Relationship Between Plasma Lipopolysaccharides, Gut Microbiota, and Dementia: A Cross-Sectional Study.

BACKGROUND: Previous studies have demonstrated associations between gut microbiota, microbial metabolites, and cognitive decline. However, relationships between these factors and lipopolysaccharides (LPS; molecules of the outer membrane of gram-negative bacteria) remain controversial. OBJECTIVE: To evaluate associations between plasma LPS, gut microbiota, and cognitive function. METHODS: We performed a cross-sectional sub-analysis of data of 127 participants (women: 58%, mean age: 76 years) from our prospective cohort study regarding the relationship between gut microbiota and cognitive function. We enrolled patients who visited our memory clinic and assessed demographics, dementia-related risk factors, cognitive function, brain imaging, gut microbiomes, and microbial metabolites. We evaluated relationships between cognitive decline and plasma LPS using multivariable logistic regression analyses. RESULTS: Plasma LPS concentration increased with increasing degree of cognitive decline and total cerebral small vessel disease (SVD) score (Kruskal-Wallis test; p = 0.016 and 0.007, respectively). Participants with high plasma LPS concentrations tended to have lower concentrations of gut microbial metabolites, such as lactic acid and acetic acid, and were less likely to consume fish and shellfish (44.7% versus 69.6%, p = 0.027) than those with low plasma LPS concentrations. Multivariable analyses revealed that plasma LPS concentration was independently associated with the presence of mild cognitive impairment in participants without dementia (odds ratio: 2.09, 95% confidence interval: 1.14-3.84, p = 0.007). CONCLUSION: In this preliminary study, plasma LPS concentration was associated with both cognitive decline and cerebral SVD and significantly correlated with beneficial gut microbial metabolites. Plasma LPS may be a risk factor for cognitive decline.

Relationship Between Plasma Neurofilament Light Chain, Gut Microbiota, and Dementia: A Cross-Sectional Study.

BACKGROUND: Previous studies have demonstrated associations between gut microbiota, microbial metabolites, and cognitive decline. However, relationships between these factors and neurofilament light chain (NfL; a disease-nonspecific biomarker of neural damage) remain controversial. OBJECTIVE: To evaluate the associations between plasma NfL, gut microbiota, and cognitive function. METHODS: We performed a cross-sectional sub-analysis of data from our prospective cohort study that was designed to investigate the relationship between gut microbiota and cognitive function. Patients who visited our memory clinic were enrolled and demographics, dementia-related risk factors, cognitive function, brain imaging, gut microbiomes, and microbial metabolites were assessed. We evaluated the relationships between the gut microbiome, microbial metabolites, and plasma NfL. Moreover, the relationships between plasma NfL and cognitive function were assessed using multivariable logistic regression analyses. RESULTS: We analyzed 128 participants (women: 59%, mean age: 74 years). Participants with high (above the median) plasma NfL concentrations tended to be older, women, and hypertensive and have a history of stroke, chronic kidney disease, and dementia. Plasma NfL was also associated with cerebral small vessel disease. However, plasma NfL levels were not significantly correlated with gut microbial metabolites. Multivariable analyses revealed that a higher plasma NfL concentration was independently associated with the presence of dementia (odds ratio: 9.94, 95% confidence interval: 2.75-48.2, p < 0.001). CONCLUSION: High plasma NfL concentration was independently associated with the presence of dementia as previously reported. However, plasma NfL levels were not significantly correlated with gut microbial metabolites in this preliminary study.

Relationship between the Japanese-style diet, gut microbiota, and dementia: A cross-sectional study.

