Association between dietary inflammatory potential and frailty is mediated by inflammation among patients with colorectal cancer: A cross-sectional study.

Patients with colorectal cancer (CRC) are at high risk of frailty, leading to reduced quality of life and survival. Diet is associated with frailty in the elderly through regulating inflammation. Thus, we hypothesized that dietary inflammatory potential (as assessed by dietary inflammatory index [DII]) might be associated with frailty in patients with CRC through regulating inflammatory biomarkers. A total of 231 patients with CRC were included in this cross-sectional study. Dietary intake was evaluated by 3-day, 24-hour dietary recalls, and frailty status was assessed in accordance with the Fried frailty criteria. Plasma inflammatory cytokines were determined in 126 blood samples. A total of 67 patients (29.0%) were frail, with significantly higher DII scores than nonfrail patients, accompanied with significantly increased interleukin-6 (IL-6) and decreased interleukin-10 (IL-10) concentrations. Each 1-point increase of DII was related to a 25.0% increased risk of frailty. IL-6 was positively correlated with frailty and DII, whereas IL-10 was negatively correlated. After adjusting for age, sex, body mass index, education level, smoking status, and energy, mediation analysis revealed that the association between DII and frailty was significantly mediated by IL-6 (average causal mediation effect [ACME], 0.052; 95% confidence interval, 0.020-0.087; P = .002) and IL-10 (ACME, 0.025; 95% confidence interval, 0.004-0.063; P = .016). The ρ values for the sensitivity measure at which estimated ACMEs were zero were 0.3 and -0.2 for IL-6 and IL-10, respectively. Therefore, a pro-inflammatory diet was associated with frailty in patients with CRC possibly in part by affecting circulating IL-6 and IL-10 concentrations.

Diet Is Associated with Frailty in Lung Cancer: A Possible Role of Gut Microbiota.

This study investigated the associations between diet and frailty in lung cancer patients and the potential role of the gut microbiota involved. We assessed dietary intake and frailty status in 231 lung cancer patients by 3-day, 24-h dietary recalls and Fried frailty criteria, respectively, and collected 50 fecal samples for next-generation sequencing. A total of 75 (32.5%) patients were frail, which might be related to significantly lower intake of energy, protein, carbohydrate, dietary fiber, niacin, leucine, some minerals, and a poorer dietary quality as indicated by the Chinese Healthy Eating Index (p < 0.05). Among these, carbohydrate (OR = 0.98; 95% CI 0.96-0.99; p = 0.010), calcium (OR = 0.99; 95% CI 0.99-1.00; p = 0.025), and selenium (OR = 1.03; 95% CI 1.00-1.06; p = 0.022) were all significantly associated with frailty. A multivariate logistic regression analysis showed that the mean risk of frailty was 0.94 times lower (95% CI 0.90-0.99; p = 0.009) among participants with higher CHEI scores. Additionally, the frail patients demonstrated significantly lower gut microbiota ß diversity (p = 0.001) and higher relative abundance of Actinobacteriota (p = 0.033). Frailty in lung cancer patients might be associated with insufficient nutrients intake and a poor dietary quality through gut microbiota regulation.

Whey protein isolate attenuates depression-like behavior developed in a mouse model of breast tumor.

Increasing evidence indicates that tryptophan (Trp) metabolism disturbance controls hippocampal 5-hydroxytryptamine (5-HT) and thereby affecting depression-like behavior, in which the gut microbiota (GM) might be involved. This study investigated the effect of Trp-rich whey protein isolate (WPI) on depressive-like behavior in 4T1 tumor-bearing mice. Female BALB/c mice were subcutaneously inoculated with murine 4T1 mammary carcinoma cells and received 2 g/kg of WPI by gavage daily for 21 days. The results showed that WPI exerted no significant effects on tumor weight and volume, but abrogated tumor-induced depression-like behavior, as evidenced by remarkably increased time and distance in the center of the open-field test, decreased immobility time in the tail suspension test, increased time and number of entries to the open arms in the elevated plus maze and sucrose preference. Moreover, WPI promoted the hippocampal Trp, 5-hydroxytryptophan (5-HTP), 5-HT, 5-hydroxyindoleacetic acid (5-HIAA) levels and inhibited kynurenine (Kyn) through up-regulating serotonin transporter (SERT) and down-regulating indoleamine 2, 3-dioxygenase (IDO). WPI showed an enriched microbial diversity indicated by increased Shannon index and decreased Simpson index, reduced the abundances of Proteobacteria, Rikenellaceae_RC9_gut_group, Alloprevotella and Prevotellaceae_UCG-001, and increased the abundance of unclassified_k__norank_d__Bacteria in tumor-bearing mice (P < 0.05). At level 3, WPI enhanced the function of microbial gene related to Trp metabolism in the KEGG pathways (P < 0.05). Our results suggest that WPI exhibits a potent antidepressant-like effect via the regulation of hippocampal Trp metabolism and alteration of GM composition and function, and it may be an effective prevention for cancer-related depression.

