Chronic Endurance Exercise Impairs Niacin Nutritional Status in Mice.

Niacin is a cofactor in many biological reactions related to energy metabolism, redox reactions, DNA repair and longevity. Although it has been considered that increasing energy expenditure increases NAD consumption, little study has directly demonstrated the effect of exercise on niacin nutritional status. We have recently established the niacin insufficient model mice using kynurenine 3-monooxygenase knock out (KMO-/-) mice with niacin-limited diet, which lack the de novo NAD synthesis pathway from tryptophan. To evaluate the effects of chronic endurance exercise on niacin nutritional status, 4 wk old KMO-/- mice were fed 4 or 30 mg/kg nicotinic acid containing diets, and forced to swim in a running water pool every other day for 35 d. The swim-exercised mice fed 4 mg/kg nicotinic acid diet showed lower body weight gain and niacin nutritional markers such as liver and blood NAD, and urine nicotinamide metabolites than the sedentary mice. These animals did not show any difference in the NAD synthesis, NAD salvage and nicotinamide catabolic pathways. Chronic endurance exercise failed to affect any indices in the mice fed the 30 mg/kg nicotinic acid diet. When the diet was exchanged the 4 mg/kg for 30 mg/kg nicotinic acid diet to the mice showed chronic endurance exercise-induced growth retardation, their body weight rapidly increased. These results show that chronic endurance exercise impairs niacin nutritional status in the niacin insufficient mice, and enough niacin intake can prevent this impairment. Our findings also suggest that chronic endurance exercise increases niacin requirement by increase of NAD consumption.

Adrenalectomy exacerbates stress-induced impairment in fear discrimination: A causal role for kynurenic acid?

Impaired activity of the hypothalamic-pituitary axis and reduced blood levels of glucocorticoids (GCs) are signature features of stress-related maladies. Recent evidence suggests a possible role of the tryptophan metabolite kynurenic acid (KYNA) in this context. Here we investigated possible causal relationships in adult male rats, using stress-induced fear discrimination as a translationally relevant behavioral outcome measure. One week following adrenalectomy (ADX) or sham surgery, animals were for 2 h either physically restrained or exposed to a predator odor, which caused a much milder stress response. Extracellular KYNA levels were determined before, during and after stress by in vivo microdialysis in the prefrontal cortex. Separate cohorts underwent a fear discrimination procedure starting immediately after stress termination. Different auditory conditioned stimuli (CS) were either paired with a foot shock (CS+) or non-reinforced (CS-). One week later, fear was assessed by re-exposing the animals to each CS. Separate groups of rats were treated with the KYNA synthesis inhibitor BFF-816 prior to stress initiation to test a causal role of KYNA in fear discrimination. Restraint stress raised extracellular KYNA levels by ∼85 % in ADX rats for several hours, and these animals were unable to discriminate between CS+ and CS-. Both effects were prevented by BFF-816 and were not observed after exposure to predator odor or in sham-operated rats. These findings suggest that a causal connection exists between adrenal function, stress-induced KYNA increases, and behavioral deficits. Pharmacological inhibition of KYNA synthesis may therefore be an attractive, novel option for the treatment of stress-related disorders.

Chronic Ethanol Intake Impairs Niacin Nutritional Status in Mice.

