scholarly journals Normal development and fertility of Fut1, Fut2, and Sec1 triple knockout mice

2019 ◽  
Author(s):  
Jiaxi Chen ◽  
Zhipeng Su ◽  
Chunlei Zhang ◽  
Fenge Li ◽  
Patrick Hwu ◽  
...  
Keyword(s):  
Blood Group ◽  
Cancer Progression ◽  
Knockout Mice ◽  
Gut Microbiome ◽  
Normal Development ◽  
Multiple Organs ◽  
Microbe Interactions ◽  
Blastocyst Implantation ◽  
Host Microbe Interactions ◽  
Blood Group H

AbstractThe fucose alpha(1,2) galactose structure (H antigen) is synthesized by α1,2 fucosyltransferases Fut1, Fut2 and Sec1. H antigen has been reported to be involved in cancer progression, neurite migration, synaptic plasticity, host-microbe interaction, blastocyst implantation, and the maintenance of gut microbiome. Genetic depletion of Fut1 or Fut2 only cause defects of alpha1,2 fucosylation in limited tissues because of enzyme redundancy. In this study, we generated mice with deficiencies in Fut1, Fut2, and Sec1 genes to deplete H antigen through BAC Engineering for the generation of ES Cell-Targeting construct. The homogenous triple knockout mice showed no significant decrease of viability or development. Mass spectrometry and Western blot analysis confirmed the absence of H blood group antigen in multiple organs. These results indicate normal development and fertility of mice devoid of blood group H. The fine pathophysiological alterations in these mice remain to be carefully studied, and they may serve as valuable tools to study gut microbiome and host-microbe interactions.

scholarly journals Health and disease markers correlate with gut microbiome composition across thousands of people

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Ohad Manor ◽  
Chengzhen L. Dai ◽  
Sergey A. Kornilov ◽  
Brett Smith ◽  
Nathan D. Price ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Lifestyle Factors ◽  
Clinical Markers ◽  
Human Gut ◽  
Microbiome Composition ◽  
Targeted Interventions ◽  
Human Gut Microbiome ◽  
Host Diet ◽  
Microbe Interactions ◽  
Host Microbe Interactions

Abstract Variation in the human gut microbiome can reflect host lifestyle and behaviors and influence disease biomarker levels in the blood. Understanding the relationships between gut microbes and host phenotypes are critical for understanding wellness and disease. Here, we examine associations between the gut microbiota and ~150 host phenotypic features across ~3,400 individuals. We identify major axes of taxonomic variance in the gut and a putative diversity maximum along the Firmicutes-to-Bacteroidetes axis. Our analyses reveal both known and unknown associations between microbiome composition and host clinical markers and lifestyle factors, including host-microbe associations that are composition-specific. These results suggest potential opportunities for targeted interventions that alter the composition of the microbiome to improve host health. By uncovering the interrelationships between host diet and lifestyle factors, clinical blood markers, and the human gut microbiome at the population-scale, our results serve as a roadmap for future studies on host-microbe interactions and interventions.

scholarly journals Gut microbiome stability and resilience: elucidating the response to perturbations in order to modulate gut health

Gut ◽  
2020 ◽  
pp. gutjnl-2020-321747
Author(s):  
Marina Fassarella ◽  
Ellen E Blaak ◽  
John Penders ◽  
Arjen Nauta ◽  
Hauke Smidt ◽  
...  
Keyword(s):  
Environmental Factors ◽  
Microbial Diversity ◽  
Gut Microbiome ◽  
Gut Health ◽  
Stable States ◽  
Host Genotype ◽  
Functional Richness ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
Stability And Resilience

