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At least 73 records · Page 4
All sourcesNASA NTRSDOE OSTI
DOE OSTI2021

Biogeography of microbial bile acid transformations along the murine gut

Bile acids, which are synthesized from cholesterol by the liver, are chemically transformed along the intestinal tract by the gut microbiota, and the products of these transformations signal through host receptors, affecting overall host health. These transformations include bile acid deconjugation, oxidation, and 7α-dehydroxylation. An understanding of the biogeography of bile acid transformations in the gut is critical because deconjugation is a prerequisite for 7α-dehydroxylation and because most gut microorganisms harbor bile acid transformation capacity. Here, we used a coupled metabolomic and metaproteomic approach to probe in vivo activity of the gut microbial community in a gnotobiotic mouse model. Results revealed the involvement of Clostridium scindens in 7α-dehydroxylation, of the genera Muribaculum and Bacteroides in deconjugation, and of six additional organisms in oxidation (the genera Clostridium, Muribaculum, Bacteroides, Bifidobacterium, Acutalibacter, and Akkermansia). Furthermore, the bile acid profile in mice with a more complex microbiota, a dysbiosed microbiota, or no microbiota was considered. For instance, conventional mice harbor a large diversity of bile acids, but treatment with an antibiotic such as clindamycin results in the complete inhibition of 7α-dehydroxylation, underscoring the strong inhibition of organisms that are capable of carrying out this process by this compound. Finally, a comparison of the hepatic bile acid pool size as a function of microbiota revealed that a reduced microbiota affects host signaling but not necessarily bile acid synthesis. In this study, bile acid transformations were mapped to the associated active microorganisms, offering a systematic characterization of the relationship between microbiota and bile acid composition.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Chemical composition of cold‐pressed blackberry seed flour extract and its potential health‐beneficial properties

Abstract The blackberry seed flour was cold‐extracted using 50% acetone and examined for its phytochemical composition and health‐beneficial properties including in vitro gut microbiota modulatory, free radical scavenging, anti‐inflammatory, and antiproliferative capacities. Among identified thirteen components of blackberry seed flour extract through UHPLC‐MS analysis, sanguiin H6 was the primary component and followed by ellagic acid and pedunculagin. For health‐beneficial properties, the blackberry seed flour extract increased the total number of gut bacteria and shifted the abundance of specific bacterial phylum, family, or genus. The extract had RDSC, ORAC, HOSC, and ABTS •+ scavenging capacities of 362, 304, 2,531, and 267 μmol Trolox equivalents (TE)/g, respectively. In addition, the blackberry seed flour extract showed capacities for anti‐inflammation and antiproliferation by suppressing LPS induced IL‐1β mRNA expressions in the cultured J774A.1 mouse macrophages and the proliferation of LNCaP prostate cancer cells. The results suggest potential health benefits and further utilization of blackberry seed flour as functional foods.

Choe, Uyory↗
DOE OSTI2024

An efficient cre‐based workflow for genomic integration and expression of large biosynthetic pathways in Eubacterium limosum

Abstract Acetogenic Clostridia are obligate anaerobes that have emerged as promising microbes for the renewable production of biochemicals owing to their ability to efficiently metabolize sustainable single‐carbon feedstocks. Additionally, Clostridia are increasingly recognized for their biosynthetic potential, with recent discoveries of diverse secondary metabolites ranging from antibiotics to pigments to modulators of the human gut microbiota. Lack of efficient methods for genomic integration and expression of large heterologous DNA constructs remains a major challenge in studying biosynthesis in Clostridia and using them for metabolic engineering applications. To overcome this problem, we harnessed chassis‐independent recombinase‐assisted genome engineering (CRAGE) to develop a workflow for facile integration of large gene clusters (>10 kb) into the human gut acetogen Eubacterium limosum . We then integrated a non‐ribosomal peptide synthetase gene cluster from the gut anaerobe Clostridium leptum , which previously produced no detectable product in traditional heterologous hosts. Chromosomal expression in E. limosum without further optimization led to production of phevalin at 2.4 mg/L. These results further expand the molecular toolkit for a highly tractable member of the Clostridia, paving the way for sophisticated pathway engineering efforts, and highlighting the potential of E. limosum as a Clostridial chassis for exploration of anaerobic natural product biosynthesis.

