Animals in the wild are able to subsist on pathogen-infected and poisonous food and show immunity to various diseases. These may be due to their microbiota, yet we have a poor understanding of animal ...microbial diversity and function. We used metagenomics to analyze the gut microbiota of more than 180 species in the wild, covering diverse classes, feeding behaviors, geographies, and traits. Using de novo metagenome assembly, we constructed and functionally annotated a database of more than 5000 genomes, comprising 1209 bacterial species of which 75% are unknown. The microbial composition, diversity, and functional content exhibit associations with animal taxonomy, diet, activity, social structure, and life span. We identify the gut microbiota of wild animals as a largely untapped resource for the discovery of therapeutics and biotechnology applications.
Complex diseases, such as coronary artery disease (CAD), are often multifactorial, caused by multiple underlying pathological mechanisms. Here, to study the multifactorial nature of CAD, we performed ...comprehensive clinical and multi-omic profiling, including serum metabolomics and gut microbiome data, for 199 patients with acute coronary syndrome (ACS) recruited from two major Israeli hospitals, and validated these results in a geographically distinct cohort. ACS patients had distinct serum metabolome and gut microbial signatures as compared with control individuals, and were depleted in a previously unknown bacterial species of the Clostridiaceae family. This bacterial species was associated with levels of multiple circulating metabolites in control individuals, several of which have previously been linked to an increased risk of CAD. Metabolic deviations in ACS patients were found to be person specific with respect to their potential genetic or environmental origin, and to correlate with clinical parameters and cardiovascular outcomes. Moreover, metabolic aberrations in ACS patients linked to microbiome and diet were also observed to a lesser extent in control individuals with metabolic impairment, suggesting the involvement of these aberrations in earlier dysmetabolic phases preceding clinically overt CAD. Finally, a metabolomics-based model of body mass index (BMI) trained on the non-ACS cohort predicted higher-than-actual BMI when applied to ACS patients, and the excess BMI predictions independently correlated with both diabetes mellitus (DM) and CAD severity, as defined by the number of vessels involved. These results highlight the utility of the serum metabolome in understanding the basis of risk-factor heterogeneity in CAD.
Dietary modifications are crucial for managing newly diagnosed type 2 diabetes mellitus (T2DM) and preventing its health complications, but many patients fail to achieve clinical goals with diet ...alone. We sought to evaluate the clinical effects of a personalized postprandial-targeting (PPT) diet on glycemic control and metabolic health in individuals with newly diagnosed T2DM as compared to the commonly recommended Mediterranean-style (MED) diet.
We enrolled 23 adults with newly diagnosed T2DM (aged 53.5 ± 8.9 years, 48% males) for a randomized crossover trial of two 2-week-long dietary interventions. Participants were blinded to their assignment to one of the two sequence groups: either PPT-MED or MED-PPT diets. The PPT diet relies on a machine learning algorithm that integrates clinical and microbiome features to predict personal postprandial glucose responses (PPGR). We further evaluated the long-term effects of PPT diet on glycemic control and metabolic health by an additional 6-month PPT intervention (n = 16). Participants were connected to continuous glucose monitoring (CGM) throughout the study and self-recorded dietary intake using a smartphone application.
In the crossover intervention, the PPT diet lead to significant lower levels of CGM-based measures as compared to the MED diet, including average PPGR (mean difference between diets, - 19.8 ± 16.3 mg/dl × h, p < 0.001), mean glucose (mean difference between diets, - 7.8 ± 5.5 mg/dl, p < 0.001), and daily time of glucose levels > 140 mg/dl (mean difference between diets, - 2.42 ± 1.7 h/day, p < 0.001). Blood fructosamine also decreased significantly more during PPT compared to MED intervention (mean change difference between diets, - 16.4 ± 37 μmol/dl, p < 0.0001). At the end of 6 months, the PPT intervention leads to significant improvements in multiple metabolic health parameters, among them HbA1c (mean ± SD, - 0.39 ± 0.48%, p < 0.001), fasting glucose (- 16.4 ± 24.2 mg/dl, p = 0.02) and triglycerides (- 49 ± 46 mg/dl, p < 0.001). Importantly, 61% of the participants exhibited diabetes remission, as measured by HbA1c < 6.5%. Finally, some clinical improvements were significantly associated with gut microbiome changes per person.
In this crossover trial in subjects with newly diagnosed T2DM, a PPT diet improved CGM-based glycemic measures significantly more than a Mediterranean-style MED diet. Additional 6-month PPT intervention further improved glycemic control and metabolic health parameters, supporting the clinical efficacy of this approach.
