scholarly journals Gut Microbiota as a Source of Uremic Toxins

2022 ◽  
Vol 23 (1) ◽  
pp. 483
Author(s):  
Vasily A. Popkov ◽  
Anastasia A. Zharikova ◽  
Evgenia A. Demchenko ◽  
Nadezda V. Andrianova ◽  
Dmitry B. Zorov ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Bacterial Species ◽  
Human Microbiome ◽  
Human Microbiome Project ◽  
Uremic Toxins ◽  
Enzymatic Reactions ◽  
Bacterial Strains ◽  
Excretory Function ◽  
High Concentrations ◽  
Stage Renal Disease

Uremic retention solutes are the compounds that accumulate in the blood when kidney excretory function is impaired. Some of these compounds are toxic at high concentrations and are usually known as “uremic toxins”. The cumulative detrimental effect of uremic toxins results in numerous health problems and eventually mortality during acute or chronic uremia, especially in end-stage renal disease. More than 100 different solutes increase during uremia; however, the exact origin for most of them is still debatable. There are three main sources for such compounds: exogenous ones are consumed with food, whereas endogenous ones are produced by the host metabolism or by symbiotic microbiota metabolism. In this article, we identify uremic retention solutes presumably of gut microbiota origin. We used database analysis to obtain data on the enzymatic reactions in bacteria and human organisms that potentially yield uremic retention solutes and hence to determine what toxins could be synthesized in bacteria residing in the human gut. We selected biochemical pathways resulting in uremic retention solutes synthesis related to specific bacterial strains and revealed links between toxin concentration in uremia and the proportion of different bacteria species which can synthesize the toxin. The detected bacterial species essential for the synthesis of uremic retention solutes were then verified using the Human Microbiome Project database. Moreover, we defined the relative abundance of human toxin-generating enzymes as well as the possibility of the synthesis of a particular toxin by the human metabolism. Our study presents a novel bioinformatics approach for the elucidation of the origin of both uremic retention solutes and uremic toxins and for searching for the most likely human microbiome producers of toxins that can be targeted and used for the therapy of adverse consequences of uremia.

scholarly journals Negative Impact of Pseudomonas aeruginosa Y12 on Its Host Musca domestica

2021 ◽  
Vol 12 ◽  
Author(s):  
Qian Zhang ◽  
Shumin Wang ◽  
Xinyu Zhang ◽  
Ruiling Zhang ◽  
Zhong Zhang
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Gut Microbiota ◽  
Negative Impact ◽  
Bacterial Species ◽  
Intestinal Flora ◽  
Interaction Network ◽  
High Concentration ◽  
Feeding Experiments ◽  
Relative Abundances ◽  
High Concentrations

High concentrations of Pseudomonas aeruginosa Y12 significantly inhibit the development of housefly larvae and accelerate larvae death. In this study, the dynamic distribution of the gut microbiota of housefly larvae fed different concentrations of P. aeruginosa Y12 was investigated. Compared with low-concentration P. aeruginosa diets, orally administered high-concentration P. aeruginosa diets caused higher mortality and had a greater impact on the community structure and interaction network of intestinal flora in housefly larvae. The bacterial community of the gut microbiota in housefly larvae was reconstructed in 4 days. Bacterial abundance and diversity were significantly reduced in housefly larvae fed high concentrations of P. aeruginosa. With the growth of larvae, the relative abundances of Providencia, Proteus, Myroides, Klebsiella, and Alcaligenes increased significantly in housefly larvae fed with high concentrations of P. aeruginosa, while the relative abundances of Bordetella, Enterobacter, Morganella, Ochrobactrum, Alcaligenaceae, and Empedobacter were significantly reduced. To analyze the role of the gut microorganisms played on housefly development, a total of 10 cultivable bacterial species belonging to 9 genera were isolated from the intestine of housefly larvae among which Enterobacter hormaechei, Klebsiella pneumoniae, Enterobacter cloacae, Lysinibacillus fusiformis, and Bacillus safensis promoted the growth of larvae through feeding experiments. This study is the first to analyze the influence of high concentrations of P. aeruginosa on the gut microbiota of houseflies. Our study provides a basis for exploring the pathogenic mechanism of high concentrations of P. aeruginosa Y12 in houseflies.

scholarly journals A high-resolution pipeline for 16S-sequencing identifies bacterial strains in human microbiome

