Search NASA⌕ Search

SEARCH · Search NASA

Results for “gut microbiota”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

104 records · Page 6
All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

Antibiotic resistance and host immune system-induced metal bactericidal control are key factors for microbial persistence in the developing human preterm infant gut microbiome

The human gut microbiome, which develops and stabilizes during the early stages of infant life, plays an essential role in host health through the production of metabolic resources and the stimulation and training of the immune system. To study colonization and community functional dynamics of the microbiota based on responses to host immune processes during the normal and dysbiotic establishment of the gut, metaproteomics was conducted on 91 fecal samples collected over the first 90 days of life from 17 hospitalized premature infants. Microbial responses to antibiotic administration and host-imposed metal bactericidal control correlated with community assembly and resiliency of microbes in the developing preterm gut. Specifically, proteins related to antibiotic resistance and metal homeostasis mechanisms were predominant in persisting members in the infant gut environment over the first several weeks of life. Overall, this metaproteomics study provides a unique approach to examine the temporal expansion and resilience of microbial colonization, as it allows simultaneous examination of both host and microbial metabolic activities. Understanding the interplay between host and microbes may elucidate the microbiome’s potential immunomodulatory roles relevant to necrotizing enterocolitis and other dysbiotic conditions in preterm infants.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Xanthohumol microbiome and signature in adults with Crohn’s disease (the XMaS trial): a protocol for a phase II triple-masked, placebo-controlled clinical trial

Xanthohumol (XN), a bioactive flavonoid from Humulus lupulus with anti-inflammatory properties, has potential benefits for patients with Crohn’s disease (CD), a type of inflammatory bowel disease. We recently completed and published results of a placebo-controlled phase I clinical trial demonstrating the safety and tolerability of 24 mg XN daily for 8 weeks. The present study aims to evaluate the safety and tolerability of the same dose of XN adults with clinically active CD in a placebo-controlled phase II clinical trial. Additional aims will assess the impact of XN on inflammatory biomarkers, platelet function, CD clinical activity, and stool microbial composition. The metabolism of XN will also be evaluated. This article provides a model protocol for consideration in investigations of XN or other natural products in disease states. A triple-masked, randomized, placebo-controlled trial will be conducted in adults with clinically active CD. Participants (n ≤ 32) will be randomized to either 24 mg encapsulated XN per day or placebo and followed for 8 weeks. Throughout the trial, participants will be queried for adverse events. Biomarkers of clinical safety, blood and stool markers of inflammation, platelet function, Crohn’s Disease Activity Index score, stool microbial composition, and XN metabolite profiles in blood, urine, and stool will be assessed every 2 weeks. We describe the protocol for a phase II clinical trial that evaluates the safety and tolerability of XN in adults with active CD, as well as evaluate metabolism and mechanisms that are relevant to CD and other diseases with underlying inflammation and/or gut permeability. The effects of XN on inflammatory biomarkers, platelet function, the microbiota, and multi-omics biomarkers measured in this phase II trial of adults with CD will be compared to the effects of XN in healthy adults in our previous phase I trial. The results of the study will advance the evidence guiding the use of XN in patients with CD.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Activity-based protein profiling identifies alternating activation of enzymes involved in the bifidobacterium shunt pathway or mucin degradation in the gut microbiome response to soluble dietary fiber

While deprivation of dietary fiber has been associated with adverse health outcomes, investigations concerning the effect of dietary fiber on the gut microbiome have been largely limited to compositional sequence-based analyses or utilize a defined microbiota not native to the host. To extend understanding of the microbiome’s functional response to dietary fiber deprivation beyond correlative evidence from sequence-based analyses, approaches capable of measuring functional enzymatic activity are needed. In this study, we use an activity-based protein profiling (ABPP) approach to identify sugar metabolizing and transport proteins in native mouse gut microbiomes that respond with differential activity to the deprivation or supplementation of the soluble dietary fibers inulin and pectin. We found that the microbiome of mice subjected to a high fiber diet high in soluble fiber had increased functional activity of multiple proteins, including glycoside hydrolases, polysaccharide lyases, and sugar transport proteins from diverse taxa. The results point to an increase in activity of the Bifidobacterium shunt metabolic pathway in the microbiome of mice fed high fiber diets. In those subjected to a low fiber diet, we identified a shift from the degradation of dietary fibers to that of gut mucins, in particular by the recently isolated taxon “Musculibacterium intestinale”, which experienced dramatic growth in response to fiber deprivation. When combined with metabolomics and shotgun metagenomics analyses, our findings provide a functional investigation of dietary fiber metabolism in the gut microbiome and demonstrates the power of a combined ABPP-multiomics approach for characterizing the response of the gut microbiome to perturbations.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Genomic and functional analyses of fungal and bacterial consortia that enable lignocellulose breakdown in goat gut microbiomes

