scholarly journals Discovery of novel community-relevant small proteins in a simplified human intestinal microbiome

Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Hannes Petruschke ◽  
Christian Schori ◽  
Sebastian Canzler ◽  
Sarah Riesbeck ◽  
Anja Poehlein ◽  
...  
Keyword(s):  
Microbial Communities ◽  
Intestinal Microbiota ◽  
De Novo ◽  
Bacterial Species ◽  
Intestinal Microbiome ◽  
Single Strain ◽  
Small Proteins ◽  
Human Intestinal Microbiota ◽  
Wide Range

Abstract Background The intestinal microbiota plays a crucial role in protecting the host from pathogenic microbes, modulating immunity and regulating metabolic processes. We studied the simplified human intestinal microbiota (SIHUMIx) consisting of eight bacterial species with a particular focus on the discovery of novel small proteins with less than 100 amino acids (= sProteins), some of which may contribute to shape the simplified human intestinal microbiota. Although sProteins carry out a wide range of important functions, they are still often missed in genome annotations, and little is known about their structure and function in individual microbes and especially in microbial communities. Results We created a multi-species integrated proteogenomics search database (iPtgxDB) to enable a comprehensive identification of novel sProteins. Six of the eight SIHUMIx species, for which no complete genomes were available, were sequenced and de novo assembled. Several proteomics approaches including two earlier optimized sProtein enrichment strategies were applied to specifically increase the chances for novel sProtein discovery. The search of tandem mass spectrometry (MS/MS) data against the multi-species iPtgxDB enabled the identification of 31 novel sProteins, of which the expression of 30 was supported by metatranscriptomics data. Using synthetic peptides, we were able to validate the expression of 25 novel sProteins. The comparison of sProtein expression in each single strain versus a multi-species community cultivation showed that six of these sProteins were only identified in the SIHUMIx community indicating a potentially important role of sProteins in the organization of microbial communities. Two of these novel sProteins have a potential antimicrobial function. Metabolic modelling revealed that a third sProtein is located in a genomic region encoding several enzymes relevant for the community metabolism within SIHUMIx. Conclusions We outline an integrated experimental and bioinformatics workflow for the discovery of novel sProteins in a simplified intestinal model system that can be generically applied to other microbial communities. The further analysis of novel sProteins uniquely expressed in the SIHUMIx multi-species community is expected to enable new insights into the role of sProteins on the functionality of bacterial communities such as those of the human intestinal tract.

scholarly journals The Intestinal Microbiota: Impacts of Antibiotics Therapy, Colonization Resistance, and Diseases

2021 ◽  
Vol 22 (12) ◽  
pp. 6597
Author(s):  
Taif Shah ◽  
Zulqarnain Baloch ◽  
Zahir Shah ◽  
Xiuming Cui ◽  
Xueshan Xia
Keyword(s):  
Intestinal Microbiota ◽  
Short Chain Fatty Acids ◽  
Intestinal Microbiome ◽  
Main Role ◽  
Colonization Resistance ◽  
Wide Range ◽  
Pathogenic Microbes ◽  
Pathogen Colonization ◽  
Antimicrobial Metabolites

Trillions of microbes exist in the human body, particularly the gastrointestinal tract, coevolved with the host in a mutually beneficial relationship. The main role of the intestinal microbiome is the fermentation of non-digestible substrates and increased growth of beneficial microbes that produce key antimicrobial metabolites such as short-chain fatty acids, etc., to inhibit the growth of pathogenic microbes besides other functions. Intestinal microbiota can prevent pathogen colonization through the mechanism of colonization resistance. A wide range of resistomes are present in both beneficial and pathogenic microbes. Giving antibiotic exposure to the intestinal microbiome (both beneficial and hostile) can trigger a resistome response, affecting colonization resistance. The following review provides a mechanistic overview of the intestinal microbiome and the impacts of antibiotic therapy on pathogen colonization and diseases. Further, we also discuss the epidemiology of immunocompromised patients who are at high risk for nosocomial infections, colonization and decolonization of multi-drug resistant organisms in the intestine, and the direct and indirect mechanisms that govern colonization resistance to the pathogens.

