| 1. |
- Alneberg, Johannes
(author)
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Bioinformatic Methods in Metagenomics
- 2018
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Doctoral thesis (other academic/artistic)abstract
- Microbial organisms are a vital part of our global ecosystem. Yet, our knowledge of them is still lacking. Direct sequencing of microbial communities, i.e. metagenomics, have enabled detailed studies of these microscopic organisms by inspection of their DNA sequences without the need to culture them. Furthermore, the development of modern high- throughput sequencing technologies have made this approach more powerful and cost-effective. Taken together, this has shifted the field of microbiology from previously being centered around microscopy and culturing studies, to largely consist of computational analyses of DNA sequences. One such computational analysis which is the main focus of this thesis, aims at reconstruction of the complete DNA sequence of an organism, i.e. its genome, directly from short metagenomic sequences.This thesis consists of an introduction to the subject followed by five papers. Paper I describes a large metagenomic data resource spanning the Baltic Sea microbial communities. This dataset is complemented with a web-interface allowing researchers to easily extract and visualize detailed information. Paper II introduces a bioinformatic method which is able to reconstruct genomes from metagenomic data. This method, which is termed CONCOCT, is applied on Baltic Sea metagenomics data in Paper III and Paper V. This enabled the reconstruction of a large number of genomes. Analysis of these genomes in Paper III led to the proposal of, and evidence for, a global brackish microbiome. Paper IV presents a comparison between genomes reconstructed from metagenomes with single-cell sequenced genomes. This further validated the technique presented in Paper II as it was found to produce larger and more complete genomes than single-cell sequencing.
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| 2. |
- Asnicar, Francesco, et al.
(author)
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Blue poo : Impact of gut transit time on the gut microbiome using a novel marker
- 2021
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In: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 70:9, s. 1665-1674
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Journal article (peer-reviewed)abstract
- Background and aims: Gut transit time is a key modulator of host-microbiome interactions, yet this is often overlooked, partly because reliable methods are typically expensive or burdensome. The aim of this single-arm, single-blinded intervention study is to assess (1) the relationship between gut transit time and the human gut microbiome, and (2) the utility of the a € blue dye' method as an inexpensive and scalable technique to measure transit time. Methods: We assessed interactions between the taxonomic and functional potential profiles of the gut microbiome (profiled via shotgun metagenomic sequencing), gut transit time (measured via the blue dye method), cardiometabolic health and diet in 863 healthy individuals from the PREDICT 1 study. Results: We found that gut microbiome taxonomic composition can accurately discriminate between gut transit time classes (0.82 area under the receiver operating characteristic curve) and longer gut transit time is linked with specific microbial species such as Akkermansia muciniphila, Bacteroides spp and Alistipes spp (false discovery rate-adjusted p values <0.01). The blue dye measure of gut transit time had the strongest association with the gut microbiome over typical transit time proxies such as stool consistency and frequency. Conclusions: Gut transit time, measured via the blue dye method, is a more informative marker of gut microbiome function than traditional measures of stool consistency and frequency. The blue dye method can be applied in large-scale epidemiological studies to advance diet-microbiome-health research. Clinical trial registry website https://clinicaltrials.gov/ct2/show/NCT03479866 and trial number NCT03479866.
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| 3. |
- Asnicar, Francesco, et al.