Sanford, Patrick A.↗
DOE OSTI2023

Herbivorous Fish Microbiome Adaptations to Sulfated Dietary Polysaccharides

Marine herbivorous fish that feed primarily on macroalgae, such as those from the genus Kyphosus, are essential for maintaining coral health and abundance on tropical reefs. Here, deep metagenomic sequencing and assembly of gut compartment-specific samples from three sympatric, macroalgivorous Hawaiian kyphosid species have been used to connect host gut microbial taxa with predicted protein functional capacities likely to contribute to efficient macroalgal digestion. Bacterial community compositions, algal dietary sources, and predicted enzyme functionalities were analyzed in parallel for 16 metagenomes spanning the mid- and hindgut digestive regions of wild-caught fishes. Gene colocalization patterns of expanded carbohydrate (CAZy) and sulfatase (SulfAtlas) digestive enzyme families on assembled contigs were used to identify likely polysaccharide utilization locus associations and to visualize potential cooperative networks of extracellularly exported proteins targeting complex sulfated polysaccharides. These insights into the gut microbiota of herbivorous marine fish and their functional capabilities improve our understanding of the enzymes and microorganisms involved in digesting complex macroalgal sulfated polysaccharides.

09 BIOMASS FUELS↗
DOE OSTI2025

Effect of in utero and lactational exposure to antiretroviral therapy on the gut microbial composition and metabolic function in aged rat offspring

Despite the highly effective impact of antiretroviral therapy (ART) in reducing mother-to-child transmission of human immunodeficiency virus (HIV), there are concerns of long-term impacts of ART on the health of the offspring. The implications of perinatal exposure to antiviral drugs on the gut bacterial population and metabolic function in the offspring is unclear but may influence health outcomes given the various reported effects of the microbiome in human health. This study aims to gain insight into the potential effect ofin uteroand lactational exposure to ART on gut microbiota populations and short‐chain fatty acids (SCFAs) production in aged rat offspring. Pregnant rats were administered a combination of antiretroviral drugs (abacavir/dolutegravir/lamivudine) at two different dose levels during gestation and throughout lactation, and the fecal bacterial abundance and SCFA levels of the offspring were analyzed when they reached 12 months of age. Our results showed dose-dependent and sex-based differences in fecal microbial abundance at various taxonomic levels. Specifically, we found a decline inFirmicutesin males, and an increase inActinobacteriaamong males and females. Furthermore, a sex-specific distribution reorganization ofLactobacillus,Bifidobacterium, andAkkermansiawas identified. No significant difference in the concentration of prominent SCFAs and IgA levels were identified. These findings provide preliminary information indicating the need to evaluate perinatal effects of ART more comprehensively on the gut bacterial and metabolic function in future studies, and their potential role in offspring health outcomes.

Research & Experimental Medicine↗
DOE OSTI2021

Predicting drug-metagenome interactions: Variation in the microbial β-glucuronidase level in the human gut metagenomes

Characterizing the gut microbiota in terms of their capacity to interfere with drug metabolism is necessary to achieve drug efficacy and safety. Although examples of drug-microbiome interactions are well-documented, little has been reported about a computational pipeline for systematically identifying and characterizing bacterial enzymes that process particular classes of drugs. The goal of our study is to develop a computational approach that compiles drugs whose metabolism may be influenced by a particular class of microbial enzymes and that quantifies the variability in the collective level of those enzymes among individuals. The present paper describes this approach, with microbial β-glucuronidases as an example, which break down drug-glucuronide conjugates and reactivate the drugs or their metabolites. We identified 100 medications that may be metabolized by β-glucuronidases from the gut microbiome. These medications included morphine, estrogen, ibuprofen, midazolam, and their structural analogues. The analysis of metagenomic data available through the Sequence Read Archive (SRA) showed that the level of β-glucuronidase in the gut metagenomes was higher in males than in females, which provides a potential explanation for the sex-based differences in efficacy and toxicity for several drugs, reported in previous studies. Our analysis also showed that infant gut metagenomes at birth and 12 months of age have higher levels of β-glucuronidase than the metagenomes of their mothers and the implication of this observed variability was discussed in the context of breastfeeding as well as infant hyperbilirubinemia. Overall, despite important limitations discussed in this paper, our analysis provided useful insights on the role of the human gut metagenome in the variability in drug response among individuals. Importantly, this approach exploits drug and metagenome data available in public databases as well as open-source cheminformatics and bioinformatics tools to predict drug-metagenome interactions.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Association of Diet and Antimicrobial Resistance in Healthy U.S. Adults