Abstract The herbivore digestive tract is home to a complex community of anaerobic microbes that work together to break down lignocellulose. These microbiota are an untapped resource of strains, pathways and enzymes that could be applied to convert plant waste into sugar substrates for green biotechnology. We carried out more than 400 parallel enrichment experiments from goat faeces to determine how substrate and antibiotic selection influence membership, activity, stability and chemical productivity of herbivore gut communities. We assembled 719 high-quality metagenome-assembled genomes (MAGs) that are unique at the species level. More than 90% of these MAGs are from previously unidentified herbivore gut microorganisms. Microbial consortia dominated by anaerobic fungi outperformed bacterially dominated consortia in terms of both methane production and extent of cellulose degradation, which indicates that fungi have an important role in methane release. Metabolic pathway reconstructions from MAGs of 737 bacteria, archaea and fungi suggest that cross-domain partnerships between fungi and methanogens enabled production of acetate, formate and methane, whereas bacterially dominated consortia mainly produced short-chain fatty acids, including propionate and butyrate. Analyses of carbohydrate-active enzyme domains present in each anaerobic consortium suggest that anaerobic bacteria and fungi employ mostly complementary hydrolytic strategies. The division of labour among herbivore anaerobes to degrade plant biomass could be harnessed for industrial bioprocessing.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

CeMbio - The Caenorhabditis elegans Microbiome Resource

The study of microbiomes by sequencing has revealed a plethora of correlations between microbial community composition and various life-history characteristics of the corresponding host species. However, inferring causation from correlation is often hampered by the sheer compositional complexity of microbiomes, even in simple organisms. Synthetic communities offer an effective approach to infer cause-effect relationships in host-microbiome systems. Yet the available communities suffer from several drawbacks, such as artificial (thus non-natural) choice of microbes, microbe-host mismatch (e.g., human microbes in gnotobiotic mice), or hosts lacking genetic tractability. Here we introduce CeMbio, a simplified natural Caenorhabditis elegans microbiota derived from our previous meta-analysis of the natural microbiome of this nematode. The CeMbio resource is amenable to all strengths of the C. elegans model system, strains included are readily culturable, they all colonize the worm gut individually, and comprise a robust community that distinctly affects nematode life-history. Several tools have additionally been developed for the CeMbio strains, including diagnostic PCR primers, completely sequenced genomes, and metabolic network models. With CeMbio, we provide a versatile resource and toolbox for the in-depth dissection of naturally relevant host-microbiome interactions in C. elegans.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Enrichable consortia of microbial symbionts degrade macroalgal polysaccharides in Kyphosus fish

ABSTRACT Coastal herbivorous fishes consume macroalgae, which is then degraded by microbes along their digestive tract. However, there is scarce genomic information about the microbiota that perform this degradation. This study explores the potential of Kyphosus gastrointestinal microbial symbionts to collaboratively degrade and ferment polysaccharides from red, green, and brown macroalgae through in silico study of carbohydrate-active enzyme and sulfatase sequences. Recovery of metagenome-assembled genomes (MAGs) from previously described Kyphosus gut metagenomes and newly sequenced bioreactor enrichments reveals differences in enzymatic capabilities between the major microbial taxa in Kyphosus guts. The most versatile of the recovered MAGs were from the Bacteroidota phylum, whose MAGs house enzyme collections able to decompose a variety of algal polysaccharides. Unique enzymes and predicted degradative capacities of genomes from the Bacillota (genus Vallitalea ) and Verrucomicrobiota (order Kiritimatiellales ) highlight the importance of metabolic contributions from multiple phyla to broaden polysaccharide degradation capabilities. Few genomes contain the required enzymes to fully degrade any complex sulfated algal polysaccharide alone. The distribution of suitable enzymes between MAGs originating from different taxa, along with the widespread detection of signal peptides in candidate enzymes, is consistent with cooperative extracellular degradation of these carbohydrates. This study leverages genomic evidence to reveal an untapped diversity at the enzyme and strain level among Kyphosus symbionts and their contributions to macroalgae decomposition. Bioreactor enrichments provide a genomic foundation for degradative and fermentative processes central to translating the knowledge gained from this system to the aquaculture and bioenergy sectors. IMPORTANCE Seaweed has long been considered a promising source of sustainable biomass for bioenergy and aquaculture feed, but scalable industrial methods for decomposing terrestrial compounds can struggle to break down seaweed polysaccharides efficiently due to their unique sulfated structures. Fish of the genus Kyphosus feed on seaweed by leveraging gastrointestinal bacteria to degrade algal polysaccharides into simple sugars. This study reconstructs metagenome-assembled genomes for these gastrointestinal bacteria to enhance our understanding of herbivorous fish digestion and fermentation of algal sugars. Investigations at the gene level identify Kyphosus guts as an untapped source of seaweed-degrading enzymes ripe for further characterization. These discoveries set the stage for future work incorporating marine enzymes and microbial communities in the industrial degradation of algal polysaccharides.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Effects of ingested nanocellulose on intestinal microbiota and homeostasis in Wistar Han rats

