Contribution of mono- and co-culture of Pseudomonas paralactis, Acinetobacter MN21 and Stenotrophomonas maltophilia to the spoilage of chill-stored lamb.

Exploring the contribution of common microorganisms to spoilage is of great significance in inhibiting spoilage in lamb. This work investigated the extent of protein degradation and profile changes of free amino acids (FAAs), free fatty acids (FFAs) and volatile organic compounds (VOCs) in lamb caused by single- and co-culture of the common aerobic spoilage bacteria, P. paralactis, Ac. MN21 and S. maltophilia. Meanwhile, some key VOCs produced by the three bacteria during lamb spoilage were also screened by orthogonal partial least square discriminant analysis and difference value in VOCs content between inoculated groups and sterile group. Lamb inoculated with P. paralactis had the higher total viable counts, pH, total volatile base nitrogen and TCA-soluble peptides than those with the other two bacteria. Some FAAs and FFAs could be uniquely degraded by P. paralactis but not Ac. MN21 and S. maltophilia, such as Arg, Glu, C15:0, C18:0 and C18:1n9t. Co-culture of the three bacteria significantly promoted the overall spoilage, including bacterial growth, proteolysis and lipolysis. Key VOCs produced by P. paralactis were 2, 3-octanedione, those by Ac. MN21 were 1-octanol, octanal, hexanoic acid, 1-pentanol and hexanoic acid methyl ester, and that by S. maltophilia were hexanoic acid. The production of extensive key-VOCs was significantly and negatively correlated with C20:0, C23:0 and C18:ln9t degradation. This study can provide a basis for inhibiting common spoilage bacteria and promoting high-quality processing of fresh lamb.

Plant Protein Blend Ingestion Stimulates Postexercise Myofibrillar Protein Synthesis Rates Equivalently to Whey in Resistance-Trained Adults.

PURPOSE: Whey protein ingestion is typically considered an optimal dietary strategy to maximize myofibrillar protein synthesis (MyoPS) after resistance exercise. Although single-source plant protein ingestion is typically less effective, at least partly, due to less favorable amino acid profiles, this could theoretically be overcome by blending plant-based proteins with complementary amino acid profiles. We compared the postexercise MyoPS response after the ingestion of a novel plant-derived protein blend with an isonitrogenous bolus of whey protein. METHODS: Ten healthy, resistance-trained, young adults (male/female: 8/2; age: 26 ± 6 yr; BMI: 24 ± 3 kg·m -2 ) received a primed continuous infusion of L-[ ring - 2 H 5 ]-phenylalanine and completed a bout of bilateral leg resistance exercise before ingesting 32 g protein from whey (WHEY) or a plant protein blend (BLEND; 39.5% pea, 39.5% brown rice, 21.0% canola) in a randomized, double-blind crossover fashion. Blood and muscle samples were collected at rest, and 2 and 4 h after exercise and protein ingestion, to assess plasma amino acid concentrations, and postabsorptive and postexercise MyoPS rates. RESULTS: Plasma essential amino acid availability over the 4 h postprandial postexercise period was ~44% higher in WHEY compared with BLEND ( P = 0.04). From equivalent postabsorptive values (WHEY, 0.042 ± 0.020%·h -1 ; BLEND, 0.043 ± 0.015%·h -1 ) MyoPS rates increased after exercise and protein ingestion (time effect; P < 0.001) over a 0- to 2-h period (WHEY, 0.085 ± 0.037%·h -1 ; BLEND, 0.080 ± 0.037%·h -1 ) and 2- to 4-h period (WHEY, 0.085 ± 0.036%·h -1 ; BLEND, 0.086 ± 0.034%·h -1 ), with no differences between conditions during either period or throughout the entire (0-4 h) postprandial period (time-condition interactions; all P > 0.05). CONCLUSIONS: Ingestion of a novel plant-based protein blend stimulates postexercise MyoPS to an equivalent extent as whey protein, demonstrating the utility of plant protein blends to optimize postexercise skeletal muscle reconditioning.

Meta-analysis of the human gut microbiome uncovers shared and distinct microbial signatures between diseases.

