Taxonomic Profiles Research Articles

Taxonomic and functional profiling of microbial community in municipal solid waste dumpsite

Taxonomic and functional profiling of microbial community in municipal solid waste dumpsite

A step-by-step procedure for analysing the 16S rRNA-based microbiome diversity using QIIME 2 and comprehensive PICRUSt2 illustration for functional prediction.

Short-read sequencing technology has emerged as a preferred tool to analyse the bacterial composition of a niche by targeting hypervariable regions of the 16S rRNA gene. It targets the short hypervariable regions of the 16S rRNA gene and uncovers the taxonomic profile and their associated pathways. QIIME 2 is preferred and ready-to-use pipelines that perform stepwise analysis of massive short reads of 16S rRNA genes. This wrapper comprises several tools that include quality checking, denoising, taxonomic classification, alignment, and diversity analysis. However, it demands huge bioinformatic analysis practices which are quite challenging to many microbiologists working in the field of traditional microbiology. This paper, therefore, aimsto make microbiologists familiar with the steps of computational analysis for processing 16S rRNA-based sequences. Here, we are presenting stepwise processing of NGS sequences using the QIIME 2 platform along with their analyses, which include installing QIIME 2, importing and processing data, quality checks, taxonomy assignments, and diversity analysis. Besides, the Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt2) has also been illustrated to understand the correlation between metabolic and physiological footprints of the different species observed during microbiome analysis. Therefore, this paper can be used as a handy toolkit for those researchers who are less familiar with its associated bioinformatic analysis.

A Comparative Analysis of the Ocular Microbiome: Insights into Healthy Eyes and Anophthalmic Sockets

The purpose of this study is to characterize the ocular surface microbiota of patients with an anophthalmic cavity. An eNAT with 1 mL of Liquid Amies Medium was used to collect samples. Microbial DNA from anophthalmic socket and healthy fellow control eye samples was isolated and sequenced. Raw reads were analyzed with GAIA (v 2.02). The richness and Shannon alpha diversity metrics, as well as Bray–Curtis beta diversity and Wilcoxon signed-rank test values, were computed with R packages such as phyloseq, mia, or DESeq2 to allow for microbiome analysis. Principal coordinate analysis (PCoA) was performed using the function plotReducedDim from the R package scater. The different taxonomic profiles were described under the concept of eye community state type (ECST). The microbiomes of both eyes from 25 patients with an anophthalmic cavity were analyzed in this study. While the microbial communities of paired eyes from the same patients showed notable dissimilarity, no consistent patterns emerged when comparing healthy eyes to anophthalmic sockets. Alpha diversity values did not significantly differ between healthy eyes and anophthalmic socket samples, though there was considerable variability within each group. Notably, anophthalmic socket samples generally exhibited lower abundances of genera such as Staphylococcus, Enterococcus, Paenibacillus, and Sediminibacterium compared to their healthy counterparts. Microbial variability between healthy eyes and anophthalmic sockets may be due to anatomical differences. Further research is needed to determine whether patients without anophthalmic sockets exhibit similar microbiome patterns in both eyes.

The mOTUs online database provides web-accessible genomic context to taxonomic profiling of microbial communities.

Determining the taxonomic composition (taxonomic profiling) is a fundamental task in studying environmental and host-associated microbial communities. However, genome-resolved microbial diversity on Earth remains undersampled, and accessing the genomic context of taxa detected during taxonomic profiling remains a challenging task. Here, we present the mOTUs online database (mOTUs-db), which is consistent with and interfaces with the mOTUs taxonomic profiling tool. It comprises 2.83 million metagenome-assembled genomes (MAGs) and 919090 single-cell and isolate genomes from 124295 species-level taxonomic units. In addition to being one of the largest prokaryotic genome resources to date, all MAGs in the mOTUs-db were reconstructed de novo in 117902 individual samples by abundance correlation of scaffolds across multiple samples for improved quality metrics. The database complements the Genome Taxonomy Database, with over 50% of its species-level taxonomic groups being unique. It also offers interactive querying, enabling users to explore and download genomes at various taxonomic levels. The mOTUs-db is accessible at https://motus-db.org.

