Prominent members of the human gut microbiota express endo-acting O-glycanases to initiate mucin breakdown

AbstractThe human gut microbiota (HGM) are closely associated with health, development and disease. The thick intestinal mucus layer, especially in the colon, is the key barrier between the contents of the lumen and the epithelial cells, providing protection against infiltration by the microbiota as well potential pathogens. The upper layer of the colonic mucus is a niche for a subset of the microbiota which utilise the mucin glycoproteins as a nutrient source and mucin grazing by the microbiota appears to play a key role in maintaining barrier function as well as community stability. Despite the importance of mucin breakdown for gut health, the mechanisms by which gut bacteria access this complex glycoprotein are not well understood. The current model for mucin degradation involves exclusively exo-acting glycosidases that sequentially trim monosaccharides from the termini of the glycan chains to eventually allow access to the mucin peptide backbone by proteases. However, this model is in direct contrast to the Sus paradigm of glycan breakdown used by the Bacteroidetes which involves extracellular cleavage of glycans by surface located endo-acting enzymes prior to import of the oligosaccharide products. Here we describe the discovery and characterisation of endo-acting family 16 glycoside hydrolases (GH16s) from prominent mucin degrading gut bacteria that specifically target the oligosaccharide side chains of intestinal mucins from both animals and humans. These endo-acting O-glycanases display β1,4-glactosidase activity and in several cases are surface located indicating they are involved in the initial step in mucin breakdown. The data suggest a new paradigm for mucin breakdown by the microbiota and the endo-mucinases provide a potential tool to explore changes that occur in mucin structure in intestinal disorders such as inflammatory bowel disease and colon cancer.

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Design, Synthesis and Bioactivity of Core 1 O-glycan and its Derivative on Human Gut Microbiota

Letters in Drug Design & Discovery ◽

10.2174/1570180816666181218143207 ◽

2019 ◽

Vol 16 (12) ◽

pp. 1348-1353

Author(s):

Huanhuan Qu ◽

Baixue Li ◽

Jingyi Yang ◽

Huaiwen Liang ◽

Meixia Li ◽

...

Keyword(s):

Gut Microbiota ◽

Initial Step ◽

Building Blocks ◽

Glycan Structure ◽

Human Gut ◽

Design Synthesis ◽

The Core ◽

Human Gut Microbiota ◽

Biochemical Studies ◽

Gut Symbionts

Background: Disaccharide core 1 (Galβ1-3GalNAc) is a common O-glycan structure in nature. Biochemical studies have confirmed that the formation of the core 1 structure is an important initial step in O-glycan biosynthesis and it is of great importance for human body. Objective: Our study will provide meaningful and useful sights for O-glycan synthesis and their bioassay. And all the synthetic glycosides would be used as intermediate building blocks in the scheme developed for oligosaccharide construction. Methods: In this article, we firstly used chemical procedures to prepare core 1 and its derivative, and a novel disaccharide was efficiently synthesized. The structures of the synthesized compounds were elucidated and confirmed by 1H NMR, 13C NMR and MS. Then we employed three human gut symbionts belonging to Bacteroidetes, a predominantphyla in the distal gut, as models to study the bioactivity of core 1 and its derivative on human gut microbiota. Results: According to our results, both core 1 and derivative could support the growth of B. fragilis, especially the core 1 derivative, while failed to support the growth of B. thetaiotaomicron and B. ovatus. Conclusion: This suggested that the B. fragilis might have the specificity glycohydrolase to cut the glycosidic bond for acquiring monosaccharide.

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Wood-Derived Dietary Fibers Promote Beneficial Human Gut Microbiota

mSphere ◽

10.1128/msphere.00554-18 ◽

2019 ◽

Vol 4 (1) ◽

Cited By ~ 13

Author(s):

Sabina Leanti La Rosa ◽

Vasiliki Kachrimanidou ◽

Fanny Buffetto ◽

Phillip B. Pope ◽

Nicholas A. Pudlo ◽

...

Keyword(s):

Gut Microbiota ◽

Well Being ◽

Gut Health ◽

Human Gut ◽

Content Type ◽

Human Gut Microbiota ◽

Lignocellulosic Feedstocks ◽

Host Health ◽

Clostridial Cluster ◽

Gut Microbiota Composition

The architecture of the gut bacterial ecosystem has a profound effect on the physiology and well-being of the host. Modulation of the gut microbiota and the intestinal microenvironment via administration of prebiotics represents a valuable strategy to promote host health. This work provides insights into the ability of two novel wood-derived preparations, AcGGM and AcAGX, to influence human gut microbiota composition and activity. These compounds were selectively fermented by commensal bacteria such as Bifidobacterium, Bacteroides-Prevotella, F. prausnitzii, and clostridial cluster IX spp. This promoted the microbial synthesis of acetate, propionate, and butyrate, which are beneﬁcial to the microbial ecosystem and host colonic epithelial cells. Thus, our results demonstrate potential prebiotic properties for both AcGGM and AcAGX from lignocellulosic feedstocks. These findings represent pivotal requirements for rationally designing intervention strategies based on the dietary supplementation of AcGGM and AcAGX to improve or restore gut health.