Microbiome studies have revealed gut microbiota's potential impact on complex diseases. However, many studies often focus on one disease per cohort. We developed a meta-analysis workflow for gut microbiome profiles and analyzed shotgun metagenomic data covering 11 diseases. Using interpretable machine learning and differential abundance analysis, our findings reinforce the generalization of binary classifiers for Crohn's disease (CD) and colorectal cancer (CRC) to hold-out cohorts and highlight the key microbes driving these classifications. We identified high microbial similarity in disease pairs like CD vs ulcerative colitis (UC), CD vs CRC, Parkinson's disease vs type 2 diabetes (T2D), and schizophrenia vs T2D. We also found strong inverse correlations in Alzheimer's disease vs CD and UC. These findings detected by our pipeline provide valuable insights into these diseases.

Perspectives on the role of nutrition in influencing academy soccer player development and performance: A qualitative case study of key stakeholders from an English category one soccer academy.

This study aimed to explore player and stakeholder perceptions of the role of nutrition in influencing the development of male academy soccer players. Semi-structured interviews (28 ± 13 mins in length) were conducted with 31 participants from an English category one academy, including players (Youth Development Phase, YDP: n = 6; Professional Development Phase, PDP: n = 4), parents/guardians (n = 10), coaches (n = 3), sport scientists (n = 3), physiotherapists (n = 3), and catering (n = 2). Via reflexive thematic analysis, data demonstrate an apparent lack of understanding and awareness on the role of nutrition in influencing player development, especially in relation to growth, maturation and reducing injury risk. Players highlighted the influence of their parents on their dietary behaviours, whilst parents also called for education to better support their sons. Notably, players and stakeholders perceived that the daily schedule of an academy soccer player presents as "too busy to eat", especially in relation to before school, and before and after training. The results demonstrate the necessity for the co-creation of player and stakeholder specific nutrition education programmes as an initial step towards positively impacting the nutrition culture associated with the academy soccer environment.

Energy Expenditure of Elite Male and Female Professional Tennis Players During Habitual Training.

Understanding the daily energy expenditure of athletes during training is important to support recovery, adaptation, and the maintenance of performance. The aim of the current research was to assess the total daily energy expenditure (TDEE) and the acute energy expenditure (EE) of tennis training sessions during habitual training of elite tennis players. Using a cohort study design, 27 (n = 10, male; age; 22.3 ± 3.2 years and n = 17, female; age: 23.8 ± 3.5 years) elite singles tennis players were assessed for TDEE and tennis training EE. Using Actiheart activity monitors during a 2- to 5-day training period, male players were analyzed for 26 days and 33 (1.3 ± 0.5 sessions/day) tennis training sessions, and female players for 43 days and 58 (1.2 ± 0.4 sessions/day) tennis training sessions. Male TDEE (4,708 ± 583 kcal/day) was significantly higher than female (3,639 ± 305 kcal/day). Male absolute and relative tennis training EEs (10.2 ± 2.3 kcal/min and 7.9 ± 1.4 kcal·hr-1·kg-1) were significantly higher than those of females (7.6 ± 1.0 kcal/min and 6.8 ± 0.9 kcal·hr-1·kg-1). The resting metabolic rate was assessed via indirect calorimetry. The physical activity level for both groups was 2.3 AU. The TDEE of male and female players during habitual training now highlights the continual cycle of high energy demands experienced by the elite tennis player. The broad ranges of TDEE and EE reported here suggest individual assessment and nutritional planning be prioritized, with a particular focus on carbohydrate requirements.

The Relationships Between External and Internal Training Loads in Mixed Martial Arts.

