Oral Exposure to Polystyrene Microplastics of Mice on a Normal or High-Fat Diet and Intestinal and Metabolic Outcomes

マイクロプラスチックの経口摂取が高脂肪食条件下での代謝障害を悪化させる. 京都大学プレスリリース. 2023-02-24.[Background:] Microplastics (MPs) are small particles of plastic (≤ 5mm 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⁺/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

Incisional Negative Pressure Wound Therapy for Wounds in Patients with Lower Intestinal Perforations

Objectives: Laparotomy for lower intestinal perforation is associated with a high incidence of surgical site infections. This study aimed to assess whether incisional negative pressure wound therapy (iNPWT) could reduce the incidence of these infections and wound dehiscence in patients with lower intestinal perforation. Methods: This single-center prospective study was conducted between September 2019 and July 2022. In the therapy group, wounds were closed with subcuticular sutures, and iNPWT was applied at -120 mmHg for 5 days. A total of 10 days of iNPWT was employed. These patients were compared with a historical control group. The iNPWT group (Group A) comprised 22 patients.The historical control group (Group B) had 65 patients. outlines patient characteristics and compares the two study groups. Results: Patient characteristics were demographically similar. The incidence of surgical site infections was lower in the therapy group than in the control group (9.1% vs. 52.3%, p < 0.001). Wound dehiscence was not observed in the therapy group but was noted in three patients (4.6%) in the control group. In univariate and multivariate analysis, an application of the therapy device was associated with reduced incidence of surgical site infections (p < 0.001 and p = 0.002, respectively). Conclusions: The application of iNPWT in patients with lower intestinal perforation was associated with reduced surgical site infections

Milk protects against sarcopenic obesity due to increase in the genus Akkermansia in faeces of db/db mice

Abstract Background Sarcopenic obesity, a combination of sarcopenia and obesity, is a pathological feature of type 2 diabetes. Several human studies have shown that milk is useful in the prevention of sarcopenia. This study was aimed at clarifying the effect of milk on the prevention of sarcopenic obesity in db/db mice. Methods A randomized and investigator‐blinded study was conducted using male db/db mice. Eight‐week‐old db/db mice were housed for 8 weeks and fed milk (100 μL/day) using a sonde. The faecal microbiota transplantation (FMT) group received antibiotics for 2 weeks, starting at 6 weeks of age, followed by FMT twice a week until 16 weeks of age. Results Milk administration to db/db mice increased grip strength (Milk−: 164.2 ± 4.7 g, Milk+: 230.2 ± 56.0 g, P = 0.017), muscle mass (soleus muscle, Milk−: 164.2 ± 4.7 mg, Milk+: 230.2 ± 56.0 mg, P < 0.001; plantaris muscle, Milk−: 13.3 ± 1.2 mg, Milk+: 16.0 ± 1.7 mg, P < 0.001) and decreased visceral fat mass (Milk−: 2.39 ± 0.08 g, Milk+: 1.98 ± 0.04 mg, P < 0.001), resulting in a significant increase in physical activity (light: P = 0.013, dark: P = 0.034). FMT from mice fed milk not only improved sarcopenic obesity but also significantly improved glucose intolerance. Microarray analysis of gene expression in the small intestine revealed that the expression of amino acid absorption transporter genes, namely, SIc7a5 (P = 0.010), SIc7a1 (P = 0.015), Ppp1r15a (P = 0.041) and SIc7a11 (P = 0.029), was elevated in mice fed milk. In 16S rRNA sequencing of gut microbiota, the genus Akkermansia was increased in both the mice fed milk and the FMT group from the mice fed milk. Conclusions The findings of this study suggest that besides increasing the intake of nutrients, such as amino acids, milk consumption also changes the intestinal environment, which might contribute to the mechanism of milk‐induced improvement of sarcopenic obesity

Characterization of Peripheral Blood TCR in Patients with Type 1 Diabetes Mellitus by BD RhapsodyTM VDJ CDR3 Assay

The sequence of complementarity-determining region 3 of the T-cell receptor (TCR) varies widely due to the insertion of random bases during V-(D)-J recombination. In this study, we used single-cell VDJ sequencing using the latest technology, BD Rhapsody, to identify the TCR sequences of autoreactive T-cells characteristic of Japanese type 1 diabetes mellitus (T1DM) and to clarify the pairing of TCR of peripheral blood mononuclear cells from four patients with T1DM at the single-cell level. The expression levels of the TCR alpha variable (TRAV) 17 and TRAV21 in T1DM patients were higher than those in healthy Japanese subjects. Furthermore, the Shannon index of CD8+ T cells and FOXP3+ cells in T1DM patients was lower than that of healthy subjects. The gene expression of PRF1, GZMH, ITGB2, NKG7, CTSW, and CST7 was increased, while the expression of CD4, CD7, CD5, HLA-A, CD27, and IL-32 was decreased in the CD8+ T cells of T1DM patients. The upregulated gene expression was IL4R and TNFRSF4 in FOXP3+ cells of T1DM patients. Overall, these findings demonstrate that TCR diversity and gene expression of CD8+ and FOXP3+ cells are different in patients with T1DM and healthy subjects

Reasons for Discontinuing Treatment with Sodium-Glucose Cotransporter 2 Inhibitors in Patients with Diabetes in Real-World Settings: The KAMOGAWA-A Study

Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are a class of antidiabetic agents known to exert cardioprotective, renoprotective, and hypoglycemic effects. However, these agents have been associated with adverse effects, such as genital infection, volume depletion, hypoglycemia, and diabetic ketoacidosis, resulting in drug discontinuation. Herein, we aimed to determine the reasons for discontinuing treatment with SGLT2is among Japanese patients with diabetes. This retrospective cohort study enrolled 766 patients with diabetes who had initiated SGLT2is between January 2014 and September 2021. The follow-up period was 2 years from the initiation of the SGLT2is. Overall, 97 patients (12.7%) discontinued the SGLT2is during the follow-up period. The most common reasons for discontinuing the SGLT2is were frequent urination (19.6%), followed by genital infection (11.3%), improved glycemic control (10.6%), and renal dysfunction (8.2%). A comparison of the characteristics between the continuation and the discontinuation group was conducted, excluding those who discontinued the SGLT2is because of improved glycemic control. The patients in the discontinuation group (68 [55–75] years) were older than those in the continuation group (64 [53–71] years; p = 0.003). Importantly, we found no significant association between diabetes duration, diabetic control, renal function, or complications of diabetes in both groups. This real-world study revealed that frequent urination was the most common reason underlying SGLT2i discontinuation among Japanese patients with diabetes. To avoid discontinuation, precautions against various factors that may cause frequent urination must be implemented

Eating Speed Is Associated with the Presence of Sarcopenia in Older Patients with Type 2 Diabetes: A Cross-Sectional Study of the KAMOGAWA-DM Cohort

To determine the relationship between eating speed and the presence of sarcopenia in older patients with type 2 diabetes (T2D), in this cross-sectional study, patient eating speeds were classified as “fast-”, “normal-” and “slow-speed eating.” A multifrequency impedance analyzer was used to evaluate patient body compositions. Sarcopenia was defined as having both low muscle strength, a handgrip strength 2 for men and 2 for women. Among 239 individuals, the frequencies of fast-, normal-, and slow-speed eating were 47.3%, 32.2%, and 20.5%, respectively; and the prevalence of sarcopenia was 15.9%. Patients with a slow eating speed had greater prevalence of low skeletal muscle mass, low muscle strength, and sarcopenia than those with a fast or normal eating speed. After adjusting for covariates, compared to slow eaters, the odds ratio of having sarcopenia among fast- and normal-speed eaters was 0.31 [95% CI: 0.12–0.80] and 0.18 [95% CI: 0.06–0.53], respectively. Having a slow eating speed is associated with a heightened risk of sarcopenia in older patients with T2D

Dental care and oral conditions are associated with the prevalence of sarcopenia in people with type 2 diabetes: a cross-sectional study

Abstract Background Insulin resistance, which is closely associated with type 2 diabetes mellitus (T2DM), is a cause of sarcopenia and people with T2DM have a high risk of sarcopenia. Keeping good oral condition by dental care is important for people with T2DM. Keeping good oral condition by dental care is important for people with T2DM. This study has investigated the association between dental care or oral conditions and sarcopenia in people with T2DM. Methods Dental care and oral conditions were evaluated based on a self-reported questionnaire. Individuals with both low handgrip strength and low skeletal muscle mass index were diagnosed with sarcopenia. Results Among 266 people with T2DM, the proportions of sarcopenia, not having a family dentist, not having a toothbrushing behavior, poor chewing ability, and use of complete dentures were 18.0%, 30.5%, 33.1%, 25.2%, and 14.3%, respectively. The proportions of sarcopenia in people not having a family dentist (27.2% vs. 14.1%, p = 0.017), those with poor chewing ability (26.9% vs. 15.1%, p = 0.047), and use of complete dentures (36.8% vs. 14.9%, p = 0.002) were higher than those in people without. The proportion of sarcopenia in people without toothbrushing behavior tended to be higher than that in people with toothbrushing behavior (25.0% vs. 14.6%, p = 0.057). Not having a family dentist (adjusted odds ratio [OR] 2.48 [95% confidence interval (CI): 1.21–5.09], p = 0.013), poor chewing ability (adjusted OR 2.12 [95% CI: 1.01–4.46], p = 0.048), and use of complete dentures (adjusted OR 2.38 [95% CI: 1.01–5.99], p = 0.046) were related to the prevalence of sarcopenia. Conclusions This study revealed that dental care and oral conditions were associated with the prevalence of sarcopenia

Association between Geriatric Nutrition Risk Index and The Presence of Sarcopenia in People with Type 2 Diabetes Mellitus: A Cross-Sectional Study

The aim of this cross-sectional study was to examine the association between the geriatric nutritional risk index (GNRI) and the prevalence of sarcopenia in people with type 2 diabetes (T2DM). Having both low handgrip strength (2 for men and 2 for women) was diagnosed as sarcopenia. GNRI was estimated by the formula as below: GNRI = (1.489 × serum albumin level [g/L]) + (41.7 × [current body weight (kg)/ideal body weight (kg)]). Participants were dichotomized on the basis of their GNRI scores (GNRI n = 67/526) and 5.1% (n = 27/526), respectively. The proportion of sarcopenia in participants with low-GNRI was higher than that with high GNRI (44.4% [n = 12/27] vs. 11.0% [n = 55/499], p r = 0.232, p r = 0.514, p p = 0.001). The GNRI, as a continuous variable, was also related to the prevalence of sarcopenia (adjusted odds ratio, 0.89 [95% confidence interval: 0.86–0.93], p < 0.001). The present study revealed that low GNRI was related to the prevalence of sarcopenia