ClinicalTrials.gov number, NCT01892956.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Diabetes and associated comorbidities are a global health threat on the rise. We conducted a six-month dietary intervention in pre-diabetic individuals (NCT03222791), to mitigate the ...hyperglycemia and enhance metabolic health. The current work explores early diabetes markers in the 200 individuals who completed the trial. We find 166 of 2,803 measured features, including oral and gut microbial species and pathways, serum metabolites and cytokines, show significant change in response to a personalized postprandial glucose-targeting diet or the standard of care Mediterranean diet. These changes include established markers of hyperglycemia as well as novel features that can now be investigated as potential therapeutic targets. Our results indicate the microbiome mediates the effect of diet on glycemic, metabolic and immune measurements, with gut microbiome compositional change explaining 12.25% of serum metabolites variance. Although the gut microbiome displays greater compositional changes compared to the oral microbiome, the oral microbiome demonstrates more changes at the genetic level, with trends dependent on environmental richness and species prevalence in the population. In conclusion, our study shows dietary interventions can affect the microbiome, cardiometabolic profile and immune response of the host, and that these factors are well associated with each other, and can be harnessed for new therapeutic modalities.
The 10 K is a large-scale prospective longitudinal cohort and biobank that was established in Israel. The primary aims of the study include development of prediction models for disease onset and ...progression and identification of novel molecular markers with a diagnostic, prognostic and therapeutic value. The recruitment was initiated in 2018 and is expected to complete in 2021. Between 28/01/2019 and 13/12/2020, 4,629 from the expected 10,000 participants were recruited (46 %). Follow-up visits are scheduled every year for a total of 25 years. The cohort includes individuals between the ages of 40 and 70 years. Predefined medical conditions were determined as exclusions. Information collected at baseline includes medical history, lifestyle and nutritional habits, vital signs, anthropometrics, blood tests results, Electrocardiography, Ankle–brachial pressure index (ABI), liver US and Dual-energy X-ray absorptiometry (DXA) tests. Molecular profiling includes transcriptome, proteome, gut and oral microbiome, metabolome and immune system profiling. Continuous measurements include glucose levels using a continuous glucose monitoring device for 2 weeks and sleep monitoring by a home sleep apnea test device for 3 nights. Blood and stool samples are collected and stored at − 80 °C in a storage facility for future research. Linkage is being established with national disease registries.
Background
Atopic dermatitis (AD) is a remitting relapsing chronic eczematous pruritic disease. Several studies suggest that gut microbiota may influence AD by immune system regulation.
Methods
We ...performed the first in‐human efficacy and safety assessment of fecal microbiota transplantation (FMT) for AD adult patients. All patients received 2 placebo transplantations followed by 4 FMTs each 2 weeks apart. AD severity and fecal microbiome profile were evaluated by the Scoring Atopic Dermatitis Score (SCORAD), the weekly frequency of topical corticosteroids usage, and gut microbiota metagenomic analysis, at the study beginning, before every FMT, and 1–8 months after the last FMT.
Results
Nine patients completed the study protocol. There was no significant change in the SCORAD score following the two placebo transplants. The average SCORAD score significantly decreased from baseline at Weeks 4–12 (before and 2 weeks after 4 times of FMT) (59.2 ± 34.9%, Wilcoxon p = .011), 50% and 75% decrease was achieved by 7 (77%) and 4 (44%) patients, respectively. At Week 18 (8 weeks after the last FMT) the average SCORAD score decreased from baseline at Week 4 (85.5 ± 8.4%, Wilcoxon p = .018), 50% and 75% decrease was achieved by 7 (77%) and 6 (66.7%) patients respectively. Weekly topical corticosteroids usage was diminished during the study and follow‐up period as well. Two patients had a quick relapse and were switched to a different treatment. Two patients developed exacerbations alleviated after an additional fifth FMT.
Metagenomic analysis of the fecal microbiota of patients and donors showed bacterial strains transmission from donors to patients. No adverse events were recorded during the study and follow‐up period.
Conclusions
FMT may be a safe and effective therapeutic intervention for AD patients, associated with transfer of specific microbial species from the donors to the patients. Further studies are required to reconfirm these results.
Graphical
Fecal microbiota transplantation may be a safe and effective therapeutic intervention for AD patients, associated with transfer of specific microbial species from the donors to the patients.
Multiple sclerosis (MS) is an immune-mediated disease whose precise etiology is unknown. Several studies found alterations in the microbiome of individuals with MS, but the mechanism by which it may ...affect MS is poorly understood. Here we analyze the microbiome of 129 individuals with MS and find that they harbor distinct microbial patterns compared with controls. To study the functional consequences of these differences, we measure levels of 1,251 serum metabolites in a subgroup of subjects and unravel a distinct metabolite signature that separates affected individuals from controls nearly perfectly (AUC = 0.97). Individuals with MS are found to be depleted in butyrate-producing bacteria and in bacteria that produce indolelactate, an intermediate in generation of the potent neuroprotective antioxidant indolepropionate, which we found to be lower in their serum. We identify microbial and metabolite candidates that may contribute to MS and should be explored further for their causal role and therapeutic potential.
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Gut microbiota and metabolites profiles of individuals with MS differ from healthy controlsIndividuals with MS have reduced serum levels of indolepropionateIndividuals with MS have reduced serum levels of indolelactate and its producing bacteriaIndividuals with MS have lower levels of species and genes involved in butyrate production
Levi et al. perform a coupled analysis of gut microbiota, untargeted metabolomics, gene expression, nutritional records, and clinical data of individuals with MS. The results suggest that increasing the levels of butyrate-producing species and the levels of the tryptophan metabolites indolepropionate and indolelactate in individuals with MS may have potential benefits.
