Explore the vast range of titles available.

The gut microbiome is an important determinant in various diseases. Here we perform a cross-sectional study of Japanese adults and identify the Blautia genus, especially B. wexlerae , as a commensal bacterium that is inversely correlated with obesity and type 2 diabetes mellitus. Oral administration of B. wexlerae to mice induce metabolic changes and anti-inflammatory effects that decrease both high-fat diet–induced obesity and diabetes. The beneficial effects of B. wexlerae are correlated with unique amino-acid metabolism to produce S-adenosylmethionine, acetylcholine, and l -ornithine and carbohydrate metabolism resulting in the accumulation of amylopectin and production of succinate, lactate, and acetate, with simultaneous modification of the gut bacterial composition. These findings reveal unique regulatory pathways of host and microbial metabolism that may provide novel strategies in preventive and therapeutic approaches for metabolic disorders. Here, the authors inversely associate Blautia wexlerae with obesity and type 2 diabetes mellitus in humans and further show that administration of B. wexlerae to mice decrease both high-fat diet–induced obesity and diabetes via modulating gut microbial metabolism.

Atherosclerosis is a chronic inflammatory disease associated with macrophage aggregate and transformation into foam cells. In this study, we sought to investigate the impact of dietary intake of ω3 fatty acid on the development of atherosclerosis, and demonstrate the mechanism of action by identifying anti-inflammatory lipid metabolite. Mice were exposed to a high-fat diet (HFD) supplemented with either conventional soybean oil or α-linolenic acid-rich linseed oil. We found that as mice became obese they also showed increased pulsatility and resistive indexes in the common carotid artery. In sharp contrast, the addition of linseed oil to the HFD improved pulsatility and resistive indexes without affecting weight gain. Histological analysis revealed that dietary linseed oil inhibited foam cell formation in the aortic valve. Lipidomic analysis demonstrated a particularly marked increase in the eicosapentaenoic acid-derived metabolite 12-hydroxyeicosapentaenoic acid (12-HEPE) in the serum from mice fed with linseed oil. When we gave 12-HEPE to mice with HFD, the pulsatility and resistive indexes was improved. Indeed, 12-HEPE inhibited the foamy transformation of macrophages in a peroxisome proliferator-activated receptor (PPAR)γ-dependent manner. These results demonstrate that the 12-HEPE-PPARγ axis ameliorates the pathogenesis of atherosclerosis by inhibiting foam cell formation.

The metabolism and generation of bioactive lipid mediators are key events in the exertion of the beneficial effects of dietary omega-3 fatty acids in the regulation of allergic inflammation. Here, we found that dietary linseed oil, which contains high amounts of alpha-linolenic acid (ALA) dampened allergic rhinitis through eosinophilic production of 15-hydroxyeicosapentaenoic acid (15-HEPE), a metabolite of eicosapentaenoic acid (EPA). Lipidomic analysis revealed that 15-HEPE was particularly accumulated in the nasal passage of linseed oil-fed mice after the development of allergic rhinitis with the increasing number of eosinophils. Indeed, the conversion of EPA to 15-HEPE was mediated by the 15-lipoxygenase activity of eosinophils. Intranasal injection of 15-HEPE dampened allergic symptoms by inhibiting mast cell degranulation, which was mediated by the action of peroxisome proliferator-activated receptor gamma. These findings identify 15-HEPE as a novel EPA-derived, and eosinophil-dependent anti-allergic metabolite, and provide a preventive and therapeutic strategy against allergic rhinitis.

Dietary ω3 fatty acids have important health benefits and exert their potent bioactivity through conversion to lipid mediators. Here, we demonstrate that microbiota play an essential role in the body's use of dietary lipids for the control of inflammatory diseases. We found that amounts of 10-hydroxy-cis-12-cis-15-octadecadienoic acid (αHYA) and 10-oxo-cis-12-cis-15-octadecadienoic acid (αKetoA) increased in the feces and serum of specific-pathogen-free, but not germ-free, mice when they were maintained on a linseed oil diet, which is high in α-linolenic acid. Intake of αKetoA, but not αHYA, exerted anti-inflammatory properties through a peroxisome proliferator-activated receptor (PPAR)γ-dependent pathway and ameliorated hapten-induced contact hypersensitivity by inhibiting the development of inducible skin-associated lymphoid tissue through suppression of chemokine secretion from macrophages and inhibition of NF-κB activation in mice and cynomolgus macaques. Administering αKetoA also improved diabetic glucose intolerance by inhibiting adipose tissue inflammation and fibrosis through decreased macrophage infiltration in adipose tissues and altering macrophage M1/M2 polarization in mice fed a high-fat diet. These results collectively indicate that αKetoA is a novel postbiotic derived from α-linolenic acid, which controls macrophage-associated inflammatory diseases and may have potential for developing therapeutic drugs as well as probiotic food products.