The human gut microbiome is a complex ecosystem, densely colonised by thousands of microbial species. It varies among individuals and depends on host genotype and environmental factors, such as diet and antibiotics. In this review, we focus on stability and resilience as essential ecological characteristics of the gut microbiome and its relevance for human health. Microbial diversity, metabolic flexibility, functional redundancy, microbe–microbe and host–microbe interactions seem to be critical for maintaining resilience. The equilibrium of the gut ecosystem can be disrupted by perturbations, such as antibiotic therapy, causing significant decreases in functional richness and microbial diversity as well as impacting metabolic health. As a consequence, unbalanced states or even unhealthy stable states can develop, potentially leading to or supporting diseases. Accordingly, strategies have been developed to manipulate the gut microbiome in order to prevent or revert unhealthy states caused by perturbations, including faecal microbiota transplantation, supplementation with probiotics or non-digestible carbohydrates, and more extensive dietary modifications. Nevertheless, an increasing number of studies has evidenced interindividual variability in extent and direction of response to diet and perturbations, which has been attributed to the unique characteristics of each individual’s microbiome. From a clinical, translational perspective, the ability to improve resilience of the gut microbial ecosystem prior to perturbations, or to restore its equilibrium afterwards, would offer significant benefits. To be effective, this therapeutic approach will likely need a personalised or subgroup-based understanding of individual genetics, diet, gut microbiome and other environmental factors that might be involved.

Metagenomic Analysis of the Gut Microbiome in Psoriasis Reveals Three Subgroups with Distinct Host-Microbe Interactions

2020 ◽  
Author(s):  
Hsin-Wen Chang ◽  
Di Yan ◽  
Rasnik Singh ◽  
Audrey Bui ◽  
Kristina Lee ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Disease Heterogeneity ◽  
Microbial Function ◽  
Diagnostic Potential ◽  
Patients At Risk ◽  
Microbe Interactions ◽  
Inflammatory Bowel ◽  
Host Microbe Interactions ◽  
Global Population ◽  
Increased Susceptibility

Abstract Background Psoriasis is a chronic, inflammatory skin disease that impacts 2–3% of the global population. Besides skin manifestations, psoriasis patients have increased susceptibility to a number of comorbidities including psoriatic arthritis, cardiovascular disease, and inflammatory bowel disease. To understand the systemic component of psoriasis pathogenesis, we examined the fecal metagenome, host colonic transcriptome, and host peripheral blood immune profiles of psoriasis patients and healthy controls. Results Our analysis showed increased functional diversity in the gut microbiome of psoriasis patients. In addition, we identified microbial species that preferentially associate with psoriasis patients and which have been previously found to associate with other autoimmune diseases. Intriguingly, our data reveal new insights about psoriasis disease heterogeneity, as we identified three psoriasis subgroups that have distinct microbial and host features. Finally, integrating microbial and host features revealed host-microbe interactions that are specific to psoriasis or particular psoriasis subgroups. Conclusion To our knowledge, this is the first study that provides a comprehensive view of gut microbial function and corresponding host response in psoriasis patients. Our findings provide insight into factors that may affect the development of comorbidities in psoriasis patients and may hold diagnostic potential for early identification of psoriasis patients at risk for these comorbidities.

scholarly journals Minimizing confounders and increasing data quality in murine models for studies of the gut microbiome

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5166 ◽  
Author(s):  
Jun Miyoshi ◽  
Vanessa Leone ◽  
Kentaro Nobutani ◽  
Mark W. Musch ◽  
Kristina Martinez-Guryn ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Standard Operating Procedure ◽  
Individual Variability ◽  
Rrna Gene ◽  
Murine Models ◽  
Single Room ◽  
Specific Pathogen ◽  
Microbe Interactions ◽  
Host Microbe Interactions

Murine models are widely used to explore host-microbe interactions because of the challenges and limitations inherent to human studies. However, microbiome studies in murine models are not without their nuances. Inter-individual variations in gut microbiota are frequent even in animals housed within the same room. We therefore sought to find an efficient and effective standard operating procedure (SOP) to minimize these effects to improve consistency and reproducibility in murine microbiota studies. Mice were housed in a single room under specific-pathogen free conditions. Soiled cage bedding was routinely mixed weekly and distributed among all cages from weaning (three weeks old) until the onset of the study. Females and males were separated by sex and group-housed (up to five mice/cage) at weaning. 16S rRNA gene analyses of fecal samples showed that this protocol significantly reduced pre-study variability of gut microbiota amongst animals compared to other conventional measures used to normalize microbiota when large experimental cohorts have been required. A significant and consistent effect size was observed in gut microbiota when mice were switched from regular chow to purified diet in both sexes. However, sex and aging appeared to be independent drivers of gut microbial assemblage and should be taken into account in studies of this nature. In summary, we report a practical and effective pre-study SOP for normalizing the gut microbiome of murine cohorts that minimizes inter-individual variability and resolves co-housing problems inherent to male mice. This SOP may increase quality, rigor, and reproducibility of data acquisition and analysis.