Niacin is involved in many biological reactions relating energy metabolism, redox reactions, DNA repair and longevity. Since niacin deficiency has been reported in alcoholic patients, and niacin coenzyme NAD is used as substrate to dehydrogenate ethanol in the liver, ethanol consumption can be a factor to impair niacin nutritional status. We have recently established the niacin insufficient model mice using kynurenine 3-monooxygenase knock out (KMO-/-) mice with niacin-limited diet, which lack the de novo NAD synthesis pathway from tryptophan. To evaluate the effects of chronic ethanol intake on niacin nutritional status, 4 wk old KMO-/- mice were fed 4 or 30 mg/kg nicotinic acid containing diets with or without 15% ethanol for 35 d. The mice fed 4 mg/kg nicotinic acid diet with ethanol showed lower body weight gain and niacin nutritional markers such as liver and blood NAD, and urine nicotinamide metabolites than the mice without ethanol. These animals did not show any difference in the NAD synthesis, NAD salvage and nicotinamide catabolic pathways. Chronic ethanol intake failed to affect any indices in the mice fed the 30 mg/kg nicotinic acid diet. When the diet was exchanged the 4 mg/kg for 30 mg/kg nicotinic acid diet to the mice showed chronic ethanol-induced growth retardation, their body weight rapidly increased. These results show that chronic ethanol intake impairs niacin nutritional status in the niacin insufficient mice, and enough niacin intake can prevent this impairment. Our findings also suggest that chronic ethanol intake increases niacin requirement by increase of NAD consumption.

Establishment of Model Mice to Evaluate Low Niacin Nutritional Status.

Niacin is involved in many biological reactions relating energy metabolism, redox reactions, DNA repair and longevity, and low NAD levels with aging and feeding high fat diets develop and progress age-related diseases. Although recent findings suggest the requirement of niacin insufficient animal model to further study, appropriate animal models have not been established yet because niacin is biosynthesized from tryptophan via tryptophan-nicotinamide pathway. To establish model mice to evaluate niacin nutritional status, we used kynurenine 3-monooxygenase knock out (KMO-/-) mice which lack NAD biosynthesis pathway from tryptophan. To determine the niacin requirement and assess niacin nutritional markers, 4 wk old KMO-/- mice were fed 2-30 mg/kg nicotinic acid containing diets for 28 d. More than 4 mg/kg but not less than 3 mg/kg nicotinic acid containing diets induced maximum growth, and niacin nutritional markers in the blood, liver and urine increased with increase of dietary nicotinic acid. These results showed that several niacin nutritional markers reflect niacin nutritional status, niacin nutritional status can be controlled by dietary nicotinic acid, and niacin requirement for maximum growth is 4 mg/kg nicotinic acid diets in the KMO-/- mice. This animal model useful to investigate pathophysiology and mechanism of niacin deficiency, clarify the relationships between niacin nutritional status and age-related and lifestyle diseases, and evaluate factors affecting niacin nutritional status.

Physiological Functions of Proteinogenic Amino Acid.

The symposium entitled "Physiological Functions of Proteinogenic Amino Acid" is being held at the 22nd IUNS-ICN International Congress of Nutrition in December 2022 in Tokyo, Japan. The symposium is cochaired by Dr. Shigeki Furuya from Kyushu University and Dr. Tsutomu Fukuwatari from The University of Shiga Prefecture, co-organized by the International Council on Amino Acid Science and Japanese Society for Amino Acid Sciences. In recent years, amino acid researchers have made great strides in finding the physiological functions of proteinogenic amino acids and their metabolites, and opened a new era for amino acid and nutritional sciences. The goal of this symposium is to highlight the novel and important physiological function of proteinogenic amino acids from nutritional aspects. This amino acids symposium features 4 speakers, each presenting novel insights into mechanisms by which amino acids participate in brain function, diabetes, taste functions and energy metabolism, respectively. Dr. Gilles Bonvento from University Paris-Saclay/CNRS/CEA talks about the role of serine in brain function. Dr. Ara Koh from Pohang University of Science and Technology, POSTECH, presents histidine-derived microbial imidazole propionate in diabetes. Dr. Hisayuki Uneyama from Ajinomoto Co., Inc., talks about taste functions of amino acids for improving health and wellbeing. Dr. Jorge L Ruas from Karolinska Institute describes the tryptophan-kynurenine pathway in the regulation of energy metabolism.

Effects of B-Group Vitamin Administration on Daily Change in Urine 2-Oxo Acids in Young Japanese Women.

