An intact gut microbiome protects genetically predisposed mice against leukemia

Abstract The majority of childhood leukemias are precursor B-cell acute lymphoblastic leukemias (pB-ALLs) caused by a combination of prenatal genetic predispositions and oncogenic events occurring after birth. Although genetic predispositions are frequent in children (>1% to 5%), fewer than 1% of genetically predisposed carriers will develop pB-ALL. Although infectious stimuli are believed to play a major role in leukemogenesis, the critical determinants are not well defined. Here, by using murine models of pB-ALL, we show that microbiome disturbances incurred by antibiotic treatment early in life were sufficient to induce leukemia in genetically predisposed mice, even in the absence of infectious stimuli and independent of T cells. By using V4 and full-length 16S ribosomal RNA sequencing of a series of fecal samples, we found that genetic predisposition to pB-ALL (Pax5 heterozygosity or ETV6-RUNX1 fusion) shaped a distinct gut microbiome. Machine learning accurately (96.8%) predicted genetic predisposition using 40 of 3983 amplicon sequence variants as proxies for bacterial species. Transplantation of either wild-type (WT) or Pax5+/– hematopoietic bone marrow cells into WT recipient mice revealed that the microbiome is shaped and determined in a donor genotype–specific manner. Gas chromatography-mass spectrometry (GC-MS) analyses of sera from WT and Pax5+/– mice demonstrated the presence of a genotype-specific distinct metabolomic profile. Taken together, our data indicate that it is a lack of commensal microbiota rather than the presence of specific bacteria that promotes leukemia in genetically predisposed mice. Future large-scale longitudinal studies are required to determine whether targeted microbiome modification in children predisposed to pB-ALL could become a successful prevention strategy.

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Development and study of a method for cell separation during white blood cell segmentation on images of bone marrow preparations in information and measurement systems for diagnostics of acute leukemia

Izmeritel`naya Tekhnika ◽

10.32446/0368-1025it.2020-7-68-72 ◽

2020 ◽

pp. 68-72

Author(s):

V.G. Nikitaev ◽

A.N. Pronichev ◽

V.V. Dmitrieva ◽

E.V. Polyakov ◽

A.D. Samsonova ◽

...

Keyword(s):

Bone Marrow ◽

Blood Cell ◽

Acute Leukemia ◽

White Blood Cell ◽

Cell Separation ◽

Large Scale ◽

Bone Marrow Cells ◽

Automated Analysis ◽

Cell Segmentation ◽

Measurement Systems

The issues of using of information and measurement systems based on processing of digital images of microscopic preparations for solving large-scale tasks of automating the diagnosis of acute leukemia are considered. The high density of leukocyte cells in the preparation (hypercellularity) is a feature of microscopic images of bone marrow preparations. It causes the proximity of cells to eachother and their contact with the formation of conglomerates. Measuring of the characteristics of bone marrow cells in such conditions leads to unacceptable errors (more than 50%). The work is devoted to segmentation of contiguous cells in images of bone marrow preparations. A method of cell separation during white blood cell segmentation on images of bone marrow preparations under conditions of hypercellularity of the preparation has been developed. The peculiarity of the proposed method is the use of an approach to segmentation of cell images based on the watershed method with markers. Key stages of the method: the formation of initial markers and builds the lines of watershed, a threshold binarization, shading inside the outline. The parameters of the separation of contiguous cells are determined. The experiment confirmed the effectiveness of the proposed method. The relative segmentation error was 5 %. The use of the proposed method in information and measurement systems of computer microscopy for automated analysis of bone marrow preparations will help to improve the accuracy of diagnosis of acute leukemia.