(author)
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Microbiome connections with host metabolism and habitual diet from 1,098 deeply phenotyped individuals
- 2021
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In: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 27:2, s. 321-332
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Journal article (peer-reviewed)abstract
- The gut microbiome is shaped by diet and influences host metabolism; however, these links are complex and can be unique to each individual. We performed deep metagenomic sequencing of 1,203 gut microbiomes from 1,098 individuals enrolled in the Personalised Responses to Dietary Composition Trial (PREDICT 1) study, whose detailed long-term diet information, as well as hundreds of fasting and same-meal postprandial cardiometabolic blood marker measurements were available. We found many significant associations between microbes and specific nutrients, foods, food groups and general dietary indices, which were driven especially by the presence and diversity of healthy and plant-based foods. Microbial biomarkers of obesity were reproducible across external publicly available cohorts and in agreement with circulating blood metabolites that are indicators of cardiovascular disease risk. While some microbes, such as Prevotella copri and Blastocystis spp., were indicators of favorable postprandial glucose metabolism, overall microbiome composition was predictive for a large panel of cardiometabolic blood markers including fasting and postprandial glycemic, lipemic and inflammatory indices. The panel of intestinal species associated with healthy dietary habits overlapped with those associated with favorable cardiometabolic and postprandial markers, indicating that our large-scale resource can potentially stratify the gut microbiome into generalizable health levels in individuals without clinically manifest disease.
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| 4. |
- Bazzani, Davide, et al.
(author)
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Favorable subgingival plaque microbiome shifts are associated with clinical treatment for peri-implant diseases
- 2024
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In: NPJ BIOFILMS AND MICROBIOMES. - 2055-5008. ; 10:1
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Journal article (peer-reviewed)abstract
- We performed a longitudinal shotgun metagenomic investigation of the plaque microbiome associated with peri-implant diseases in a cohort of 91 subjects with 320 quality-controlled metagenomes. Through recently improved taxonomic profiling methods, we identified the most discriminative species between healthy and diseased subjects at baseline, evaluated their change over time, and provided evidence that clinical treatment had a positive effect on plaque microbiome composition in patients affected by mucositis and peri-implantitis.
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| 5. |
- Bermingham, Kate M., et al.
(author)
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Exploring the relationship between social jetlag with gut microbial composition, diet and cardiometabolic health, in the ZOE PREDICT 1 cohort
- 2023
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In: European Journal of Nutrition. - 1436-6207. ; 62:8, s. 3135-3147
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Journal article (peer-reviewed)abstract
- Purpose: In this study, we explore the relationship between social jetlag (SJL), a parameter of circadian misalignment, and gut microbial composition, diet and cardiometabolic health in the ZOE PREDICT 1 cohort (NCT03479866). Methods: We assessed demographic, diet, cardiometabolic, stool metagenomics and postprandial metabolic measures (n = 1002). We used self-reported habitual sleep (n = 934) to calculate SJL (difference in mid-sleep time point of ≥ 1.5 h on week versus weekend days). We tested group differences (SJL vs no-SJL) in cardiometabolic markers and diet (ANCOVA) adjusting for sex, age, BMI, ethnicity, and socio-economic status. We performed comparisons of gut microbial composition using machine learning and association analyses on the species level genome bins present in at least 20% of the samples. Results: The SJL group (16%, n = 145) had a greater proportion of males (39% vs 25%), shorter sleepers (average sleep < 7 h; 5% vs 3%), and were younger (38.4 ± 11.3y vs 46.8 ± 11.7y) compared to the no-SJL group. SJL was associated with a higher relative abundance of 9 gut bacteria and lower abundance of 8 gut bacteria (q < 0.2 and absolute Cohen’s effect size > 0.2), in part mediated by diet. SJL was associated with unfavourable diet quality (less healthful Plant-based Diet Index), higher intakes of potatoes and sugar-sweetened beverages, and lower intakes of fruits, and nuts, and slightly higher markers of inflammation (GlycA and IL-6) compared with no-SJL (P < 0.05 adjusted for covariates); rendered non-significant after multiple testing adjustments. Conclusions: Novel associations between SJL and a more disadvantageous gut microbiome in a cohort of predominantly adequate sleepers highlight the potential implications of SJL for health.
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| 6. |
- Bermingham, Kate M., et al.
