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Introduction: Oral exposure to microplastics (MPs) is a global health concern. In our previous study, MPs induced glucose intolerance and non-alcoholic fatty liver disease (NAFLD) under a high-fat diet-induced leaky gut syndrome (LGS). This study aims to evaluate the effects of high concentrations of MP on lipid metabolism under normal dietary conditions and to assess the changes in the intestinal tract resulting from MP exposure. Methods: C57BL6/J mice were fed a normal diet (ND) without polystyrene MPs (PS-MPs) or with PS-MPs (1000 µg/L or 5000 µg/L) for six weeks. Subsequently, intestinal permeability, gut microbiota, and metabolite levels in the serum, feces, and liver were determined. Results: Mice fed the ND showed no increase in intestinal permeability in either group. However, high MPs concentrations led to increased serum lipid levels and exacerbated fatty liver function. Oral exposure to MPs did not affect the number of innate lymphoid cells or short-chain fatty acids in the intestine. However, it increased the number of natural killer cells, altered the gut microbiota, induced inflammation, and modulated the expression of genes related to nutrient transport in the intestine. The severity of intestinal disturbance tended to worsen with dose. Discussion: Despite the absence of LGS, high concentrations of MPs induced dyslipidemia and NAFLD. Oral exposure to MPs triggered intestinal inflammation via natural killer cells, altered the gut microbiota, and modulated nutrient metabolism. Our study highlights the need for environmental measures to reduce oral MPs exposure in the future. [ABSTRACT FROM AUTHOR]

Background/Objectives: Western-type diets (WDs) damage the intestinal barrier by disrupting the gut microbiota composition and causing inflammation, leading to the development of obesity, type 2 diabetes, and non-alcoholic fatty liver disease. Short-chain fatty acids (SCFAs) are produced by the gut microbiota and found in fermented foods and can stimulate the anti-inflammatory action of type 3 innate lymphoid cells (ILCS3s) in the intestine. This study hypothesised that supplementing miso, a Japanese fermented food, to a WD could increase the levels of SCFAs and thus stimulate ILC3s, decreasing inflammation in the intestine and protecting intestinal barrier integrity. Methods: Mice with RORγt total (KI/KI) or partial (KI/w) knockout were fed a high-fat high-sugar diet (HFHSD) for eight weeks as a model of WD. Half of the mice received miso supplementation in addition to the HFHSD. Weight gain, glucose tolerance and insulin resistance, intestinal barrier integrity, intestinal immunity, and liver condition were assessed. Results: Miso supplementation increased SCFA levels in the small intestine, which stimulated ILC3 function in KI/w mice. Glucose tolerance was improved, intestinal barrier integrity was ameliorated, and mucus production was increased. The level of IL-22 was increased, while pro-inflammatory ILC1s, M1 macrophages, TNF-α, and IL-1β were decreased. Liver condition was not affected. Conclusions: This study demonstrated that miso supplementation influenced several factors involved in inflammation and intestinal barrier integrity by stimulating ILC3s in RORγt heterozygous mice. Moreover, it showed that the number of ILC3s is not the key factor in immune regulation, but rather the ability of ILC3 to produce IL-22 and employ it to control the immune response in the small intestine. [ABSTRACT FROM AUTHOR]

Aims/Introduction: Efficacy of long‐term low‐carbohydrate diets (LCD) to improve glycemic management for type 2 diabetes remains controversial. Thus, we investigated the association between long‐term LCD and glycemic control in individuals with type 2 diabetes. Materials and Methods: We searched PubMed, Embase and the Cochrane Database for articles published up to June 2023, and included randomized controlled trials conducted on LCD interventions for >12 months in adults with type 2 diabetes. Primary outcome was the difference in glycated hemoglobin between long‐term LCD and control groups. Additionally, we evaluated the differences in changes in systolic and diastolic blood pressure, low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol, triglyceride, and weight between long‐term LCD and control groups. Results: Six studies were identified and met the inclusion criteria. This study did not show significant differences in changes in glycated hemoglobin between long‐term LCD and control diets (standardized mean difference −0.11, 95% confidence interval −0.33 to 0.11, P = 0.32). As with glycemic control, there were no significant differences in the changes in weight loss, blood pressure, and low‐density lipoprotein cholesterol between long‐term LCD and control diets. However, long‐term LCD were associated with greater elevation in high‐density lipoprotein cholesterol (standardized mean difference 0.22, 95% confidence interval 0.04–0.41; P = 0.02) and decrease in triglyceride (standardized mean difference −0.19; 95% confidence interval −0.37 to 0.02; P = 0.03) than that in control diets. Conclusions: Our findings suggest efficacy of long‐term LCD in treating dyslipidemia in individuals with type 2 diabetes, but do not recommend long‐term LCD for glycemic control in the individuals. [ABSTRACT FROM AUTHOR]