GutMetaNet: an integrated database for exploring horizontal gene transfer and functional redundancy in the human gut microbiome.

Metagenomic studies have revealed the critical roles of complex microbial interactions, including horizontal gene transfer (HGT) and functional redundancy (FR), in shaping the gut microbiome's functional capacity and resilience. However, the lack of comprehensive data integration and systematic analysis approaches has limited the in-depth exploration of HGT and FR dynamics across large-scale gut microbiome datasets. To address this gap, we present GutMetaNet (https://gutmetanet.deepomics.org/), a first-of-its-kind database integrating extensive human gut microbiome data with comprehensive HGT and FR analyses. GutMetaNet contains 21567 human gut metagenome samples with whole-genome shotgun sequencing data related to various health conditions. Through systematic analysis, we have characterized the taxonomic profiles andFR profiles, and identified 14636 HGT events using a shared reference genome database across the collected samples. These HGT events have been curated into 8049 clusters, which are annotated with categorized mobile genetic elements, including transposons, prophages, integrative mobilizable elements, genomic islands, integrative conjugative elements and group II introns. Additionally, GutMetaNet incorporates automated analyses and visualizations for the HGT events and FR, serving as an efficient platform for in-depth exploration of the interactions among gut microbiome taxa and their implications for human health.

Metagenomic Analysis of Microbial Diversity in the Moroccan Coastal Water of the Gibraltar Strait

Coastal waters are known for higher productivity and organic matter levels, which support a high diversity and abundance of microorganisms compared to some aquatic environments. The characterization of marine microbiomes can provide valuable information for evaluating the sustainability of coastal waters that are increasingly subjected to environmental and human impacts. Our study is the first metagenomic study realized on Moroccan Mediterranean coastal seawater. We analyzed and described the Gibraltar Detroit marine microbiome taxonomic and functional profiling using MG-RAST software. Shotgun sequencing revealed a predominance of bacterial taxa, particularly the Proteobacteria (57.29%) and Bacteroidetes (27.06%) phyla, alongside notable populations of eukaryotes, viruses, and archaea. Alphaproteobacteria and Gammaproteobacteria emerged as the dominant bacterial classes, while Flavobacteria represented a significant portion of Bacteroidetes. Functional profiling of the microbial community highlighted a wide array of metabolic pathways, emphasizing genes related to carbohydrate metabolism, amino acid synthesis, and protein processing. The marine microbiome exhibited essential biogeochemical activities, particularly in nitrogen, sulfur, and carbon cycles, with notable pathways including denitrification, thiosulfate oxidation, and carbon fixation. This functional diversity underlines the microbiome’s role in sustaining ecosystem health through nutrient cycling and organic matter degradation. Our findings offer a crucial baseline for understanding microbial community structure and resilience in Mediterranean coastal ecosystems, with implications for assessing future environmental and anthropogenic impacts on these microbial dynamics.

Early-life gut microbiota assembly patterns are conserved between laboratory and wild mice

Assembly of the mammalian gut microbiota during early life is known to shape key aspects of organismal development, including immunity, metabolism and behaviour. While house mice (Mus musculus) are the major laboratory model organism for gut microbiota research, their artificial lab-based lifestyle could fundamentally alter ecological processes of microbiota assembly and dynamics, in ways that affect their usefulness as a model system. To examine this, here we directly compared patterns of gut microbiota assembly in house mice from the lab and from the wild, making use of a tractable, individually-marked wild population where we could examine patterns of gut microbiota assembly during early life. Despite lab and wild mice harbouring taxonomically distinct communities, we identify striking similarities in multiple patterns of their gut microbiota assembly. Specifically, age-related changes in both alpha and beta diversity, as well as the abundance of predominant phyla and aerotolerance of the microbiota followed parallel trajectories in both settings. These results suggest some degree of intrinsic programme in gut microbiota assembly that transcends variation in taxonomic profiles, and the genetic and environmental background of the host. They further support the notion that despite their artificial environment, lab mice can provide meaningful insights into natural microbiota ecological dynamics in early life and their interplay with host development.

