scholarly journals Flavonoid-modifying capabilities of the gut microbiome – an in silico study

2021 ◽  
Author(s):  
Tobias Goris ◽  
Rafael Cuadrat ◽  
Annett Braune
Keyword(s):  
Large Scale ◽  
Health Impact ◽  
Gut Bacteria ◽  
Human Gut ◽  
Positive Health ◽  
Nutritional Recommendations ◽  
In Silico Study ◽  
Gut Metagenome ◽  
Insight Into ◽  
Large Scale Screening

Abstract 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 human gut metagenome data and the assembly of hundreds of thousands of bacterial metagenome-assembled genomes (MAGs), large-scale screening for potential flavonoid-modifying enzymes is now feasible. With sequences from characterized flavonoid-transforming enzymes as queries, the Unified Human Gastrointestinal Protein catalog was analyzed and quantification of putative flavonoid-modifying enzymes was carried out. The results revealed that flavonoid-modifying enzymes are often highly abundant in bacteria hitherto not considered as flavonoid-modifying gut bacteria. The enzymes for the physiologically important daidzein to equol conversion, well studied in Slackia isoflavoniconvertens, were encoded only to a low extent in Slackia MAGs, but more abundant in Adlercreutzia equolifaciens and an uncharacterizedEggerthellaceae species. In addition, a high abundance of genes with a similarity of only about 35% in uncultivated Collinsella species suggest 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). Phloretin hydrolase, flavanonol/flavanone-cleaving reductase and flavone reductase (all three most abundant in Flavonifractor plautii) and O-demethylase (Intestinibacter bartlettii) homologs were of intermediate prevalence (several hundreds of MAGs). 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 key organisms in flavonoid modification by the human gut microbiota. 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 which rely on novel enzymes catalyzing potentially useful flavonoid modification reactions.

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

Nutrients ◽  
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.

scholarly journals Bacterial Atlas of Mouse Gut Microbiota

2021 ◽  
Author(s):  
Mengqi Chu ◽  
Xiaobo Zhang
Keyword(s):  
Complex System ◽  
Gut Microbiota ◽  
Bacterial Communities ◽  
Large Scale ◽  
Gut Bacteria ◽  
Human Gut ◽  
The Core ◽  
Human Gut Microbiota ◽  
Human Immunity ◽  
Mouse Gut Microbiota

Abstract Background: Mouse model is one of of the most widely used animal models for exploring the roles of human gut microbiota, a complex system involving in human immunity and metabolism. However, the structure of mouse gut bacterial community has not been explored at a large scale. To address this concern, the diversity and composition of the gut bacteria of 600 mice was characterized in this study. Results: The results showed that the bacteria belonging to 8 genera were found in the gut microbiota of all mouse individuals, indicating that the 8 bacteria were the core bacteria of mouse gut microbiota. The dominant genera of the mouse gut bacteria contained 15 bacterial genera. It was found that the bacteria in the gut microbiota were mainly involved in host’s metabolisms via the collaborations between the gut bacteria. The further analysis demonstrated that the composition of mouse gut microbiota was similar to that of human gut microbiota. Conclusion: Our study presented a bacterial atlas of mouse gut microbiota, providing a solid basis for investing the bacterial communities of mouse gut microbiota.

scholarly journals An Expanded Genetic Code Enables Trimethylamine Metabolism in Human Gut Bacteria

mSystems ◽  
2020 ◽  
Vol 5 (5) ◽  
Author(s):  
Veronika Kivenson ◽  
Stephen J. Giovannoni
Keyword(s):  
Cardiovascular Disease ◽  
Genetic Code ◽  
Human Health ◽  
Cell Biology ◽  
Meta Analysis ◽  
Health Impact ◽  
Gut Bacteria ◽  
Human Gut ◽  
Demethylation Pathway ◽  
Genetic Code Expansion