Antimicrobial resistance (AMR) represents a significant source of morbidity and mortality worldwide, with expectations that AMR-associated consequences will continue to worsen throughout the coming decades. Since resistance to antibiotics is encoded in the microbiome, interventions aimed at altering the taxonomic composition of the gut might allow us to prophylactically engineer microbiomes that harbor fewer antibiotic resistant genes (ARGs). Diet is one method of intervention, and yet little is known about the association between diet and antimicrobial resistance. To address this knowledge gap, we examined diet using the food frequency questionnaire (FFQ; habitual diet) and 24-h dietary recalls (Automated Self-Administered 24-h [ASA24 ® ] tool) coupled with an analysis of the microbiome using shotgun metagenome sequencing in 290 healthy adult participants of the United States Department of Agriculture (USDA) Nutritional Phenotyping Study. We found that aminoglycosides were the most abundant and prevalent mechanism of AMR in these healthy adults and that aminoglycoside-O-phosphotransferases (aph3-dprime) correlated negatively with total calories and soluble fiber intake. Individuals in the lowest quartile of ARGs (low-ARG) consumed significantly more fiber in their diets than medium- and high-ARG individuals, which was concomitant with increased abundances of obligate anaerobes, especially from the family Clostridiaceae, in their gut microbiota. Finally, we applied machine learning to examine 387 dietary, physiological, and lifestyle features for associations with antimicrobial resistance, finding that increased phylogenetic diversity of diet was associated with low-ARG individuals. These data suggest diet may be a potential method for reducing the burden of AMR.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Biotechnological advances in algae-based foods: applications in nutrition and microbiome health

Algae are a sustainable, nutrient-rich resource with growing potential in food biotechnology. Their ability to thrive in diverse environments makes them a promising alternative to conventional crops. Rich in proteins, essential fatty acids, and bioactive compounds, algae support the development of functional foods, including plant-based meat and seafood alternatives. Advances in synthetic biology and fermentation have enhanced algal nutrient profiles and enabled novel applications. Algae-derived polysaccharides, such as alginate, fucoidan, laminarin, and porphyran, exhibit prebiotic effects by modulating the gut microbiota and promoting SCFA production. Enzymatic hydrolysis efficiently produces bioactive oligosaccharides, while engineered microbial systems support scalable production. Algae also enable synbiotic food development by serving as both prebiotic substrates and probiotic carriers.

Yu, Sora↗
DOE OSTI2022

How a Formate Dehydrogenase Responds to Oxygen: Unexpected O 2 Insensitivity of an Enzyme Harboring Tungstopterin, Selenocysteine, and [4Fe–4S] Clusters