PURPOSE: As a multidisciplined combat sport, relationships between external and internal training loads and intensities of mixed martial arts (MMA) have not been described. The aim of this study was to determine the external loads and intensities of MMA training categories and their relationship to internal loads and intensities. METHODS: Twenty MMA athletes (age = 23.3 [5.3] y, mass = 72.1 [7.2] kg, stature = 171.5 [8.4] cm) were observed for 2 consecutive weeks. Internal load and intensity (session rating of perceived exertion [sRPE]) were calculated using the Foster RPE for the session overall (sRPE-training load [TL]) and segmented RPE (segRPE-TL) for each training category: warm-up, striking drills, wrestling drills, Brazilian jiujitsu (BJJ) drills, striking sparring, wrestling sparring, BJJ sparring, and MMA sparring. External load and intensity were measured via Catapult OptimEye S5 for the full duration of each session using accumulated Playerload (PLdACC) and PLdACC per minute (PLdACC·min-1). Differences in loads between categories and days were assessed via Bayesian analysis of variance (BF10 ≥ 3). Predictive relationships between internal and external variables were calculated using Bayesian regression. RESULTS: Session overall sRPE-TL = 448.6 (191.1) arbitrary units (AU); PLdACC = 310.6 (112) AU. Category segRPE-TL range = 33.8 (22.6) AU (warm-up) to 122.8 (54.6) AU (BJJ drills). Category PLdACC range = 44 (36.3) AU (warm-up) to 125 (58.8) AU (MMA sparring). Neither sRPE-TL nor PLdACC changed between days. PLdACC was different between categories. Evidence for regressions was strong-decisive except for BJJ drills (BF10 = 7, moderate). R2 range = .50 to .77, except for warm-up (R2 = .17), BJJ drills (R2 = .27), BJJ sparring (R2 = .49), and session overall (R2 = .13). CONCLUSIONS: While MMA training categories may be differentiated in terms of external load, overall session external load does not change within or between weeks. Resultant regression equations may be used to appropriately plan MMA technical/tactical training loads.

Learning sequence, structure, and function representations of proteins with language models.

The sequence-structure-function relationships that ultimately generate the diversity of extant observed proteins is complex, as proteins bridge the gap between multiple informational and physical scales involved in nearly all cellular processes. One limitation of existing protein annotation databases such as UniProt is that less than 1% of proteins have experimentally verified functions, and computational methods are needed to fill in the missing information. Here, we demonstrate that a multi-aspect framework based on protein language models can learn sequence-structure-function representations of amino acid sequences, and can provide the foundation for sensitive sequence-structure-function aware protein sequence search and annotation. Based on this model, we introduce a multi-aspect information retrieval system for proteins, Protein-Vec, covering sequence, structure, and function aspects, that enables computational protein annotation and function prediction at tree-of-life scales.

Under-Fuelling for the Work Required? Assessment of Dietary Practices and Physical Loading of Adolescent Female Soccer Players during an Intensive International Training and Game Schedule.

Previous studies demonstrate that "under-fuelling" (i.e., reduced carbohydrate (CHO) and energy intake (EI) in relation to recommended guidelines) is prevalent within adult female soccer players, the consequence of which may have acute performance and chronic health implications. However, the dietary practices of adolescent female soccer players, a population who may be particularly at risk for the negative aspects of low energy availability (LEA), are not well documented. Accordingly, we aimed to quantify EI and CHO intake, physical loading and estimated energy availability (EA) in elite national team adolescent female soccer players (n = twenty-three; age, 17.9 ± 0.5 years) during a 10-day training and game schedule comprising two match days on day six (MDa) and nine (MDb). The players self-reported their EI via the remote food photography method, whilst the physical loading and associated exercise energy expenditure were assessed via GPS technology. The relative CHO intake was significantly greater (all p < 0.05) on the day before the first match (MD-1a) (4.1 ± 0.8 g·kg-1), on the day before the second match (MD-1b) (4.3 ± 1.1 g·kg-1), MDa (4.8 ± 1.2 g·kg-1) and MDb (4.8 ± 1.4 g·kg-1) in comparison to most other days (<4 g·kg-1). The mean daily measured EA over the 10-day period was 34 ± 12 kcal·kg FFM-1·day-1 (with six players, i.e., 34%, presenting LEA), though, when adjusting the energy intake for potential under-reporting, these values changed substantially (44 ± 14 kcal·kg FFM-1·day-1, only one player was classed as presenting LEA). Such data suggest that the prevalence of LEA amongst female team sport athletes may be over-estimated. Nonetheless, players are still likely under-fuelling for the work required in relation to the daily CHO recommendations (i.e., >6 g·kg-1) for intensive training and game schedules. These data provide further evidence for the requirement to create and deliver targeted player and stakeholder education and behaviour change interventions (especially for younger athletes) that aim to promote increased daily CHO intake in female soccer players.