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Flavonoid-Modifying Capabilities of the Human Gut Microbiome—An In Silico Study

Nutrients ◽

10.3390/nu13082688 ◽

2021 ◽

Vol 13 (8) ◽

pp. 2688

Author(s):

Tobias Goris ◽

Rafael R. C. Cuadrat ◽

Annett Braune

Keyword(s):

Gut Microbiome ◽

Large Scale ◽

Health Impact ◽

Gut Bacteria ◽

Human Gut ◽

Positive Health ◽

Human Gut Microbiome ◽

Nutritional Recommendations ◽

Genes Encoding ◽

A Minor

Flavonoids are a major group of dietary plant polyphenols and have a positive health impact, but their modification and degradation in the human gut is still widely unknown. Due to the rise of metagenome data of the human gut microbiome and the assembly of hundreds of thousands of bacterial metagenome-assembled genomes (MAGs), large-scale screening for potential flavonoid-modifying enzymes of human gut bacteria is now feasible. With sequences of characterized flavonoid-transforming enzymes as queries, the Unified Human Gastrointestinal Protein catalog was analyzed and genes encoding putative flavonoid-modifying enzymes were quantified. The results revealed that flavonoid-modifying enzymes are often encoded in gut bacteria hitherto not considered to modify flavonoids. The enzymes for the physiologically important daidzein-to-equol conversion, well studied in Slackiaisoflavoniconvertens, were encoded only to a minor extent in Slackia MAGs, but were more abundant in Adlercreutzia equolifaciens and an uncharacterized Eggerthellaceae species. In addition, enzymes with a sequence identity of about 35% were encoded in highly abundant MAGs of uncultivated Collinsella species, which suggests a hitherto uncharacterized daidzein-to-equol potential in these bacteria. Of all potential flavonoid modification steps, O-deglycosylation (including derhamnosylation) was by far the most abundant in this analysis. In contrast, enzymes putatively involved in C-deglycosylation were detected less often in human gut bacteria and mainly found in Agathobacter faecis (formerly Roseburia faecis). Homologs to phloretin hydrolase, flavanonol/flavanone-cleaving reductase and flavone reductase were of intermediate abundance (several hundred MAGs) and mainly prevalent in Flavonifractor plautii. This first comprehensive insight into the black box of flavonoid modification in the human gut highlights many hitherto overlooked and uncultured bacterial genera and species as potential key organisms in flavonoid modification. This could lead to a significant contribution to future biochemical-microbiological investigations on gut bacterial flavonoid transformation. In addition, our results are important for individual nutritional recommendations and for biotechnological applications that rely on novel enzymes catalyzing potentially useful flavonoid modification reactions.

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The structure of Brazilian Amazonian gut microbiomes in the process of urbanisation

npj Biofilms and Microbiomes ◽

10.1038/s41522-021-00237-0 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Ana Paula Schaan ◽

Dionison Sarquis ◽

Giovanna C. Cavalcante ◽

Leandro Magalhães ◽

Eliene R. P. Sacuena ◽

...

Keyword(s):

Native American ◽

Ribosomal Rna ◽

Gut Microbiome ◽

Brazilian Amazon ◽

American People ◽

South American ◽

Subsistence Strategy ◽

Urban Populations ◽

Gradual Loss ◽

Agricultural Societies

AbstractShifts in subsistence strategy among Native American people of the Amazon may be the cause of typically western diseases previously linked to modifications of gut microbial communities. Here, we used 16S ribosomal RNA sequencing to characterise the gut microbiome of 114 rural individuals, namely Xikrin, Suruí and Tupaiú, and urban individuals from Belém city, in the Brazilian Amazon. Our findings show the degree of potential urbanisation occurring in the gut microbiome of rural Amazonian communities characterised by the gradual loss and substitution of taxa associated with rural lifestyles, such as Treponema. Comparisons to worldwide populations indicated that Native American groups are similar to South American agricultural societies and urban groups are comparable to African urban and semi-urban populations. The transitioning profile observed among traditional populations is concerning in light of increasingly urban lifestyles. Lastly, we propose the term “tropical urban” to classify the microbiome of urban populations living in tropical zones.

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Comparative genomics suggests a taxonomic revision of the Staphylococcus cohnii species complex

Genome Biology and Evolution ◽

10.1093/gbe/evab020 ◽

2021 ◽

Author(s):

Anna Lavecchia ◽

Matteo Chiara ◽

Caterina De Virgilio ◽

Caterina Manzari ◽

Carlo Pazzani ◽

...