B-group vitamins are required in amino acid catabolism, and recent findings suggest that urine 2-oxo acids, catabolites of amino acid, could be functional biomarkers indicating the nutritional status of B-group vitamins. To clarify the relationship between B-group vitamins and urine 2-oxo acids, we investigated the effects of B-group vitamin administration on daily changes in urinary amounts of 2-oxo acids in humans. Twenty-nine young Japanese women collected 24-h urine samples for 8 d, and took B-group vitamins for 7 d beginning on the second day of urine collection. The participants were divided into three groups on the basis of the amounts of total branched-chain 2-oxo acids, 2-oxoglutaric acid, 2-oxoadipic acid, and pyruvic acid excreted in urine. In the upper tertile, but not the middle and lower tertiles, each urine 2-oxo acid decreased from the first day of vitamin administration, and completely decreased to a normal level on the second day of administration. These results indicate that administration of B-group vitamins immediately affects 2-oxo acid metabolism in some young Japanese women. Thus, urinary 2-oxo acids could be useful and functional biomarkers for B-group vitamin status.

Differences in gut microbial patterns associated with salivary biomarkers in young Japanese adults.

Recent evidence suggests that psychological stress is associated with gut microbiota; however, there are no reports of its association with gut microbial structure. This cross-sectional study examined the relationship between psychological stress and gut microbial patterns in young Japanese adults. Analysis of fecal microbiota was performed using terminal restriction fragment length polymorphism (T-RFLP). Psychological stress was assessed using salivary biomarkers, including cortisol, alpha-amylase, and secretory IgA (S-IgA). Fecal microbial patterns were defined using principal component analysis of the T-RFLP profile and were classified into two enterotype-like clusters, which were defined by the B (microbiota dominated by Bacteroides) and BL patterns (microbiota dominated by Bifidobacterium and Lactobacillales), respectively. The Simpson index was significantly higher for the BL pattern than for the B pattern. The salivary cortisol level was significantly lower for the BL pattern than for the B pattern. Salivary alpha-amylase and S-IgA levels showed a negative correlation with the Simpson index. Our results raise the possibility that salivary biomarkers may be involved in the observed differences in microbial patterns.

Dysregulation at multiple points of the kynurenine pathway is a ubiquitous feature of renal cancer: implications for tumour immune evasion.

BACKGROUND: Indoleamine 2,3-dioxygenase (IDO), the first step in the kynurenine pathway (KP), is upregulated in some cancers and represents an attractive therapeutic target given its role in tumour immune evasion. However, the recent failure of an IDO inhibitor in a late phase trial raises questions about this strategy. METHODS: Matched renal cell carcinoma (RCC) and normal kidney tissues were subject to proteomic profiling. Tissue immunohistochemistry and gene expression data were used to validate findings. Phenotypic effects of loss/gain of expression were examined in vitro. RESULTS: Quinolate phosphoribosyltransferase (QPRT), the final and rate-limiting enzyme in the KP, was identified as being downregulated in RCC. Loss of QPRT expression led to increased potential for anchorage-independent growth. Gene expression, mass spectrometry (clear cell and chromophobe RCC) and tissue immunohistochemistry (clear cell, papillary and chromophobe), confirmed loss or decreased expression of QPRT and showed downregulation of other KP enzymes, including kynurenine 3-monoxygenase (KMO) and 3-hydroxyanthranilate-3,4-dioxygenase (HAAO), with a concomitant maintenance or upregulation of nicotinamide phosphoribosyltransferase (NAMPT), the key enzyme in the NAD+ salvage pathway. CONCLUSIONS: Widespread dysregulation of the KP is common in RCC and is likely to contribute to tumour immune evasion, carrying implications for effective therapeutic targeting of this critical pathway.

Possibility of Amino Acid Treatment to Prevent the Psychiatric Disorders via Modulation of the Production of Tryptophan Metabolite Kynurenic Acid.