scholarly journals Interactions between the gut microbiome and host gene regulation in cystic fibrosis

2019 ◽  
Author(s):  
Gargi Dayama ◽  
Sambhawa Priya ◽  
David E. Niccum ◽  
Alexander Khoruts ◽  
Ran Blekhman
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Cystic Fibrosis ◽  
Gut Microbiome ◽  
Critical Role ◽  
Host Gene ◽  
Healthy Controls ◽  
Host Gene Expression ◽  
Microbe Interactions ◽  
Host Microbe Interactions

AbstractCystic Fibrosis (CF) is the most common autosomal recessive genetic disease in Caucasians. It is caused by mutations in theCFTRgene, leading to poor hydration of mucus and impairment of the respiratory, digestive, and reproductive organ functions. Advancements in medical care have lead to markedly increased longevity of patients with CF, but new complications have emerged, such as early onset of colorectal cancer (CRC). Although the pathogenesis of CRC in CF remains unclear, altered host-microbe interactions might play a critical role. Here, we characterize the changes in the gut microbiome and host gene expression in colonic mucosa of CF patients relative to healthy controls. We find that CF patients show decreased microbial diversity, decreased abundance of taxa such asButyricimonas, Sutterella,and Ruminococcaceae, and increased abundance of other taxa, such as Actinobacteria and Firmicutes. We find that 1543 genes, includingCFTR,show differential expression in the colon of CF patients compared to healthy controls. Interestingly, we find that these genes are enriched with functions related to gastrointestinal and colorectal cancer, such as metastasis of CRC, tumor suppression, cellular dysfunction, p53 and mTOR signaling pathways. Lastly, we modeled associations between relative abundances of specific bacterial taxa in the gut mucosa and host gene expression, and identified CRC-related genes, includingLCN2andDUOX2,for which gene expression is correlated with the abundance of CRC-associated bacteria, such as Ruminococcaceae andVeillonella. Our results provide new insight into the role of host-microbe interactions in the etiology of CRC in CF.

scholarly journals Probiotics and MicroRNA: Their Roles in the Host–Microbe Interactions

2021 ◽  
Vol 11 ◽  
Author(s):  
Ying Zhao ◽  
Yan Zeng ◽  
Dong Zeng ◽  
Hesong Wang ◽  
Mengjia Zhou ◽  
...  
Keyword(s):  
Disease Management ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Molecular Mechanisms ◽  
Comprehensive Description ◽  
Future Studies ◽  
Gut Homeostasis ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
Gut Microorganisms

Probiotics are widely accepted to be beneficial for the maintenance of the gut homeostasis – the dynamic and healthy interactions between host and gut microorganisms. In addition, emerging as a key molecule of inter-domain communication, microRNAs (miRNAs) can also mediate the host–microbe interactions. However, a comprehensive description and summary of the association between miRNAs and probiotics have not been reported yet. In this review, we have discussed the roles of probiotics and miRNAs in host–microbe interactions and proposed the association of probiotics with altered miRNAs in various intestinal diseases and potential molecular mechanisms underlying the action of probiotics. Furthermore, we provided a perspective of probiotics–miRNA–host/gut microbiota axis applied in search of disease management highly associated with the gut microbiome, which will potentially prove to be beneficial for future studies.

scholarly journals In vivo augmentation of a complex gut bacterial community

2021 ◽  
Author(s):  
Alice G Cheng ◽  
Po-Yi Ho ◽  
Sunit Jain ◽  
Xiandong Meng ◽  
Min Wang ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Immune Cell ◽  
Human Gut ◽  
Human Gut Microbiome ◽  
Pathogenic Escherichia Coli ◽  
Human Fecal Sample ◽  
Microbe Interactions ◽  
Experimental Process ◽  
Host Microbe Interactions