(author)
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Menopause is associated with postprandial metabolism, metabolic health and lifestyle : The ZOE PREDICT study
- 2022
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In: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 85
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Journal article (peer-reviewed)abstract
- Background: The menopause transition is associated with unfavourable alterations in health. However, postprandial metabolic changes and their mediating factors are poorly understood. Methods: The PREDICT 1 UK cohort (n=1002; pre- n=366, peri- n=55, and post-menopausal females n=206) assessed phenotypic characteristics, anthropometric, diet and gut microbiome data, and fasting and postprandial (0–6 h) cardiometabolic blood measurements, including continuous glucose monitoring (CGM) data. Differences between menopausal groups were assessed in the cohort and in an age-matched subgroup, adjusting for age, BMI, menopausal hormone therapy (MHT) use, and smoking status. Findings: Post-menopausal females had higher fasting blood measures (glucose, HbA1c and inflammation (GlycA), 6%, 5% and 4% respectively), sugar intakes (12%) and poorer sleep (12%) compared with pre-menopausal females (p<0.05 for all). Postprandial metabolic responses for glucose2hiauc and insulin2hiauc were higher (42% and 4% respectively) and CGM measures (glycaemic variability and time in range) were unfavourable post- versus pre-menopause (p<0.05 for all). In age-matched subgroups (n=150), postprandial glucose responses remained higher post-menopause (peak0-2h 4%). MHT was associated with favourable visceral fat, fasting (glucose and insulin) and postprandial (triglyceride6hiauc) measures. Mediation analysis showed that associations between menopause and metabolic health indicators (visceral fat, GlycA360mins and glycaemia (peak0-2h)) were in part mediated by diet and gut bacterial species. Interpretation: Findings from this large scale, in-depth nutrition metabolic study of menopause, support the importance of monitoring risk factors for type-2 diabetes and cardiovascular disease in mid-life to older women to reduce morbidity and mortality associated with oestrogen decline. Funding: Zoe Ltd.
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| 7. |
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| 8. |
- Berry, Sarah E., et al.
(author)
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Human postprandial responses to food and potential for precision nutrition
- 2020
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In: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 26:6, s. 964-973
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Journal article (peer-reviewed)abstract
- Metabolic responses to food influence risk of cardiometabolic disease, but large-scale high-resolution studies are lacking. We recruited n = 1,002 twins and unrelated healthy adults in the United Kingdom to the PREDICT 1 study and assessed postprandial metabolic responses in a clinical setting and at home. We observed large inter-individual variability (as measured by the population coefficient of variation (s.d./mean, %)) in postprandial responses of blood triglyceride (103%), glucose (68%) and insulin (59%) following identical meals. Person-specific factors, such as gut microbiome, had a greater influence (7.1% of variance) than did meal macronutrients (3.6%) for postprandial lipemia, but not for postprandial glycemia (6.0% and 15.4%, respectively); genetic variants had a modest impact on predictions (9.5% for glucose, 0.8% for triglyceride, 0.2% for C-peptide). Findings were independently validated in a US cohort (n = 100 people). We developed a machine-learning model that predicted both triglyceride (r = 0.47) and glycemic (r = 0.77) responses to food intake. These findings may be informative for developing personalized diet strategies. The ClinicalTrials.gov registration identifier is NCT03479866.
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| 9. |
- Fluckiger, Aurélie, et al.
(author)
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Cross-reactivity between tumor MHC class I-restricted antigens and an enterococcal bacteriophage
- 2020
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 369:6506, s. 936-942
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Journal article (peer-reviewed)abstract
- Intestinal microbiota have been proposed to induce commensal-specific memory T cells that cross-react with tumor-associated antigens. We identified major histocompatibility complex (MHC) class I-binding epitopes in the tail length tape measure protein (TMP) of a prophage found in the genome of the bacteriophage Enterococcus hirae. Mice bearing E. hirae harboring this prophage mounted a TMP-specific H-2K(b)-restricted CD8(+) T lymphocyte response upon immunotherapy with cyclophosphamide or anti-PD-1 antibodies. Administration of bacterial strains engineered to express the TMP epitope improved immunotherapy in mice. In renal and lung cancer patients, the presence of the enterococcal prophage in stools and expression of a TMP-cross-reactive antigen by tumors correlated with long-term benefit of PD-1 blockade therapy. In melanoma patients, T cell clones recognizing naturally processed cancer antigens that are cross-reactive with microbial peptides were detected.