Kynurenic acid, a metabolite of the kynurenine pathway of tryptophan catabolism, acts as an antagonist for both the α7 nicotinic acetylcholine receptor and glycine coagonist sites of the N-methyl-d-aspartic acid receptor at endogenous brain concentrations. Elevation of brain kynurenic acid levels reduces the release of neurotransmitters such as dopamine and glutamate, and kynurenic acid is considered to be involved in psychiatric disorders such as schizophrenia and depression. Thus, the control of kynurenine pathway, especially kynurenic acid production, in the brain is an important target for the improvement of brain function or the effective treatment of brain disorders. Astrocytes uptake kynurenine, the immediate precursor of kynurenic acid, via large neutral amino acid transporters, and metabolize kynurenine to kynurenic acid by kynurenine aminotransferases. The former transport both branched-chain and aromatic amino acids, and the latter have substrate specificity for amino acids and their metabolites. Recent studies have suggested the possibility that amino acids may suppress kynurenic acid production via the blockade of kynurenine transport or via kynurenic acid synthesis reactions. This approach may be useful in the treatment and prevention of neurological and psychiatric diseases associated with elevated kynurenic acid levels.

Stress-induced impairment in fear discrimination is causally related to increased kynurenic acid formation in the prefrontal cortex.

RATIONALE: Stress is related to cognitive impairments which are observed in most major brain diseases. Prior studies showed that the brain concentration of the tryptophan metabolite kynurenic acid (KYNA) is modulated by stress, and that changes in cerebral KYNA levels impact cognition. However, the link between these phenomena has not been tested directly so far. OBJECTIVES: To investigate a possible causal relationship between acute stress, KYNA, and fear discrimination. METHODS: Adult rats were exposed to one of three acute stressors-predator odor, restraint, or inescapable foot shocks (ISS)-and KYNA in the prefrontal cortex was measured using microdialysis. Corticosterone was analyzed in a subset of rats. Another cohort underwent a fear discrimination procedure immediately after experiencing stress. Different auditory conditioned stimuli (CSs) were either paired with foot shock (CS+) or were non-reinforced (CS-). One week later, fear was assessed by re-exposing rats to each CS. Finally, to test whether stress-induced changes in KYNA causally impacted fear discrimination, a group of rats that received ISS were pre-treated with the selective KYNA synthesis inhibitor PF-04859989. RESULTS: ISS caused the greatest increase in circulating corticosterone levels and raised extracellular KYNA levels by ~ 85%. The two other stressors affected KYNA much less (< 25% increase). Moreover, only rats that received ISS were unable to discriminate between CS+ and CS-. PF-04859989 abolished the stress-induced KYNA increase and also prevented the impairment in fear discrimination in animals that experienced ISS. CONCLUSIONS: These findings demonstrate a causal connection between stress-induced KYNA increases and cognitive deficits. Pharmacological manipulation of KYNA synthesis therefore offers a novel approach to modulate cognitive processes in stress-related disorders.

Pillar[6]arene acts as a biosensor for quantitative detection of a vitamin metabolite in crude biological samples.

Metabolic syndrome is associated with obesity, hypertension, and dyslipidemia, and increased cardiovascular risk. Therefore, quick and accurate measurements of specific metabolites are critical for diagnosis; however, detection methods are limited. Here we describe the synthesis of pillar[n]arenes to target 1-methylnicotinamide (1-MNA), which is one metabolite of vitamin B3 (nicotinamide) produced by the cancer-associated nicotinamide N-methyltransferase (NNMT). We found that water-soluble pillar[5]arene (P5A) forms host-guest complexes with both 1-MNA and nicotinamide, and water-soluble pillar[6]arene (P6A) selectively binds to 1-MNA at the micromolar level. P6A can be used as a "turn-off sensor" by photoinduced electron transfer (detection limit is 4.38 × 10-6 M). In our cell-free reaction, P6A is used to quantitatively monitor the activity of NNMT. Moreover, studies using NNMT-deficient mice reveal that P6A exclusively binds to 1-MNA in crude urinary samples. Our findings demonstrate that P6A can be used as a biosensor to quantify 1-MNA in crude biological samples.

Japanese Diet Score Is Associated with Gut Microbiota Composition in Young Japanese Adults.