Background: Sarcopenia, characterized by muscle mass decline due to aging or other causes, is exacerbated by decreased estrogen levels after menopause in women. Isoflavones, a class of flavonoids acting on estrogen receptors, may have beneficial effects on metabolic disorders. We examined these effects in ovariectomized mice fed a high-fat, high-sucrose diet (HFHSD). Methods: At 7 weeks old, female C57BL6/J mice (18–20 g, n = 12) underwent bilateral ovariectomy (OVX), and were then fed a high-fat, high-sucrose diet starting at 8 weeks of age. Half of the mice received isoflavone water (0.1%). Metabolic analyses, including glucose and insulin tolerance tests, were conducted. Muscle analysis involved grip strength assays, next-generation sequencing, quantitative RT–PCR, and western blotting of skeletal muscle after euthanizing the mice at 14 weeks old. Additionally, 16S rRNA gene sequence analysis of the gut microbiota was performed. Results: The results demonstrated that isoflavone administration did not affect body weight, glucose tolerance, or lipid metabolism. In contrast, isoflavone-treated mice had higher grip strength. Gene expression analysis of the soleus muscle revealed decreased Trim63 expression, and western blotting showed inactivation of muscle-specific RING finger protein 1 in isoflavone-treated mice. Gut microbiota analysis indicated higher Bacteroidetes and lower Firmicutes abundance in the isoflavone group, along with increased microbiota diversity. Gene sets related to TNF-α signaling via NF-κB and unfolded protein response were negatively associated with isoflavones. Conclusions: Isoflavone intake alters gut microbiota and increases muscle strength, suggesting a potential role in improving sarcopenia in menopausal women. [ABSTRACT FROM AUTHOR]

Background: Sarcopenic obesity, which is associated with a poorer prognosis than that of sarcopenia alone, may be positively affected by soy isoflavones, known inhibitors of muscle atrophy. Herein, we hypothesize that these compounds may prevent sarcopenic obesity by upregulating the gut metabolites with anti-inflammatory effects. Methods: To explore the effects of soy isoflavones on sarcopenic obesity and its mechanisms, we employed both in vivo and in vitro experiments. Mice were fed a high-fat, high-sucrose diet with or without soy isoflavone supplementation. Additionally, the mouse C2C12 myotube cells were treated with palmitic acid and daidzein in vitro. Results: The isoflavone considerably reduced muscle atrophy and the expression of the muscle atrophy genes in the treated group compared to the control group (Fbxo32, p = 0.0012; Trim63, p < 0.0001; Foxo1, p < 0.0001; Tnfa, p = 0.1343). Elevated levels of daidzein were found in the muscles and feces of the experimental group compared to the control group (feces, p = 0.0122; muscle, p = 0.0020). The real-time PCR results demonstrated that the daidzein decreased the expression of the palmitate-induced inflammation and muscle atrophy genes in the C2C12 myotube cells (Tnfa, p = 0.0201; Il6, p = 0.0008; Fbxo32, p < 0.0001; Hdac4, p = 0.0002; Trim63, p = 0.0114; Foxo1, p < 0.0001). Additionally, it reduced the palmitate-induced protein expression related to the muscle atrophy in the C2C12 myotube cells (Foxo1, p = 0.0078; MuRF1, p = 0.0119). Conclusions: The daidzein suppressed inflammatory cytokine- and muscle atrophy-related gene expression in the C2C12 myotubes, thereby inhibiting muscle atrophy. [ABSTRACT FROM AUTHOR]

