Shigenori Suzuki

Introduction: A higher urinary sodium-to-potassium (Na/K) ratio has been associated with increased risk of hypertension and cardiovascular diseases, which are known risk factors for Alzheimer's Disease (AD). Mendelian Randomization (MR), which uses genetic variants as instrumental variables to infer causality while reducing confounding and reverse causation, was applied to investigate whether the urinary Na/K ratio is causally associated with AD risk. Methods: A two-sample MR study was conducted using 31 single-nucleotide polymorphisms associated with urinary Na/K ratio as instrumental variables. The primary analysis employed Genome- Wide Association Study (GWAS) summary statistics for AD (n=85,934 individuals, including ADby- proxy). For sensitivity analysis, GWAS data specific to clinically diagnosed late-onset AD (n=21,982 individuals) were analyzed. Results: Genetically predicted urinary Na/K ratio was not statistically significantly associated with AD risk in the primary analysis; odds ratio (OR per 1 mol/mol increase) = 1.02, 95% confidence interval (CI): 0.77-1.36. In the sensitivity analysis using clinically diagnosed late-onset AD, the point estimate was higher (OR = 1.49, 95% CI: 0.99-2.24), although the association was not statistically significant. Discussion: Although no statistically significant causal association was observed, the study’s findings may be consistent with previous observational studies linking higher sodium intake or a higher urine Na/K ratio to poorer cognitive performance. However, the sensitivity analysis suggested a possible association that warrants further investigation in larger MR studies using clinically confirmed AD datasets. As all data were derived from individuals of European ancestry, generalizability to other populations may be limited. Conclusion: This MR study did not provide clear evidence supporting a causal association between urinary Na/K ratio and AD risk.

Background: Energy metabolism progressively deteriorates from a healthy state to non-alcoholic fatty liver disease (NAFLD), and circulating lipopolysaccharide (LPS) may contribute to this process. However, previous studies have analyzed healthy individuals and NAFLD patients together, leaving stage-specific associations unclear. Whether LPS and its surrogate marker, lipopolysaccharide-binding protein (LBP), show similar relationships during NAFLD development also remains unknown. This study evaluated the associations between plasma LPS and LBP concentrations with clinical parameters in healthy individuals and NAFLD patients. Methods: We conducted a cross-sectional study of 31 healthy individuals (median age [IQR]: 31 (26–43) years) and 31 NAFLD patients (59 (54–70) years). Plasma LPS and LBP concentrations and clinical parameters were measured. Correlations were assessed using Spearman’s rank analysis, followed by multivariate regression adjusting for age, sex, and BMI. Results: Plasma LPS and LBP concentrations were significantly higher in NAFLD patients compared to healthy individuals. Additionally, in the univariate regression analysis for all study participants, plasma LPS concentrations were correlated with obesity, blood pressure, liver function, lipid metabolism, and glucose metabolism. Plasma LBP concentrations were also correlated with age, obesity, blood pressure, liver function, lipid metabolism, glucose metabolism, and inflammatory cytokines. In healthy individuals, LPS correlated positively with triglycerides (TG), remaining significant after adjustment and exclusion of participants with any clinical test values outside the normal range. This association was not observed in NAFLD patients. Plasma LBP did not correlate with TG in either group; however, it was inversely associated with hepatic fat fraction in NAFLD patients, although this association was attenuated after adjusting for alanine aminotransferase. Conclusions: Plasma LPS correlates with TG even in clinically healthy individuals, suggesting LPS may influence lipid metabolism before NAFLD onset.

Recently, web-based dietary assessment tools for the targeted population have been developed and used to estimate the dietary intake level in several epidemiological studies. This study aimed to examine the validity of estimating energy and nutrient intake by the web-based 24 h dietary recall (Web24HR), which we developed for the Japanese population. Overall, 228 adults aged ≥20 years who agreed to participate were included. Web24HR was administered three times per person: twice within 3 weeks and once 3 months later. The data on 3-day weighed food records (WFR) at 3-month intervals in the four seasons were collected using the reference method. The intake of energy and nutrients between Web24HR and WFR were compared using Pearson’s correlation coefficients and the Bland–Altman analysis. As results, the correlations were moderate for both men (median r = 0.51) and women (median r = 0.38) except for iodine, retinol, retinol equivalents, and β-tocopherol. The Bland–Altman method revealed that the bias in intake was within ±10% for most nutrients, except for cholesterol, iodine, vitamin C, and the water content, in both sexes. Additionally, monounsaturated fatty acids in men and β-cryptoxanthin in women exhibited an underestimation of more than 10%. In conclusion, the Web24HR intake assessment showed moderate correlations for most nutrients in both sexes. The bias in intake was within ±10% for most nutrients, but there were discrepancies for some nutrients. This tool’s performance is comparable to Japan’s standard dietary exposure assessment methods and will be helpful for future applications in epidemiological studies, though caution is needed for certain nutrient assessments.