Keyword(s):

Comparative Genomics ◽

Species Complex ◽

Large Scale ◽

Genomic Sequence ◽

Bacterial Species ◽

Taxonomic Revision ◽

Distinct Species ◽

The Novel ◽

Staphylococcus Cohnii ◽

Taxonomic Assignments

Abstract Staphylococcus cohnii (SC), a coagulase-negative bacterium, was first isolated in 1975 from human skin. Early phenotypic analyses led to the delineation of two subspecies (subsp.), Staphylococcus cohnii subsp. cohnii (SCC) and Staphylococcus cohnii subsp. urealyticus (SCU). SCC was considered to be specific to humans whereas SCU apparently demonstrated a wider host range, from lower primates to humans. The type strains ATCC 29974 and ATCC 49330 have been designated for SCC and SCU, respectively. Comparative analysis of 66 complete genome sequences—including a novel SC isolate—revealed unexpected patterns within the SC complex, both in terms of genomic sequence identity and gene content, highlighting the presence of 3 phylogenetically distinct groups. Based on our observations, and on the current guidelines for taxonomic classification for bacterial species, we propose a revision of the SC species complex. We suggest that SCC and SCU should be regarded as two distinct species: SC and SU (Staphylococcus urealyticus), and that two distinct subspecies, SCC and SCB (SC subsp. barensis, represented by the novel strain isolated in Bari) should be recognized within SC. Furthermore, since large scale comparative genomics studies recurrently suggest inconsistencies or conflicts in taxonomic assignments of bacterial species, we believe that the approach proposed here might be considered for more general application.

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Gut Microbiome in Psoriasis: An Updated Review

Pathogens ◽

10.3390/pathogens9060463 ◽

2020 ◽

Vol 9 (6) ◽

pp. 463

Author(s):

Mariusz Sikora ◽

Albert Stec ◽

Magdalena Chrabaszcz ◽

Aleksandra Knot ◽

Anna Waskiel-Burnat ◽

...

Keyword(s):

Gut Microbiome ◽

Beta Diversity ◽

Large Scale ◽

Skin Diseases ◽

Intestinal Barrier ◽

Alpha Diversity ◽

Current Data ◽

Intestinal Microbiome ◽

Microbial Composition ◽

Alpha And Beta Diversity

(1) Background: A growing body of evidence highlights that intestinal dysbiosis is associated with the development of psoriasis. The gut–skin axis is the novel concept of the interaction between skin diseases and microbiome through inflammatory mediators, metabolites and the intestinal barrier. The objective of this study was to synthesize current data on the gut microbial composition in psoriasis. (2) Methods: We conducted a systematic review of studies investigating intestinal microbiome in psoriasis, using the PRISMA checklist. We searched MEDLINE, EMBASE, and Web of Science databases for relevant published articles (2000–2020). (3) Results: All of the 10 retrieved studies reported alterations in the gut microbiome in patients with psoriasis. Eight studies assessed alpha- and beta-diversity. Four of them reported a lack of change in alpha-diversity, but all confirmed significant changes in beta-diversity. At the phylum-level, at least two or more studies reported a lower relative abundance of Bacteroidetes, and higher Firmicutes in psoriasis patients versus healthy controls. (4) Conclusions: There is a significant association between alterations in gut microbial composition and psoriasis; however, there is high heterogeneity between studies. More unified methodological standards in large-scale studies are needed to understand microbiota’s contribution to psoriasis pathogenesis and its modulation as a potential therapeutic strategy.

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Consistent Metagenome-Derived Metrics Verify and Delineate Bacterial Species Boundaries

mSystems ◽

10.1128/msystems.00731-19 ◽

2020 ◽

Vol 5 (1) ◽

Cited By ~ 14

Author(s):

Matthew R. Olm ◽

Alexander Crits-Christoph ◽

Spencer Diamond ◽

Adi Lavy ◽

Paula B. Matheus Carnevali ◽

...

