Liver disease encompasses pathologies as non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, alcohol liver disease, hepatocellular carcinoma, viral hepatitis, and autoimmune hepatitis. ...Nowadays, underlying mechanisms associating gut permeability and liver disease development are not well understood, although evidence points to the involvement of intestinal microbiota and their metabolites. Animal studies have shown alterations in Toll-like receptor signaling related to the leaky gut syndrome by the action of bacterial lipopolysaccharide. In humans, modifications of the intestinal microbiota in intestinal permeability have also been related to liver disease. Some of these changes were observed in bacterial species belonging
,
, and
. Currently, numerous strategies to treat liver disease are being assessed. This review summarizes and discusses studies addressed to determine mechanisms associated with the microbiota able to alter the intestinal barrier complementing the progress and advancement of liver disease, as well as the main strategies under development to manage these pathologies. We highlight those approaches that have shown improvement in intestinal microbiota and barrier function, namely lifestyle changes (diet and physical activity) and probiotics intervention. Nevertheless, knowledge about how such modifications are beneficial is still limited and specific mechanisms involved are not clear. Thus, further in-vitro, animal, and human studies are needed.
Breast cancer ranks first in women, and is the second cause of death in this gender. In addition to genetics, the environment contributes to the development of the disease, although the factors ...involved are not well known. Among the latter is the influence of microorganisms and, therefore, attention is recently being paid to the mammary microbiota. We hypothesize that the risk of breast cancer could be associated with the composition and functionality of the mammary/gut microbiota, and that exposure to environmental contaminants (endocrine disruptors, EDCs) might contribute to alter these microbiota.
We describe a case-control clinical study that will be performed in women between 25 and 70 years of age. Cases will be women diagnosed and surgically intervened of breast cancer (stages I and II). Women with antecedents of cancer or advanced tumor stage (metastasis), or who have received antibiotic treatment within a period of 3 months prior to recruitment, or any neoadjuvant therapy, will be excluded. Controls will be women surgically intervened of breast augmentation or reduction. Women with oncological, gynecological or endocrine history, and those who have received antibiotic treatment within a period of 3 months prior to recruitment will also be excluded. Blood, urine, breast tissue and stool samples will be collected. Data regarding anthropometric, sociodemographic, reproductive history, tumor features and dietary habits will be gathered. Metabolomic studies will be carried out in stool and breast tissue samples. Metagenomic studies will also be performed in stool and breast tissue samples to ascertain the viral, fungal, bacterial and archaea populations of the microbiota. Quantitation of estrogens, estrogen metabolites and EDCs in samples of serum, urine and breast tissue will also be performed.
This is the first time that the contribution of bacteria, archaea, viruses and fungi together with their alteration by environmental contaminants to the risk of breast cancer will be evaluated in the same study. Results obtained could contribute to elucidate risk factors, improve the prognosis, as well as to propose novel intervention studies in this disease.
ClinicalTrials.gov NCT03885648 , 03/25/2019. Retrospectively registered.
Abstract
STUDY QUESTION
Does endometrium harbour functionally active microorganisms and whether the microbial composition differs between proliferative and mid-secretory phases?
SUMMARY ANSWER
...Endometrium harbours functionally alive microorganisms including bacteria, viruses, archaea and fungi whose composition and metabolic functions change along the menstrual cycle.
WHAT IS KNOWN ALREADY
Resident microbes in the endometrium have been detected, where microbial dysfunction has been associated with reproductive health and disease. Nevertheless, the core microorganismal composition in healthy endometrium is not determined and whether the identified bacterial DNA sequences refer to alive/functionally active microbes is not clear. Furthermore, whether there are cyclical changes in the microbial composition remains an open issue.
STUDY DESIGN, SIZE, DURATION
RNA sequencing (RNAseq) data from 14 endometrial paired samples from healthy women, 7 samples from the mid-secretory phase and 7 samples from the consecutive proliferative phase were analysed for the microbial RNA sequences.
PARTICIPANTS/MATERIALS, SETTING, METHODS
The raw RNAseq data were converted into FASTQ format using SRA Toolkit. The unmapped reads to human sequences were aligned to the reference database Kraken2 and visualised with Krona software. Menstrual phase taxonomic differences were performed by R package metagenomeSeq. The functional analysis of endometrial microbiota was obtained with HUMANn2 and the comparison between menstrual phases was conducted by one-way ANOVA. Human RNAseq analysis was performed using miARma-Seq and the functional enrichment analysis was carried out using gene set enrichment analysis (GSEA; HumanCyc). The integration of metabolic pathways between host and microbes was investigated. The developed method of active microbiota mapping was validated in independent sample set.