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| 10. |
- Kissling, W. Daniel, et al.
(author)
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Building essential biodiversity variables (EBVs) of species distribution and abundance at a global scale
- 2018
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In: Biological Reviews. - : Wiley. - 1464-7931 .- 1469-185X. ; 93:1, s. 600-625
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Journal article (peer-reviewed)abstract
- © 2017 Cambridge Philosophical Society. Much biodiversity data is collected worldwide, but it remains challenging to assemble the scattered knowledge for assessing biodiversity status and trends. The concept of Essential Biodiversity Variables (EBVs) was introduced to structure biodiversity monitoring globally, and to harmonize and standardize biodiversity data from disparate sources to capture a minimum set of critical variables required to study, report and manage biodiversity change. Here, we assess the challenges of a 'Big Data' approach to building global EBV data products across taxa and spatiotemporal scales, focusing on species distribution and abundance. The majority of currently available data on species distributions derives from incidentally reported observations or from surveys where presence-only or presence-absence data are sampled repeatedly with standardized protocols. Most abundance data come from opportunistic population counts or from population time series using standardized protocols (e.g. repeated surveys of the same population from single or multiple sites). Enormous complexity exists in integrating these heterogeneous, multi-source data sets across space, time, taxa and different sampling methods. Integration of such data into global EBV data products requires correcting biases introduced by imperfect detection and varying sampling effort, dealing with different spatial resolution and extents, harmonizing measurement units from different data sources or sampling methods, applying statistical tools and models for spatial inter- or extrapolation, and quantifying sources of uncertainty and errors in data and models. To support the development of EBVs by the Group on Earth Observations Biodiversity Observation Network (GEO BON), we identify 11 key workflow steps that will operationalize the process of building EBV data products within and across research infrastructures worldwide. These workflow steps take multiple sequential activities into account, including identification and aggregation of various raw data sources, data quality control, taxonomic name matching and statistical modelling of integrated data. We illustrate these steps with concrete examples from existing citizen science and professional monitoring projects, including eBird, the Tropical Ecology Assessment and Monitoring network, the Living Planet Index and the Baltic Sea zooplankton monitoring. The identified workflow steps are applicable to both terrestrial and aquatic systems and a broad range of spatial, temporal and taxonomic scales. They depend on clear, findable and accessible metadata, and we provide an overview of current data and metadata standards. Several challenges remain to be solved for building global EBV data products: (i) developing tools and models for combining heterogeneous, multi-source data sets and filling data gaps in geographic, temporal and taxonomic coverage, (ii) integrating emerging methods and technologies for data collection such as citizen science, sensor networks, DNA-based techniques and satellite remote sensing, (iii) solving major technical issues related to data product structure, data storage, execution of workflows and the production process/cycle as well as approaching technical interoperability among research infrastructures, (iv) allowing semantic interoperability by developing and adopting standards and tools for capturing consistent data and metadata, and (v) ensuring legal interoperability by endorsing open data or data that are free from restrictions on use, modification and sharing. Addressing these challenges is critical for biodiversity research and for assessing progress towards conservation policy targets and sustainable development goals.
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| 11. |
- Louca, Panayiotis, et al.