scholarly journals A Review of the Role of the Intestinal Microbiota in Age-Related Macular Degeneration

2021 ◽  
Vol 10 (10) ◽  
pp. 2072
Author(s):  
Phoebe Lin ◽  
Scott M. McClintic ◽  
Urooba Nadeem ◽  
Dimitra Skondra
Keyword(s):  
Macular Degeneration ◽  
Intestinal Microbiota ◽  
Retinal Disease ◽  
Age Related Macular Degeneration ◽  
Intestinal Microbiome ◽  
Age Related ◽  
Intestinal Dysbiosis ◽  
Apo E ◽  
Dry Amd

Blindness from age-related macular degeneration (AMD) is an escalating problem, yet AMD pathogenesis is incompletely understood and treatments are limited. The intestinal microbiota is highly influential in ocular and extraocular diseases with inflammatory components, such as AMD. This article reviews data supporting the role of the intestinal microbiota in AMD pathogenesis. Multiple groups have found an intestinal dysbiosis in advanced AMD. There is growing evidence that environmental factors associated with AMD progression potentially work through the intestinal microbiota. A high-fat diet in apo-E-/- mice exacerbated wet and dry AMD features, presumably through changes in the intestinal microbiome, though other independent mechanisms related to lipid metabolism are also likely at play. AREDS supplementation reversed some adverse intestinal microbial changes in AMD patients. Part of the mechanism of intestinal microbial effects on retinal disease progression is via microbiota-induced microglial activation. The microbiota are at the intersection of genetics and AMD. Higher genetic risk was associated with lower intestinal bacterial diversity in AMD. Microbiota-induced metabolite production and gene expression occur in pathways important in AMD pathogenesis. These studies suggest a crucial link between the intestinal microbiota and AMD pathogenesis, thus providing a novel potential therapeutic target. Thus, the need for large longitudinal studies in patients and germ-free or gnotobiotic animal models has never been more pressing.

scholarly journals CAMISIM: Simulating metagenomes and microbial communities

2018 ◽  
Author(s):  
Adrian Fritz ◽  
Peter Hofmann ◽  
Stephan Majda ◽  
Eik Dahms ◽  
Johannes Dröge ◽  
...  
Keyword(s):  
Microbial Communities ◽  
De Novo ◽  
Real Data ◽  
Small Data ◽  
Data Sets ◽  
Sequencing Data ◽  
Taxonomic Profiling ◽  
Benchmark Data ◽  
Sequencing Technologies ◽  
Wide Range

Shotgun metagenome data sets of microbial communities are highly diverse, not only due to the natural variation of the underlying biological systems, but also due to differences in laboratory protocols, replicate numbers, and sequencing technologies. Accordingly, to effectively assess the performance of metagenomic analysis software, a wide range of benchmark data sets are required. Here, we describe the CAMISIM microbial community and metagenome simulator. The software can model different microbial abundance profiles, multi-sample time series and differential abundance studies, includes real and simulated strain-level diversity, and generates second and third generation sequencing data from taxonomic profiles or de novo. Gold standards are created for sequence assembly, genome binning, taxonomic binning, and taxonomic profiling. CAMSIM generated the benchmark data sets of the first CAMI challenge. For two simulated multi-sample data sets of the human and mouse gut microbiomes we observed high functional congruence to the real data. As further applications, we investigated the effect of varying evolutionary genome divergence, sequencing depth, and read error profiles on two popular metagenome assemblers, MEGAHIT and metaSPAdes, on several thousand small data sets generated with CAMISIM. CAMISIM can simulate a wide variety of microbial communities and metagenome data sets together with truth standards for method evaluation. All data sets and the software are freely available at: https://github.com/CAMI-challenge/CAMISIM

scholarly journals sPepFinder expedites genome-wide identification of small proteins in bacteria