Keyword(s):

Bacterial Diversity ◽

Ribosomal Proteins ◽

Large Scale ◽

Bacterial Species ◽

Bacterial Genome ◽

16S Rrna Genes ◽

Rrna Genes ◽

Species Discrimination ◽

Bacterial Genomes ◽

Discrimination Power

ABSTRACT Longstanding questions relate to the existence of naturally distinct bacterial species and genetic approaches to distinguish them. Bacterial genomes in public databases form distinct groups, but these databases are subject to isolation and deposition biases. To avoid these biases, we compared 5,203 bacterial genomes from 1,457 environmental metagenomic samples to test for distinct clouds of diversity and evaluated metrics that could be used to define the species boundary. Bacterial genomes from the human gut, soil, and the ocean all exhibited gaps in whole-genome average nucleotide identities (ANI) near the previously suggested species threshold of 95% ANI. While genome-wide ratios of nonsynonymous and synonymous nucleotide differences (dN/dS) decrease until ANI values approach ∼98%, two methods for estimating homologous recombination approached zero at ∼95% ANI, supporting breakdown of recombination due to sequence divergence as a species-forming force. We evaluated 107 genome-based metrics for their ability to distinguish species when full genomes are not recovered. Full-length 16S rRNA genes were least useful, in part because they were underrecovered from metagenomes. However, many ribosomal proteins displayed both high metagenomic recoverability and species discrimination power. Taken together, our results verify the existence of sequence-discrete microbial species in metagenome-derived genomes and highlight the usefulness of ribosomal genes for gene-level species discrimination. IMPORTANCE There is controversy about whether bacterial diversity is clustered into distinct species groups or exists as a continuum. To address this issue, we analyzed bacterial genome databases and reports from several previous large-scale environment studies and identified clear discrete groups of species-level bacterial diversity in all cases. Genetic analysis further revealed that quasi-sexual reproduction via horizontal gene transfer is likely a key evolutionary force that maintains bacterial species integrity. We next benchmarked over 100 metrics to distinguish these bacterial species from each other and identified several genes encoding ribosomal proteins with high species discrimination power. Overall, the results from this study provide best practices for bacterial species delineation based on genome content and insight into the nature of bacterial species population genetics.

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Volatile scents of influenza A and S. pyogenes (co-)infected cells

Scientific Reports ◽

10.1038/s41598-019-55334-0 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 4

Author(s):

Selina Traxler ◽

Gina Barkowsky ◽

Radost Saß ◽

Ann-Christin Klemenz ◽

Nadja Patenge ◽

...

Keyword(s):

Influenza A ◽

Early Recognition ◽

Bacterial Species ◽

Bacterial Load ◽

Gas Chromatography Mass Spectrometry ◽

Sampling System ◽

Infected Cells ◽

Infection Processes ◽

Non Destructive

AbstractInfluenza A is a serious pathogen itself, but often leads to dangerous co-infections in combination with bacterial species such as Streptococcus pyogenes. In comparison to classical biochemical methods, analysis of volatile organic compounds (VOCs) in headspace above cultures can enable destruction free monitoring of metabolic processes in vitro. Thus, volatile biomarkers emitted from biological cell cultures and pathogens could serve for monitoring of infection processes in vitro. In this study we analysed VOCs from headspace above (co)-infected human cells by using a customized sampling system. For investigating the influenza A mono-infection and the viral-bacterial co-infection in vitro, we analysed VOCs from Detroit cells inoculated with influenza A virus and S. pyogenes by means of needle-trap micro-extraction (NTME) and gas chromatography mass spectrometry (GC-MS). Besides the determination of microbiological data such as cell count, cytokines, virus load and bacterial load, emissions from cell medium, uninfected cells and bacteria mono-infected cells were analysed. Significant differences in emitted VOC concentrations were identified between non-infected and infected cells. After inoculation with S. pyogenes, bacterial infection was mirrored by increased emissions of acetaldehyde and propanal. N-propyl acetate was linked to viral infection. Non-destructive monitoring of infections by means of VOC analysis may open a new window for infection research and clinical applications. VOC analysis could enable early recognition of pathogen presence and in-depth understanding of their etiopathology.