This study explores the impact of royal jelly (RJ) on small intestinal epigenomic changes. RJ, produced by honeybees, is known for its effects on metabolic diseases. The hypothesis is that RJ induces epigenomic modifications in small intestinal epithelial cells, affecting gene expression and contributing to metabolic health. Male db/m and db/db mice were used to examine RJ's effects through mRNA sequencing and CUT&Tag methods. This study focused on histone modifications and gene expression changes, with statistical significance set at p < 0.05. RJ administration improved insulin sensitivity and lipid metabolism without affecting body weight. GO and KEGG pathway analyses showed significant enrichment in metabolic processes, cellular components, and molecular functions. RJ altered histone modifications, increasing H3K27me3 and decreasing H3K23Ac in genes associated with the G2M checkpoint. These genes, including Smc2, Mcm3, Ccnd1, Rasal2, Mcm6, and Mad2l1, are linked to cancer progression and metabolic regulation. RJ induces beneficial epigenomic changes in small intestinal epithelial cells, improving metabolic health and reducing cancer-associated gene expression. These findings highlight RJ's potential as a therapeutic agent for metabolic disorders. Further research is needed to fully understand the mechanisms behind these effects and their implications for human health. [ABSTRACT FROM AUTHOR]

BACKGROUND: Microplastics (MPs) are small particles of plastic ([less than or equal to] 5 mm in diameter). In recent years, oral exposure to MPs in living organisms has been a cause of concern. Leaky gut syndrome (LGS), associated with a high-fat diet (HFD) in mice, can increase the entry of foreign substances into the body through the intestinal mucosa. OBJECTIVES: We aimed to evaluate the pathophysiology of intestinal outcomes associated with consuming a high-fat diet and simultaneous intake of MPs, focusing on endocrine and metabolic systems. METHODS: C57BL6/J mice were fed a normal diet (ND) or HFD with or without polystyrene MP for 4 wk to investigate differences in glucose tolerance, intestinal permeability, gut microbiota, as well as metabolites in serum, feces, and liver. RESULTS: In comparison with HFD mice, mice fed the HFD with MPs had higher blood glucose, serum lipid concentrations, and nonalcoholic fatty liver disease (NAFLD) activity scores. Permeability and goblet cell count of the small intestine (SI) in HFD-fed mice were higher and lower, respectively, than in ND-fed mice. There was no obvious difference in the number of inflammatory cells in the SI lamina propria between mice fed the ND and mice fed the ND with MP, but there were more inflammatory cells and fewer anti-inflammatory cells in mice fed the HFD with MPs in comparison with mice fed the HFD without MPs. The expression of genes related to inflammation, long-chain fatty acid transporter, and [Na.sup.+]/glucose cotransporter was significantly higher in mice fed the HFD with MPs than in mice fed the HFD without MPs. Furthermore, the genus Desulfovibrio was significantly more abundant in the intestines of mice fed the HFD with MPs in comparison with mice fed the HFD without MPs. Muc2 gene expression was decreased when palmitic acid and microplastics were added to the murine intestinal epithelial cell line MODE-K cells, and Muc2 gene expression was increased when IL-22 was added. DISCUSSION: Our findings suggest that in this study, MP induced metabolic disturbances, such as diabetes and NAFLD, only in mice fed a high-fat diet. These findings suggest that LGS might have been triggered by HFD, causing MPs to be deposited in the intestinal mucosa, resulting in inflammation of the intestinal mucosal intrinsic layer and thereby altering nutrient absorption. These results highlight the need for reducing oral exposure to MPs through remedial environmental measures to improve metabolic disturbance under high-fat diet conditions. https://doi.org/10.1289/EHP11072, Introduction Over the past few decades, the use of plastics has increased dramatically. (1) The production, use, and consumption of plastics, which has been ongoing since the 1950s, has caused [...]