Micron scale crystalline and fibrillar cellulose materials are “generally regarded as safe” (GRAS) as binders and thickeners in food products. Yet, partly due to a lack of relevant toxicological data, nanocellulose (NC) materials, which have unique properties that can be exploited to improve food quality and safety, have yet to receive FDA approval as food ingredients. Results of in vitro and in vivo toxicological studies of ingested NC, detailed in a recent companion report, revealed minimal acute in vitro cytotoxicity, and no toxicity in a subacute rat gavage model, suggesting that NC materials are non-hazardous. However, ingested materials may also modulate gut microbial populations, or alter aspects of intestinal function not evaluated in standard totoxicity testing, which could have important health implications. Here, we report the results of studies of the effects of ingested cellulose nanofibrils (CNF) on the fecal microbiome and metabolome, intestinal (ileal) epithelial cell mRNA expression of cell junction genes, and ileal cytokine production. Feces, plasma, and ileum samples were collected from Wistar Han rats before and after five weeks of biweekly gavages of water or cream, with or without 1% w/w CNF. Analysis of fecal microbial populations revealed that CNF caused changes in both genus and species diversity, with specific effects on species that produce short chain fatty acids, and that have been associated with increased IgA production and elevation of insulin levels. Fecal metabolomic analysis revealed relatively few effects of CNF, with significant changes in the levels of only ten metabolites out of 366 measured. Exposure to CNF also caused differential regulation of mRNA expression of several genes involved in epithelial cell junctions, and increased production of cytokines that both promote and inhibit proliferation of CD8 T cells. These perturbations in intestinal homeostasis contrast somewhat with the absence of in vitro and in vivo toxicity observed previously but would appear to represent minor effects. Additionally, the gut microbiome is highly sensitive to ingested substances, and such disturbances of the intestinal microbial ecosystem do not necessarily represent or predict meaningful pathology. Further studies, including chronic feeding studies, are needed to assess the real health implications, if any, of these changes.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Xanthohumol microbiome and signature in healthy adults (the XMaS trial): a phase I triple-masked, placebo-controlled clinical trial

Natural products may provide a source for the discovery and development of adjunctive pharmacological interventions to modulate the inflammatory pathways contributing to chronic disease. Xanthohumol, a flavonoid from the hops plant (Humulus lupulus), has antioxidant and anti-inflammatory properties and may act as a prebiotic to the intestinal microbiota. Xanthohumol is not currently approved as a drug by the US Food and Drug Administration (FDA), but is available as a dietary supplement and ingredient in medical foods. To formally test the safety of xanthohumol, a phase I clinical trial (“XMaS”) was designed and approved under an Investigational New Drug application to the US FDA. The main objective is to examine the clinical safety and subjective tolerability of xanthohumol in healthy adults compared to placebo. Additional aims are to monitor biomarkers related to inflammation, gut permeability, bile acid metabolism, routes, and in vivo products of xanthohumol metabolism, and to evaluate xanthohumol’s impact on gut microbial composition.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Targeted curation of the gut microbial gene content modulating human cardiovascular disease