Impact of Gut Microbiota on the Association between Diet and Depressive Symptoms in Breast Cancer.

Little is known about the relationship between diet and depression through the gut microbiota among breast cancer patients. This study aimed to examine the dietary intake differences between depressed breast cancer (DBC) and non-depressed breast cancer (NBC) patients, and whether the differences could lead to gut microbiota changes that affect depressive symptoms. Participants completed the Center for Epidemiological Studies-Depression Scale (CES-D) and 24 h dietary recall. Fecal samples of 18 DBC patients and 37 NBC patients were collected for next-generation sequencing. A total of 60 out of 205 breast cancer patients reported significant depressive symptoms suggested by a CES-D score ≥ 16, which might be related to lower intakes of energy, protein, dietary fiber, vitamin A, vitamin B2, niacin, calcium, phosphorus, potassium, iron, zinc, selenium, manganese and tryptophan, and a poor diet quality indicated by a lower total Chinese Healthy Eating Index (CHEI) score. Additionally, NBC patients demonstrated greater gut microbiota diversity and a healthier composition, in which the relative abundances of Proteobacteria and Escherichia-Shigella were both lower than in the DBC patients (p < 0.05). Alpha diversity was a significant mediator between diet quality and depression, while calcium, phosphorus and selenium significantly regulated depression independent of the gut microbiota. Breast cancer-related depressive symptoms might be associated with a poor diet quality via gut microbiota-dependent pathways and lower micronutrient intake via microbiota-independent pathways.

TNF-α Mediates the Association between Dietary Inflammatory Index and Depressive Symptoms in Breast Cancer.

This study examined the association between the energy-adjusted Dietary Inflammatory Index (E-DII)-based dietary inflammatory potential and depressive symptoms (DepS) among patients with breast cancer and explores whether systemic inflammation mediates this association. We assessed dietary intake and DepS in 220 breast cancer patients by three 24 h dietary recalls and the Center for Epidemiological Studies Depression Scale (CES-D), respectively, and determined plasma levels of C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin (IL)-1ß, IL-4, and IL-6 in 123 blood samples. We found that each one-point increase of E-DII was related to a 53% elevated risk of DepS. Patients with the most pro-inflammatory diets had a 5.13 times higher risk of DepS than those with the most anti-inflammatory diets. Among the E-DII components, vitamin B2, zinc, and iron were inversely associated with DepS risk. Furthermore, E-DII scores were positively associated with CRP and TNF-α. Higher levels of TNF-α and IL-6 were associated with higher DepS risk. A significant mediating effect of TNF-α was revealed between E-DII and DepS. Our findings suggest that a pro-inflammatory diet is positively associated with breast cancer-related DepS, which may be mediated by TNF-α.

Niga-ichigoside F1 ameliorates high-fat diet-induced hepatic steatosis in male mice by Nrf2 activation.

Hepatic lipid accumulation and oxidative stress (OS) lead to non-alcoholic fatty liver disease (NAFLD). Thus, we hypothesized that antihyperlipidemic and antioxidant activities of niga-ichigoside F1 (NI) would ameliorate events leading to NAFLD. Lanbuzheng (Geum japonicum Thunb. var. chinense), a type of wild vegetable found in Southwest China, was used to extract NI. Male C57BL/6J mice were fed a standard diet (Con) or a high-fat diet (HFD) (denoted as diet) with or without 40 mg kg-1 NI (defined as treatment) for 12 weeks. Diet-treatment interactions were observed in the final body weight, fat pad mass, respiratory exchange ratio (RER) in the daytime, and energy expenditure during the whole day. Moreover, NI alleviated hepatic steatosis, possibly by significantly interacting with HFD to regulate lipid metabolism genes (including Srebp1c, Acc1, Fasn, Scd1, Cpt1a and Fabp5). We also found significant diet-treatment interactions on superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) activities, and thiobarbituric acid reactive substance (TBARS) levels, as well as the nuclear and cellular Nrf2 protein levels. Significant free fatty acid (FFA)-treatment interactions on Nrf2 nuclear translocation, antioxidant enzymes activities, genes in lipogenesis (Srebp1c, Acc1, Fasn, and Scd1), and fatty acid oxidation (Pparα) and transport (Fabp5 and Cd36) were also detected in 1 mM FFA-treated HepG2 cells with or without 20 µM NI. These beneficial effects of NI on oxidative stress and lipid accumulation were abolished by Nrf2 siRNA. Our data revealed that dietary NI could prevent HFD-induced hepatic steatosis, possibly via interacting with HFD to activate Nrf2 nuclear translocation to maintain a redox status, thus regulating lipid metabolism genes expressions.