MAIN RESULTS AND THE ROLE OF CHANCE
With the novel metatranscriptomic approach, we mapped the entire alive microbiota composing of >5300 microorganisms within the endometrium of healthy women. Microbes such as bacteria, fungi, viruses and archaea were identified. The validation of three independent endometrial samples from different ethnicity confirmed the findings. Significant differences in the microbial abundances in the mid-secretory vs. proliferative phases were detected with possible metabolic activity in the host-microbiota crosstalk in receptive phase endometrium, specifically in the prostanoid biosynthesis pathway and L-tryptophan metabolism.
LARGE SCALE DATA
The raw RNAseq data used in the current study are available at GEO GSE86491 and at BioProject PRJNA379542.
LIMITATIONS, REASONS FOR CAUTION
These pioneering results should be confirmed in a bigger sample size.
WIDER IMPLICATIONS OF THE FINDINGS
Our study confirms the presence of active microbes, bacteria, fungi, viruses and archaea in the healthy human endometrium with implications in receptive phase endometrial functions, meaning that microbial dysfunction could impair the metabolic pathways important for endometrial receptivity. The results of this study contribute to the better understanding of endometrial microbiota composition in healthy women and its possible role in endometrial functions. In addition, our novel methodological pipeline for analysing alive microbes with transcriptional and metabolic activities could serve to inspire new analysis approaches in reproductive medicine.
STUDY FUNDING/COMPETING INTERESTS
This work is supported by the Spanish Ministry of Economy, Industry and Competitiveness (MINECO) and European Regional Development Fund (FEDER): grants RYC-2016-21199 and ENDORE SAF2017-87526-R; FEDER/Junta de Andalucía-Consejería de Economía y Conocimiento: MENDO (B-CTS-500-UGR18) and by the University of Granada Plan Propio de Investigación 2016 - Excellence actions: Unit of Excellence on Exercise and Health (UCEES) (SOMM17/6107/UGR). A.S.-L. and N.M.M. are funded by the Spanish Ministry of Science, Innovation and Universities (PRE2018-0854409 and FPU19/01638). S.A. has received honoraria for lectures from Merck. The funder had no role in this study.
We aimed to test whether high-intensity high-volume training (HIHVT) swimming would induce more robust signaling than sprint interval training (SIT) swimming within the m. triceps brachii due to ...lower metabolic and oxidation. Nine well-trained swimmers performed the two training procedures on separate randomized days. Muscle biopsies from m. triceps brachii and blood samples were collected at three different time points: a) before the intervention (pre), b) immediately after the swimming procedures (post) and c) after 3 h of rest (3 h). Hydroperoxides, creatine kinase (CK), and lactate dehydrogenase (LDH) were quantified from blood samples, and peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) and the AMPK.sup.pTHR172 /AMPK ratio were quantified by Western blot analysis. PGC-1alpha, sirtuin 3 (SIRT3), superoxide-dismutase 2 (SOD2), and vascular endothelial growth factor (VEGF) mRNA levels were also quantified. SIT induced a higher release of LDH (p 0.01 at all time points) and CK (p 0.01 at post) than HIHVT, but neither SIT nor HIHVT altered systemic hydroperoxides. Additionally, neither SIRT3 nor SOD2 mRNA levels increased, while PGC-1alpha transcription increased at 3 h after SIT (p 0.01) and after HIHVT (p 0.001). However, PGC-1alpha protein was higher after HIHVT than after SIT (p 0.05). Moreover, the AMPK.sup.pTHR172 /AMPK ratio increased at post after SIT (p 0.05), whereas this effect was delayed after HIHVT as it increased after 3 h (p 0.05). In addition, VEGF transcription was higher in response to HIHVT (p 0.05). In conclusion, SIT induces higher muscular stress than HIHVT without increasing systemic oxidation. In addition, HIHVT may induce more robust oxidative adaptations through PGC-1alpha and AMPK.