The reversible two-electron interconversion of formate and CO 2 is catalyzed by both nonmetallo- and metallo-formate dehydrogenases (FDHs). The latter group comprises molybdenum- or tungsten-containing enzymes with the metal coordinated by two equivalents of a pyranopterin cofactor, a cysteinyl or selenocysteinyl (Sec) ligand supplied by the polypeptide, and a catalytically essential terminal sulfido ligand. In addition, these biocatalysts incorporate one or more [4Fe–4S] clusters for facilitating long-distance electron transfer. However, an interesting dichotomy arises when attempting to understand how the metallo-FDHs react with O 2 . Whereas existing scholarship portrays these enzymes as being unable to perform in air due to extreme O 2 lability of their metal centers, studies dating as far back as the 1930s emphasize that some of these systems exhibit formate oxidase (FOX) activity, coupling formate oxidation to O 2 reduction. Therefore, to reconcile these conflicting views, we explored context-dependent functional linkages between metallo-FDHs and their cognate electron acceptors within the same organism vis-à-vis catalysis under atmospheric O 2 . Here, we report the discovery and characterization of an O 2 -insensitive FDH2 from the sulfate-reducing bacterium Desulfovibrio vulgaris Hildenborough (DvH) that ligates tungsten, Sec, and four [4Fe–4S] clusters. By advancing a robust expression platform for its recombinant production, we eliminate both the requirement of nitrate or azide during purification and reductive activation with thiols and/or formate prior to catalysis. Because the distinctive spectral signatures of formate-reduced DvH-FDH2 remain invariant under anaerobic and aerobic conditions, we benchmarked the enzyme activity in air, identifying CO 2 as the catalytic product. Full reaction progress curve analysis discloses a high catalytic efficiency when probed with a high-potential artificial electron acceptor. Furthermore, we show that DvH-FDH2 enables near-stoichiometric hydrogen peroxide production without superoxide release to achieve O 2 insensitivity. Notably, simultaneous electron transfer to cytochrome c and O 2 reveals that metal-based electron bifurcation is operational in this system. Taken together, our work proves the co-occurrence of redox bifurcated FDH and FOX activities within a metalloenzyme scaffold. These findings set the stage for uncovering previously unknown O 2 -insensitive flavin-based electron bifurcation mechanisms, as well as for developing authentic formate/air biofuel cells, engineering O 2 -stable FDHs and biohybrid metallocatalysts, and discerning formate bioenergetics of gut microbiota.

13C NMR↗
DOE OSTI2021

Species- and site-specific genome editing in complex bacterial communities

Knowledge of microbial gene functions comes from manipulating the DNA of individual strains in isolation from their natural communities. While this approach to microbial genetics has been foundational, its requirement for culturable microorganisms has left the majority of microbes and their interactions genetically unexplored. Here, we describe a generalizable strategy for editing the genomes of specific organisms within microbial communities. We identified genetically tractable bacteria within a community using Environmental Transformation Sequencing (ET-Seq), an approach in which non-targeted transposon integrations are mapped and quantified following community delivery. We next developed and used DNA-editing All-in-one RNA-guided CRISPR-Cas Transposase (DART) systems for targeted DNA insertion into organisms identified as tractable by ET-Seq, enabling organism- and locus-specific genetic manipulation within the community context. To illustrate the utility of our approach, we selectively edited closely related strains, measured gene fitness, and enriched targeted members within soil and infant gut microbiota. These results establish a new paradigm for targeted community editing relevant to research and applications on medical, agricultural, and industrial microbiomes.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

A small molecule inhibitor prevents gut bacterial genotoxin production

Abstract The human gut bacterial genotoxin colibactin is a possible key driver of colorectal cancer (CRC) development. Understanding colibactin’s biological effects remains difficult owing to the instability of the proposed active species and the complexity of the gut microbiota. Here, we report small molecule boronic acid inhibitors of colibactin biosynthesis. Designed to mimic the biosynthetic precursor precolibactin, these compounds potently inhibit the colibactin-activating peptidase ClbP. Using biochemical assays and crystallography, we show that they engage the ClbP binding pocket, forming a covalent bond with the catalytic serine. These inhibitors reproduce the phenotypes observed in a clbP deletion mutant and block the genotoxic effects of colibactin on eukaryotic cells. The availability of ClbP inhibitors will allow precise, temporal control over colibactin production, enabling further study of its contributions to CRC. Finally, application of our inhibitors to related peptidase-encoding pathways highlights the power of chemical tools to probe natural product biosynthesis.

Biochemistry & Molecular Biology↗
DOE OSTI2023

Structural basis of the amidase ClbL central to the biosynthesis of the genotoxin colibactin

Colibactin is a genotoxic natural product produced by select commensal bacteria in the human gut microbiota. The compound is a bis-electrophile that is predicted to form interstrand DNA cross-links in target cells, leading to double-strand DNA breaks. The biosynthesis of colibactin is carried out by a mixed NRPS–PKS assembly line with several noncanonical features. An amidase, ClbL, plays a key role in the pathway, catalyzing the final step in the formation of the pseudodimeric scaffold. ClbL couples α-aminoketone and β-ketothioester intermediates attached to separate carrier domains on the NRPS–PKS assembly. Here, the 1.9 Å resolution structure of ClbL is reported, providing a structural basis for this key step in the colibactin biosynthetic pathway. The structure reveals an open hydrophobic active site surrounded by flexible loops, and comparison with homologous amidases supports its unusual function and predicts macromolecular interactions with pathway carrier-protein substrates. Modeling protein–protein interactions supports a predicted molecular basis for enzyme–carrier domain interactions. Overall, the work provides structural insight into this unique enzyme that is central to the biosynthesis of colibactin.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Anaerobic Microbial Metabolism of Dichloroacetate

