient of >0.4 for all the items except salt. Regarding the compatibility between the app and FFQs, the percentage errors for total energy and nutrients were >40-50%, suggesting no agreement between the app and the two FFQs. In conclusion, careful attention should be paid to the impact of different dietary assessment methods on nutrient assessment.
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Registros de Dieta , Aplicativos Móveis , Humanos , Feminino , Masculino , Japão , Pessoa de Meia-Idade , Adulto , Inquéritos e Questionários , Inquéritos sobre Dietas/métodos , Avaliação Nutricional , Ingestão de Energia , Dieta/estatística & dados numéricos , Idoso , Voluntários Saudáveis , População do Leste AsiáticoRESUMO
The condition of being underweight is a social problem in Japan among women. However, there is a lack of evidence for dietary guidance for underweight women because there has been no comparison of lipids or HbA1c among underweight, normal weight, and overweight women in different age groups. We analyzed the effect of body size and age on the serum lipid and hemoglobin A1c levels in Japanese women in a cross-sectional study. A total of 26,118 women aged >20-65 years underwent physical examinations between 2012 and 2022. Seventeen percent of women aged >20-29 years were underweight, and 8% of those aged 50-65 years were underweight. Total cholesterol and non-HDL-C concentrations increased with age, but the difference between underweight and overweight individuals was lowest among women aged 50-65 years. On the other hand, the differences in HDL-C, TG, and HbA1c levels between underweight and overweight subjects were greatest in the 50-65 age group, but the differences between underweight and normal weight subjects were much smaller. Considering that, unlike HDL-C, TG, and HbA1c, TC and non-HDL-C increase to levels comparable to overweight levels in underweight women in aged 50-65 years, educating people about a diet that lowers non-HDL-C is necessary even in young underweight women.
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Undernutrition among young women at "Cinderella weight" is socially important in Japan. To determine the nutritional status of Cinderella-weight women, we conducted an exploratory cross-sectional study on the health examination results of employees aged 20 to 39 (n = 1457 and 643 for women and men, respectively). The percentage of underweight women was found to be much higher than that of men (16.8% vs. 4.5%, respectively). In underweight women (n = 245), handgrip strength (22.82 ± 5.55 vs. 25.73 ± 5.81 kg, p < 0.001), cholesterol level (177.8 ± 25.2 vs. 194.7 ± 31.2 mg/dL, p < 0.05), and lymphocyte count (1883 ± 503 vs. 2148 ± 765/µL, p < 0.001) were significantly lower than in overweight women (n = 116). Then, the BMI < 17.5 group (n = 44) was referred to the outpatient nutrition evaluation clinic. Lower prealbumin, cholesterol, and lymphocyte levels were also observed in 34%, 59%, and 32% of the patients, respectively. Regarding dietary characteristics, 32% of the underweight women in this study skipped breakfast, and 50% had low dietary diversity scores. Lower total energy intake, carbohydrate and fiber intake, and Ca and Fe intake were also observed in 90% of the patients. Deficiencies in vitamin B1, B12, D, and folate were diagnosed in 4.6%, 25%, 14%, and 98% of the patients, respectively. Thus, young underweight women may be prone to malnutrition.
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Deficiência de Vitaminas , Desnutrição , Estado Nutricional , Feminino , Humanos , Masculino , Deficiência de Vitaminas/epidemiologia , Colesterol , Estudos Transversais , População do Leste Asiático , Força da Mão , Desnutrição/epidemiologia , Magreza/epidemiologia , Adulto Jovem , AdultoRESUMO
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.