OBJECTIVE: Previous studies have shown associations between the gut microbiota, microbial metabolites, and cognitive decline. However, the effect of the dietary composition on such associations has not been fully investigated. The aims of this study were to evaluate the relationships between adherence to a Japanese-style diet, the gut microbiota, and cognitive decline. Furthermore, we aimed to evaluate the three forms of the Japanese diet index (JDI; the conventional [JDI9], updated [JDI12], and a newly modified JDI) to determine which would show the closest relationships with cognition and the gut microbiota. METHODS: We performed a cross-sectional subanalysis of data from a prospective hospital-based cohort study. We assessed the patients' demographic characteristics, dietary composition, risk factors, cognitive function, brain imaging, gut microbiome, and microbial metabolites. On the basis of previous studies, a nine-component traditional JDI (JDI9), a 12-component modern JDI (JDI12), and a 12-component revised JDI (rJDI12), were defined. We evaluated the relationships between the JDI scores, cognitive function, and the gut microbiome and microbial metabolites using multivariable logistic regression analyses. RESULTS: We analyzed data from 85 eligible participants (61% women; mean age: 74.6 ± 7.4 y). Compared with participants who had dementia, those without dementia were more likely to consume foods in the JDI12, including fish and shellfish (64.5 versus 39.1%, P = 0.048), mushrooms (61.3 versus 30.4%, P = 0.015), soybeans and soybean-derived foods (62.9 versus 30.4%, P = 0.013), and coffee (71 versus 43.5%, P = 0.024). There were non-significant trends toward lower fecal concentrations of gut microbial metabolites in participants with a more traditional Japanese diet. Participants with dementia had lower JDI scores than those without dementia (dementia versus non-dementia, median JDI9 score: 5 versus 7, P = 0.049; JDI12: 7 versus 8, P = 0.017; and rJDI12: 7 versus 9, P = 0.006, respectively). CONCLUSIONS: Adherence to a traditional Japanese diet was found to be inversely associated with cognitive decline and tended to be associated with lower concentrations of gut microbial metabolites.

Dietary oleic acid contributes to the regulation of food intake through the synthesis of intestinal oleoylethanolamide.

Introduction: Among the fatty acid ethanolamides (FAEs), oleoylethanolamide (OEA), linoleoylethanolamide (LEA), and palmitoylethanolamide (PEA) are reported to be involved in feeding regulation. In particular, OEA is well characterized as a satiety signal. Following food consumption, OEA is synthesized from oleic acid (OA) via an N-acyl phosphatidylethanolamine-specific phospholipase D-dependent pathway in the gastroenterocytes, and OEA induces satiety by recruiting sensory fibers. Thus, we hypothesized that dietary OA is an important satiety-inducing molecule. However, there has been no direct demonstration of the effect of dietary OA on satiety induction without the influence of the endogenous biosynthesis of OA from stearic acid (SA) or other FAEs. Methods: In this study, we used two experimental diets to test our hypothesis: (i) an OA diet (OAD; 38.4 mg of OA/g and 7.2 mg of SA/g) and (ii) a low OA diet (LOAD; 3.1 mg of OA/g and 42.4 mg of SA/g). Results: Relative to mice fed the OAD, mice fed the LOAD for two weeks exhibited reduced levels of jejunal OEA but not jejunal LEA and PEA. The LOAD-fed mice showed an increase in food intake and body weight gain. Moreover, LOAD-induced increase in food intake was immediately observed after the switch from the OAD, whereas these effects were diminished by the switch back to the OAD. Furthermore, treatment with OA and OEA diminished the effects of LOAD on food intake. Conclusion: Collectively, these results show that dietary OA is a key factor in the reduction of food intake and increase in satiety mediated by OEA signaling.

Embryonal erythropoiesis and aging exploit ferroptosis.

Ferroptosis is a form of regulated cell necrosis, as a consequence of Fe(II)-dependent lipid peroxidation. Although ferroptosis has been linked to cancer cell death, neurodegeneration and reperfusion injury, physiological roles of ferroptosis have not been elucidated to date mostly due to the lack of appropriate methodologies. Here, we show that 4-hydroxy-2-nonenal (HNE)-modified proteins detected by a HNEJ-1 mouse monoclonal antibody is a robust immunohistochemical technology to locate ferroptosis in tissues in combination with morphological nuclear information, based on various models of ferroptosis, including erastin-induced cysteine-deprivation, conditional Gpx4 knockout and Fe(II)-dependent renal tubular injury, as well as other types of regulated cell death. Specificity of HNEJ-1 with ferroptosis was endorsed by non-selective identification of HNE-modified proteins in an Fe(II)-dependent renal tubular injury model. We further comprehensively searched for signs of ferroptosis in different developmental stages of Fischer-344 rats from E9.5-2.5 years of age. We observed that there was a significant age-dependent increase in ferroptosis in the kidney, spleen, liver, ovary, uterus, cerebellum and bone marrow, which was accompanied by iron accumulation. Not only phagocytic cells but also parenchymal cells were affected. Epidermal ferroptosis in ageing SAMP8 mice was significantly promoted by high-fat or carbohydrate-restricted diets. During embryogenesis of Fischer-344 rats, we found ferroptosis in nucleated erythrocytes at E13.5, which disappeared in enucleated erythrocytes at E18.5. Administration of a ferroptosis inhibitor, liproxstatin-1, significantly delayed erythrocyte enucleation. Therefore, our results demonstrate for the first time the involvement of ferroptosis in physiological processes, such as embryonic erythropoiesis and aging, suggesting the evolutionally acquired mechanism and the inevitable side effects, respectively.