(author)
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The secondary bile acid isoursodeoxycholate correlates with post-prandial lipemia, inflammation, and appetite and changes post-bariatric surgery
- 2023
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In: Cell Reports Medicine. - 2666-3791. ; 4:4
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Journal article (peer-reviewed)abstract
- Primary and secondary bile acids (BAs) influence metabolism and inflammation, and the gut microbiome modulates levels of BAs. We systematically explore the host genetic, gut microbial, and habitual dietary contribution to a panel of 19 serum and 15 stool BAs in two population-based cohorts (TwinsUK, n = 2,382; ZOE PREDICT-1, n = 327) and assess changes post-bariatric surgery and after nutritional interventions. We report that BAs have a moderately heritable genetic component, and the gut microbiome accurately predicts their levels in serum and stool. The secondary BA isoursodeoxycholate (isoUDCA) can be explained mostly by gut microbes (area under the receiver operating characteristic curve [AUC] = ∼80%) and associates with post-prandial lipemia and inflammation (GlycA). Furthermore, circulating isoUDCA decreases significantly 1 year after bariatric surgery (β = −0.72, p = 1 × 10−5) and in response to fiber supplementation (β = −0.37, p < 0.03) but not omega-3 supplementation. In healthy individuals, isoUDCA fasting levels correlate with pre-meal appetite (p < 1 × 10−4). Our findings indicate an important role for isoUDCA in lipid metabolism, appetite, and, potentially, cardiometabolic risk.
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| 12. |
- Mazidi, Mohsen, et al.
(author)
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Meal-induced inflammation : postprandial insights from the Personalised REsponses to DIetary Composition Trial (PREDICT) study in 1000 participants
- 2021
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In: The American journal of clinical nutrition. - : Elsevier BV. - 1938-3207 .- 0002-9165. ; 114:3, s. 1028-1038
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Journal article (peer-reviewed)abstract
- BACKGROUND: Meal-induced metabolic changes trigger an acute inflammatory response, contributing to chronic inflammation and associated diseases. OBJECTIVES: We aimed to characterize variability in postprandial inflammatory responses using traditional (IL-6) and novel [glycoprotein acetylation (GlycA)] biomarkers of inflammation and dissect their biological determinants with a focus on postprandial glycemia and lipemia. METHODS: Postprandial (0-6 h) glucose, triglyceride (TG), IL-6, and GlycA responses were measured at multiple intervals after sequential mixed-nutrient meals (0 h and 4 h) in 1002 healthy adults aged 18-65 y from the PREDICT (Personalised REsponses to DIetary Composition Trial) 1 study, a single-arm dietary intervention study. Measures of habitual diet, blood biochemistry, gut microbiome composition, and visceral fat mass (VFM) were also collected. RESULTS: The postprandial changes in GlycA and IL-6 concentrations were highly variable between individuals. Participants eliciting an increase in GlycA and IL-6 (60% and 94% of the total participants, respectively) had mean 6-h increases of 11% and 190%, respectively. Peak postprandial TG and glucose concentrations were significantly associated with 6-h GlycA (r = 0.83 and r = 0.24, respectively; both P < 0.001) but not with 6-h IL-6 (both P > 0.26). A random forest model revealed the maximum TG concentration was the strongest postprandial TG predictor of postprandial GlycA and structural equation modeling revealed that VFM and fasting TG were most strongly associated with fasting and postprandial GlycA. Network Mendelian randomization demonstrated a causal link between VFM and fasting GlycA, mediated (28%) by fasting TG. Individuals eliciting enhanced GlycA responses had higher predicted cardiovascular disease risk (using the atherosclerotic disease risk score) than the rest of the cohort. CONCLUSIONS: The variable postprandial increases in GlycA and their associations with TG metabolism highlight the importance of modulating TG in concert with obesity to reduce GlycA and associated low-grade inflammation-related diseases.This trial was registered at clinicaltrials.gov as NCT03479866.
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| 13. |
- Nogal, Ana, et al.