Eating behavior problems are characteristic of children with autism spectrum disorders (ASD) with a highly restricted range of food choices, which may pose an associated risk of nutritional problems. ...Hence, detailed knowledge of the dietary patterns (DPs) and nutrient intakes of ASD patients is necessary to carry out intervention strategies if required. The present study aimed to determine the DPs and macro-and micronutrient intakes in a sample of Spanish preschool children with ASD compared to typically developing control children. Fifty-four children with ASD (two to six years of age) diagnosed with ASD according to the Diagnostic Manual-5 criteria), and a control group of 57 typically developing children of similar ages were recruited. A validated food frequency questionnaire was used, and the intake of energy and nutrients was estimated through three non-consecutive 24-h dietary registrations. DPs were assessed using principal component analysis and hierarchical clustering analysis. Children with ASD exhibited a DP characterized by high energy and fat intakes and a low intake of vegetables and fruits. Likewise, meat intake of any type, both lean and fatty, was associated with higher consumption of fish and dietary fat. Furthermore, the increased consumption of dairy products was associated with increased consumption of cereals and pasta. In addition, they had frequent consumption of manufactured products with poor nutritional quality, e.g., beverages, sweets, snacks and bakery products. The percentages of children with ASD complying with the adequacy of nutrient intakes were higher for energy, saturated fat, calcium, and vitamin C, and lower for iron, iodine, and vitamins of group B when compared with control children. In conclusion, this study emphasizes the need to assess the DPs and nutrient intakes of children with ASD to correct their alterations and discard some potential nutritional diseases.
There are many differences in the fecal infant microbiota associated with various feeding methods. The aim of this study was to examine the major differences in the fecal microbiota of breast-fed ...(BF) and formula-fed (FF) infants and to describe the principal bacterial components that would explain the variability in the predominant bacterial families and genus clusters.
Fecal samples from 58 infants, 31 of whom were exclusively BF and 27 of whom were exclusively FF with a standard formula in agreement with the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition recommendations, were analyzed by fluorescent in situ hybridization combined with flow cytometry. Principal component analysis was used to maximize the information gained for the predominant bacterial families and genus clusters using a minimal number of bacterial groups.
The predominant detected group was Bifidobacterium, followed by Enterobacteriaceae and Bacteroides in both BF and FF infants. The Lactobacillus group was the only independent variable associated with FF infants. We also found that 3 principal components were sufficient to describe the association between the bacterial group, genus, and species studied in BF and FF infants; however, these components differed between BF and FF infants. For the former, the 3 factors found were Bifidobacterium/Enterobacteriaceae, Lactobacillus/Bacteroides, and Clostridium coccoides/Atopobium; for the latter, Bifidobacterium/Enterobacteriaceae, Bacteroides and C coccoides were observed.
There is a clear clustering of components of infant microbiota based on the feeding method.
We have previously described the safety and immunomodulatory effects of Lactobacillus paracasei CNCM I-4034, Bifidobacterium breve CNCM I-4035 and Lactobacillus rhamnosus CNCM I-4036 in healthy ...volunteers. The scope of this work was to evaluate the effects of these probiotic strains on the hepatic steatosis of obese rats. We used the Zucker rat as a genetic model of obesity. Zucker-Lepr(fa/fa) rats received one of three probiotic strains, a mixture of L. paracasei CNCM I-4034 and B. breve CNCM I-4035, or a placebo for 30 days. An additional group of Zucker-lean+/fa rats received a placebo for 30 days. No alterations in intestinal histology, in the epithelial, lamina propria, muscular layers of the ileal or colonic mucosa, or the submucosae, were observed in any of the experimental groups. Triacylglycerol content decreased in the liver of Zucker-Lepr(fa/fa) rats that were fed L. rhamnosus, B. breve, or the mixture of B. breve and L. paracasei. Likewise, the area corresponding to neutral lipids was significantly smaller in the liver of all four groups of Zucker-Lepr(fa/fa) rats that received probiotics than in rats fed the placebo. Zucker-Lepr(fa/fa) rats exhibited significantly greater serum LPS levels than Zucker-lean+/fa rats upon administration of placebo for 30 days. In contrast, all four groups of obese Zucker-Lepr(fa/fa) rats that received LAB strains exhibited serum LPS concentrations similar to those of Zucker-lean+/fa rats. Serum TNF-α levels decreased in the Zucker-Lepr(fa/fa) rats that received B. breve, L. rhamnosus, or the mixture, whereas L. paracasei feeding decreased IL-6 levels in the serum of Zucker-Lepr(fa/fa) rats. In conclusion, the probiotic strains reduced hepatic steatosis in part by lowering serum LPS, and had an anti-inflammatory effect in obese Zucker rats.