Efforts to model the human gut microbiome in mice have led to important insights into the mechanisms of host-microbe interactions. However, the model communities studied to date have been defined or complex but not both, limiting their utility. In accompanying work, we constructed a complex synthetic community (104 strains, hCom1) containing the most common taxa in the human gut microbiome. Here, we used an iterative experimental process to improve hCom1 by filling open metabolic and/or anatomical niches. When we colonized germ-free mice with hCom1 and then challenged it with a human fecal sample, the consortium exhibited surprising stability; 89% of the cells and 58% of the taxa derive from the original community, and the pre- and post-challenge communities share a similar overall structure. We used these data to construct a second version of the community, adding 22 strains that engrafted following fecal challenge and omitting 7 that dropped out (119 strains, hCom2). In gnotobiotic mice, hCom2 exhibited increased stability to fecal challenge and robust colonization resistance against pathogenic Escherichia coli. Mice colonized by hCom2 versus human feces are similar in terms of microbiota-derived metabolites, immune cell profile, and bacterial density in the gut, suggesting that this consortium is a prototype of a model system for the human gut microbiome.

The Gut Microbiome and Inflammatory Bowel Diseases

2021 ◽  
Vol 73 (1) ◽  
Author(s):  
Yue Shan ◽  
Mirae Lee ◽  
Eugene B. Chang
Keyword(s):  
Gut Microbiota ◽  
Inflammatory Bowel Diseases ◽  
Gut Microbiome ◽  
Annual Review ◽  
Publication Date ◽  
Bowel Diseases ◽  
Microbe Interactions ◽  
Inflammatory Bowel ◽  
Host Microbe Interactions ◽  
And Function

Inflammatory bowel diseases (IBD) arise from a convergence of genetic risk, environmental factors, and gut microbiota, where each is necessary but not sufficient to cause disease. Emerging evidence supports a bidirectional relationship between disease progression and changes in microbiota membership and function. Thus, the study of the gut microbiome and host–microbe interactions should provide critical insights into disease pathogenesis as well as leads for developing microbiome-based diagnostics and interventions for IBD. In this article, we review the most recent advances in understanding the relationship between the gut microbiota and IBD and highlight the importance of going beyond establishing description and association to gain mechanistic insights into causes and consequences of IBD. The review aims to contextualize recent findings to form conceptional frameworks for understanding the etiopathogenesis of IBD and for the future development of microbiome-based diagnostics and interventions. Expected final online publication date for the Annual Review of Medicine, Volume 73 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Systematic evaluation of the gut microbiome of swamp eel (Monopterus albus) by 16S rRNA gene sequencing

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e8176 ◽  
Author(s):  
Xuan Chen ◽  
Shaoming Fang ◽  
Lili Wei ◽  
Qiwang Zhong
Keyword(s):  
16S Rrna ◽  
Gut Microbiome ◽  
Immune Modulation ◽  
Rrna Gene ◽  
Nutrient Metabolism ◽  
Monopterus Albus ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
And Function ◽  
Swamp Eel

Background The swamp eel (Monopterus albus) is a commercially important farmed species in China. The dysbiosis and homeostasis of gut microbiota has been suggested to be associated with the swamp eel’s disease pathogenesis and food digestion. Although the contributions of gut microbiome in fish growth and health has been increasingly recognized, little is known about the microbial community in the intestine of the swamp eel (Monopterus albus). Methods The intestinal microbiomes of the five distinct gut sections (midgut content and mucosa, hindgut content and mucosa, and stools) of swamp eel were compared using Illumina MiSeq sequencing of the bacterial 16S rRNA gene sequence and statistical analysis. Results The results showed that the number of observed OTUs in the intestine decreased proximally to distally. Principal coordinate analysis revealed significant separations among samples from different gut sections. There were 54 core OTUs shared by all gut sections and 36 of these core OTUs varied significantly in their abundances. Additionally, we discovered 66 section-specific enriched KEGG pathways. These section-specific enriched microbial taxa (e.g., Bacillus, Lactobacillus) and potential function capacities (e.g., amino acid metabolism, carbohydrate metabolism) might play vital roles in nutrient metabolism, immune modulation and host-microbe interactions of the swamp eel. Conclusions Our results showed that microbial diversity, composition and function capacity varied substantially across different gut sections. The gut section-specific enriched core microbial taxa and function capacities may perform important roles in swamp eel’s nutrient metabolism, immune modulation, and host-microbe interactions. This study should provide insights into the gut microbiome of the swamp eel.

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