The Japanese diet (JD) is accepted as a healthy dietary pattern, which has protective effects against cancer and cardiovascular diseases. However, it remains unclear whether there is any association between the JD and fecal microbiota composition. This cross-sectional study examined the relationship between JD scores and fecal microbiota in young Japanese adults, through the analysis of fecal microbiota using the terminal restriction fragment length polymorphism (T-RFLP) method. JD scores were calculated with regard to nine food groups (rice, miso soup, pickles, green and yellow vegetables, seaweeds, fish, green tea, meat, and coffee) based on a brief self-administered diet-history questionnaire. JD total scores were categorized as low (score 0-3) or high (score 4-8). The high-scoring JD group exhibited a significantly higher relative abundance of Bacteroides than the low JD group, whereas the low JD group exhibited a significantly higher relative abundance of Prevotella than the high JD group. With regard to food group intakes, a higher consumption of rice was associated with a significantly lower relative abundance of Prevotella, whereas a higher consumption of green tea was associated with a significantly higher relative abundance of Bifidobacterium. To the best of our knowledge, this is the first study demonstrating an association between JD score and fecal microbiota and may allow the prediction of changes in fecal microbiota due to changes in the JD.

Blood concentrations and renal clearance of water-soluble vitamins in outpatients with ulcerative colitis.

Few studies have investigated the association between dietary intake and blood concentrations of water-soluble vitamins in patients with ulcerative colitis (UC). In the present study, vitamin concentrations were measured in the blood and urinary excretion of 23 outpatients with UC and compared against a control group of 20 healthy participants. A weighed food record procedure was used to ensure controlled macronutrient and vitamin intakes of the UC cohort. Individuals in the control group were given a semi-purified diet for 8 days prior to assessment. Multiple linear regression analysis was used to identify important differences in vitamin concentrations, independent of sex, age and other confounding variables. The blood concentrations of vitamins B2, C, niacin and folate were markedly lower in the patients with UC than those in the control group, and the renal clearance of vitamins B1, B6, B12 and folate was notably higher in the UC cohort. It was concluded that vitamins B2, C, niacin and folate were at significantly lower concentrations in patients with UC following adjustment for coexisting factors. The lower levels of niacin may be partially due to impaired reabsorption. Chronic inflammation, common in patients with UC, with may contribute to the lower levels of other vitamins by rendering amino acid and carbohydrate metabolism into a hypermetabolic state. As the role of vitamins in metabolic activity is constant and pervasive, nutritional management including the application of water-soluble vitamins appears important for patients suffering from UC.

Acute liver failure increases kynurenic acid production in rat brain via changes in tryptophan metabolism in the periphery.

The tryptophan metabolite, kynurenic acid (KYNA), is a preferential antagonist of the α7 nicotinic acetylcholine receptor and N-methyl-d-aspartic acid receptor at endogenous brain concentrations. Recent studies have suggested that increased brain KYNA levels are involved in psychiatric disorders such as schizophrenia and depression. Most of the brain kynurenine (KYN), the KYNA precursor, comes from the periphery, and the liver has a central role in the peripheral tryptophan metabolism. In this study, the effect of acute liver failure (ALF) on brain KYNA production and on the peripheral tryptophan metabolism was investigated in rats. ALF was induced by administration of the hepatotoxin, thioacetamide (TAA). Brain KYNA levels were increased by TAA-induced ALF, and these increases were consistent with KYN levels in the brain, serum and liver. These results suggest that the ALF-induced increase in serum KYN contributes to the increase in brain KYNA via elevated KYN uptake within the brain. This increase in serum KYN level can be caused by the changes in tryptophan-2,3-dioxygenase activity in the liver and the immune-related activation of indoleamine-2,3-dioxygenase in extrahepatic tissues. These findings suggest that hepatic dysfunction may contribute to neurological and psychiatric diseases associated with increased KYNA levels.