ABSTRACT Cardiovascular disease (CVD) has been linked to animal-based diets, which are a major source of trimethylamine (TMA), a precursor of the proatherogenic compound trimethylamine-N-oxide (TMAO). Human gut bacteria in the genus Bilophila have genomic signatures for genetic code expansion that could enable them to metabolize both TMA and its precursors without production of TMAO. We uncovered evidence that the Bilophila demethylation pathway is actively transcribed in gut microbiomes and that animal-based diets cause Bilophila to rapidly increase in abundance. CVD occurrence and Bilophila abundance in humans were significantly negatively correlated. These data lead us to propose that Bilophila, which is commonly regarded as a pathobiont, may play a role in mitigating cardiovascular disease. Human gut microbiomes have been shown to affect the development of a myriad of disease states, but mechanistic connections between diet, health, and microbiota have been challenging to establish. The hypothesis that Bilophila reduces cardiovascular disease by circumventing TMAO production offers a clearly defined mechanism with a potential human health impact, but investigations of Bilophila cell biology and ecology will be needed to fully evaluate these ideas. IMPORTANCE Links between trimethylamine-N-oxide (TMAO) and cardiovascular disease (CVD) have focused attention on mechanisms by which animal-based diets have negative health consequences. In a meta-analysis of data from foundational gut microbiome studies, we found evidence that specialized bacteria have and express a metabolic pathway that circumvents TMAO production and is often misannotated because it relies on genetic code expansion. This naturally occurring mechanism for TMAO attenuation is negatively correlated with CVD. Ultimately, these findings point to new avenues of research that could increase microbiome-informed understanding of human health and hint at potential biomedical applications in which specialized bacteria are used to curtail CVD development.

scholarly journals A single bacterial sulfatase is required for metabolism of colonic mucin O-glycans and intestinal colonization by a symbiotic human gut bacterium

2020 ◽  
Author(s):  
Ana S. Luis ◽  
Chunsheng Jin ◽  
Gabriel Vasconcelos Pereira ◽  
Robert W. P. Glowacki ◽  
Sadie Gugel ◽  
...  
Keyword(s):  
Gut Bacteria ◽  
Human Gut ◽  
Colonic Mucin ◽  
Gut Colonization ◽  
Lower Intestine ◽  
Inflammatory Bowel ◽  
Microbial Symbionts ◽  
Insight Into

SummaryHumans have co-evolved with a dense community of microbial symbionts that inhabit the lower intestine. In the colon, secreted mucus creates a physical barrier that separates these microbes from the intestinal epithelium. Some gut bacteria are able to utilize mucin glycoproteins, the main mucus component, as a nutrient source. However, it remains unclear which bacterial enzymes initiate the degradation of the highly complex O-glycans found in mucins. In the colon, these glycans are heavily sulfated, but the specific sulfatases that are active on colonic mucins have not been identified. Here, we show that sulfatases are essential to the utilization of colonic mucin O-glycans by the human gut symbiont Bacteroides thetaiotaomicron. We have characterized the activity of 12 different sulfatases encoded by this species, showing that these enzymes collectively are active on all of the known sulfate linkages in colonic O-glycans. Crystal structures of 3 enzymes provide mechanistic insight into the molecular basis of substrate-specificity. Unexpectedly, we found that a single sulfatase is essential for utilization of sulfated O-glycans in vitro and also plays a major role in vivo. Our results provide insight into the mechanisms of mucin degradation by gut bacteria, an important process for both normal microbial gut colonization and diseases such as inflammatory bowel disease (IBD). Sulfatase activity is likely to be a keystone step in bacterial mucin degradation and inhibition of these enzymes may therefore represent a viable therapeutic path for treatment of IBD and other diseases.

scholarly journals A single bacterial sulfatase is required for metabolism of colonic mucin O-glycans and intestinal colonization by a symbiotic human gut bacterium

2021 ◽  
Author(s):  
Eric Martens ◽  
Ana Luis ◽  
Chunsheng Jin ◽  
Gabriel Pereira ◽  
Robert Glowacki ◽  
...  
Keyword(s):  
Gut Bacteria ◽  
Human Gut ◽  
Colonic Mucin ◽  
Gut Colonization ◽  
Lower Intestine ◽  
Inflammatory Bowel ◽  
Microbial Symbionts ◽  
Insight Into