2019 ◽  
Author(s):  
Igor Segota ◽  
Tao Long
Keyword(s):  
Bacterial Species ◽  
Human Microbiome ◽  
Amplicon Sequencing ◽  
R Package ◽  
Strain Level ◽  
Sequencing Data ◽  
Bacterial Strains ◽  
16S Sequencing ◽  
16S Amplicon Sequencing ◽  
Sequencing Data Analysis

We developed a High-resolution Microbial Analysis Pipeline (HiMAP) for 16S amplicon sequencing data analysis, aiming at bacterial species or strain-level identification from human microbiome to enable experimental validation for causal effects of the associated bacterial strains on health and diseases. HiMAP achieved higher accuracy in identifying species in human microbiome mock community than other pipelines. HiMAP identified majority of the species, with strain-level resolution wherever possible, as detected by whole genome shotgun sequencing using MetaPhlAn2 and reported comparable relative abundances. HiMAP is an open-source R package available at https://github.com/taolonglab/himap.

scholarly journals Depletion of microbiome-derived molecules in the host using Clostridium genetics

2018 ◽  
Author(s):  
Chun-Jun Guo ◽  
Breanna M. Allen ◽  
Kamir J. Hiam ◽  
Dylan Dodd ◽  
Will van Treuren ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Gut Microbiota ◽  
Metabolic Pathways ◽  
General System ◽  
Short Chain Fatty Acids ◽  
Wild Type ◽  
Bacterial Strains ◽  
High Concentrations ◽  
Host Tissues ◽  
Molecule Production

ABSTRACTThe gut microbiota produce hundreds of molecules that are present at high concentrations in circulation and whose levels vary widely among humans. In most cases, molecule production has not been linked to specific bacterial strains or metabolic pathways, and unraveling the contribution of each molecule to host biology remains difficult. A general system to ‘toggle’ molecules in this pool on/off in the host would enable interrogation of the mechanisms by which they modulate host biology and disease processes. Such a system has been elusive due to limitations in the genetic manipulability of Clostridium and its relatives, the source of many molecules in this pool. Here, we describe a method for reliably constructing clean deletions in a model commensal Clostridium, C. sporogenes (Cs), including multiply mutated strains. We demonstrate the utility of this method by using it to ‘toggle’ off the production of ten Cs-derived molecules that accumulate in host tissues. By comparing mice colonized by wild-type Cs versus a mutant deficient in the production of branched short-chain fatty acids, we discover a previously unknown IgA-modulatory activity of these abundant microbiome-derived molecules. Our method opens the door to interrogating and sculpting a highly concentrated pool of chemicals from the microbiome.

scholarly journals Diversification of Type VI Secretion System Toxins Reveals Ancient Antagonism among Bee Gut Microbes

mBio ◽  
2017 ◽  
Vol 8 (6) ◽  
Author(s):  
Margaret I. Steele ◽  
Waldan K. Kwong ◽  
Marvin Whiteley ◽  
Nancy A. Moran
Keyword(s):  
Escherichia Coli ◽  
Gut Microbiota ◽  
Microbial Communities ◽  
Protein Complexes ◽  
Bacterial Species ◽  
Bacterial Strains ◽  
Secretion Systems ◽  
Type Vi Secretion ◽  
Immunity Genes