IntroductionBreast cancer survivors treated with adjuvant endocrine therapy commonly experience weight gain, which has been associated with low adherence to therapy and worse breast cancer prognosis. ...We aim to assess whether a personalised postprandial glucose targeting diet will be beneficial for weight management as compared with the recommended Mediterranean diet in this patient populationMethods and analysisThe BREAst Cancer Personalised NuTrition study is a phase-2 randomised trial in hormone receptor positive patients with breast cancer, treated with adjuvant endocrine therapy. The study objective is to assess whether dietary intervention intended to improve postprandial glycaemic response to meals results in better weight and glycaemic control in this population as compared with the standard recommended Mediterranean diet. Consenting participants will be assigned in a single blinded fashion to either of two dietary arms (Mediterranean diet or an algorithm-based personalised diet). They will be asked to provide a stool sample for microbiome analysis and will undergo continuous glucose monitoring for 2 weeks, at the initiation and termination of the intervention period. Microbiome composition data will be used to tailor personal dietary recommendations. After randomisation and provision of dietary recommendations, participants will be asked to continuously log their diet and lifestyle activities on a designated smartphone application during the 6-month intervention period, during which they will be monthly monitored by a certified dietitian. Participants’ clinical records will be followed twice yearly for 5 years for treatment adherence, disease-free survival and recurrence.Ethics and disseminationThe study has been approved by the ethics committee in the Sheba medical centre (file 5725-18-SMC, Ramat Gan, Israel) and the Weizmann Institutional Review Board (file 693-2, Rehovot, Israel). The findings of this study will be published in a peer reviewed publication.Trial registration numberNCT04079270.
IntroductionMetformin and diets aimed at promoting healthy body weight are the first line in treating type 2 diabetes mellitus (T2DM). Clinical practice, backed by clinical trials, suggests that many ...individuals do not reach glycaemic targets using this approach alone. The primary aim of the Personalised Medicine in Pre-diabetes—Towards Preventing Diabetes in Individuals at Risk (PREDICT) Study is to test the efficacy of personalised diet as adjuvant to metformin in improving glycaemic control in individuals with dysglycaemia.Methods and analysisPREDICT is a two-arm, parallel group, single-masked randomised controlled trial in adults with pre-diabetes or early-stage T2DM (with glycated haemoglobin (HbA1c) up to 8.0% (64 mmol/mol)), not treated with glucose-lowering medication. PREDICT is conducted at the Clinical Research Facility at the Garvan Institute of Medical Research (Sydney). Enrolment of participants commenced in December 2018 and expected to complete in December 2021. Participants are commenced on metformin (Extended Release, titrated to a target dose of 1500 mg/day) and randomised with equal allocation to either (1) the Personalised Nutrition Project algorithm-based diet or (2) low-fat high-dietary fibre diet, designed to provide caloric restriction (75%) in individuals with body mass index >25 kg/m2. Treatment duration is 6 months and participants visit the Clinical Research Facility five times over approximately 7 months. The primary outcome measure is HbA1c. The secondary outcomes are (1) time of interstitial glucose <7.8 mmol/L and (2) glycaemic variability (continuous glucose monitoring), (3) body weight, (4) fat mass and (5) abdominal visceral fat volume (dual-energy X-ray absorptiometry), serum (6) low-density lipoprotein cholesterol (7) high-density lipoprotein cholesterol and (8) triglycerides concentrations, (9) blood pressure, and (10) liver fat (Fibroscan).Ethics and disseminationThe study has been approved by the St Vincent’s Hospital Human Research Ethics Committee (File 17/080, Sydney, Australia) and the Weizmann Institutional Review Board (File 528-3, Rehovot, Israel). The findings will be published in peer-reviewed open access medical journals.Trial registration numberNCT03558867; Pre-results.
Abstract
Dogs have a key role in law enforcement and military work, and research with the goal of improving working dog performance is ongoing. While there have been intriguing studies from lab ...animal models showing a potential connection between the gut microbiome and behavior or mental health there is a dearth of studies investigating the microbiome-behavior relationship in working dogs. The overall objective of this study was to characterize the microbiota of working dogs and to determine if the composition of the microbiota is associated with behavioral and performance outcomes. Freshly passed stools from each working canine (Total
n
= 134) were collected and subject to shotgun metagenomic sequencing using Illumina technology. Behavior, performance, and demographic metadata were collected. Descriptive statistics and prediction models of behavioral/phenotypic outcomes using gradient boosting classification based on Xgboost were used to study associations between the microbiome and outcomes. Regarding machine learning methodology, only microbiome features were used for training and predictors were estimated in cross-validation. Microbiome markers were statistically associated with motivation, aggression, cowardice/hesitation, sociability, obedience to one trainer vs many, and body condition score (BCS). When prediction models were developed based on machine learning, moderate predictive power was observed for motivation, sociability, and gastrointestinal issues. Findings from this study suggest potential gut microbiome markers of performance and could potentially advance care for working canines.
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