Abstract Humans have co-evolved with a dense community of microbial symbionts that inhabit the lower intestine. In the colon, secreted mucus creates a physical barrier that separates these microbes from the intestinal epithelium. Some gut bacteria are able to utilize mucin glycoproteins, the main mucus component, as a nutrient source. However, it remains unclear which bacterial enzymes initiate the degradation of the highly complex O-glycans found in mucins. In the colon, these glycans are heavily sulfated, but the specific sulfatases that are active on colonic mucins have not been identified. Here, we show that sulfatases are essential to the utilization of colonic mucin O-glycans by the human gut symbiont Bacteroides thetaiotaomicron. We have characterized the activity of 12 different sulfatases encoded by this species, showing that these enzymes collectively are active on all of the known sulfate linkages in colonic O-glycans. Crystal structures of 3 enzymes provide mechanistic insight into the molecular basis of substrate-specificity. Unexpectedly, we found that a single sulfatase is essential for utilization of sulfated O-glycans in vitro and also plays a major role in vivo. Our results provide insight into the mechanisms of mucin degradation by gut bacteria, an important process for both normal microbial gut colonization and diseases such as inflammatory bowel disease (IBD). Sulfatase activity is likely to be a keystone step in bacterial mucin degradation and inhibition of these enzymes may therefore represent a viable therapeutic path for treatment of IBD and other diseases.

scholarly journals Revealing microbial assemblage structure in the human gut microbiome using latent Dirichlet allocation

2019 ◽  
Author(s):  
Shion Hosoda ◽  
Suguru Nishijima ◽  
Tsukasa Fukunaga ◽  
Masahira Hattori ◽  
Michiaki Hamada
Keyword(s):  
Data Mining ◽  
Cluster Analysis ◽  
Gut Microbiome ◽  
Large Scale ◽  
Latent Dirichlet Allocation ◽  
Human Gut ◽  
Human Gut Microbiome ◽  
Mining Methods ◽  
Gut Metagenome ◽  
Dirichlet Allocation

AbstractRecent research has revealed that there are various microbial species in the human gut microbiome. To clarify the structure of the human gut microbiome, many data mining methods have been applied to microbial composition data. Cluster analysis, one of the key data mining methods that have been used in human gut microbiome research, can classify the human gut microbiome into three clusters, called enterotypes. The human gut microbiome has been suggested to be composed of the microbial assemblages or groups of co-occurring microbes, and one human gut microbiome can contain several microbial assemblages. However, cluster analysis can cluster samples into groups without capturing minor assemblages. In addition, a reliable method of assemblage detection has not been established, and little is known about the distributions of microbial assemblages at a population-level scale. Accordingly, the purpose of this study was to clarify the microbial assemblages in the human gut microbiome. In this study, we detected gut microbiome assemblages using a latent Dirichlet allocation (LDA) method, which was first proposed for the classification of documents in natural language processing. We applied LDA to a large-scale human gut metagenome dataset and found that a four-assemblage LDA model can represent relationships between enterotypes and assemblages with high interpretability. This model indicates that each individual tends to have several assemblages, and each of three assemblages corresponded to each enterotype. However, the C-assemblage can exist in all enterotypes. Interestingly, the dominant genera of the C-assemblage (Clostridium, Eubacterium, Faecalibacterium, Roseburia, Coprococcus, and Butyrivibrio) included butyrate-producing species such as Faecalibacterium prausnitzii. Finally, we revealed that genera mainly appearing in the same assemblage were correlated to each other. We conducted an assemblage analysis on a large-scale human gut metagenome dataset using LDA, a powerful method for detection of microbial assemblages. This approach has the potential to reveal the structure of the human gut microbiome.

Training Aides to Screen Children for Speech and Language Problems

1976 ◽  
Vol 7 (4) ◽  
pp. 236-241 ◽  
Author(s):  
Marisue Pickering ◽  
William R. Dopheide
Keyword(s):  
Rural Areas ◽  
Large Scale ◽  
School Personnel ◽  
School Age Children ◽  
Speech And Language ◽  
Elementary School Age ◽  
Evaluation Procedures ◽  
Language Problems ◽  
Competency Based ◽  
Large Scale Screening

This report deals with an effort to begin the process of effectively identifying children in rural areas with speech and language problems using existing school personnel. A two-day competency-based workshop for the purpose of training aides to conduct a large-scale screening of speech and language problems in elementary-school-age children is described. Training strategies, implementation, and evaluation procedures are discussed.

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