Daily energy requirements of male academy soccer players are greater than age-matched non-academy soccer players: A doubly labelled water investigation.

This study aimed to test the hypothesis that the total daily energy expenditure (TDEE) of male academy soccer players is greater than players not enrolled on a formalised academy programme. English Premier League academy (ACAD: n = 8, 13 years, 50 ± 6 kg, 88 ± 3% predicted adult stature, PAS) and non-academy players (NON-ACAD: n = 6, 13 years, 53 ± 12 kg, 89 ± 3% PAS) were assessed for TDEE (via doubly labelled water) during a 14-day in-season period. External loading was evaluated during training (ACAD: 8 sessions, NON-ACAD: 2 sessions) and games (2 games for both ACAD and NON-ACAD) via GPS, and daily physical activity was evaluated using triaxial accelerometry. Accumulative duration of soccer activity (ACAD: 975 ± 23 min, NON-ACAD: 397 ± 2 min; p < 0.01), distance covered (ACAD: 54.2 ± 8.3 km, NON-ACAD: 21.6 ± 4.7 km; p < 0.05) and time engaged in daily moderate-to-vigorous (ACAD: 124 ± 17 min, NON-ACAD: 79 ± 18 min; p < 0.01) activity was greater in academy players. Academy players displayed greater absolute (ACAD: 3380 ± 517 kcal · d-1, NON-ACAD: 2641 ± 308 kcal · d-1; p < 0.05) and relative TDEE (ACAD: 66 ± 6 kcal · kg · d-1, NON-ACAD: 52 ± 10 kcal · kg · d-1; p < 0.05) versus non-academy players. Given the injury risk associated with high training volumes during growth and maturation, data demonstrate the requirement for academy players to consume sufficient energy (and carbohydrate) intake to support the enhanced energy cost of academy programmes.

Protein remote homology detection and structural alignment using deep learning.

Exploiting sequence-structure-function relationships in biotechnology requires improved methods for aligning proteins that have low sequence similarity to previously annotated proteins. We develop two deep learning methods to address this gap, TM-Vec and DeepBLAST. TM-Vec allows searching for structure-structure similarities in large sequence databases. It is trained to accurately predict TM-scores as a metric of structural similarity directly from sequence pairs without the need for intermediate computation or solution of structures. Once structurally similar proteins have been identified, DeepBLAST can structurally align proteins using only sequence information by identifying structurally homologous regions between proteins. It outperforms traditional sequence alignment methods and performs similarly to structure-based alignment methods. We show the merits of TM-Vec and DeepBLAST on a variety of datasets, including better identification of remotely homologous proteins compared with state-of-the-art sequence alignment and structure prediction methods.

Metabolomic evolution of the postpartum dairy cow uterus.

High rates of early pregnancy loss are a critical issue in dairy herds, particularly in seasonal, grazing systems. Components of the uterine luminal fluid (ULF), on which the early embryo depends for sustenance and growth, partly determine early pregnancy losses. Here, changes in ULF from early to mid-postpartum in crossbred dairy cows were explored, linking them with divergent embryo development. For this, the uteri of 87 cows at Day 7 of pregnancy at first and third estrus postpartum were flushed to collect ULF. Eighteen metabolites (chiefly organic acids and sugars) significantly varied in abundance across postpartum, indicating a molecular signature of physiological recovery consistent of the upregulation of pyrimidine metabolism and glycerophospholipid metabolism, and downregulation of pentose phosphate and taurine metabolism pathways. Joint pathway analysis of metabolomics data and a previously generated proteomics data set on the same ULF samples suggests key links between postpartum recovery and subsequent successful embryo development. These include upregulation of VEGFA and downregulation of metabolism, NRF2, T-cell receptor, which appear to improve the ULF's capacity of sustaining normal embryo development, and a putative osmo-protectant role of beta-alanine. These relationships should be further investigated to develop tools to detect and reduce early pregnancy loss in dairy cows.