2020 ◽  
Author(s):  
Lei Li ◽  
Yanjie Chao
Keyword(s):  
De Novo ◽  
Bacterial Species ◽  
Computational Prediction ◽  
Ribosome Profiling ◽  
Support Vector ◽  
Initiation Rate ◽  
E Coli ◽  
Small Proteins ◽  
Genome Wide ◽  
A Genome

ABSTRACTSmall proteins shorter than 50 amino acids have been long overlooked. A number of small proteins have been identified in several model bacteria using experimental approaches and assigned important functions in diverse cellular processes. The recent development of ribosome profiling technologies has allowed a genome-wide identification of small proteins and small ORFs (smORFs), but our incomplete understanding of small proteins hinders de novo computational prediction of smORFs in non-model bacterial species. Here, we have identified several sequence features for smORFs by a systematic analysis of all the known small proteins in E. coli, among which the translation initiation rate is the strongest determinant. By integrating these features into a support vector machine learning model, we have developed a novel sPepFinder algorithm that can predict conserved smORFs in bacterial genomes with a high accuracy of 92.8%. De novo prediction in E. coli has revealed several novel smORFs with evidence of translation supported by ribosome profiling. Further application of sPepFinder in 549 bacterial species has led to the identification of > 100,000 novel smORFs, many of which are conserved at the amino acid and nucleotide levels under purifying selection. Overall, we have established sPepFinder as a valuable tool to identify novel smORFs in both model and non-model bacterial organisms, and provided a large resource of small proteins for functional characterizations.

scholarly journals Heat Shock Proteins Are Essential Components in Transformation and Tumor Progression: Cancer Cell Intrinsic Pathways and Beyond

2019 ◽  
Vol 20 (18) ◽  
pp. 4507 ◽  
Author(s):  
Lang ◽  
Guerrero-Giménez ◽  
Prince ◽  
Ackerman ◽  
Bonorino ◽  
...  
Keyword(s):  
Heat Shock ◽  
Cancer Cells ◽  
Stress Proteins ◽  
De Novo ◽  
Human Cancer ◽  
Essential Components ◽  
Wide Range ◽  
Cancer Types ◽  
Shock Proteins

Heat shock protein (HSP) synthesis is switched on in a remarkably wide range of tumor cells, in both experimental animal systems and in human cancer, in which these proteins accumulate in high levels. In each case, elevated HSP concentrations bode ill for the patient, and are associated with a poor outlook in terms of survival in most cancer types. The significance of elevated HSPs is underpinned by their essential roles in mediating tumor cell intrinsic traits such as unscheduled cell division, escape from programmed cell death and senescence, de novo angiogenesis, and increased invasion and metastasis. An increased HSP expression thus seems essential for tumorigenesis. Perhaps of equal significance is the pronounced interplay between cancer cells and the tumor milieu, with essential roles for intracellular HSPs in the properties of the stromal cells, and their roles in programming malignant cells and in the release of HSPs from cancer cells to influence the behavior of the adjacent tumor and infiltrating the normal cells. These findings of a triple role for elevated HSP expression in tumorigenesis strongly support the targeting of HSPs in cancer, especially given the role of such stress proteins in resistance to conventional therapies.

scholarly journals Intestinal Microbiota: A Novel Target to Improve Anti-Tumor Treatment?

2019 ◽  
Vol 20 (18) ◽  
pp. 4584 ◽  
Author(s):  
Romain Villéger ◽  
Amélie Lopès ◽  
Guillaume Carrier ◽  
Julie Veziant ◽  
Elisabeth Billard ◽  
...  
Keyword(s):  
Side Effects ◽  
Gut Microbiota ◽  
Host Response ◽  
Fecal Microbiota Transplantation ◽  
Direct Interaction ◽  
Fecal Microbiota ◽  
Intestinal Microbiome ◽  
Wide Range ◽  
Novel Target