Dichloroacetate (DCA) commonly occurs in the environment due to natural production and anthropogenic releases, but its fate under anoxic conditions is uncertain. Mixed culture RM comprising “Candidatus Dichloromethanomonas elyunquensis” strain RM utilizes DCA as an energy source, and the transient formation of formate, H 2 , and carbon monoxide (CO) was observed during growth. Only about half of the DCA was recovered as acetate, suggesting a fermentative catabolic route rather than a reductive dechlorination pathway. Sequencing of 16S rRNA gene amplicons and 16S rRNA gene-targeted quantitative real-time PCR (qPCR) implicated “Candidatus Dichloromethanomonas elyunquensis” strain RM in DCA degradation. An (S)-2-haloacid dehalogenase (HAD) encoded on the genome of strain RM was heterologously expressed, and the purified HAD demonstrated the cofactor-independent stoichiometric conversion of DCA to glyoxylate at a rate of 90 ± 4.6 nkat mg -1 protein. Differential protein expression analysis identified enzymes catalyzing the conversion of DCA to acetyl coenzyme A (acetyl-CoA) via glyoxylate as well as enzymes of the Wood-Ljungdahl pathway. Glyoxylate carboligase, which catalyzes the condensation of two molecules of glyoxylate to form tartronate semialdehyde, was highly abundant in DCA-grown cells. The physiological, biochemical, and proteogenomic data demonstrate the involvement of an HAD and the Wood-Ljungdahl pathway in the anaerobic fermentation of DCA, which has implications for DCA turnover in natural and engineered environments, as well as the metabolism of the cancer drug DCA by gut microbiota.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Identification of a Novel Cobamide Remodeling Enzyme in the Beneficial Human Gut Bacterium Akkermansia muciniphila

The beneficial human gut bacterium Akkermansia muciniphila provides metabolites to other members of the gut microbiota by breaking down host mucin, but most of its other metabolic functions have not been investigated. A. muciniphila strain Muc T is known to use cobamides, the vitamin B 12 family of cofactors with structural diversity in the lower ligand. However, A. muciniphila Muc T is unable to synthesize cobamides de novo, and the specific forms that can be used by A. muciniphila have not been examined. We found that the levels of growth of A. muciniphila Muc T were nearly identical with each of seven cobamides tested, in contrast to nearly all bacteria that had been studied previously. Unexpectedly, this promiscuity is due to cobamide remodeling—the removal and replacement of the lower ligand—despite the absence of the canonical remodeling enzyme CbiZ in A. muciniphila. We identified a novel enzyme, CbiR, that is capable of initiating the remodeling process by hydrolyzing the phosphoribosyl bond in the nucleotide loop of cobamides. CbiR does not share similarity with other cobamide remodeling enzymes or B12-binding domains and is instead a member of the apurinic/apyrimidinic (AP) endonuclease 2 enzyme superfamily. We speculate that CbiR enables bacteria to repurpose cobamides that they cannot otherwise use in order to grow under cobamide-requiring conditions; this function was confirmed by heterologous expression of cbiR in Escherichia coli. Homologs of CbiR are found in over 200 microbial taxa across 22 phyla, suggesting that many bacteria may use CbiR to gain access to the diverse cobamides present in their environment.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

BinaRena: a dedicated interactive platform for human-guided exploration and binning of metagenomes