Mind the gap: limited knowledge of carbohydrate guidelines for competition in an international cohort of endurance athletes.

Despite the well-documented role of carbohydrate (CHO) in promoting endurance exercise performance, endurance athletes typically fail to meet current recommendations in competition. Adequate nutrition knowledge is key to drive athletes' behaviour, but the current level of knowledge in this population is not known. The present study assessed knowledge of CHO for competition in an international cohort of endurance athletes using the Carbohydrates for Endurance Athletes in Competition Questionnaire (CEAC-Q). The CEAC-Q was completed by 1016 individuals (45 % female), from the United Kingdom (40 %), Australia/New Zealand (22 %), the United States of America/Canada (18 %) and other countries (21 %). Total CEAC-Q scores were 50 ± 20 % (mean ± sd), with no differences in scores between the five subsections (10 ± 5 points, P < 0⋅001). Based on typical knowledge and frequency of correct answers, we defined questions with low (0-39 %), moderate (40-69 %) and high (70-100 %) knowledge at a population level. Knowledge deficiencies were identified in questions related to CHO metabolism (Low: 2 out of 5 questions (2/5), Moderate: 3/5), CHO-loading (Low: 2/5, Moderate: 1/5), pre-event CHO (Low: 2/5, Moderate: 2/5), CHO during exercise (Moderate: 4/5) and CHO for recovery (Low: 3/5, Moderate: 1/5). Current CHO amounts recommendations were identified correctly for CHO-loading, pre-competition meal, during competition >2⋅5 h) and post-competition recovery by 28% (Low), 45 % (Moderate), 48 % (Moderate), and 29 % (Low), respectively. Our findings indicate that endurance athletes typically have limited knowledge of carbohydrate guidelines for competition, and we identify specific knowledge gaps that can guide targeted nutrition education to improve knowledge as an initial step towards optimal dietary practice.

Greengenes2 unifies microbial data in a single reference tree.

Studies using 16S rRNA and shotgun metagenomics typically yield different results, usually attributed to PCR amplification biases. We introduce Greengenes2, a reference tree that unifies genomic and 16S rRNA databases in a consistent, integrated resource. By inserting sequences into a whole-genome phylogeny, we show that 16S rRNA and shotgun metagenomic data generated from the same samples agree in principal coordinates space, taxonomy and phenotype effect size when analyzed with the same tree.

Environmental heat stress offsets adaptation associated with carbohydrate periodization in trained male triathletes.

PURPOSE: Carbohydrate (CHO) intake periodization via the sleep low train low (SL-TL) diet-exercise model increases fat oxidation during exercise and may enhance endurance-training adaptation and performance. Conversely, training under environmental heat stress increases CHO oxidation, but the potential of combined SL-TL and heat stress to enhance metabolic and performance outcomes is unknown. METHODS: Twenty-three endurance-trained males were randomly assigned to either control (n = 7, CON), SL-TL (n = 8, SLTemp ) or SL-TL + heat stress (n = 8, SLHeat ) groups and prescribed identical 2-week cycling training interventions. CON and SLTemp completed all sessions at 20°C, but SLHeat at 35°C. All groups consumed matched CHO intake (6 g·kg-1 ·day-1 ) but timed differently to promote low CHO availability overnight and during morning exercise in both SL groups. Submaximal substrate utilization was assessed (at 20°C), and 30-min performance tests (at 20 and 35°C) were performed Pre-, Post-, and 1-week post-intervention (Post+1). RESULTS: SLTemp improved fat oxidation rates at 60% MAP (~66% VO2peak ) at Post+1 compared with CON (p < 0.01). Compared with SLTemp , fat oxidation rates were significantly lower in SLHeat at Post (p = 0.02) and Post+1 (p < 0.05). Compared with CON, performance was improved at Post in SLTemp in temperate conditions. Performance was not different between any groups or time points in hot conditions. CONCLUSION: SL-TL enhanced metabolic adaptation and performance compared with CON and combined SL-TL and heat stress. Additional environmental heat stress may impair positive adaptations associated with SL-TL.