Despite the promise of the gut microbiome to predict human health, few studies expose the molecular-scale processes underpinning such forecasts. We mined over 200,000 gut-derived genomes from cultivated and uncultivated microbial lineages to inventory the gut microorganisms and their gene content that control trimethylamine-induced cardiovascular disease. We assigned an atherosclerotic profile to the 6,341 microbial genomes that encoded metabolisms associated with heart disease, creating the Methylated Amine Gene Inventory of Catabolism database (MAGICdb). From microbiome gene expression data sets, we demonstrate that MAGICdb enhanced the recovery of disease-relevant genes and identified the most active microorganisms, unveiling future therapeutic targets. From the feces of healthy and diseased subjects, we show that MAGICdb predicted cardiovascular disease status as effectively as traditional lipid blood tests. This functional microbiome catalog is a public, exploitable resource, designed to enable a new era of microbiota-based therapeutics and diagnostics

metatranscriptomics↗
DOE OSTI2025

Diet outperforms microbial transplant to drive microbiome recovery in mice

A high-fat, low-fibre Western-style diet (WD) induces microbiome dysbiosis characterized by reduced taxonomic diversity and metabolic breadth, which in turn increases risk for a wide array of metabolic, immune and systemic pathologies. Recent work has established that WD can impair microbiome resilience to acute perturbations such as antibiotic treatment, although little is known about the mechanism of impairment and the specific consequences for the host of prolonged post-antibiotic dysbiosis. Here, in this study, we characterize the trajectory by which the gut microbiome recovers its taxonomic and functional profile after antibiotic treatment in mice on regular chow (RC) or WD, and find that only mice on RC undergo a rapid successional process of recovery. Metabolic modelling indicates that a RC diet promotes the development of syntrophic cross-feeding interactions, whereas in mice on WD, a dominant taxon monopolizes readily available resources without releasing syntrophic byproducts. Intervention experiments reveal that an appropriate dietary resource environment is both necessary and sufficient for rapid and robust microbiome recovery, whereas microbial transplant is neither. Furthermore, prolonged post-antibiotic dysbiosis in mice on WD renders them susceptible to infection by the intestinal pathogen Salmonella enterica serovar Typhimurium. Our data challenge widespread enthusiasm for faecal microbiota transplant (FMT) as a strategy to address dysbiosis, and demonstrate that specific dietary interventions are, at a minimum, an essential prerequisite for effective FMT, and may afford a safer, more natural and less invasive alternative.

Kennedy, M. S. [University of Chicago, IL (United ↗
DOE OSTI2022

A soil-inspired dynamically responsive chemical system for microbial modulation

Interactions between the microbiota and their colonized environments mediate critical pathways from biogeochemical cycles to homeostasis in human health. Here, in this study, we report a soil-inspired chemical system that consists of nanostructured minerals, starch granules and liquid metals. Fabricated via a bottom-up synthesis, the soil-inspired chemical system can enable chemical redistribution and modulation of microbial communities. We characterize the composite, confirming its structural similarity to the soil, with three-dimensional X-ray fluorescence and ptychographic tomography and electron microscopy imaging. We also demonstrate that post-synthetic modifications formed by laser irradiation led to chemical heterogeneities from the atomic to the macroscopic level. The soil-inspired material possesses chemical, optical and mechanical responsiveness to yield write-erase functions in electrical performance. The composite can also enhance microbial culture/biofilm growth and biofuel production in vitro. Finally, we show that the soil-inspired system enriches gut bacteria diversity, rectifies tetracycline-induced gut microbiome dysbiosis and ameliorates dextran sulfate sodium-induced rodent colitis symptoms within in vivo rodent models.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2021

Five key aspects of metaproteomics as a tool to understand functional interactions in host-associated microbiomes