Membrane damage as first and DNA as the secondary target for anti-candidal activity of antimicrobial peptide P7 derived from cell-penetrating peptide ppTG20 against Candida albicans.

P7, a peptide analogue derived from cell-penetrating peptide ppTG20, possesses antibacterial and antitumor activities without significant hemolytic activity. In this study, we investigated the antifungal effect of P7 and its anti-Candida acting mode in Candida albicans. P7 displayed antifungal activity against the reference C. albicans (MIC = 4 µM), Aspergilla niger (MIC = 32 µM), Aspergillus flavus (MIC = 8 µM), and Trichopyton rubrum (MIC = 16 µM). The effect of P7 on the C. albicans cell membrane was examined by investigating the calcein leakage from fungal membrane models made of egg yolk l-phosphatidylcholine/ergosterol (10 : 1, w/w) liposomes. P7 showed potent leakage effects against fungal liposomes similar to Melittin-treated cells. C. albicans protoplast regeneration assay demonstrated that P7 interacted with the C. albicans plasma membrane. Flow cytometry of the plasma membrane potential and integrity of C. albicans showed that P7 caused 60.9 ± 1.8% depolarization of the membrane potential of intact C. albicans cells and caused 58.1 ± 3.2% C. albicans cell membrane damage. Confocal laser scanning microscopy demonstrated that part of FITC-P7 accumulated in the cytoplasm. DNA retardation analysis was also performed, which showed that P7 interacted with C. albicans genomic DNA after penetrating the cell membrane, completely inhibiting the migration of genomic DNA above the weight ratio (peptide : DNA) of 6. Our results indicated that the plasma membrane was the primary target, and DNA was the secondary intracellular target of the mode of action of P7 against C. albicans. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.

Effects of resveratrol on gut microbiota and fat storage in a mouse model with high-fat-induced obesity.

Recent studies have investigated the anti-obesity effect of resveratrol, but the pathways through which resveratrol resists obesity are not clear. In the present study, we hypothesize that resveratrol exerts anti-obesity effects that are likely mediated by mechanisms of regulating gut microbes, and in turn, improving fat storage and metabolism. Gut microbes, glucose and lipid metabolism in high-fat diet (HF) mice in vivo are investigated after resveratrol treatment. Several biochemical markers are measured. Fluorescence in situ hybridization and flow cytometry are used to monitor and quantify the changes in gut microbiota. The key genes related to fat storage and metabolism in the liver and visceral adipose tissues are measured by real-time PCR. The results show that resveratrol (200 mg per kg per day) significantly lowers both body and visceral adipose weights, and reduces blood glucose and lipid levels in HF mice. Resveratrol improves the gut microbiota dysbiosis induced by the HF diet, including increasing the Bacteroidetes-to-Firmicutes ratios, significantly inhibiting the growth of Enterococcus faecalis, and increasing the growth of Lactobacillus and Bifidobacterium. Furthermore, resveratrol significantly increases the fasting-induced adipose factor (Fiaf, a key gene negatively regulated by intestinal microbes) expression in the intestine. Resveratrol significantly decreases mRNA expression of Lpl, Scd1, Ppar-γ, Acc1, and Fas related to fatty acids synthesis, adipogenesis and lipogenesis, which may be driven by increased Fiaf expression. The Pearson's correlation coefficient shows that there is a negative correlation between the body weight and the ratios of Bacteroidetes-to-Firmicutes. Therefore, resveratrol mediates the composition of gut microbes, and in turn, through the Fiaf signaling pathway, accelerates the development of obesity.