The present study involves the precise identification and safety evaluation of Enterococcus casseliflavus KB1733, previously identified using 16S rRNA analysis, through whole-genome sequencing, phenotypic analysis, and preclinical toxicity studies. Analyses based on the genome sequencing data confirm the identity of KB1733 as E. casseliflavus and show that the genes related to vancomycin resistance are only present on the chromosome, while no virulence factor genes are present on the chromosome or plasmid. Phenotypic analyses of antibiotic resistance and hemolytic activity also indicated no safety concerns. A bacterial reverse mutation test showed there was no increase in revertant colonies of heat-killed KB1733. An acute toxicity test employing heat-killed KB1733 at a dose of 2000 mg/kg body weight in rats resulted in no deaths and no weight gain or other abnormalities in the general condition of the animals, with renal depression foci and renal cysts only occurring at the same frequency as in the control. Taking the background data into consideration, the effects on the kidneys observed in the current study were not caused by KB1733. Our findings suggest that KB1733 is non-pathogenic to humans/animals, although further studies involving repeated oral toxicity tests and/or clinical tests are required.

It remains unclear how the various environmental factors are combined in practice to influence vegetable preferences in school-aged children. This study aimed to clarify the environmental factors during infancy and their association with vegetable preference in school-aged children. To find clusters of early childhood environmental factors, we conducted a factor analysis on 58 items related to early childhood environmental factors and a k-means cluster analysis using the factors obtained. The association of the extracted factors and clusters with vegetable preferences was assessed by multiple regression analysis. Twelve factors relating to vegetable eating, cooking and harvesting experience, and parental attitudes were extracted by factor analysis. Three clusters, “low awareness of experiences”, “high awareness” and “low positive encouragement”, were then extracted. In the multiple regression analysis, all 12 factors were found to be associated with vegetable preferences. Furthermore, it was found that the “high awareness” group had a significantly higher score for vegetable preference than the “low awareness of experiences” group (β = 0.56, 95% CI: 0.37–0.74). Thus, the study found that environmental factors during infancy, in isolation and combination, influenced vegetable preferences in school-aged children. Assessing the combination of various environmental factors during infancy may contribute to a better understanding of future vegetable preferences.

In a previous study, we demonstrated that the carotenoid neoxanthin was contained in young leafy vegetables including spinach and showed a fat accumulation inhibitory effect in vitro. To evaluate the bioavailability of neoxanthin, a raw young spinach leaf (100 g day^–1 for 4 weeks) intake test was performed on 14 participants (36.5 ± 8.0 years; male:female ratio = 9:5). Neoxanthin, neochrome, β–carotene, and lutein concentration in the spinach and blood of participants (before and after the test) was measured using high performance liquid chromatography. Neither neoxanthin nor neochrome was detected in the blood samples, whereas β–carotene and lutein concentration significantly increased (1.4– and 1.9–fold, respectively) during testing. Neoxanthin bioavailability in humans is low; thus, it is unlikely to have a fat accumulation inhibitory effect in vivo, contrary to the result in vitro. Ingesting the leafy vegetables raw can help maintain high neoxanthin levels, but it is not beneficial for neoxanthin bioavailability.

Daily dietary habits directly or indirectly influence the intestinal microbiota, and the resulting changes in its composition and metabolic activity alter the health conditions of the host. Although many studies have analyzed the association between individual nutrients/food items and intestinal microbiota, the assessment of the diet and intestinal microbiota from a macroscopic perspective has not yet been performed in Japan. Therefore, we focused on vegetables and fruits and aimed to identify dietary patterns of high intake of these foods and to examine their relationship with the intestinal microbiota. This cross-sectional study included 1019 healthy individuals aged ≥20 years in a rural area in northern Japan. Six dietary patterns were detected by factor analysis using the brief-type self-administered diet history questionnaire (BDHQ) data to identify the “vege pattern”, which was the dietary pattern rich in vegetables and fruits. Permutational multivariate analysis of variance revealed changes in β-diversity according to dietary patterns. In multivariable-adjusted models, the adherence to the vege pattern was positively correlated with α-diversity. This is the first study to reveal a correlation between intestinal microbiota and dietary habits rich in vegetables and fruits in a rural area of Japan.