(author)
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A Fecal Metabolite Signature of Impaired Fasting Glucose : Results From Two Independent Population-Based Cohorts
- 2023
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In: Diabetes. - 0012-1797. ; 72:12, s. 1870-1880
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Journal article (peer-reviewed)abstract
- Prediabetes is a metabolic condition associated with gut mi-crobiome composition, although mechanisms remain elu-sive. We searched for fecal metabolites, a readout of gut microbiome function, associated with impaired fasting glucose (IFG) in 142 individuals with IFG and 1,105 healthy individuals from the UK Adult Twin Registry (TwinsUK). We used the Cooperative Health Research in the Region of Augsburg (KORA) cohort (318 IFG individuals, 689 healthy individuals) to replicate our findings. We linearly combined eight IFG-positively associated metabolites (1-methylxantine, nicoti-nate, glucuronate, uridine, cholesterol, serine, caffeine, and protoporphyrin IX) into an IFG-metabolite score, which was significantly associated with higher odds ratios (ORs) for IFG (TwinsUK: OR 3.9 [95% CI 3.02–5.02], P < 0.0001, KORA: OR 1.3 [95% CI 1.16–1.52], P < 0.0001) and incident type 2 diabetes (T2D; TwinsUK: hazard ratio 4 [95% CI 1.97–8], P = 0.0002). Although these are host-produced me-tabolites, we found that the gut microbiome is strongly associated with their fecal levels (area under the curve >70%). Abundances of Faecalibacillus intestinalis, Dorea formicigenerans, Ruminococcus torques, and Dorea sp. AF24-7LB were positively associated with IFG, and such associations were partially mediated by 1-methylxanthine and nicotinate (variance accounted for mean 14.4% [SD 5.1], P < 0.05). Our results suggest that the gut microbiome is linked to prediabetes not only via the production of microbial metabolites but also by affecting intestinal absorption/excretion of host-produced metabolites and xenobiotics, which are correlated with the risk of IFG. Fecal metabolites enable modeling of another mechanism of gut microbiome effect on prediabetes and T2D onset.
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| 14. |
- Nogal, Ana, et al.
(author)
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Genetic and gut microbiome determinants of SCFA circulating and fecal levels, postprandial responses and links to chronic and acute inflammation
- 2023
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In: Gut microbes. - 1949-0976. ; 15:1
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Journal article (peer-reviewed)abstract
- Short-chain fatty acids (SCFA) are involved in immune system and inflammatory responses. We comprehensively assessed the host genetic and gut microbial contribution to a panel of eight serum and stool SCFAs in two cohorts (TwinsUK, n = 2507; ZOE PREDICT-1, n = 328), examined their postprandial changes and explored their links with chronic and acute inflammatory responses in healthy individuals and trauma patients. We report low concordance between circulating and fecal SCFAs, significant postprandial changes in most circulating SCFAs, and a heritable genetic component (average h2 : serum = 14%(SD = 14%); stool = 12%(SD = 6%)). Furthermore, we find that gut microbiome can accurately predict their fecal levels (AUC>0.71) while presenting weaker associations with serum. Finally, we report different correlation patterns with inflammatory markers depending on the type of inflammatory response (chronic or acute trauma). Our results illustrate the breadth of the physiological relevance of SCFAs on human inflammatory and metabolic responses highlighting the need for a deeper understanding of this important class of molecules.
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| 15. |
- Tsereteli, Neli, et al.