Host-associated microbial communities (microbiomes) play critical roles in human, animal, and plant health and development. However, interactions between the host, members of the microbiome, and invading pathogens are in most cases still poorly understood. Such interactions are multidimensional and can alter the taxonomic composition and/or the functional metabolic activities of the microbiome in response to disease or treatment conditions. For example, after 2 days of antibiotic treatment, the mouse gut microbiome is altered and more susceptible to invasion by the pathogen Clostridioides difficile. Studies of these multidimensional interactions have been fueled by the ability to use high-throughput sequencing of phylogenetic marker genes to profile microbial community composition and shotgun metagenomics to profile functional potential. However, many protein-coding genes predicted from metagenomes are not necessarily expressed under a given condition, and thus, it is difficult to assess the activities and functional interactions in microbial communities based on DNA sequencing data alone. The physiological and pathological processes expressed in these communities under specific conditions are better reflected by the abundances of transcripts or proteins. In this Pearl, we provide a brief introduction to metaproteomics, which is a tool for the large-scale analysis of proteins in microbiomes that allows researchers to address a diversity of questions related to functions and interactions in microbiomes. The term “metaproteomics” was first used in 2004 for “the large-scale characterization of the entire protein complement of environmental microbiota at a given point in time”, and since then, a large array of metaproteomics approaches have been developed. Our objective in this Pearl is to highlight what we feel are 5 essential elements to be considered for a metaproteomics research campaign and to introduce nonexpert readers to the topic without going into too much technical detail.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Identification and characterization of a skin microbiome on Caenorhabditis elegans suggests environmental microbes confer cuticle protection

ABSTRACT In the wild, C. elegans are emersed in environments teeming with a veritable menagerie of microorganisms. The C. elegans cuticular surface serves as a barrier and first point of contact with their microbial environments. In this study, we identify microbes from C. elegans natural habitats that associate with its cuticle, constituting a simple “skin microbiome.” We rear our animals on a modified CeMbio, mCeMbio, a consortium of ecologically relevant microbes. We first combine standard microbiological methods with an adapted micro skin-swabbing tool to describe the skin-resident bacteria on the C. elegans surface. Furthermore, we conduct 16S rRNA gene sequencing studies to identify relative shifts in the proportion of mCeMbio bacteria upon surface-sterilization, implying distinct skin- and gut-microbiomes. We find that some strains of bacteria, including Enterobacter sp. JUb101 , are primarily found on the nematode skin, while others like Stenotrophomonas indicatrix JUb19 and Ochrobactrum vermis MYb71 are predominantly found in the animal’s gut. Finally, we show that this skin microbiome promotes host cuticle integrity in harsh environments. Together, we identify a skin microbiome for the well-studied nematode model and propose its value in conferring host fitness advantages in naturalized contexts. IMPORTANCE The genetic model organism C. elegans has recently emerged as a tool for understanding host–microbiome interactions. Nearly all of these studies either focus on pathogenic or gut-resident microbes. Little is known about the existence of native, nonpathogenic skin microbes or their function. We demonstrate that members of a modified C. elegans model microbiome, mCeMbio, can adhere to the animal's cuticle and confer protection from noxious environments. We combine a novel micro-swab tool, the first 16S microbial sequencing data from relatively unperturbed C. elegans , and physiological assays to demonstrate microbially mediated protection of the skin. This work serves as a foundation to explore wild C. elegans skin microbiomes and use C. elegans as a model for skin research.

16S RNA↗
DOE OSTI2022

Global trends in Akkermansia muciniphila research: A bibliometric visualization

Background Akkermansia muciniphila is a member of the gut microbiome, using mucin as sources of carbon, nitrogen, and energy. Since the first discovery of this unique bacterium in 2004, A. muciniphila has been extensively studied. It is considered a promising “next-generation beneficial microbe.” The purpose of this paper is to sort out the research status and summarize the hotspots through bibliometric analysis of the publications of A. muciniphila. Methods The publications about A. muciniphila from January 2004 to February 2022 were obtained from the Web of Science Core Collection. Visualization analyses were performed using three bibliometric tools and GraphPad Prism. Results A total of 1,478 published documents were analyzed. Annual publication number grew from 1 in 2004 to 336 in 2021, with China being the leading producer (33.36%). De Vos, Willem M was the most productive author with the highest H-index (documents = 56, H-index = 37), followed by Cani, Patrice D (documents = 35, H-index = 25). And Scientific Reports published the most papers. PNAS was the keystone taxa in this field, with high betweenness centrality (0.11) and high frequency. The keywords with high frequency in recent years include: oxidative stress, diet, metformin, fecal microbiota transplantation, short-chain fatty acids, polyphenols, microbiota metabolites and so on. The keyword “oxidative stress” was observed to be increasing in frequency recently. Conclusion Over time, the scope of the research on the clinical uses of A. muciniphila has gradually increased, and was gradually deepened and developed toward a more precise level. A. muciniphila is likely to remain a research hotspot in the foreseeable future and may contribute to human health.

Li, Zitong↗