Recently, preclinical and clinical studies targeting several types of cancer strongly supported the key role of the gut microbiota in the modulation of host response to anti-tumoral therapies such as chemotherapy, immunotherapy, radiotherapy and even surgery. Intestinal microbiome has been shown to participate in the resistance to a wide range of anticancer treatments by direct interaction with the treatment or by indirectly stimulating host response through immunomodulation. Interestingly, these effects were described on colorectal cancer but also in other types of malignancies. In addition to their role in therapy efficacy, gut microbiota could also impact side effects induced by anticancer treatments. In the first part of this review, we summarized the role of the gut microbiome on the efficacy and side effects of various anticancer treatments and underlying mechanisms. In the second part, we described the new microbiota-targeting strategies, such as probiotics and prebiotics, antibiotics, fecal microbiota transplantation and physical activity, which could be effective adjuvant therapies developed in order to improve anticancer therapeutic efficiency.

scholarly journals Bacterial Relationships in Aquaponics: New Research Directions

2019 ◽  
pp. 145-161 ◽  
Author(s):  
Alyssa Joyce ◽  
Mike Timmons ◽  
Simon Goddek ◽  
Timea Pentz
Keyword(s):  
Microbial Communities ◽  
Plant Production ◽  
Microbial Decomposition ◽  
Recirculating Aquaculture ◽  
Recirculating Aquaculture Systems ◽  
Wide Range ◽  
Technical Specifications ◽  
New Research ◽  
System 1

AbstractThe growth rates and welfare of fish and the quality of plant production in aquaponics system rely on the composition and health of the system’s microbiota. The overall productivity depends on technical specifications for water quality and its movement amongst components of the system, including a wide range of parameters  including factors such as pH and flow rates which ensure that microbial components can act effectively in nitrification and remineralization processes. In this chapter, we explore current research examining the role of microbial communities in three units of an aquaponics system: (1) the recirculating aquaculture system (RAS) for fish production which includes biofiltration systems for denitrification; (2) the hydroponics units for plant production; and (3) biofilters and bioreactors, including sludge digester systems (SDS) involved in microbial decomposition and recovery/remineralization of solid wastes. In the various sub-disciplines related to each of these components, there is existing literature about microbial communities and their importance within each system (e.g. recirculating aquaculture systems (RAS), hydroponics, biofilters and digesters), but there is currently limited work examining interactions between these components in aquaponics system, thus making it an important area for further research.

scholarly journals Trypsin Mediates Growth Phase-Dependent Transcriptional Regulation of Genes Involved in Biosynthesis of Ruminococcin A, a Lantibiotic Produced by a Ruminococcus gnavus Strain from a Human Intestinal Microbiota

2002 ◽  
Vol 184 (1) ◽  
pp. 18-28 ◽  
Author(s):  
Ana Gomez ◽  
Monique Ladiré ◽  
Françoise Marcille ◽  
Michel Fons
Keyword(s):  
Intestinal Microbiota ◽  
Growth Phase ◽  
Transcriptional Activation ◽  
Biosynthetic Gene Cluster ◽  
Proteolytic Processing ◽  
Open Reading Frames ◽  
Signaling Mechanism ◽  
Human Intestinal Microbiota ◽  
Complex Signaling

ABSTRACT Ruminococcin A (RumA) is a trypsin-dependent lantibiotic produced by Ruminococcus gnavus E1, a gram-positive strict anaerobic strain isolated from a human intestinal microbiota. A 12.8-kb region from R. gnavus E1 chromosome, containing the biosynthetic gene cluster of RumA, has been cloned and sequenced. It consisted of 13 open reading frames, organized in three operons with predicted functions in lantibiotic biosynthesis, signal transduction regulation, and immunity. One unusual feature of the locus is the presence of three almost identical structural genes, all of them encoding the RumA precursor. In order to determine the role of trypsin in RumA production, the transcription of the rum genes has been investigated under inducing and noninducing conditions. Trypsin activity is needed for the growth phase-dependent transcriptional activation of RumA operons. Our results suggest that bacteriocin production by R. gnavus E1 is controlled through a complex signaling mechanism involving the proteolytic processing of a putative extracellular inducer-peptide by trypsin, a specific environmental cue of the digestive ecosystem.