The influx of intestinal bacteria-derived lipopolysaccharide (LPS) into the blood has attracted attention as a cause of diseases. The aim of this study is investigating the associations between the influx of LPS, dietary factors, gut microbiota, and health status in the general adult population. Food/nutrient intake, gut microbiota, health status and plasma LPS-binding protein (LBP; LPS exposure indicator) were measured in 896 residents (58.1% female, mean age 54.7 years) of the rural Iwaki district of Japan, and each correlation was analyzed. As the results, plasma LBP concentration correlated with physical (right/left arms’ muscle mass [β = −0.02, −0.03]), renal (plasma renin activity [β = 0.27], urine albumin creatinine ratio [β = 0.50]), adrenal cortical (cortisol [β = 0.14]), and thyroid function (free thyroxine [β = 0.05]), iron metabolism (serum iron [β = −0.14]), and markers of lifestyle-related diseases (all Qs < 0.20). Plasma LBP concentration were mainly negatively correlated with vegetables/their nutrients intake (all βs ≤ −0.004, Qs < 0.20). Plasma LBP concentration was positively correlated with the proportion of Prevotella (β = 0.32), Megamonas (β = 0.56), and Streptococcus (β = 0.65); and negatively correlated with Roseburia (β = −0.57) (all Qs < 0.20). Dietary factors correlated with plasma LBP concentration correlated with positively (all βs ≥ 0.07) or negatively (all βs ≤ −0.07) the proportion of these bacteria (all Qs < 0.20). Our results suggested that plasma LBP concentration in the Japanese general adult population was associated with various health issues, and that dietary habit was associated with plasma LBP concentration in relation to the intestinal bacteria.

様々な食シーンにおいて, しばしばトマトと組み合わせて摂取される食品としてチーズがある. そこで, チーズと組み合わせることによりトマトからのリコピン吸収率が向上するか否かを, 非盲検クロスオーバー比較試験にて検証した. 研究対象者に, トマトピューレーのみ (リコピン24mg) , またはトマトピューレーとチーズとを組み合わせたもの (リコピン 24mg, 脂質 19.5g) を単回摂取させ, 摂取0, 2, 4, 6, 9時間後の血清中及び血清におけるtriglyceride-rich lipoprotein fraction (TRL画分) 中のリコピン濃度を測定した. その結果, トマトピューレーのみを摂取した場合と比較して, トマトピューレーとチーズとを組み合わせて摂取した場合の方が, 血清中及び血清TRL画分中のリコピン濃度が有意に高値を示した. したがって, チーズと組み合わせることによりトマトからのリコピン吸収率が向上することが明らかとなった.

The association between lactic acid bacteria (LAB) and their immunostimulatory effects has attracted considerable attention; however, it remains unclear whether LAB can induce interferon-lambdas (IFN-λs) in human epithelial cells under conditions that do not mimic infection. In this study, we first employed a reporter assay to screen for a potential strain capable of inducing IFN-λ3 among 135 LAB strains derived from traditional Japanese pickles. Next, we assessed the strain’s ability to induce the expression of IFN-λ genes and interferon-stimulated genes (ISGs), and to produce IFN-λs. As a result, we screened and isolated Enterococcus casseliflavus KB1733 (KB1733) as a potential strain capable of inducing IFN-λ3 expression. Furthermore, we clarified that KB1733 induced the expression of IFN-λ genes and ISGs related to antiviral functions, and that KB1733 induced IFN-λ1 and -λ3 expression in a dose-dependent manner up to 10 μg/mL. In addition, KB1733 significantly increased IFN-λ1 production compared to Enterococcus casseliflavus JCM8723^T, which belongs to the same genera and species as KB1733. In conclusion, we isolated a unique LAB strain from traditional Japanese pickles that is capable of stimulating IFN-λ production, although further study is needed to investigate how KB1733 protects against viruses in mice and humans.