Maternal exposure to a Western-style diet causes differences in intestinal microbiota composition and gene expression of suckling mouse pups

Scope:The long-lasting consequences of nutritional programming during the early phase of life have become increasingly evident. The effects of maternal nutrition on the developing intestine are still underexplored. Methods and results: In this study we observed 1) altered microbiota composition of the colonic luminal content, and 2) differential gene expression in the intestinal wall in two-week-old mouse pups born from dams exposed to a Western-style (WS) diet during the perinatal period. A sexually dimorphic effect was found for the differentially expressed genes in the offspring of WS diet-exposed dams but no differences between male and female pups were found for the microbiota composition. Integrative analysis of the microbiota and gene expression data revealed that the maternal WS diet independently affected gene expression and microbiota composition. However, the abundance of bacterial families not affected by the WS diet (Bacteroidaceae, Porphyromonadaceae and Lachnospiraceae) correlated with the expression of genes playing a key role in intestinal development and functioning (e.g. Pitx2 and Ace2). Conclusion: Our data reveal that maternal consumption of a WS diet during the perinatal period alters both gene expression and microbiota composition in the intestinal tract of two-week-old offspring

The influence of diet and environment on the gut microbial community of field crickets

The extent to which diet and environment influence gut community membership (presence or absence of taxa) and structure (individual taxon abundance) is the subject of growing interest in microbiome research. Here, we examined the gut bacterial communities of three cricket groups: (1) wild caught field crickets, (2) laboratory-reared crickets fed cat chow, and (3) laboratory-reared crickets fed chemically defined diets. We found that both environment and diet greatly altered the structure of the gut bacterial community. Wild crickets had greater gut microbial diversity and higher Firmicutes to Bacteroidetes ratios, in contrast to laboratory-reared crickets. Predictive metagenomes revealed that laboratory-reared crickets were significantly enriched in amino acid degradation pathways, while wild crickets had a higher relative abundance of peptidases that would aid in amino acid release. Although wild and laboratory animals differ greatly in their bacterial communities, we show that the community proportional membership remains stable from Phylum to Family taxonomic levels regardless of differences in environment and diet, suggesting that endogenous factors, such as host genetics, have greater control in shaping gut community membership

Cause of Death and Predictors of All-Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation : Data From ROCKET AF

M. Kaste on työryhmän ROCKET AF Steering Comm jäsen.Background-Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all-cause mortality may guide interventions. Methods and Results-In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all-cause mortality in the 14 171 participants in the intention-to-treat population. The median age was 73 years, and the mean CHADS(2) score was 3.5. Over 1.9 years of median follow-up, 1214 (8.6%) patients died. Kaplan-Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all-cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33-1.70, P= 75 years (hazard ratio 1.69, 95% CI 1.51-1.90, P Conclusions-In a large population of patients anticoagulated for nonvalvular atrial fibrillation, approximate to 7 in 10 deaths were cardiovascular, whereasPeer reviewe

Neanderthal behaviour, diet, and disease inferred from ancient DNA in dental calculus

Recent genomic data have revealed multiple interactions between Neanderthals and modern humans, but there is currently little genetic evidence regarding Neanderthal behaviour, diet, or disease. Here we describe the shotgun-sequencing of ancient DNA from five specimens of Neanderthal calcified dental plaque (calculus) and the characterization of regional differences in Neanderthal ecology. At Spy cave, Belgium, Neanderthal diet was heavily meat based and included woolly rhinoceros and wild sheep (mouflon), characteristic of a steppe environment. In contrast, no meat was detected in the diet of Neanderthals from El Sidrón cave, Spain, and dietary components of mushrooms, pine nuts, and moss reflected forest gathering. Differences in diet were also linked to an overall shift in the oral bacterial community (microbiota) and suggested that meat consumption contributed to substantial variation within Neanderthal microbiota. Evidence for self-medication was detected in an El Sidrón Neanderthal with a dental abscess and a chronic gastrointestinal pathogen (Enterocytozoon bieneusi). Metagenomic data from this individual also contained a nearly complete genome of the archaeal commensal Methanobrevibacter oralis (10.2× depth of coverage)-the oldest draft microbial genome generated to date, at around 48,000 years old. DNA preserved within dental calculus represents a notable source of information about the behaviour and health of ancient hominin specimens, as well as a unique system that is useful for the study of long-term microbial evolution