Dietary plant lignans are converted inside the gut to enterolignans enterodiol (ED) and enterolactone (EL), which have several biological functions, and health benefits. In this study, we characterized the gut microbiome composition associated with enterolignan production using data from a cross-sectional study in the Japanese population. We identified enterolignan producers by measuring ED and EL levels in subject’s serum using liquid chromatography-tandem mass spectrometry. Enterolignan producers show more abundant proportion of Ruminococcaceae and Lachnospiraceae than non-enterolignan producers. In particular, subjects with EL in their serum had a highly diverse gut microbiome that was rich in Ruminococcaceae and Rikenellaceae. Moreover, we built a random forest classification model to classify subjects to either EL producers or not using three characteristic bacteria. In conclusion, our analysis revealed the composition of gut microbiome that is associated with lignan metabolism. We also confirmed that it can be used to classify the microbiome ability to metabolize lignan using machine learning approach.

The effects of docosahexaenoic acid supplements on cognitive function have long been demonstrated, but the effects of alpha-linolenic acid, a precursor of docosahexaenoic acid, have not been fully tested. The search for functional foods that delay cognitive decline in the older adults is considered a very important area from a preventive perspective. The aim of this study was to conduct an exploratory evaluation of alpha-linolenic acid on various cognitive functions in healthy older subjects. Sixty healthy older adults aged 65 to 80 years, living in Miyagi prefecture, without cognitive impairment or depression, were included in the randomized, double-blinded, placebo-controlled clinical trial. Study subjects were randomly divided into two groups and received either 3.7 g/day of flaxseed oil containing 2.2 g of alpha-linolenic acid, or an isocaloric placebo (corn oil) containing 0.04 g of alpha-linolenic acid for 12 weeks. The primary endpoints were six cognitive functions closely related to everyday life: attention and concentration, executive function, perceptual reasoning, working memory, processing speed and memory function. After 12 weeks of intake, changes in verbal fluency scores on the frontal assessment battery at bedside, a neuropsychological test assessing executive function, in which participants are asked to answer as many words as possible in Japanese, were significantly greater in the intervention group (0.30 ± 0.53) than in the control group (0.03 ± 0.49, p < 0.05). All other cognitive test scores were not significantly different between the groups. In conclusion, daily consumption of flaxseed oil containing 2.2 g alpha-linolenic acid improved cognitive function, specifically verbal fluency, despite the age-related decline, in healthy individuals with no cognitive abnormalities. Further validation studies focusing on the effects of alpha-linolenic acid on verbal fluency and executive function in older adults are needed, as verbal fluency is a predictor of Alzheimer’s disease development, important for cognitive health.

Adiposity rebound (AR) corresponds to the start of the second rise in the body mass index curve during infant growth. Early AR (before age 5) confers increased risk of adiposity and metabolic disorders but is less likely to occur in breastfed infants. Although lipids in breast milk are important in child growth, information is limited regarding which lipids are involved in AR. The object of this study was to explore the association between breast milk lipids and AR status in children. We designed a case-control study of 184 mother–child pairs (AR cases: n = 93; controls: n = 91) included from the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. Breast milk was collected 1 month postpartum and comprehensive lipid analysis was performed. Partial least square-discriminant analysis was used to explore candidate lipids, and multivariable logistic regression analysis was used to evaluate associations with the AR status of children. We detected 667 lipid molecules in 12 lipid classes in breast milk. Partial least square-discriminant analysis revealed the association of fatty acid-hydroxy fatty acid (FAHFA) and cholesterol ester (ChE) with AR status. Multivariable logistic regression analysis showed that in pairs with exclusive breastfeeding at 1 month postpartum, FAHFA (odds ratio 1.57 [95% confidence interval, 1.06–2.32]) was positively associated with early AR, and ChE (odds ratio 0.55 [95% confidence interval, 0.36–0.86]) was negatively associated. Breast milk lipids (FAHFA, ChE) associated with the AR status of children, indicating the potential to regulate a child's adiposity and possible metabolic disorders in adulthood. •Early adiposity rebound (AR) during childhood increases the risk of adiposity and metabolic disorders in children.•Association between breast milk lipids and early AR in children was explored.•Fatty acid-hydroxy fatty acid was positively and cholesterol ester was negatively associated with early AR.•Comprehensive lipid analysis highlights the potential role of breast milk in influencing childhood growth and long-term metabolic health.