Influence of bisphenol A and its analogues on human gut microbiota composition and metabolic activity: Insights from an in vitro model

Food contamination is a primary route of human exposure to bisphenols (BPs), which are known to affect gut microbiota (GM) and intestinal health. This study comprehensively assessed the impact of bisphenol A (BPA) and three of its substitutes—bisphenol S (BPS), bisphenol F (BPF), and tetramethyl bisphenol F (TMBPF, the monomer of valPure V70) — on the taxonomic and functional profile of human GM using an in vitro model. Human GM was acutely exposed to 1 mM concentrations of these BPs during a 48 h anaerobic cultivation. We first examined the effects of BPA, BPS, BPF, and TMBPF on GM taxonomic and metabolic profiles, mainly focusing on short-chain fatty acids (SCFAs) production. We then evaluated the degradation potential of these BPs by GM and its influence on their estrogenic activity. Finally, we assessed the impact of GM metabolites from BPs-exposed cultures on the viability of intestinal epithelial cells (Caco-2). BPA, BPS, and BPF severely disrupted GM taxonomic composition and metabolite profiles, significantly reducing SCFAs production. In contrast, TMBPF exhibited the least disruptive effects, suggesting it may be a safer alternative. Although the GM did not biotransform the BPs, bioadsorption occurred, with affinity correlating to hydrophobicity in the order of TMBPF > BPA > BPF > BPS. GM reduced the estrogenic activity of BPs primarily through bioadsorption. However, exposure of gut epithelial cells to Post-Culture Supernatants of BPA, BPF, and TMBPF significantly reduced Caco-2 cell viability, indicating the potential formation of harmful GM-derived metabolites and/or a depletion of beneficial GM metabolites.

Microbial diversity and secondary metabolism potential in relation to dark alterations in Paleolithic Lascaux Cave

Tourism in Paleolithic caves can cause an imbalance in cave microbiota and lead to cave wall alterations, such as dark zones. However, the mechanisms driving dark zone formation remain unclear. Using shotgun metagenomics in Lascaux Cave’s Apse and Passage across two years, we tested metabarcoding-derived functional hypotheses regarding microbial diversity and metabolic potential in dark zones vs unmarked surfaces nearby. Taxonomic and functional metagenomic profiles were consistent across years but divergent between cave locations. Aromatic compound degradation genes were prevalent inside and outside dark zones, as expected from past biocide usage. Dark zones exhibited enhanced pigment biosynthesis potential (melanin and carotenoids) and melanin was evidenced chemically, while unmarked surfaces showed genes for antimicrobials production, suggesting that antibiosis might restrict the development of pigmented microorganisms and dark zone extension. Thus, this work revealed key functional microbial traits associated with dark zone formation, which helps understand cave alteration processes under severe anthropization.

Taxonomic and metabolic characterisation of biofilms colonising Roman stuccoes at Baia’s thermal baths and restoration strategies

Stuccoes are very delicate decorative elements of Roman age. Very few of them survived almost intact to present days and, for this reason, they are of great interest to restorers and conservators. In this study, we combined metabarcoding and untargeted metabolomics to characterise the taxonomic and metabolic profiles of the microorganisms forming biofilms on the stuccoes located on the ceiling of the laconicum, a small thermal environment in the archaeological park of Baia (southern Italy). We found that some samples were dominated by bacteria while others by eukaryotes. Additionally, we observed high heterogeneity in the type and abundance of bacterial taxa, while the eukaryotic communities, except in one sample (at prevalence of fungi), were dominated by green algae. The metabolic profiles were comparable across samples, with lipids, lipid-like molecules and carbohydrates accounting for roughly the 50% of metabolites. In vitro and in vivo tests to remove biofilms on stuccoes using essential oils blends were successful at a 50% dilution for one hour and half. This integrative study advanced our knowledge on taxonomic and metabolic profiles of biofilms on ancient stuccoes and highlighted the potential impacts of these techniques in the field of cultural heritage conservation.