ABSTRACT Microbial communities are shaped by interactions among their constituent members. Some Gram-negative bacteria employ type VI secretion systems (T6SSs) to inject protein toxins into neighboring cells. These interactions have been theorized to affect the composition of host-associated microbiomes, but the role of T6SSs in the evolution of gut communities is not well understood. We report the discovery of two T6SSs and numerous T6SS-associated Rhs toxins within the gut bacteria of honey bees and bumble bees. We sequenced the genomes of 28 strains of Snodgrassella alvi, a characteristic bee gut microbe, and found tremendous variability in their Rhs toxin complements: altogether, these strains appear to encode hundreds of unique toxins. Some toxins are shared with Gilliamella apicola, a coresident gut symbiont, implicating horizontal gene transfer as a source of toxin diversity in the bee gut. We use data from a transposon mutagenesis screen to identify toxins with antibacterial function in the bee gut and validate the function and specificity of a subset of these toxin and immunity genes in Escherichia coli. Using transcriptome sequencing, we demonstrate that S. alvi T6SSs and associated toxins are upregulated in the gut environment. We find that S. alvi Rhs loci have a conserved architecture, consistent with the C-terminal displacement model of toxin diversification, with Rhs toxins, toxin fragments, and cognate immunity genes that are expressed and confer strong fitness effects in vivo. Our findings of T6SS activity and Rhs toxin diversity suggest that T6SS-mediated competition may be an important driver of coevolution within the bee gut microbiota. IMPORTANCE The structure and composition of host-associated bacterial communities are of broad interest, because these communities affect host health. Bees have a simple, conserved gut microbiota, which provides an opportunity to explore interactions between species that have coevolved within their host over millions of years. This study examined the role of type VI secretion systems (T6SSs)—protein complexes used to deliver toxic proteins into bacterial competitors—within the bee gut microbiota. We identified two T6SSs and diverse T6SS-associated toxins in bacterial strains from bees. Expression of these genes is increased in bacteria in the bee gut, and toxin and immunity genes demonstrate antibacterial and protective functions, respectively, when expressed in Escherichia coli. Our results suggest that coevolution among bacterial species in the bee gut has favored toxin diversification and maintenance of T6SS machinery, and demonstrate the importance of antagonistic interactions within host-associated microbial communities. IMPORTANCE The structure and composition of host-associated bacterial communities are of broad interest, because these communities affect host health. Bees have a simple, conserved gut microbiota, which provides an opportunity to explore interactions between species that have coevolved within their host over millions of years. This study examined the role of type VI secretion systems (T6SSs)—protein complexes used to deliver toxic proteins into bacterial competitors—within the bee gut microbiota. We identified two T6SSs and diverse T6SS-associated toxins in bacterial strains from bees. Expression of these genes is increased in bacteria in the bee gut, and toxin and immunity genes demonstrate antibacterial and protective functions, respectively, when expressed in Escherichia coli. Our results suggest that coevolution among bacterial species in the bee gut has favored toxin diversification and maintenance of T6SS machinery, and demonstrate the importance of antagonistic interactions within host-associated microbial communities.

Gut Microbiota: In Dynamics of Life and Homoeopathy

2020 ◽  
Author(s):  
Eiphrangdaka L. Suchiang ◽  
Deepak Kumar ◽  
Shabana Yeasmin ◽  
Monisha Singh ◽  
James Michael ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Chronic Diseases ◽  
Human Microbiome ◽  
Human Microbiome Project ◽  
Present Review ◽  
Human Beings ◽  
Art And Science ◽  
Health And Disease ◽  
Therapeutic Measures ◽  
Micro Organisms

AbstractThe Human Microbiome Project (HMP) launched in 2008 by the National Institute of Health (NIH) fascinated microbiologists with discoveries of micro-organisms inside and outside of human beings. Their correlation with health and disease brings a new insight to preventive and therapeutic measures. At present, focus is more on the micro-organisms residing in the gut and various factors capable of altering their composition. The conclusion made by Dr. Edward Bach regarding the ability of homoeopathic potencies to alter bowel flora and its relation with chronic diseases was investigated and experimented way back. The present review attempts to correlate gut microbiota with the art and science of homoeopathy.

scholarly journals Improving characterization of understudied human microbiomes using targeted phylogenetics

2019 ◽  
Author(s):  
Bruce A Rosa ◽  
Kathie Mihindukulasuriya ◽  
Kymberlie Hallsworth-Pepin ◽  
Aye Wollam ◽  
John Martin ◽  
...  
Keyword(s):  
Human Microbiome ◽  
Human Microbiome Project ◽  
Genomic Sequences ◽  
Bacterial Strains ◽  
Bacterial Genomes ◽  
Genomic Databases ◽  
Disease States ◽  
Health And Disease ◽  
Taxonomic Groups