Multi-level analysis of the gut-brain axis shows autism spectrum disorder-associated molecular and microbial profiles.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by heterogeneous cognitive, behavioral and communication impairments. Disruption of the gut-brain axis (GBA) has been implicated in ASD although with limited reproducibility across studies. In this study, we developed a Bayesian differential ranking algorithm to identify ASD-associated molecular and taxa profiles across 10 cross-sectional microbiome datasets and 15 other datasets, including dietary patterns, metabolomics, cytokine profiles and human brain gene expression profiles. We found a functional architecture along the GBA that correlates with heterogeneity of ASD phenotypes, and it is characterized by ASD-associated amino acid, carbohydrate and lipid profiles predominantly encoded by microbial species in the genera Prevotella, Bifidobacterium, Desulfovibrio and Bacteroides and correlates with brain gene expression changes, restrictive dietary patterns and pro-inflammatory cytokine profiles. The functional architecture revealed in age-matched and sex-matched cohorts is not present in sibling-matched cohorts. We also show a strong association between temporal changes in microbiome composition and ASD phenotypes. In summary, we propose a framework to leverage multi-omic datasets from well-defined cohorts and investigate how the GBA influences ASD.

Earth Worming-An Evaluation of Earthworm (Eisenia andrei) as an Alternative Food Source.

Aside from their bioremediation roles, little is known about the food and feed value of earthworms. In this study, a comprehensive evaluation of the nutritional composition (proximate analysis and profiles of fatty acids and minerals) and techno-functional properties (foaming and emulsion stability and capacity) of earthworm (Eisenia andrei, sourced in New Zealand) powder (EAP) were investigated. Lipid nutritional indices, ω6/ω3, atherogenicity index, thrombogenicity index, hypocholesterolemic/hypercholesterolemic acid ratio, and health-promoting index of EAP lipids are also reported. The protein, fat, and carbohydrate contents of EAP were found to be 53.75%, 19.30%, and 23.26% DW, respectively. The mineral profile obtained for the EAP consisted of 11 essential minerals, 23 non-essential minerals, and 4 heavy metals. The most abundant essential minerals were potassium (8220 mg·kg-1 DW), phosphorus (8220 mg·kg-1 DW), magnesium (744.7 mg·kg-1 DW), calcium (2396.7 mg·kg-1 DW), iron (244.7 mg·kg-1 DW), and manganese (25.6 mg·kg-1 DW). Toxic metals such as vanadium (0.2 mg·kg-1 DW), lead (0.2 mg·kg-1 DW), cadmium (2.2 mg·kg-1 DW), and arsenic (2.3 mg·kg-1 DW) were found in EAP, which pose safety considerations. Lauric acid (20.3% FA), myristoleic acid (11.20% FA), and linoleic acid (7.96% FA) were the most abundant saturated, monounsaturated, and polyunsaturated fatty acids, respectively. The lipid nutritional indices, such as IT and ω-6/ω-3, of E. andrei were within limits considered to enhance human health. A protein extract derived from EAP (EAPPE), obtained by alkaline solubilisation and pH precipitation, exhibited an isoelectric pH of ~5. The total essential amino acid content and essential amino acid index of EAPPE were 373.3 mg·g-1 and 1.36 mg·g-1 protein, respectively. Techno-functional analysis of EAPPE indicated a high foaming capacity (83.3%) and emulsion stability (88.8% after 60 min). Heat coagulation of EAPPE was greater at pH 7.0 (12.6%) compared with pH 5.0 (4.83%), corroborating the pH-solubility profile and relatively high surface hydrophobicity (1061.0). These findings demonstrate the potential of EAP and EAPPE as nutrient-rich and functional ingredients suitable as alternative food and feed material. The presence of heavy metals, however, should be carefully considered.

The Local Tumor Microbiome Is Associated with Survival in Late-Stage Colorectal Cancer Patients.