(author)
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Impact of insufficient sleep on dysregulated blood glucose control under standardised meal conditions
- 2022
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In: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 65:2, s. 356-365
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Journal article (peer-reviewed)abstract
- Aims/hypothesis: Sleep, diet and exercise are fundamental to metabolic homeostasis. In this secondary analysis of a repeated measures, nutritional intervention study, we tested whether an individual’s sleep quality, duration and timing impact glycaemic response to a breakfast meal the following morning. Methods: Healthy adults’ data (N = 953 [41% twins]) were analysed from the PREDICT dietary intervention trial. Participants consumed isoenergetic standardised meals over 2 weeks in the clinic and at home. Actigraphy was used to assess sleep variables (duration, efficiency, timing) and continuous glucose monitors were used to measure glycaemic variation (>8000 meals). Results: Sleep variables were significantly associated with postprandial glycaemic control (2 h incremental AUC), at both between- and within-person levels. Sleep period time interacted with meal type, with a smaller effect of poor sleep on postprandial blood glucose levels when high-carbohydrate (low fat/protein) (pinteraction = 0.02) and high-fat (pinteraction = 0.03) breakfasts were consumed compared with a reference 75 g OGTT. Within-person sleep period time had a similar interaction (high carbohydrate: pinteraction = 0.001, high fat: pinteraction = 0.02). Within- and between-person sleep efficiency were significantly associated with lower postprandial blood glucose levels irrespective of meal type (both p < 0.03). Later sleep midpoint (time deviation from midnight) was found to be significantly associated with higher postprandial glucose, in both between-person and within-person comparisons (p = 0.035 and p = 0.051, respectively). Conclusions/interpretation: Poor sleep efficiency and later bedtime routines are associated with more pronounced postprandial glycaemic responses to breakfast the following morning. A person’s deviation from their usual sleep pattern was also associated with poorer postprandial glycaemic control. These findings underscore sleep as a modifiable, non-pharmacological therapeutic target for the optimal regulation of human metabolic health. Trial registrationClinicalTrials.gov NCT03479866. Graphical abstract: [Figure not available: see fulltext.]
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| 16. |
- Wirbel, Jakob, et al.
(author)
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Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer
- 2019
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In: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 25:4, s. 679-689
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Journal article (peer-reviewed)abstract
- Association studies have linked microbiome alterations with many human diseases. However, they have not always reported consistent results, thereby necessitating cross-study comparisons. Here, a meta-analysis of eight geographically and technically diverse fecal shotgun metagenomic studies of colorectal cancer (CRC, n = 768), which was controlled for several confounders, identified a core set of 29 species significantly enriched in CRC metagenomes (false discovery rate (FDR) < 1 × 10 −5 ). CRC signatures derived from single studies maintained their accuracy in other studies. By training on multiple studies, we improved detection accuracy and disease specificity for CRC. Functional analysis of CRC metagenomes revealed enriched protein and mucin catabolism genes and depleted carbohydrate degradation genes. Moreover, we inferred elevated production of secondary bile acids from CRC metagenomes, suggesting a metabolic link between cancer-associated gut microbes and a fat- and meat-rich diet. Through extensive validations, this meta-analysis firmly establishes globally generalizable, predictive taxonomic and functional microbiome CRC signatures as a basis for future diagnostics.
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| 17. |
- Wylensek, David, et al.
(author)
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A collection of bacterial isolates from the pig intestine reveals functional and taxonomic diversity
- 2020
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In: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 11:1
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Journal article (peer-reviewed)abstract
- Our knowledge about the gut microbiota of pigs is still scarce, despite the importance of these animals for biomedical research and agriculture. Here, we present a collection of cultured bacteria from the pig gut, including 110 species across 40 families and nine phyla. We provide taxonomic descriptions for 22 novel species and 16 genera. Meta-analysis of 16S rRNA amplicon sequence data and metagenome-assembled genomes reveal prevalent and pig-specific species within Lactobacillus, Streptococcus, Clostridium, Desulfovibrio, Enterococcus, Fusobacterium, and several new genera described in this study. Potentially interesting functions discovered in these organisms include a fucosyltransferase encoded in the genome of the novel species Clostridium porci, and prevalent gene clusters for biosynthesis of sactipeptide-like peptides. Many strains deconjugate primary bile acids in in vitro assays, and a Clostridium scindens strain produces secondary bile acids via dehydroxylation. In addition, cells of the novel species Bullifex porci are coccoidal or spherical under the culture conditions tested, in contrast with the usual helical shape of other members of the family Spirochaetaceae. The strain collection, called 'Pig intestinal bacterial collection' (PiBAC), is publicly available at www.dsmz.de/pibac and opens new avenues for functional studies of the pig gut microbiota. The authors present a public collection of 117 bacterial isolates from the pig gut, including the description of 38 novel taxa. Interesting functions discovered in these organisms include a new fucosyltransferease and sactipeptide-like molecules encoded by biosynthetic gene clusters.
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