The Association between Cerebral Small Vessel Disease and the Gut Microbiome: A Cross-Sectional Analysis.

BACKGROUND: Recent studies have demonstrated an association between the gut microbiome and cognitive function. However, the associations between the gut microbiome and brain parenchyma damage, and their underlying mechanisms, remain unclear. MATERIALS AND METHODS: We performed a cross-sectional sub-analysis using data from our prospective cohort study to determine the association between the gut microbiome and cerebral small vessel disease (SVD). We assessed patient demographics, risk factors, cognitive function, brain imaging, voxel-based specific regional analysis system for Alzheimer's Disease (VSRAD, indicating brain atrophy), and the gut microbiome as indicated by enterotypes and faecal microbiome metabolites. We then analysed the associations between total SVD scores, cognitive function, and the gut microbiome. RESULTS: We analysed data from 87 patients without dementia or a history of stroke, 64 of whom exhibited mild cognitive impairment. Higher total SVD scores were associated with cognitive decline and behavioural and psychological symptoms. Compared with all other patients, patients with enterotype I (Bacteroides >30%) were more likely to have cognitive decline (median scores: Mini-Mental State Examination, 25 vs. 27, P = 0.047; Clinical Dementia Rating-Sum of Boxes, 1.5 vs. 0.5, P = 0.002) and present with cerebral SVD and high VSRAD scores (1.01 vs. 0.57, P = 0.012). Furthermore, faecal metabolites were significantly higher in patients with higher total SVD scores compared with those with lower scores. Multivariable logistic regression analyses indicated that certain gut microbiomes may double the risk of white matter hyperintensity. CONCLUSIONS: The gut microbiome is associated with cerebral SVD.

CYP4F13 is the Major Enzyme for Conversion of alpha-Eleostearic Acid into cis-9, trans-11-Conjugated Linoleic Acid in Mouse Hepatic Microsomes.

Our previous studies have shown that α-eleostearic acid (α-ESA; cis-9, trans-11, trans-13 (c9,t11,t13)-conjugated linolenic acid (CLnA)) is converted into c9,t11-conjugated linoleic acid (CLA) in rats. Furthermore, we have demonstrated that the conversion of α-ESA into CLA is a nicotinamide adenine dinucleotide phosphate (NADPH)-dependent enzymatic reaction, which occurs mostly in the rat liver. However, the precise metabolic pathway and enzyme involved have not been identified yet. Therefore, in this study we aimed to determine the role of cytochrome P450 (CYP) in the conversion of α-ESA into c9,t11-CLA using an in vitro reconstitution system containing mouse hepatic microsomes, NADPH, and α-ESA. The CYP4 inhibitors, 17-ODYA and HET0016, performed the highest level of inhibition of CLA formation. Furthermore, the redox partner cytochrome P450 reductase (CPR) inhibitor, 2-chloroethyl ethyl sulfide (CEES), also demonstrated a high level of inhibition. Thus, these results indicate that the NADPH-dependent CPR/CYP4 system is responsible for CLA formation. In a correlation analysis between the specific activity of CLA formation and Cyp4 family gene expression in tissues, Cyp4a14 and Cyp4f13 demonstrated the best correlations. However, the CYP4F substrate prostaglandin A1 (PGA1) exhibited the strongest inhibitory effect on CLA formation, while the CYP4A and CYP4B1 substrate lauric acid had no inhibitory effect. Therefore, we conclude that the CYP4F13 enzyme is the major enzyme involved in CLA formation. This pathway is a novel pathway for endogenous CLA synthesis, and this study provides insight into the potential application of CLnA in functional foods.

Japanese mushroom consumption alters the lipid metabolomic profile of high-fat diet-fed mice.

