Recent identification of a mammary gland-specific microbiome led to studies investigating bacteria populations in breast cancer. Malignant breast tumors have lower Lactobacillus abundance compared with benign lesions, implicating Lactobacillus as a negative regulator of breast cancer. Diet is a main determinant of gut microbial diversity. Whether diet affects breast microbiome populations is unknown. In a non-human primate model, we found that consumption of a Western or Mediterranean diet modulated mammary gland microbiota and metabolite profiles. Mediterranean diet consumption led to increased mammary gland Lactobacillus abundance compared with Western diet-fed monkeys. Moreover, mammary glands from Mediterranean diet-fed monkeys had higher levels of bile acid metabolites and increased bacterial-processed bioactive compounds. These data suggest that diet directly influences microbiome populations outside the intestinal tract in distal sites such as the mammary gland. Our study demonstrates that diet affects the mammary gland microbiome, establishing an alternative mechanistic pathway for breast cancer prevention.

Recent evidence underlines the role of Western diet in the pathogenesis of acne. Acne is absent in populations consuming Palaeolithic diets with low glycaemic load and no consumption of milk or dairy products. Two randomized controlled studies, one of which is presented in this issue of Acta Dermato-Venereologica, have provided evidence for the beneficial therapeutic effects of low glycaemic load diets in acne. Epidemiological evidence confirms that milk consumption has an acne-promoting or acne-aggravating effect. Recent progress in understanding the nutrient-sensitive kinase mammalian target of rapamycin complex 1 (mTORC1) allows a new view of nutrient signalling in acne by both high glycaemic load and increased insulin-, IGF-1-, and leucine signalling due to milk protein consumption. Acne should be regarded as an mTORC1-driven disease of civilization, like obesity, type 2 diabetes and cancer induced by Western diet. Early dietary counselling of teenage acne patients is thus a great opportunity for dermatology, which will not only help to improve acne but may reduce the long-term adverse effects of Western diet on more serious mTORC1-driven diseases of civilization.

The association of breast cancer with dietary patterns such as a western diet has not been studied in Asian women. We examined this among Shanghai Breast Cancer Study participants. Cases were of ages 25 to 64 years, diagnosed 08/1996-03/1998, and identified through a rapid case ascertainment system supplemented by the Shanghai Cancer Registry. Controls, selected from the general population of urban Shanghai, were frequency matched to cases by 5-year age group. Participants provided information on diet, lifestyle, and reproductive factors. In principal component analysis among 1,556 controls, two patterns emerged: a "vegetable-soy" pattern (tofu, cauliflower, beans, bean sprouts, green leafy vegetables) and a "meat-sweet" pattern (shrimp, chicken, beef, pork, candy, desserts). In adjusted unconditional logistic regression analyses including 1,446 cases and 1,549 controls with complete covariate data, risk was not associated with the vegetable-soy pattern. It was associated with the meat-sweet pattern (4th versus 1st quartile: odds ratio, 1.3; 95% confidence interval, 1.0-1.7; P(trend) = 0.03), but only in postmenopausal women, specifically among those with estrogen receptor-positive tumors (4th versus 1st quartile: odds ratio, 1.9; 95% confidence interval, 1.1-3.3; P(trend) = 0.03). Our findings indicate that a western diet increases breast cancer risk in postmenopausal Chinese women. They also suggest the value of quantifying aggregate risk for common combinations of foods.

Considerable evidence implicates cellular senescence in the biology of aging and chronic disease. Diet and exercise are determinants of healthy aging; however, the extent to which they affect the behavior and accretion of senescent cells within distinct tissues is not clear. Here we tested the hypothesis that exercise prevents premature senescent cell accumulation and systemic metabolic dysfunction induced by a fast food diet (FFD). Using transgenic mice that express enhanced green fluorescent protein (EGFP) in response to activation of the senescence-associated p16(INK4a) promoter, we demonstrate that FFD consumption causes deleterious changes in body weight and composition, as well as measures of physical, cardiac, and metabolic health. The harmful effects of the FFD were associated with dramatic increases in several markers of senescence, including p16, EGFP, senescence-associatedβ-galactosidase, and the senescence-associated secretory phenotype (SASP), specifically in visceral adipose tissue. We show that exercise prevents both the accumulation of senescent cells and the expression of the SASP, while nullifying the damaging effects of the FFD on parameters of health. We also demonstrate that exercise initiated following long-term FFD-feeding reduces senescent phenotype makers in visceral adipose while attenuating physical impairments, suggesting that exercise may provide restorative benefit by mitigating accrued senescent burden. These findings highlight a novel mechanism by which exercise mediates its beneficial effects and reinforce the impact of modifiable lifestyle choices on healthspan.

PURPOSE:To assess if the associations found between three previously identified dietary patterns with breast, prostate and gastric cancer are also observed for colorectal cancer (CRC).

METHODS:MCC-Spain is a multicase-control study that collected information of 1629 incident cases of CRC and 3509 population-based controls from 11 Spanish provinces. Western, Prudent and Mediterranean data-driven dietary patterns-derived in another Spanish case-control study-were reconstructed in MCC-Spain. Their association with CRC was assessed using mixed multivariable logistic regression models considering a possible interaction with sex. Risk by tumor site (proximal colon, distal colon, and rectum) was evaluated using multinomial regression models.