Impact of maternal high-fat diet on offspring gut microbiota during short-term high-fat diet exposure in mice.

Alterations in the gut microbiome have been linked to obesity, with maternal high-fat diet (HF) playing a role in shaping offspring microbiome composition. However, the sex-specific responses to maternal HF diet and the impact of subsequent dietary challenges remain unclear. This study investigated the effects of maternal HF diet on offspring gut microbiota structure and predicted functional profile in response to short-term postnatal HF diet exposure with a focus on sex-specific responses. Female and male offspring of maternal control (C) diet or maternal HF diet were weaned onto C diet or HF diet. Offspring were euthanized at 13 weeks of age and cecal contents were collected for bacterial taxonomic profiling. Maternal HF diet reduced α-diversity, notably in male offspring weaned onto HF diet. Sex-specific differences were observed in the gut microbial composition and predicted functional potential. Furthermore, the influence of maternal diet on bacterial community structure and functional potential varied depending on postnatal diet. Maternal HF diet led to increased relative abundance of Corynebacterium in female offspring and decreased abundance of Akkermansia and Roseburia in male offspring. These findings underscore the sexually dimorphic nature of maternal HF diet effects on gut microbiota composition and function, with implications for developmental programming and metabolic health.

The Microbiota of the Outer Gut Mucus Layer of the Migrating Northeast Arctic Cod (Gadus morhua) as Determined by Shotgun DNA Sequencing

Animals form functional units with their microbial communities, termed metaorganisms. Despite extensive research on some model animals, microbial diversity in many species remains unexplored. Here, we describe the taxonomic profile of the microbes from the outer gut mucus layer from the Northeast Arctic cod using a shotgun DNA sequencing approach. We focused on the mucus to determine if its microbial composition differs from that of the fecal microbiota, which could reveal unique microbial interactions and functions. Metagenomes from six individuals were analyzed, revealing three different taxonomic profiles: Type I is dominated in numbers by Pseudomonadaceae (44%) and Xanthomonadaceae (13%), Type II by Vibrionaceae (65%), and Type III by Enterobacteriaceae (76%). This stands in sharp contrast to the bacterial diversity of the transient gut content (i.e., feces). Additionally, binning of assembled reads followed by phylogenomic analyses place a high-completeness bin of Type I within the Pseudomonas fluorescens group, Type II within the Photobacterium phosphoreum clade, and Type III within the Escherichia/Shigella group. In conclusion, we describe the adherent bacterial diversity in the Northeast Arctic cod’s intestine using shotgun sequencing, revealing different taxonomic profiles compared to the more homogenous transient microbiota. This suggests that the intestine contains two separate and distinct microbial populations.

Gut Microbiota Composition Positively Correlates with Sports Performance in Competitive Non-Professional Female and Male Runners

There is still a pressing need for further investigation to bridge the gap in understanding the differences in gut microbiota composition between female runners and their male counterparts. We aimed to determine the gut microbiota composition in competitive non-professional female and male runners and to correlate the gut bacteria to performance. Our study included 40 subjects, of which 22 were runners (13 males and 9 females) and 18 control subjects (9 males and 9 females, representing the general population who perform light physical activity with a weekly running volume of ≤5 km per week). Fecal specimens were collected and analyzed for taxonomic profiling to compare species’ relative abundances between males and females based on the results of 16SrRNA analysis. Bacterial alpha and beta diversity were assessed to determine the differences in microbial composition between runners and controls, and between sexes. Each participant underwent a maximal oxygen consumption test and a time-to-exhaustion test at 85% of the measured VO2max. Blood lactate was collected every 5 min during the tests. Bacterial alpha diversity showed a significant difference (p = 0.04) between runners and controls. Taxonomic analysis of gut microbiota composition showed a lower Enterobacteriaceae abundance and a higher Methanosphaera abundance in runners compared with the control group. Ten different bacteria (Methanosphaera, Mitsuokella, Prevotellaceae, Megamonas, Rothia, Oscillospira, Bacteroides, Odoribacter, Blautia massiliensis, Butyricicoccus_pullicaecorum) were positively correlated with exercise (VO2max, lactate blood levels, time to exhaustion, and weekly training volume). We found no significant differences in the gut microbiota composition between male and female runners. Gut microbiota composition positively correlates with sports performance in competitive non-professional female and male runners, and female runners show similar gut microbiome diversity to male runners.