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Bacterial Atlas of Mouse Gut Microbiota

10.21203/rs.3.rs-829178/v1 ◽

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.

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A benzoxazole derivative as an inhibitor of anaerobic choline metabolism by human gut microbiota

RSC Medicinal Chemistry ◽

10.1039/d0md00218f ◽

2020 ◽

Vol 11 (12) ◽

pp. 1402-1412

Author(s):

Moustafa T. Gabr ◽

David Machalz ◽

Szymon Pach ◽

Gerhard Wolber

Keyword(s):

Gut Microbiota ◽

Metabolic Pathways ◽

Therapeutic Targets ◽

Gut Bacteria ◽

Human Diseases ◽

Human Gut ◽

Human Gut Microbiota ◽

Choline Metabolism

Metabolic pathways mediated by human gut bacteria have emerged as potential therapeutic targets because of their association with the pathophysiology of various human diseases.

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In vitro investigation of orange fleshed sweet potato prebiotic potential and its implication on human gut health

Functional Foods in Health and Disease ◽

10.31989/ffhd.v7i10.361 ◽

2017 ◽

Vol 7 (10) ◽

pp. 833 ◽

Cited By ~ 3

Author(s):

Mary Muchiri ◽

Anne L. McCartney

Keyword(s):

Gut Microbiota ◽

Sweet Potato ◽

Butyric Acid ◽

Gut Health ◽

Human Gut ◽

Prebiotic Activity ◽

Human Gut Microbiota ◽

Orange Fleshed Sweet Potato ◽

Total Bacteria

Background: Some food ingredients (prebiotics) have been shown to promote a healthy gut by selectively stimulating growth/activity of beneficial gastrointestinal microbes and metabolites such as short chain fatty acids (SCFA) while inhibiting pathogens. Orange fleshed sweet potato (Ipomoea batatas Lam; OFSP) root tuber is a starchy tropical crop and highly nutritious in terms of pro-vitamin A (beta carotene), dietary fibre, and natural sugars, with negligible amount of fats and cholesterol. Purpose of study: The aim of the study was to investigate using simulated human gut system whether OFSP may have prebiotic activity derived from their fibre, resistant starch, and/or the sugars.Methodology: In vitro pH controlled stirred batch culture fermentation system was used to compare the effect on human gut microbiota of four substrates: two varieties of OFSP (SPK 004 and Tainung), FOS and sucrose known for positive prebiotic and non-selective change respectively. The system was inoculated with faecal slurry from six different human healthy donors from different ethical backgrounds, age, and the effectual change recorded over 24 hours by monitoring bacterial counts (total bacteria, Bacteroides and Bifidobacterium) using qPCR molecular technique and SCFA profiles by gas chromatography.Results: The total bacteria count increased by (0.92-1.7 log10) and Bacteroides genus (1.03-1.8 log10) throughout the experimental period but with no significant differences (p<0.05) between the four substrates. However, there were significant differences (p<0.05) in the beneficial Bifidobacterium (1.66-2.66 log10) between the 2 varieties of OFSP and the two controls (FOS and sucrose). The levels of SCFA increased, with acetate as the predominant acid and lactic acid being the least. The OFSP purees elicited high butyric acid levels, which were comparable to those of positive control FOS.Conclusions: The study demonstrated that OFSP purees may have prebiotic potential that can positively modulate gut microbiota by promoting growth of beneficial bacteria, bifidobacterium genus, and stimulating production of SCFA especially butyric acid which is the favourable in human gut health. However, further research using more probiotic and pathogenic microbes in addition to in vivo clinical studies and compositional analysis of OFSP is needed to confirm prebiotic activity. Key words: Orange fleshed sweet potato, prebiotic, human gut microbiota

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Gut Health in the era of the Human Gut Microbiota: from metaphor to biovalue

Medicine Health Care and Philosophy ◽

10.1007/s11019-014-9552-2 ◽

2014 ◽

Vol 17 (4) ◽

pp. 579-597 ◽

Cited By ~ 6

Author(s):

Vincent Baty ◽

Bruno Mougin ◽

Catherine Dekeuwer ◽

Gérard Carret

Keyword(s):