RESULTS:While no effect of the Prudent pattern on CRC risk was observed, a high adherence to the Western dietary pattern was associated with increased CRC risk for both males [OR(95% CI): 1.45 (1.11;1.91)] and females [OR(95% CI): 1.50 (1.07;2.09)] but seem to be confined to distal colon [OR(95% CI): 2.02 (1.44;2.84)] and rectal [OR(95% CI): 1.46 (1.05;2.01)] tumors. The protective effect of the Mediterranean dietary pattern against CRC was observed for both sexes [males: OR(95% CI): 0.71 (0.55;0.92); females: OR(95% CI): 0.56 (0.40;0.77)] and for all cancer sites: proximal colon [OR(95% CI): 0.70 (0.51;0.97)], distal colon [OR(95% CI): 0.65 (0.48;0.89)], and rectum (OR(95% CI): 0.60 (0.45;0.81)].

CONCLUSION:Our results are consistent with most of the associations previously found between these patterns and breast, prostate and gastric cancer risk and indicate that consuming whole fruits, vegetables, legumes, olive oil, nuts, and fish and avoiding red and processed meat, refined grains, sweets, caloric drinks, juices, convenience food, and sauces might reduce CRC risk.

Crohn's disease is characterized by abnormal ileal colonization by adherent-invasive(AIEC) and expansion of mesenteric adipose tissue. This study assessed the preventive effect of spontaneous physical activity (PA) on the gut-adipose tissue in a mouse model that mimics Crohn's disease susceptibility. Thirty-five CEABAC10 male mice performed spontaneous PA (wheel group; n = 24) or not (controls; n = 11) for 12 weeks. At week 12, mice were orally challenged with the AIEC LF82 strain for 6 days. Body composition, glycaemic control, intestinal permeability, gut microbiota composition, and fecal short-chain fatty acids were assessed in both groups. Animals were fed a high fat/high sugar diet throughout the study. After exposure to AIEC, mesenteric adipose tissue weight was lower in the wheel group. Tight junction proteins expression increased with spontaneous PA, whereas systemic lipopolysaccharides were negatively correlated with the covered distance.anddecreased in controls, whereasandincreased in the wheel group. Fecal propionate and butyrate were also higher in the wheel group. In conclusion, spontaneous physical activity promotes healthy gut microbiota composition changes and increases short-chain fatty acids in CEABAC10 mice fed a Western diet and exposed to AIEC to mimic Crohn's disease.

INTRODUCTION AND OBJECTIVES:Consumption of a Western diet during the perinatal period is associated with development of cardiovascular disease. Resistance training (RT) has been used to treat cardiovascular disorders. The aim of this work was to assess the effect of RT on cardiometabolic disorders in rats exposed to a Western diet in the perinatal period.

METHODS:Female Wistar rats were fed with control or Western diet during pregnancy and lactation. The pups were divided into three groups: Control (C), Western Diet Sedentary (WDS) and Western Diet + RT (WDRT). At 60 days of age, all animals started the RT protocol (five times a week for four weeks). At the end, blood pressure was recorded for analysis of heart rate variability and baroreflex sensitivity (BRS). Blood samples were collected for biochemical analysis.

RESULTS:RT reduced blood pressure and vascular sympathetic modulation and increased BRS. There were improvements in biochemical profile, with reductions in fasting blood glucose, total cholesterol and low-density lipoprotein, and an increase in high-density lipoprotein.

CONCLUSION:RT led to beneficial adaptations in the cardiovascular system, mediated by changes in the mechanisms of autonomic control and biochemical profile of animals exposed to a Western diet in the perinatal period.

Obesity increases inflammation, both peripherally and centrally, and exercise can ameliorate some of the negative health outcomes associated with obesity. Within the brain, the effect of obesity on inflammation has been well characterized in the hypothalamus and hippocampus, but has been relatively understudied in other brain regions. The current study was designed to address two primary questions; (1) whether western diet (high fat/high sucrose) consumption would increase markers of inflammation in the prefrontal cortex and (2) whether concurrent voluntary wheel running would ameliorate any inflammation. Adult male mice were exposed to a western diet or a control diet for 8 weeks. Concurrently, half the animals were given running wheels in their home cages, while half did not have access to wheels. At the conclusion of the study, prefrontal cortex was removed and expression of 18 proinflammatory genes was assayed. Expression of a number of proinflammatory molecules was upregulated by consumption of the western diet. For two chemokines, chemokine (C-C motif) ligand 2 (CCL2) and C-X-C motif chemokine 10(CXCL10), voluntary exercise blocked the increase in the expression of these genes. Cluster analysis confirmed that the majority of the tested genes were upregulated by western diet, and identified another small cluster of genes that were downregulated by either diet or exercise. These data identify a proinflammatory phenotype within the prefrontal cortex of mice fed a western diet, and indicate that chemokine induction can be blocked by voluntary exercise.