Silencing the hsp25 gene eliminates migration capability of the highly metastatic murine 4t1 breast adenocarcinoma cell

The 25-kDa heat shock protein (Hsp25) is associated with various malignancies and is expressed at high levels in biopsies as well as circulating in the serum of breast cancer patients. In this study, we used RNA interference technology to silence the hsp25 gene in 4T1 breast adenocarcinoma cells, known as a poorly immunogenic, highly metastatic cell line. We demonstrate that transfection of 4T1 cells with short interference RNA-Hsp25 dramatically inhibits proliferation as compared with control transfected cells. In addition, we show that 4T1 cells transfected with short interference RNA-Hsp25 abrogates tumor migration potential by a mechanism that is in part due to the repression of matrix metalloproteinase 9 expression and a concomitant upregulation of its antagonist, tissue inhibitor metalloproteinase 1. Taken together, these fi ndings provide a model system for the study of metastatic potential of tumors and are suggestive of an earlier unrecognized role for Hsp25 in tumor migration.Fil: Bausero, María A.. University of Boston. School of Medicine; Estados Unidos. Universidad de la República; UruguayFil: Bharti, Ajit. University of Boston. School of Medicine; Estados UnidosFil: Page, Diana T.. University of Boston. School of Medicine; Estados UnidosFil: Perez, Kristen D.. University of Boston. School of Medicine; Estados Unidos. University System Health; Estados UnidosFil: Eng, Jason W. L.. University of Boston. School of Medicine; Estados UnidosFil: Ordoñez, Susana L.. University of Boston. School of Medicine; Estados Unidos. University System Health Science; Estados UnidosFil: Jantschitsch, Christian. University of Vienna; AustriaFil: Kindas Muegge, Ingela. Institute of Cancer Research; AustriaFil: Ciocca, Daniel Ramon. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Asea, Alexander. University System Health; Estados Unidos. University of Boston. School of Medicine; Estados Unido

Asymmetric dimethylarginine is an independent risk factor for coronary heart disease: Results from the multicenter Coronary Artery Risk Determination investigating the Influence of ADMA Concentration (CARDIAC) study

BACKGROUND: Asymmetric dimethylarginine (ADMA) plasma levels have been shown to be elevated in diseases related to endothelial dysfunction such as hypertension, hyperlipidemia, diabetes mellitus, and others. It has been shown that ADMA predicts cardiovascular mortality in patients who have coronary heart disease (CHD). However, the question whether ADMA is an independent risk factor for CHD still remains unresolved. METHODS: The CARDIAC study is a multicenter case-control study, designed to detect differences in ADMA plasma levels between patients with CHD and controls from the general population. We included in our analysis 131 cases and 131 controls, matched for age, sex, and body mass index. RESULTS: We found that cases had higher ADMA plasma levels than controls (0.70 mumol/L [0.59-0.87 mumol/L] vs 0.60 mumol/L [0.54-0.69 mumol/L], P < .001). To evaluate the predictive power of ADMA regarding CHD, we calculated 2 multivariate logistic regression models including laboratory parameters and traditional risk factors. The odds ratio for ADMA in the multivariate model including the laboratory characteristics was 2.59 (1.61-4.17; P < .001); the odds ratio for the multivariate model including other risk factors was 6.04 (2.56-14.25; P < .001) for the third tertile (>0.72 mumol/L) versus the first (<0.58 mumol/L). CONCLUSIONS: We conclude from the results of our study that ADMA is an independent risk factor for CHD