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Ribosomal RNA 2′O-methylation as a novel layer of inter-tumour heterogeneity in breast cancer

NAR Cancer ◽

10.1093/narcan/zcaa036 ◽

2020 ◽

Vol 2 (4) ◽

Author(s):

Virginie Marcel ◽

Janice Kielbassa ◽

Virginie Marchand ◽

Kundhavai S Natchiar ◽

Hermes Paraqindes ◽

...

Keyword(s):

Breast Cancer ◽

Ribosomal Rna ◽

Large Scale ◽

Gene Expression Regulation ◽

Molecular Signature ◽

Translation Control ◽

Breast Tumours ◽

Cellular Models ◽

Additional Layer ◽

Tumour Biology

Abstract Recent epitranscriptomics studies unravelled that ribosomal RNA (rRNA) 2′O-methylation is an additional layer of gene expression regulation highlighting the ribosome as a novel actor of translation control. However, this major finding lies on evidences coming mainly, if not exclusively, from cellular models. Using the innovative next-generation RiboMeth-seq technology, we established the first rRNA 2′O-methylation landscape in 195 primary human breast tumours. We uncovered the existence of compulsory/stable sites, which show limited inter-patient variability in their 2′O-methylation level, which map on functionally important sites of the human ribosome structure and which are surrounded by variable sites found from the second nucleotide layers. Our data demonstrate that some positions within the rRNA molecules can tolerate absence of 2′O-methylation in tumoral and healthy tissues. We also reveal that rRNA 2′O-methylation exhibits intra- and inter-patient variability in breast tumours. Its level is indeed differentially associated with breast cancer subtype and tumour grade. Altogether, our rRNA 2′O-methylation profiling of a large-scale human sample collection provides the first compelling evidence that ribosome variability occurs in humans and suggests that rRNA 2′O-methylation might represent a relevant element of tumour biology useful in clinic. This novel variability at molecular level offers an additional layer to capture the cancer heterogeneity and associates with specific features of tumour biology thus offering a novel targetable molecular signature in cancer.

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Comparative Genomics ofH. pyloriand Non-PyloriHelicobacterSpecies to Identify New Regions Associated with Its Pathogenicity and Adaptability

BioMed Research International ◽

10.1155/2016/6106029 ◽

2016 ◽

Vol 2016 ◽

pp. 1-15 ◽

Cited By ~ 8

Author(s):

De-Min Cao ◽

Qun-Feng Lu ◽

Song-Bo Li ◽

Ju-Ping Wang ◽

Yu-Li Chen ◽

...

Keyword(s):

Gastric Cancer ◽

Functional Annotation ◽

Human Population ◽

Large Scale ◽

Bacterial Species ◽

Human Beings ◽

Gram Negative ◽

Protein Protein Interaction ◽

H Pylori ◽

Cooperation Relationship

The genusHelicobacteris a group of Gram-negative, helical-shaped pathogens consisting of at least 36 bacterial species.Helicobacter pylori(H. pylori), infecting more than 50% of the human population, is considered as the major cause of gastritis, peptic ulcer, and gastric cancer. However, the genetic underpinnings ofH. pylorithat are responsible for its large scale epidemic and gastrointestinal environment adaption within human beings remain unclear. Core-pan genome analysis was performed among 75 representativeH. pyloriand 24 non-pylori Helicobactergenomes. There were 1173 conserved protein families ofH. pyloriand 673 of all 99Helicobactergenus strains. We found 79 genome unique regions, a total of 202,359bp, shared by at least 80% of theH. pyloribut lacked in non-pylori Helicobacterspecies. The operons, genes, and sRNAs within theH. pyloriunique regions were considered as potential ones associated with its pathogenicity and adaptability, and the relativity among them has been partially confirmed by functional annotation analysis. However, functions of at least 54 genes and 10 sRNAs were still unclear. Our analysis of protein-protein interaction showed that 30 genes within them may have the cooperation relationship.

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