Mushrooms are familiar ingredients in Japanese cuisine and large numbers are consumed in Japan. Recently, we reported that the consumption of Japanese mushrooms suppressed the accumulation of visceral fat. The purpose of this study was to examine the alteration of lipid metabolism by Japanese mushrooms consumption in high-fat diet (HFD) mice. Multivariate analysis of serum, liver, adipose tissue, cecal contents, large intestinal and fecal lipids showed differing compositions in the mice that had consumed HFD or HFD supplemented with 3% freeze-dried mushroom mixture (HFMD). There were higher concentrations of diacylglycerol in the adipose tissue, non-esterified fatty acids in the serum, and triacylglycerol in the feces of the HFMD group. These results suggest that mushroom consumption promotes the degradation of lipids in visceral fat and limits the absorption of food lipids. Moreover, the HFMD group demonstrated higher concentrations of phospholipids, some of which contained odd-chain fatty acids. Thus, we speculated that the alteration of lipid metabolism in mice such that mushroom consumption prevent obesity progression, as demonstrated by metabolomic analysis.

Relationship between dementia and gut microbiome-associated metabolites: a cross-sectional study in Japan.

Dysregulation of the gut microbiome is associated with dementia. However, the relationship between microbiome-associated metabolites and dementia has yet to be identified. Outpatients visiting a memory clinic in Japan enrolled in this cross-sectional study; 107 subjects were eligible for the study, 25 of which had dementia. We collected demographics, activities of daily living, risk factors, cognitive function, and brain imaging data. The gut microbiome was assessed using terminal restriction fragment length polymorphism analysis. Concentrations of faecal metabolite were measured. We used multivariable logistic regression analyses to identify whether metabolites were independently related to dementia. The concentrations of metabolites were significantly different between subjects with and those without dementia. Every 1 standard deviation increment in faecal ammonia concentration was associated with around a 1.6-fold risk for the presence of dementia. A higher faecal lactic acid concentration was related to a lower risk of dementia, by around 60%. A combination of higher faecal ammonia and lactic acid concentrations was indicative of the presence of dementia, and had a similar predictive value as traditional biomarkers of dementia. Thus, faecal ammonia and lactic acid are related to dementia, independently of the other risk factors for dementia and dysregulation of the gut microbiome.

The 1975 type Japanese diet improves the gut microbial flora and inhibits visceral fat accumulation in mice.

In this study, the 1975 type Japanese diet was prepared and its effects and related mechanism were examined in mice. Mice were assigned to three experimental groups, the CD group fed a control diet, the MD group fed a modern Japanese diet (MD), and the JD group fed the 1975 type Japanese diet (JD) for 4 weeks. MD and JD were low protein, high fat, and high carbohydrate diets compared to the CD. Total white adipose tissue weights were significantly increased in the MD group compared to those in the CD group and were decreased in the JD group compared to those in the MD group. In the JD group, adipocyte hypertrophy was inhibited and Hsl mRNA expression was enhanced in epididymal adipose tissue and the number of bacteria associated with the production of short chain fatty acids was increased. Therefore, the JD inhibits lipid accumulation in white adipose tissue. ABBREVIATIONS: Actb: ß-actin; ALT: alanine aminotransferase; ANOVA: analyses of variance; AST: aspartate aminotransferase; Fas: fatty acid synthase; G6pdx: glucose 6-phosphate dehydrogenase; HE: hematoxylin and eosin; HOMA-IR: Homeostatic model assessment for insulin resistance; Hsl: hormone-sensitive lipase; JD: 1975 type Japanese diet; Leptin: leptin; MD: modern Japanese diet; Me: malic enzyme; NEFA: non-esterified fatty acids; PL: phospholipids; Pparδ: peroxisome proliferator-activated receptor delta; Pparγ: peroxisome proliferator-activated receptor gamma; qRT-PCR: quantitative reverse transcriptase polymerase chain reaction; SAMP8: senescence-accelerated prone 8; SEM: standard error of the mean; Srebp1c: Sterol regulatory element binding protein 1c; TBARS: thiobarbituric acid reactive substance; TC: total cholesterol; TG: Triacylglycerol; V3: variable regions 3.

Carbohydrate-restricted diet alters the gut microbiota, promotes senescence and shortens the life span in senescence-accelerated prone mice.