Developmental psychopathology: The role of structural variation in the genome

2012 ◽  
Vol 24 (4) ◽  
pp. 1319-1334 ◽  
Author(s):  
Michael Gill
Keyword(s):  
Developmental Disorders ◽  
Developmental Psychopathology ◽  
De Novo ◽  
Copy Number Variants ◽  
Cognitive Disorders ◽  
Comparative Genome Hybridization ◽  
Diagnostic Categories ◽  
Wide Range ◽  
Technological Developments

AbstractA wide range of developmental disorders present with characteristic psychopathologies and behaviors, with diagnoses including, inter alia, cognitive disorders and learning disabilities, epilepsies, autism, and schizophrenia. Each, to varying extent, has a genetic component to etiology and is associated with cytogenetic abnormalities. Technological developments, particularly array-based comparative genome hybridization and single nucleotide polymorphism chips, has revealed a wide range of rare recurrent and de novo copy number variants (CNVs) to be associated with disorder and psychopathology. It is surprising that many apparently similar CNVs are identified across two or more disorders hitherto considered unrelated. This article describes the characteristics of CNVs and current technological restrictions that make accurately identifying small events difficult. It summarizes the latest discoveries for individual diagnostic categories and considers the implications for a shared neurobiology. It examines likely developments in the knowledge base as well as addressing the clinical implications going forward.

scholarly journals Irf4-dependent CD103+CD11b+dendritic cells and the intestinal microbiome regulate monocyte and macrophage activation and intestinal peristalsis in postoperative ileus

Gut ◽  
2017 ◽  
Vol 66 (12) ◽  
pp. 2110-2120 ◽  
Author(s):  
Judith-Mira Pohl ◽  
Sebastian Gutweiler ◽  
Stephanie Thiebes ◽  
Julia K Volke ◽  
Ludger Klein-Hitpass ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Antibiotic Treatment ◽  
Intestinal Microbiota ◽  
Postoperative Ileus ◽  
Intestinal Microbiome ◽  
Oral Antibiotic ◽  
Monocytes And Macrophages ◽  
Intestinal Peristalsis ◽  
The Impact

ObjectivePostoperative ileus (POI), the most frequent complication after intestinal surgery, depends on dendritic cells (DCs) and macrophages. Here, we have investigated the mechanism that activates these cells and the contribution of the intestinal microbiota for POI induction.DesignPOI was induced by manipulating the intestine of mice, which selectively lack DCs, monocytes or macrophages. The disease severity in the small and large intestine was analysed by determining the distribution of orally applied fluorescein isothiocyanate-dextran and by measuring the excretion time of a retrogradely inserted glass ball. The impact of the microbiota on intestinal peristalsis was evaluated after oral antibiotic treatment.ResultsWe found thatCd11c-Cre+Irf4flox/floxmice lack CD103+CD11b+DCs, a DC subset unique to the intestine whose function is poorly understood. Their absence in the intestinal muscularis reduced pathogenic inducible nitric oxide synthase (iNOS) production by monocytes and macrophages and ameliorated POI. Pathogenic iNOS was produced in the jejunum by resident Ly6C–macrophages and infiltrating chemokine receptor 2-dependent Ly6C+monocytes, but in the colon only by the latter demonstrating differential tolerance mechanisms along the intestinal tract. Consistently, depletion of both cell subsets reduced small intestinal POI, whereas the depletion of Ly6C+monocytes alone was sufficient to prevent large intestinal POI. The differential role of monocytes and macrophages in small and large intestinal POI suggested a potential role of the intestinal microbiota. Indeed, antibiotic treatment reduced iNOS levels and ameliorated POI.ConclusionsOur findings reveal that CD103+CD11b+DCs and the intestinal microbiome are a prerequisite for the activation of intestinal monocytes and macrophages and for dysregulating intestinal motility in POI.

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