AbstractWhole genome bacterial sequences are required to better understand microbial functions, niches-pecific bacterial metabolism, and disease states. Although genomic sequences are available for many of the human-associated bacteria from commonly tested body habitats (e.g. stool), as few as 13% of bacterial-derived reads from other sites such as the skin map to known bacterial genomes. To facilitate a better characterization of metagenomic shotgun reads from under-represented body sites, we collected over 10,000 bacterial isolates originating from 14 human body habitats, identified novel taxonomic groups based on full length 16S rRNA sequences, clustered the sequences to ensure that no individual taxonomic group was over-selected for sequencing, prioritized bacteria from under-represented body sites (such as skin, respiratory and urinary tract), and sequenced and assembled genomes for 665 new bacterial strains. Here we show that addition of these genomes improved read mapping rates of HMP metagenomic samples by nearly 30% for the previously under-represented phylum Fusobacteria, and 27.5% of the novel genomes generated here had high representation in at least one of the tested HMP samples, compared to 12.5% of the sequences in the public databases, indicating an enrichment of useful novel genomic sequences resulting from the prioritization procedure. As our understanding of the human microbiome continues to improve and to enter the realm of therapy developments, targeted approaches such as this to improve genomic databases will increase in importance from both an academic and clinical perspective.ImportanceThe human microbiome plays a critically important role in health and disease, but current understanding of the mechanisms underlying the interactions between the varying microbiome and the different host environments is lacking. Having access to a database of fully sequenced bacterial genomes provides invaluable insights into microbial functions, but currently sequenced genomes for the human microbiome have largely come from a limited number of body sites (primarily stool), while other sites such as the skin, respiratory tract and urinary tracts are under-represented, resulting in as little as 13% of bacterial-derived reads mapping to known bacterial genomes. Here, we sequenced and assembled 665 new bacterial genomes, prioritized from a larger database to select under-represented body sites and bacterial taxa in the existing databases. As a result, we substantially improve mapping rates for samples from the Human Microbiome Project and provide an important contribution to human bacterial genomic databases for future studies.

scholarly journals Gut microbiota alterations due to fecal transplant

2020 ◽  
Author(s):  
Evgenii I. Olekhnovich ◽  
Artem B. Ivanov ◽  
Vladimir I. Ulyantsev ◽  
Elena N. Ilina
Keyword(s):  
Gut Microbiota ◽  
Microbial Diversity ◽  
Fecal Microbiota Transplantation ◽  
Human Microbiome ◽  
Human Microbiome Project ◽  
Fecal Microbiota ◽  
Metagenomic Data ◽  
Analysis Tool ◽  
Fecal Transplant ◽  
Biological Phenomena

AbstractBackgroundFecal microbiota transplantation (FMT) is currently used to treat recurrent clostridial colitis and other diseases. However, neither the therapeutic mechanism of the FMT nor the mechanism that allows the donor bacteria to colonize the intestine of the recipient has yet been described. Moreover, FMT is a great model for studying the ecology of host-associated microbial communities. This creates the need for experimentation with approaches to metagenomic data analysis which may be useful to the interpretation of observed biological phenomena.MethodsHere the RECAST (Recipient intestinE Colonisation AnalysiS Tool) computational approach is presented, which is based on the shotgun reads sorting process in accordance with their origin in recipient metagenome. Using the RECAST algorithm, taxonomic/functional annotation, and machine learning, the shotgun metagenomic data from three FMT studies including healthy volunteers, patients with clostridial colitis and metabolic syndrome were analyzed.ResultsAccording to the analysis results, the colonizing and remaining microbial diversity in the post-FMT recipient metagenomic samples is clearly separated from the non-colonizers and lost. It is well explained by higher relative abundance in donor/pre-FMT recipient, Human Microbiome project metagenomes, and taxonomy. Moreover, the colonizing and remaining microbes are associated with lantibiotic and tetracyclines resistance genes.ConclusionBased on obtained results, the previously proposed “core” human gut microbiome concept may be elaborated. The top microbes of gut microbiota form “cores”, which, moreover, are mutually integrable between humans. Also, we assume that redistribution of microbial diversity in post-FMT recipients’ metagenomes is due to competition of donor/recipient microbes and to host immunity. The associations of top gut microbes with lantibiotic/antibiotic resistance can be related to gut microbiota colonization resistance phenomena or anthropogenic impact.

scholarly journals Implications of error-prone long-read whole-genome shotgun sequencing on characterizing reference microbiomes

2020 ◽  
Author(s):  
Yu Hu ◽  
Li Fang ◽  
Christopher Nicholson ◽  
Kai Wang
Keyword(s):  
Human Microbiome ◽  
Human Microbiome Project ◽  
Error Rates ◽  
Tool Development ◽  
Sequencing Data ◽  
Bacterial Strains ◽  
Microbial Genomes ◽  
Oxford Nanopore ◽  
Long Read ◽  
Adequate Coverage