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Microbioma Gastrointestinal , Lactobacillales , Leuconostoc mesenteroides , Probióticos , Prebióticos , Lactobacillales/metabolismo , Bactérias , FermentaçãoRESUMO
The significant increase in food allergy incidence is correlated with dietary changes in modernized countries. Here, we investigated the impact of dietary emulsifiers on food allergy by employing an experimental murine model. Mice were exposed to drinking water containing 1.0% carboxymethylcellulose (CMC) or Polysorbate-80 (P80) for 12 weeks, a treatment that was previously demonstrated to induce significant alterations in microbiota composition and function leading to chronic intestinal inflammation and metabolic abnormalities. Subsequently, the ovalbumin food allergy model was applied and characterized. As a result, we observed that dietary emulsifiers, especially P80, significantly exacerbated food allergy symptoms, with increased OVA-specific IgE induction and accelerated type 2 cytokine expressions, such as IL-4, IL-5, and IL-13, in the colon. Administration of an antibiotic regimen completely reversed the emulsifier-induced exacerbated susceptibility to food allergy, suggesting a critical role played by the intestinal microbiota in food allergy and type 2 immune responses.
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Hipersensibilidade Alimentar , Camundongos , Animais , Emulsificantes/efeitos adversos , Dieta , Ovalbumina , Polissorbatos/efeitos adversos , Inflamação/induzido quimicamente , Colo , Imunidade , Camundongos Endogâmicos BALB C , Modelos Animais de DoençasRESUMO
Fermented foods represent a significant portion of human diets with several beneficial effects. Foods produced by bacterial fermentation are enriched in short-chain fatty acids (SCFAs), which are functional products of dietary fibers via gut microbial fermentation. In addition to energy sources, SCFAs also act as signaling molecules via G-protein coupled receptors such as FFAR2 and FFAR3. Hence, dietary SCFAs in fermented foods may have a direct influence on metabolic functions. However, the detailed mechanism by dietary SCFAs remains unclear. Here, we show that dietary SCFAs protected against high-fat diet-induced obesity in mice in parallel with increased plasma SCFAs without changing cecal SCFA or gut microbial composition. Dietary SCFAs suppressed hepatic weight and lipid synthesis. These effects were abolished in FFAR3-deficient mice but not FFAR2-deficient. Thus, SCFAs supplementation improved hepatic metabolic functions via FFAR3 without influencing intestinal environment. These findings could help to promote the development of functional foods using SCFAs.
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Dieta , Ácidos Graxos Voláteis/metabolismo , Comportamento Alimentar , Fígado/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Animais , Ácidos Graxos Voláteis/sangue , Regulação da Expressão Gênica , Metabolismo dos Lipídeos/genética , Masculino , Camundongos Endogâmicos C57BL , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores Acoplados a Proteínas G/deficiência , Receptores Acoplados a Proteínas G/genéticaRESUMO
Increasing evidence indicates that molecular hydrogen-dissolved alkaline electrolyzed water (AEW) has various physiological activities such as antioxidative activity. Gut microbiota are deeply associated with our health through a symbiotic relationship. Recent reports have described that most gastrointestinal microbial species encode the genetic capacity to metabolize molecular hydrogen, meaning that molecular hydrogen might affect the gut microbial composition. Nevertheless, AEW effects on gut microbiota remain unknown. This study investigated AEW effects on the intestinal environment in mice, including microbial composition and short-chain fatty acid contents. After mice were administered AEW for 4 weeks, 16S rRNA gene sequencing analyses revealed their fecal microbiota profiles. Organic acid concentrations in cecal contents were measured using an HPLC system. Compared to the control group, AEW administration mice had significantly lower serum low-density lipoprotein cholesterol level and alanine aminotransferase activity. Organic acid concentrations of propionic, isobutyric, and isovaleric acids were higher in AEW-administered mice. Results of 16S rRNA gene sequencing analyses showed that the relative abundances of 20 taxa differed significantly in AEW-administered mice. Although the definitive role of gut microbes of AEW-administered mice remains unknown, our data demonstrate the possibility that AEW administration affects the gut microbial composition and that it has beneficial health effects in terms of cholesterol metabolism and liver protection.