Gastric and Jejunal Enteral Feeding Differently Affect Vitamin B12 Status in Subjects with Severe Motor and Intellectual Disabilities.

The absorption of vitamin B12 is a complex process involving gastric acid and intrinsic factor as the indispensable components. In this study, we have investigated the effects of the administration site in enteral feeding on vitamin B12 status in subjects with severe motor and intellectual disabilities (SMID). This is a cross-sectional study conducted from January to June 2016. Blood concentrations of vitamin B12, folate, vitamin B6, and homocysteine (Hcy) were measured in a total of 82 subjects (38 men, 44 women). Also, nutrients intake was assessed. Subjects with enteral feeding (EF) had significantly higher intakes of vitamin B12, folate, and vitamin B6 than those with oral ingestion (OI). Serum folate and vitamin B6 concentrations in subjects with EF were significantly higher than those with OI. Among the EF subjects, serum vitamin B12 concentration was significantly higher in those fed with gastric tube than those fed with jejunal tube in spite of similar vitamin B12 intakes. No significant difference was observed between the two groups regarding the circulating concentrations of folate, vitamin B6, or Hcy. Although each administration route has its own benefit, gastric tube is advantageous in the absorption of vitamin B12.

A Suitable Diet for Recovery from Starvation Is a High-Fat Diet, but Not a High-Protein Diet, in Rats.

The present study aims to determine the most suitable dietary balance of energy-producing nutrients for recovery from starvation. Rats were fed their standard high- carbohydrate diet (HCD, carbohydrate energy : protein energy : fat energy=71 : 18 : 11) for 7 d and then deprived of food for 3 d (short-term starvation) or 8 d (long-term starvation). The starved rats were then fed the HCD, a high-protein diet (HPD, 31 : 57 : 12), or a high-fat diet (HFD, 34 : 14 : 52) for 8 d. Rats had ad libitum access to drinking water throughout the experimental period, including the starvation period. The reference group was allowed free access to the HCD throughout the experimental period. Characteristically, increased drinking, increased urea nitrogen in the plasma and urine, and hypertrophy of the kidneys, were observed in the HPD group. Furthermore, the recovery of plasma glucose level was insufficient in this group. Therefore, administration of a HPD was contraindicated in recovery from starvation. The recovery of body weight after starvation was excellent in the HFD group. No effect on the metabolism of B-group vitamins involved in energy metabolism was found with the administration of any diet. The effects of HCD and HFD administration on recovery from starvation were investigated in further detail. No adverse effects were observed on the tissue to body weight mass ratios or biochemical parameters in blood in the HFD group. From the above findings, it is hypothesized that a HFD is most suitable for quickly reversing the influence of starvation.

Thirteen week toxicity study of dietary l-tryptophan in rats with a recovery period of 5 weeks.

Although l-tryptophan is nutritionally important and widely used in medical applications, toxicity data for its oral administration are limited. The purpose of this study was to evaluate the potential toxicity of an experimental diet containing added l-tryptophan at doses of 0 (basal diet), 1.25%, 2.5% and 5.0% when administered to Sprague-Dawley rats for 13 weeks. There were no toxicological changes in clinical signs, ophthalmology, urinalysis, hematology, necropsy, organ weight and histopathology between control rats and those fed additional l-tryptophan. Body weight gain and food consumption significantly decreased throughout the administration period in males in the 2.5% group and in both sexes in the 5.0% group. At the end of the dosing period, decreases in water intake in males in the 5.0% group and in serum glucose in females in the 5.0% group were observed. The changes described above were considered toxicologically significant; however, they were not observed after a 5 week recovery period, suggesting reversibility. Consequently, the no-observed-adverse-effect level of l-tryptophan in the present study was 1.25% for males and 2.5% for females (mean intake of l-tryptophan: 779 mg kg-1 body weight day-1 [males] and 1765 mg kg-1 body weight day-1 [females]). As the basal diet used in this study contained 0.27% of proteinaceous l-tryptophan, the no-observed-adverse-effect level of overall l-tryptophan was 1.52% for males and 2.77% for females (mean intake of overall l-tryptophan: 948 mg kg-1 body weight day-1 (males) and 1956 mg kg-1 body weight day-1 (females)). We conclude that l-tryptophan has a low toxicity profile in terms of human use.