SummaryLong-read sequencing techniques, such as the Oxford Nanopore Technology, can generate reads that are tens of kilobases in length, and are therefore particularly relevant for microbiome studies. However, due to the higher per-base error rates than typical short-read sequencing, the application of long-read sequencing on microbiomes remains largely unexplored. Here we deeply sequenced two human microbiota mock community samples (HM-276D and HM-277D) from the Human Microbiome Project. We showed that assembly programs consistently achieved high accuracy (~99%) and completeness (~99%) for bacterial strains with adequate coverage. We also found that long-read sequencing provides accurate estimates of species-level abundance (R=0.94 for 20 bacteria with abundance ranging from 0.005% to 64%). Our results demonstrate the feasibility to characterize complete microbial genomes and populations from error-prone Nanopore sequencing data, but also highlight necessary bioinformatics improvements for future metagenomics tool development.

scholarly journals Strain population structure varies widely across bacterial species and predicts strain colonization in unrelated individuals

2020 ◽  
Author(s):  
Jeremiah J. Faith ◽  
Alice Chen-Liaw ◽  
Varun Aggarwala ◽  
Nadeem O. Kaakoush ◽  
Thomas J. Borody ◽  
...  
Keyword(s):  
Population Structure ◽  
Gut Microbiota ◽  
Population Size ◽  
Bacterial Species ◽  
Fecal Microbiota ◽  
Small Population ◽  
Bacterial Strains ◽  
Bacterial Genomes ◽  
Population Sizes ◽  
Microbial Strain

SummaryThe population structure of strains within a bacterial species is poorly defined, despite the functional importance of strain variation in the human gut microbiota on health. Here we analyzed >1000 sequenced bacterial strains from the fecal microbiota of 47 individuals from two countries and combined them with >150,000 bacterial genomes from NCBI to quantify the strain population size of different bacterial species, as well as the frequency of finding the same strain colonized in unrelated individuals who had no opportunities for direct microbial strain transmission. Strain population sizes ranged from tens to over one-hundred thousand per species. Prevalent strains in common gut microbiota species with small population sizes were the most likely to be harbored in two or more unrelated individuals. The finite strain population size of certain species creates the opportunity to comprehensively sequence the entirety of these species’ prevalent strains and associate their presence in different individuals with health outcomes.

scholarly journals HLA-A alleles including HLA-A29 affect the composition of the gut microbiome: a potential clue to the pathogenesis of birdshot retinochoroidopathy

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Peter R. Sternes ◽  
Tammy M. Martin ◽  
Michael Paley ◽  
Sarah Diamond ◽  
Mark J. Asquith ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Bacterial Species ◽  
Human Microbiome ◽  
Human Microbiome Project ◽  
Eye Disease ◽  
Intestinal Biopsy ◽  
Healthy Individuals ◽  
Sequencing Data ◽  
Immune Mediated ◽  
Bacterial Profiling

Abstract Birdshot retinochoroidopathy occurs exclusively in individuals who are HLA-A29 positive. The mechanism to account for this association is unknown. The gut microbiome has been causally implicated in many immune-mediated diseases. We hypothesized that HLA-A29 would affect the composition of the gut microbiome, leading to a dysbiosis and immune-mediated eye disease. Fecal and intestinal biopsy samples were obtained from 107 healthy individuals from Portland, Oregon environs, 10 of whom were HLA-A29 positive, undergoing routine colonoscopy. Bacterial profiling was achieved via 16S rRNA metabarcoding. Publicly available whole meta-genome sequencing data from the Human Microbiome Project (HMP), consisting of 298 healthy controls mostly of US origin, were also interrogated. PERMANOVA and sparse partial least squares discriminant analysis (sPLSDA) demonstrated that subjects who were HLA-A29 positive differed in bacterial species composition (beta diversity) compared to HLA-A29 negative subjects in both the Portland (p = 0.019) and HMP cohorts (p = 0.0002). The Portland and HMP cohorts evidenced different subsets of bacterial species associated with HLA-A29 status, likely due to differences in the metagenomic techniques employed. The functional composition of the HMP cohort did not differ overall (p = 0.14) between HLA-A29 positive and negative subjects, although some distinct pathways such as heparan sulfate biosynthesis showed differences. As we and others have shown for various HLA alleles, the HLA allotype impacts the composition of the microbiome. We hypothesize that HLA-A29 may predispose chorioretinitis via an altered gut microbiome.

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