The gut microbiome is associated with survival in colorectal cancer. Single organisms have been identified as markers of poor prognosis. However, in situ imaging of tumors demonstrate a polymicrobial tumor-associated community. To understand the role of these polymicrobial communities in survival, we conducted a nested case-control study in late-stage cancer patients undergoing resection for primary adenocarcinoma. The microbiome of paired tumor and adjacent normal tissue samples was profiled using 16S rRNA sequencing. We found a consistent difference in the microbiome between paired tumor and adjacent tissue, despite strong individual microbial identities. Furthermore, a larger difference between normal and tumor tissue was associated with prognosis: patients with shorter survival had a larger difference between normal and tumor tissue. Within the tumor tissue, we identified a 39-member community statistic associated with survival; for every log2-fold increase in this value, an individual's odds of survival increased by 20% (odds ratio survival 1.20; 95% confidence interval = 1.04 to 1.33). Our results suggest that a polymicrobial tumor-specific microbiome is associated with survival in late-stage colorectal cancer patients. IMPORTANCE Microbiome studies in colorectal cancer (CRC) have primarily focused on the role of single organisms in cancer progression. Recent work has identified specific organisms throughout the intestinal tract, which may affect survival; however, the results are inconsistent. We found differences between the tumor microbiome and the microbiome of the rest of the intestine in patients, and the magnitude of this difference was associated with survival, or, the more like a healthy gut a tumor looked, the better a patient's prognosis. Our results suggest that future microbiome-based interventions to affect survival in CRC will need to target the tumor community.

Human skeletal muscle methylome after low-carbohydrate energy-balanced exercise.

We aimed to investigate the human skeletal muscle (SkM) DNA methylome after exercise in low-carbohydrate (CHO) energy-balance (with high-fat) conditions compared with exercise in low-CHO energy-deficit (with low-fat) conditions. The objective was to identify novel epigenetically regulated genes and pathways associated with "train-low sleep-low" paradigms. The sleep-low conditions included nine males that cycled to deplete muscle glycogen while reaching a set energy expenditure. Postexercise, low-CHO meals (protein matched) completely replaced (using high fat) or only partially replaced (low fat) the energy expended. The following morning, resting baseline biopsies were taken and the participants then undertook 75 minutes of cycling exercise, with skeletal muscle biopsies collected 30 minutes and 3.5 hours postexercise. Discovery of genome-wide DNA methylation was undertaken using Illumina EPIC arrays, and targeted gene expression analysis was conducted by quantitative RT-PCR. At baseline, participants under energy balance (high fat) demonstrated a predominantly hypermethylated (60%) profile across the genome compared to energy-deficit low-fat conditions. However, postexercise performed in energy balance (with high fat) elicited a more prominent hypomethylation signature 30 minutes postexercise in gene regulatory regions important for transcription (CpG islands within promoter regions) compared with exercise in energy-deficit (with low-fat) conditions. Such hypomethylation was enriched within pathways related to IL6-JAK-STAT signaling, metabolic processes, p53/cell cycle, and oxidative/fatty acid metabolism. Hypomethylation within the promoter regions of the genes; histone deacetylase 2 (HDAC2), MECR, IGF2, and c13orf16 were associated with significant increases in gene expression in the postexercise period in energy balance compared with an energy deficit. Furthermore, HDAC11 was oppositely regulated at the gene expression level compared with family member HDAC2, where HDAC11 was hypomethylated yet increased in energy-deficit compared with energy-balance conditions. Overall, we identify some novel epigenetically regulated genes associated with train-low sleep-low paradigms.NEW & NOTEWORTHY We identify novel epigenetically regulated genes associated with train-low sleep-low paradigms. Exercise under low-carbohydrate (CHO) energy-balance (high-fat) conditions elicited a more prominent DNA hypomethylation signature 30 minutes postexercise compared with low-CHO energy-deficit (low-fat) conditions. This was enriched within IL6-JAK-STAT signaling, metabolic processes, p53, cell cycle, oxidative phosphorylation, and fatty acid metabolism. Histone deacetylase (HDAC) family members 2, 4, 10, and 11 demonstrated hypomethylation, with HDAC2 and HDAC11 possessing alternative regulation of gene expression in energy balance versus deficit conditions.