This study examined the effects of a carbohydrate-restricted diet on aging, brain function, intestinal bacteria and the life span to determine long-term carbohydrate-restriction effects on the aging process in senescence-accelerated prone mice (SAMP8). Three-week-old male SAMP8 were divided into three groups after a week of preliminary feeding. One group was given a controlled diet, while the others fed on high-fat and carbohydrate-restricted diets, respectively. The mice in each group were further divided into two subgroups, of which one was the longevity measurement group. The other groups fed ad libitum until the mice were 50 weeks old. Before the test period termination, passive avoidance test evaluated the learning and memory abilities. Following the test period, serum and various mice organs were obtained and submitted for analysis. The carbohydrate-restricted diet group exhibited significant decrease in the survival rate as compared to the other two diet groups. The passive avoidance test revealed a remarkable decrease in the learning and memory ability of carbohydrate-restricted diet group as compared to the control-diet group. Measurement of lipid peroxide level in tissues displayed a marked increase in the brain and spleen of carbohydrate-restricted diet group than the control-diet and high-fat diet groups. Furthermore, notable serum IL-6 and IL-1ß level (inflammation indicators) elevations, decrease in Enterobacteria (with anti-inflammatory action), increase in inflammation-inducing Enterobacteria and lowering of short-chain fatty acids levels in cecum were observed in the carbohydrate-restricted diet group. Hence, carbohydrate-restricted diet was revealed to promote aging and shortening of life in SAMP8.

Japanese diet and survival time: The Ohsaki Cohort 1994 study.

BACKGROUND & AIMS: Although it has been suggested that the Japanese diet contributes to the longevity of the Japanese population, no study has examined the association between the Japanese diet and survival time. The present study investigated the association between the Japanese diet and survival time. METHODS: We analyzed 20-year follow-up data from a cohort study of 14,764 Japanese men and women aged 40-79 years. At the baseline survey in 1994, we collected dietary information using a validated 40-item food frequency questionnaire. Adherence to a Japanese diet consisting of nine components (rice, miso soup, seaweeds, pickles, green and yellow vegetables, fish, green tea, beef and pork, and coffee) was assessed in terms of a Japanese dietary index (JDI) score, the total score ranging from 0 to 9. Cox proportional hazards model and Laplace regression analysis were used to estimate the hazard ratios (HRs) and differences in median age at death (50th percentile differences - PDs in age at death) with 95% confidence intervals (CIs) according to the quartiles of the JDI score. RESULTS: During the follow-up period, we documented 4,619 deaths. We observed that a higher JDI score was associated with a lower risk of mortality and longer survival time: In comparison to participants in the lowest JDI score quartile (0-4), the multivariate-adjusted HR (95% CI) of all-cause mortality was 0.91 (0.83-0.99) and the multivariate-adjusted 50th PD in age at death (95% CI) was 10.2 (3.2-17.2) months longer for those in the highest quartile (7-9). CONCLUSIONS: Adherence to a Japanese diet is associated with a longer survival time.

Mushroom consumption and incident risk of prostate cancer in Japan: A pooled analysis of the Miyagi Cohort Study and the Ohsaki Cohort Study.

In vivo and in vitro evidence has shown that mushrooms have the potential to prevent prostate cancer. However, the relationship between mushroom consumption and incident prostate cancer in humans has never been investigated. In the present study, a total of 36,499 men, aged 40-79 years, who participated in the Miyagi Cohort Study in 1990 and in the Ohsaki Cohort Study in 1994 were followed for a median of 13.2 years. Data on mushroom consumption (categorized as <1, 1-2 and ≥3 times/week) was collected using a validated food frequency questionnaire. Cox proportional hazards regression analysis was used to estimate multivariate hazard ratios (HRs) and 95% confidence intervals (CIs) for prostate cancer incidence. During 574,397 person-years of follow-up, 1,204 (3.3%) cases of prostate cancer were identified. Compared to participants with mushroom consumption <1 time/week, frequent mushroom intake was associated with a decreased risk of prostate cancer (1-2 times/week: HRs [95% CIs] = 0.92 [0.81, 1.05]; ≥3 times/week: HRs [95% CIs] = 0.83 [0.70, 0.98]; p-trend = 0.023). This inverse relationship was especially obvious among participants aged ≥50 years and did not differ by clinical stage of cancer and intake of vegetables, fruit, meat and dairy products. The present study showed an inverse relationship between mushroom consumption and incident prostate cancer among middle-aged and elderly Japanese men, suggesting that habitual mushroom intake might help to prevent prostate cancer.