Exclusive breastfeeding is highly recommended for infants for at least the first six months of life. However, for some mothers, it may be difficult or even impossible to do so. This can lead to ...disturbances in the gut microbiota, which in turn may be related to a higher incidence of acute infectious diseases. Here, we aimed to evaluate whether a novel starting formula versus a standard formula provides a gut microbiota composition more similar to that of breastfed infants in the first 6 months of life. Two hundred and ten infants (70/group) were enrolled in the study and completed the intervention until 12 months of age. For the intervention period, infants were divided into three groups: Group 1 received formula 1 (INN) with a lower amount of protein, a proportion of casein to whey protein ratio of about 70/30 by increasing the content of α-lactalbumin, and with double the amount of docosahexaenoic acid/arachidonic acid than the standard formula; INN also contained a thermally inactivated postbiotic (
subsp.
). Group 2 received the standard formula (STD) and the third group was exclusively breastfed (BF) for exploratory analysis. During the study, visits were made at 21 days, 2, 4, and 6 months of age, with ±3 days for the visit at 21 days of age, ±1 week for the visit at 2 months, and ±2 weeks for the others. Here, we reveal how consuming the INN formula promotes a similar gut microbiota composition to those infants that were breastfed in terms of richness and diversity, genera, such as
,
, and
, and calprotectin and short-chain fatty acid levels at 21 days, 2 and 6 months. Furthermore, we observed that the major bacteria metabolic pathways were more alike between the INN formula and BF groups compared to the STD formula group. Therefore, we assume that consumption of the novel INN formula might improve gut microbiota composition, promoting a healthier intestinal microbiota more similar to that of an infant who receives exclusively human milk.
Myotonic dystrophy type 1 (DM1), the most common form of adult muscular dystrophy, is caused by an abnormal expansion of CTG repeats in the 3' untranslated region of the dystrophia myotonica protein ...kinase (DMPK) gene. The expanded repeats of the DMPK mRNA form hairpin structures in vitro, which cause misregulation and/or sequestration of proteins including the splicing regulator muscleblind-like 1 (MBNL1). In turn, misregulation and sequestration of such proteins result in the aberrant alternative splicing of diverse mRNAs and underlie, at least in part, DM1 pathogenesis. It has been previously shown that disaggregating RNA foci repletes free MBNL1, rescues DM1 spliceopathy, and alleviates associated symptoms such as myotonia. Using an FDA-approved drug library, we have screened for a reduction of CUG foci in patient muscle cells and identified the HDAC inhibitor, vorinostat, as an inhibitor of foci formation; SERCA1 (sarcoplasmic/endoplasmic reticulum Ca
-ATPase) spliceopathy was also improved by vorinostat treatment. Vorinostat treatment in a mouse model of DM1 (human skeletal actin-long repeat; HSA
) improved several spliceopathies, reduced muscle central nucleation, and restored chloride channel levels at the sarcolemma. Our in vitro and in vivo evidence showing amelioration of several DM1 disease markers marks vorinostat as a promising novel DM1 therapy.
Recent studies have shown that certain nutrients, specific food groups, or general dietary patterns (DPs) can promote health and prevent noncommunicable chronic diseases (NCCDs). Both developed and ...developing countries experience a high prevalence of NCCDs due to poor lifestyle habits, DPs, and low physical activity levels. This study aims to examine the dietary, physical activity, sociodemographic, and lifestyle patterns of Uruguayan State Electrical Company workers (the IN-UTE study). A total of 2194 workers participated in the study, providing information about their sociodemographics, lifestyles, and dietary habits through different questionnaires. To identify DPs from 16 food groups, principal component analysis (PCA) was performed. A hierarchical cluster algorithm was used to combine food groups and sociodemographic/lifestyle variables. Four DPs were extracted from the data; the first DP was related to the intake of energy-dense foods, the second DP to the characteristics of the job, the third DP to a Mediterranean-style diet, and the fourth DP to age and body mass index. In addition, cluster analysis involving a larger number of lifestyle variables produced similar results to the PCA. Lifestyle and sociodemographic factors, including night work, working outside, and moderate and intense PA, were significantly correlated with the dietary clusters, suggesting that working conditions, socioeconomic status, and PA may play an important role in determining DPs to some extent. Accordingly, these findings should be used to design lifestyle interventions to reverse the appearance of unhealthy DPs in the UTE population.
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