Gut Microbiota ◽

Gut Health ◽

Human Gut ◽

Human Gut Microbiota

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Robustness of Mammalian Gut Microbiota to Humanization in Captivity

Frontiers in Ecology and Evolution ◽

10.3389/fevo.2021.785089 ◽

2022 ◽

Vol 9 ◽

Author(s):

Brian K. Trevelline ◽

Andrew H. Moeller

Keyword(s):

Gut Microbiota ◽

Gut Bacteria ◽

Potential Importance ◽

Human Gut ◽

Human Gut Microbiota ◽

In Captivity ◽

Host Lineage

In mammals, the composition of the gut microbiota is associated with host phylogenetic history, and host-lineage specific microbiota have been shown, in some cases, to contribute to fitness-related traits of their hosts. However, in primates, captivity can disrupt the native microbiota through a process of humanization in which captive hosts acquire gut microbiota constituents found in humans. Despite the potential importance of this process for the health of captive hosts, the degree to which captivity humanizes the gut microbiota of other mammalian taxa has not been explored. Here, we analyzed hundreds of published gut microbiota profiles generated from wild and captive hosts spanning seven mammalian families to investigate the extent of humanization of the gut microbiota in captivity across the mammalian phylogeny. Comparisons of these hosts revealed compositional convergence between captive mammal and human gut microbiota in the majority of mammalian families examined. This convergence was driven by a diversity of microbial lineages, including members of the Archaea, Clostridium, and Bacteroides. However, the gut microbiota of two families—Giraffidae and Bovidae—were remarkably robust to humanization in captivity, showing no evidence of gut microbiota acquisition from humans relative to their wild confamiliars. These results demonstrate that humanization of the gut microbiota is widespread in captive mammals, but that certain mammalian lineages are resistant to colonization by human-associated gut bacteria.

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Characterization and Detection of a Widely Distributed Gene Cluster That Predicts Anaerobic Choline Utilization by Human Gut Bacteria

mBio ◽

10.1128/mbio.00042-15 ◽

2015 ◽

Vol 6 (2) ◽

Cited By ~ 77

Author(s):

Ana Martínez-del Campo ◽

Smaranda Bodea ◽

Hilary A. Hamer ◽

Jonathan A. Marks ◽

Henry J. Haiser ◽

...

Keyword(s):

Gut Microbiota ◽

Gene Cluster ◽

Gut Bacteria ◽

Functional Gene ◽

Metagenomic Data ◽

Human Gut ◽

Bacterial Gene ◽

Human Gut Microbiota ◽

Choline Metabolism

ABSTRACTElucidation of the molecular mechanisms underlying the human gut microbiota's effects on health and disease has been complicated by difficulties in linking metabolic functions associated with the gut community as a whole to individual microorganisms and activities. Anaerobic microbial choline metabolism, a disease-associated metabolic pathway, exemplifies this challenge, as the specific human gut microorganisms responsible for this transformation have not yet been clearly identified. In this study, we established the link between a bacterial gene cluster, the choline utilization (cut) cluster, and anaerobic choline metabolism in human gut isolates by combining transcriptional, biochemical, bioinformatic, and cultivation-based approaches. Quantitative reverse transcription-PCR analysis andin vitrobiochemical characterization of twocutgene products linked the entire cluster to growth on choline and supported a model for this pathway. Analyses of sequenced bacterial genomes revealed that thecutcluster is present in many human gut bacteria, is predictive of choline utilization in sequenced isolates, and is widely but discontinuously distributed across multiple bacterial phyla. Given that bacterial phylogeny is a poor marker for choline utilization, we were prompted to develop a degenerate PCR-based method for detecting the key functional gene choline TMA-lyase (cutC) in genomic and metagenomic DNA. Using this tool, we found that new choline-metabolizing gut isolates universally possessedcutC. We also demonstrated that this gene is widespread in stool metagenomic data sets. Overall, this work represents a crucial step toward understanding anaerobic choline metabolism in the human gut microbiota and underscores the importance of examining this microbial community from a function-oriented perspective.IMPORTANCEAnaerobic choline utilization is a bacterial metabolic activity that occurs in the human gut and is linked to multiple diseases. While bacterial genes responsible for choline fermentation (thecutgene cluster) have been recently identified, there has been no characterization of these genes in human gut isolates and microbial communities. In this work, we use multiple approaches to demonstrate that the pathway encoded by thecutgenes is present and functional in a diverse range of human gut bacteria and is also widespread in stool metagenomes. We also developed a PCR-based strategy to detect a key functional gene (cutC) involved in this pathway and applied it to characterize newly isolated choline-utilizing strains. Both our analyses of thecutgene cluster and this molecular tool will aid efforts to further understand the role of choline metabolism in the human gut microbiota and its link to disease.

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