Background: Exploring metagenomic contigs and “binning” them into metagenome-assembled genomes (MAGs) are essential for the delineation of functional and evolutionary guilds within microbial communities. Despite the advances in automated binning algorithms, their capabilities in recovering MAGs with accuracy and biological relevance are so far limited. Researchers often find that human involvement is necessary to achieve representative binning results. This manual process however is expertise demanding and labor intensive, and it deserves to be supported by software infrastructure. Results: We present BinaRena, a comprehensive and versatile graphic interface dedicated to aiding human operators to explore metagenome assemblies via customizable visualization and to associate contigs with bins. Contigs are rendered as an interactive scatter plot based on various data types, including sequence metrics, coverage profiles, taxonomic assignments, and functional annotations. Various contig-level operations are permitted, such as selection, masking, highlighting, focusing, and searching. Binning plans can be conveniently edited, inspected, and compared visually or using metrics including silhouette coefficient and adjusted Rand index. Completeness and contamination of user-selected contigs can be calculated in real time. In demonstration of BinaRena’s usability, we show that it facilitated biological pattern discovery, hypothesis generation, and bin refinement in a complex tropical peatland metagenome. It enabled isolation of pathogenic genomes within closely related populations from the gut microbiota of diarrheal human subjects. It significantly improved overall binning quality after curating results of automated binners using a simulated marine dataset. Conclusions: BinaRena is an installation-free, dependency-free, client-end web application that operates directly in any modern web browser, facilitating ease of deployment and accessibility for researchers of all skill levels. The program is hosted at https://github.com/qiyunlab/binarena, together with documentation, tutorials, example data, and a live demo. It effectively supports human researchers in intuitive interpretation and fine tuning of metagenomic data.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

The gut microbiome mediates adaptation to scarce food in Coleoptera

Beetles are ubiquitous cave invertebrates worldwide that adapted to scarce subterranean resources when they colonized caves. Here, we investigated the potential role of gut microbiota in the adaptation of beetles to caves from different climatic regions of the Carpathians. The beetles’ microbiota was host-specific, reflecting phylogenetic and nutritional adaptation. The microbial community structure further resolved conspecific beetles by caves suggesting microbiota-host coevolution and influences by local environmental factors. The detritivore species hosted a variety of bacteria known to decompose and ferment organic matter, suggesting turnover and host cooperative digestion of the sedimentary microbiota and allochthonous-derived nutrients. The cave Carabidae, with strong mandibula, adapted to predation and scavenging of animal and plant remains, had distinct microbiota dominated by symbiotic lineages Spiroplasma or Wolbachia. All beetles had relatively high levels of fermentative Carnobacterium and Vagococcus involved in lipid accumulation and a reduction of metabolic activity, and both features characterize adaptation to caves.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Glucuronidase Function in Clinical Samples

The purpose of this CRADA is to expand upon the work previously performed through CRADA No. PNNL/381. As explained in the previous CRADA, Glucuronidase enzymes are important for contributing to enterohepatic recycling of numerous therapeutic drug compounds, resulting in impaired or prolonged drug activity. Further, other pathways within the gut, such as bile acid metabolism through the action of bile salt hydrolase enzymes (BSH), have shown to impact both the development of colon cancers and impact recovery. Adapting the activity-based protein profiling (ABPP) technologies developed at PNNL to a microtiter plate-based chemical probe assay was the first step in demonstrating the clinical usability of the technology. With assay proof-of-concept complete through CRADA No. PNNL/381, clinical cohort testing using the developed assay is the next step towards commercialization of this technology. Some chemotherapeutic agents are mediated by gut-produced microbiota through enterohepatic circulation. For example, irinotecan, the first line treatment for many colon and other cancers, can be recycled into a patient’s system through gut microbiota produced glucuronidase enzymes. A significant percentage of patients subjected to irinotecan treatment experience dose-limiting diarrhea and gastric distress that limits treatment options and delays effective intervention. Relatedly, bile salt hydrolases modify ratios of bile acids in the gut, which alter nutrient and pharmaceutical uptake by the intestines and impact patient response to treatment. Coupled together these gut-mediated disorders can significantly decrease patient outcomes. In this project, we propose to investigate a clinical cohort of samples from colon cancer patients to better understand gut microbiome activities surrounding microbiota produced glucuronidases to aid clinician decisions and enhance therapeutic intervention. Our project will measure glucuronidase activity of individual patients and compare this activity to a variety of factors, including patient medical history, treatment response, and overall outcomes. Data will be compared with metagenomic, metabolomic, and proteomic analyses to fully defined the entire gut microbiome space and correlate results with the glucuronidase activity. Resultant analysis is expected to provide actionable information to direct decision making towards therapeutic intervention.

59 BASIC BIOLOGICAL SCIENCES↗