The relationship between the gut microbiome and mild cognitive impairment in patients without dementia: a cross-sectional study conducted in Japan.

Recent studies have revealed an association between the dysregulation of the gut microbiome and dementia. However, whether this dysregulation is associated with mild cognitive impairment (MCI), an early stage of cognitive decline, in patients without dementia remains unclear. We performed a cross-sectional analysis to determine the association between the gut microbiome and MCI. Data, including patient demographics, risk factors, cognitive function, and brain imaging, were collected. The gut microbiome was assessed through terminal restriction fragment length polymorphism analysis. Multivariable logistic regression models were used to identify factors independently associated with MCI. Graphical modelling was used to illustrate mutual associations between MCI and identified factors. We analysed 82 patients, 61 of whom exhibited MCI. Patients with MCI had a higher prevalence of Bacteroides. Furthermore, patients with more Bacteroides were more likely to present with white matter hyperintensity and high voxel-based specific regional analysis system for Alzheimer's Disease (VSRAD) scores, indicating cortical and hippocampal atrophy. A multivariable logistic regression analysis revealed that a greater prevalence of Bacteroides was independently associated with MCI. Graphical modelling also showed a close association between Bacteroides and MCI. In conclusion, an increased prevalence of Bacteroides is independently associated with the presence of MCI in patients without dementia.

The Effect of Carbohydrate-Restricted Diets on the Skin Aging of Mice.

Low-carbohydrate, high-protein diets, known as carbohydrate-restricted diets, are in contrast to the carbohydrate-centric meals typical of the Japanese diet. Carbohydrate-restricted diets were reported to reduce visceral fat, owing to which they have attracted attention and been widely implemented. If, as proposed, carbohydrate-restricted diets are effective in delaying senescence, then Japanese diets have a hidden potential to evolve further. However, long-term carbohydrate restriction in mice was reported to have a negative effect on the cardiovascular system, with shortening of lifespan due to activation of mechanistic target of rapamycin (mTOR). As a result, the safety of long-term adherence to carbohydrate-restricted diets remains doubtful. Recently, we conducted a study using senescence-accelerated mouse-prone 8 (SAMP8) mice to examine the effects of a carbohydrate-restricted diet on aging and skin senescence, and to determine the effect of long-term carbohydrate restriction on the aging process in mice. Here, we discuss the safety of long-term carbohydrate restriction based on the findings obtained from animal studies.

The Japanese Dietary Pattern Is Associated with Longer Disability-Free Survival Time in the General Elderly Population in the Ohsaki Cohort 2006 Study.

BACKGROUND: Epidemiologic observations have raised expectations that the Japanese dietary pattern could promote longer disability-free survival (DFS) times among the Japanese population; however, no previous study has examined this issue. OBJECTIVE: The aim of this study was to investigate the association between the Japanese dietary pattern and DFS time in the elderly Japanese population. METHODS: We analyzed follow-up data covering a 10-y period for 9456 elderly Japanese individuals (aged ≥65 y) participating in a community-based prospective cohort study. Dietary habits were assessed using a food-frequency questionnaire. Based on previous studies, we used 9 food items to calculate the Japanese Diet Index (JDI) score: rice, miso soup, fish and shellfish, green and yellow vegetables, seaweed, pickled vegetables, green tea (1 point for each item if the consumption value was more than or equal to the median, and 0 points otherwise), beef and pork, and coffee (0 points for each item if the consumption value was more than or equal to the median, and 1 point otherwise). Differences in median age at incident disability or death [50th percentile differences (PDs)] according to quartiles (Q1-Q4) of the JDI score were estimated using Laplace regression. RESULTS: During the follow-up period, 4233 (44.8%) incident disability or death events occurred. In addition, a higher JDI score was significantly associated with longer DFS time: compared with the lowest quartile of JDI scores (Q1), the multivariate-adjusted 50th PD (95% CI) was 7.1 (1.8, 12.4) mo longer for Q4. Each 1-SD increase of the JDI score was associated with 3.7 (1.7, 5.7) additional months of life without disability (P-trend < 0.01). No differences were seen in sex or chronic condition (no or ≥1 chronic condition) at baseline. A post hoc analysis showed a larger effect on DFS time when using a modified JDI score without coffee. CONCLUSION: These results suggest that the Japanese dietary pattern is associated with improved DFS time in the general elderly population.