Vagus nerve is involved in the changes in body temperature induced by intragastric administration of 1,8-cineole via TRPM8 in mice.

Transient Receptor Potential Melastatin 8 (TRPM8) is a cold receptor activated by mild cold temperature (<28°C). TRPM8 expressed in cutaneous sensory nerves is involved in cold sensation and thermoregulation. TRPM8 mRNA is detected in various tissues, including the gastrointestinal mucosa, and in the vagal afferent nerve. The relationship between vagal afferent nerve-specific expression of TRPM8 and thermoregulation remains unclear. In this study, we aimed to investigate whether TRPM8 expression in the vagal afferent nerve is involved in autonomic thermoregulation. We found that intragastric administration of 1,8-cineole, a TRPM8 agonist, increased intrascapular brown adipose tissue and colonic temperatures, and M8-B-treatment (TRPM8 antagonist) inhibited these responses. Intravenous administration of 1,8-cineole also showed similar effects. In vagotomized mice, the responses induced by intragastric administration of 1,8-cineole were attenuated. These results suggest that TRPM8 expressed in tissues apart from cutaneous sensory nerves are involved in autonomic thermoregulation response.

The Relationship between Habitual Dietary Intake and Gut Microbiota in Young Japanese Women.

Recent studies have shown that dietary content affects the health of the host by changing the gut microbiota. However, little is known about the association of microbiota composition with habitual diet in Japanese people. Here, we aimed to clarify the relationship between the fecal microbiota and habitual dietary intake of micronutrients, macronutrients and food groups in healthy young Japanese women. Analysis of fecal microbiota was performed by the terminal restriction fragment length polymorphism (T-RFLP) method, and a dietary survey was conducted over three consecutive days using a weighed food record method. T-RFLP pattern analysis divided the subjects into two clusters, where cluster A group had a high relative abundance of Bacteroides and Clostridium cluster IV, and cluster B group had a high relative abundance of Bifidobacterium and Lactobacillales. Cluster A group also had lower intakes of iron and vitamin K and higher intakes of mushrooms and snacks than cluster B group. Analysis of Spearman rank correlations found several significant relationships between fecal microbiota and intake of nutrients and food groups. Bifidobacterium was correlated with iron intake, and Clostridium cluster XI was negatively correlated with intakes of cholesterol and eggs. These results suggest that dietary habits may strongly affect Bifidobacterium, Bacteroides and Clostridium abundance in the gut microbiota of young Japanese women. This is the first study to show relationships between fecal microbiota and habitual dietary intake in Japanese people. Accumulation of results from similar studies will help to elucidate the relationships between dietary intake and diseases in Japanese people.

Concentrations of Water-Soluble Vitamins in Blood and Urinary Excretion in Patients with Diabetes Mellitus.

We examined the concentrations of water-soluble vitamins in blood and urinary excretion of 22 patients with type 2 diabetes mellitus (type 2DM) and 20 healthy control participants. Macronutrient and vitamin intakes of type 2DM subjects were measured using a weighed food record method. Control participants consumed a semipurified diet for eight days. Multiple linear regression models were used to determine whether significant differences existed in vitamin concentrations in blood independent of age, sex, and other confounding factors. Concentrations of vitamins B2, B6, C, niacin, and folate in blood were significantly lower in type 2DM subjects than in controls, independent of confounding factors. Renal clearances of vitamins B6, C, niacin, and folate were significantly higher in type 2DM subjects than in controls. In conclusion, concentrations of vitamins B2, B6, C, niacin, and folate in blood were significantly lower in type 2DM subjects than in controls, independent of confounding factors; based on the evidence of increased urinary clearance of these vitamins, the lower levels were likely due to impaired reabsorption processes.