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Recent studies have identified carbon monoxide (CO) as a potential therapeutic molecule for the treatment of inflammatory diseases including intestinal inflammation. In the present study, we explored the efficacy and the mechanisms of action of CO-releasing molecule (CORM)-A1 in T-cell transfer induced colitis model in mice. In addition, the impact of CORM-A1 on the T helper (Th) cell differentiation was evaluated using naïve CD4+ T cells isolated from the spleens in Balb/c mice. The results showed that CORM-A1 conferred protection against the development of intestinal inflammation and attenuated Th17 cell differentiation. Hence, the observed immunomodulatory effects of CORM-A1 could be useful for developing novel therapeutic approaches for managing intestinal inflammation through the regulation of Th17 differentiation.
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Monóxido de Carbono/farmacologia , Diferenciação Celular/efeitos dos fármacos , Colite/imunologia , Colite/patologia , Células Th17/citologia , Células Th17/efeitos dos fármacos , Animais , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos SCID , Células Th17/imunologiaRESUMO
Mucin is produced and secreted by epithelial goblet cells and is a key component of the innate immune system, acting as a barrier in the intestinal tract. However, no studies have been conducted investigating the increase in mucin secretion to enhance the intestinal barrier function. The present study investigated whether rebamipide (Reb) acts as a secretagogue of intestinal mucin and the underlying mechanisms involved, thereby focusing on the effect on goblet cells. The LS174T cell line was used as goblet celllike cells. Using Rebtreated LS174T cells, the level of mucin content was assessed by periodic acidSchiff (PAS) staining, and mucin 2, oligomeric mucus/gelforming (MUC2) mRNA expression was assessed using quantitative polymerase chain reaction (PCR). Furthermore, MUC2 secretion in the supernatant was quantified by the dot blot method. The present study additionally investigated the involvement of the epidermal growth factor receptor/Akt serine/threonine kinase 1 (Akt) pathway in mucin secretion by western blotting. The results suggested that Reb strongly enhanced the positivity of PAS staining in LS174T cells, thereby suggesting increased intracellular mucin production. The PCR results indicated that Reb significantly increased MUC2 mRNA in whole cell lysate of LS174T cells. In order to assess the subsequent secretion of mucin by LS174T, MUC2 protein expression in the supernatant was assessed using the dot blot method and it was demonstrated that Reb significantly increased the secretion of MUC2 in a concentrationdependent manner. The pAkt was significantly increased by Reb treatment, and an Akt inhibitor specifically suppressed MUC2 secretion. Overall, Reb increased mucin secretion directly via pAkt. Rebincreased mucin may act as a strong nonspecific barrier against pathogenic stimulants in various intestinal diseases.
Assuntos
Alanina/análogos & derivados , Células Caliciformes/efeitos dos fármacos , Células Caliciformes/metabolismo , Mucinas/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Quinolonas/farmacologia , Alanina/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Mucosa Intestinal/citologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucinas/genética , Fosforilação , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
We hypothesized that daily intake of nondigestible saccharides delays senescence onset through the improvement of intestinal microflora. Here, we raised senescence accelerated mice prone 8 (SAMP8) on the AIN93 diet (CONT), with sucrose being substituted for 5% of fructooligosaccharide (FOS) or 5% of glucomannan (GM), 15 mice per group. Ten SAMR1 were raised as reference of normal aging with control diet. Grading of senescence was conducted using the method developed by Hosokawa, and body weight, dietary intake, and drinking water intake were measured on alternate days. Following 38 weeks of these diets we evaluated learning and memory abilities using a passive avoidance apparatus and investigated effects on the intestinal microflora, measured oxidative stress markers, and inflammatory cytokines. Continuous intake of FOS and GM significantly enhanced learning and memory ability and decelerated senescence development when compared with the CONT group. Bifidobacterium levels were significantly increased in FOS and GM-fed mice. Urinary 8OHdG, 15-isoprostane, serum TNF- α , and IL-6 were also lower in FOS-fed mice, while IL-10 in FOS and GM groups was higher than in CONT group. These findings suggest that daily intake of nondigestible saccharides delays the onset of senescence via improvement of intestinal microflora.