Abdominal Fat in Individuals with Overweight Reduced by Consumption of a 1975 Japanese Diet: A Randomized Controlled Trial.

OBJECTIVE: This study aimed to investigate whether the intake of the 1975 Japanese diet (JD) could reduce the amount of abdominal fat in people with overweight. METHODS: Using a single-blind randomized controlled trial, the modern diet (MD) was compared with the 1975-type JD, which is based on the MD but includes five characteristics of the 1975 JD in an enhanced form. Overweight people were randomly assigned to an MD group (n = 30) and a JD group (n = 30). The participants consumed test diets that were provided three times a day for 28 days. Body composition measurements and blood biochemical examinations were performed before and after the test diet intake, and the proportions of change were compared. RESULTS: Those in the JD group had significantly decreased BMI, fat mass, and levels of low-density lipoprotein cholesterol, glycated hemoglobin, and C-reactive protein (P = 0.002, 0.015, 0.014, 0.012, and 0.039, respectively) and significantly increased high-density lipoprotein cholesterol levels compared with those in the MD group (P = 0.020). CONCLUSIONS: The intake of a diet with the characteristics of the 1975 JD may have beneficial effects on lipid metabolism in people with overweight and reduce the onset risk of metabolism-related disorders, such as obesity and diabetes.

Miso (Fermented Soybean Paste) Suppresses Visceral Fat Accumulation in Mice, Especially in Combination with Exercise.

We investigated whether the difference in miso consumption between the Japanese diets of 1975 and 2010 has influenced the observed increase in diet-induced obesity. To recreate the 2010 and 1975 Japanese high-fat diets with the corresponding proportions of miso, freeze-dried miso was added to high-fat mouse feed at 1.6% and 2.6%, respectively. When 5-week-old male Institute of Cancer Research (ICR) mice were provided each of these diets ad libitum for 8 weeks, it was found that the white adipose tissue weight and adipocyte area were lower in mice receiving the 1975 diet than in those receiving the 2010 diet. Therefore, high miso consumption is one reason why the 1975 Japanese diet tended to not lead to obesity. Next, the combined effects of treadmill exercise and miso consumption were investigated. The mice were divided into three groups, which were provided either a high-fat diet (group C), a high-fat diet with exercise (group C + E), or a miso-supplemented high-fat diet with exercise (group M + E) for 8 weeks. In this experiment, the white adipose tissue weight and adipocyte area in group M + E were lower than in group C. When the mRNA expression of lipid metabolism-associated genes in adipose tissue was measured, we found that expression of Hsl (lipase, hormone sensitive), which is involved in lipolysis, and Pparγ (peroxisome proliferator activated receptor gamma), which regulates adipocyte differentiation upstream of Hsl, was increased in group M + E. These results clearly demonstrated that lipid accumulation in the adipose tissues is suppressed by miso consumption in combination with exercise.

Analysis of the relationship between the gut microbiome and dementia: a cross-sectional study conducted in Japan.

Dysregulation of the gut microbiome is associated with several life-threatening conditions and thus might represent a useful target for the prevention of dementia. However, the relationship between the gut microbial population and dementia has not yet been fully clarified. We recruited outpatients visiting our memory clinic to participate in this study. Information on patient demographics, risk factors, and activities of daily living was collected, and cognitive function was assessed using neuropsychological tests and brain magnetic resonance imaging scans. Faecal samples were obtained, and the gut microbiome was assessed by terminal restriction fragment length polymorphism (T-RFLP) analysis, one of the most well-established and reliable 16S ribosomal RNA-based methods for classifying gut microbiota. Patients were divided into two groups, demented and non-demented. Multivariable logistic regression models were used to identify the variables independently associated with dementia. The T-RFLP analysis revealed differences in the composition of the gut microbiome: the number of Bacteroides (enterotype I) was lower and the number of 'other' bacteria (enterotype III) was higher in demented than non-demented patients. Multivariable analyses showed that the populations of enterotype I and enterotype III bacteria were strongly associated with dementia, independent of the traditional dementia biomarkers. Further studies of the metabolites of gut microbes are needed to determine the mechanism underlying this association.