Antimicrobial potential compounds of sponge associated marine Streptomyces sp.: Isolation, Taxonomy, Fermentation, and Chemical Profiling using UHPLC-QTOF-MS/MS Spectrometry

Antimicrobial potential compounds of sponge associated marine Streptomyces sp.: Isolation, Taxonomy, Fermentation, and Chemical Profiling using UHPLC-QTOF-MS/MS Spectrometry

Insights into the gut microbiome of vitiligo patients from India

BackgroundVitiligo is an autoimmune disease characterized by loss of pigmentation in the skin. It affects 0.4 to 2% of the global population, but the factors that trigger autoimmunity remain elusive. Previous work on several immune-mediated dermatological disorders has illuminated the substantial roles of the gut microbiome in disease pathogenesis. Here, we examined the gut microbiome composition in a cohort of vitiligo patients and healthy controls from India, including patients with a family history of the disease.ResultsOur results show significant alterations in the gut microbiome of vitiligo patients compared to healthy controls, affecting taxonomic and functional profiles as well as community structure. We observed a reduction in the abundance of several bacterial taxa commonly associated with a healthy gut microbiome and noted a decrease in the abundance of SCFA (Short Chain Fatty Acids) producing taxa in the vitiligo group. Observation of a higher abundance of genes linked to bacteria-mediated degradation of intestinal mucus suggested a potential compromise of the gut mucus barrier in vitiligo. Functional analysis also revealed a higher abundance of fatty acid and lipid metabolism-related genes in the vitiligo group. Combined analysis with data from a French cohort of vitiligo also led to the identification of common genera differentiating healthy and gut microbiome across populations.ConclusionOur observations, together with available data, strengthen the role of gut microbiome dysbiosis in symptom exacerbation and possibly pathogenesis in vitiligo. The reported microbiome changes also showed similarities with other autoimmune disorders, suggesting common gut microbiome-mediated mechanisms in autoimmune diseases. Further investigation can lead to the exploration of dietary interventions and probiotics for the management of these conditions.

Gut Microbiome Diversity and Composition in Captive Siberian Tigers (Panthera tigris altaica): The Influence of Diet, Health Status, and Captivity on Microbial Communities

The gut microbiome is essential for the health of carnivorous mammals, including the endangered Siberian tiger (Panthera tigris altaica). However, limited research exists on the gut microbiome of captive Siberian tigers, especially regarding how diet and health status influence microbial diversity. This study addresses this gap by investigating the gut microbiome diversity and composition of six captive-born Siberian tigers housed at the Baekdudaegan National Arboretum in South Korea, using 16S rRNA gene sequencing. The study aimed to examine how diet and health status influence microbial communities, providing baseline data for managing captive tigers. Alpha diversity analysis revealed significant variation in microbial richness and evenness, with Tigers 2 and 6 exhibiting the highest microbial diversity and Tiger 3 the lowest, likely due to its surgical history and limited diet. Beta diversity analysis showed distinct microbial community structures influenced by diet and health. Taxonomic profiling identified Firmicutes and Bacteroidota as the dominant phyla, with Clostridium sensu stricto more prevalent in healthier tigers, while Escherichia-Shigella and Proteobacteria were abundant in tigers with lower diversity, suggesting dysbiosis. Comparisons with other tiger species confirm that diet, health, and captivity significantly shape the gut microbiome. These findings highlight the need for personalized health management in captive environments.

Pharmacognostic, phytochemical and pharmacological activities of Ocimum kilimandscharicum Guerke

The family Lamiaceae encompasses a diverse array of therapeutic plants, with the genus Ocimum being particularly esteemed. The plant known as Kapur Tulsi in India, Ocimum kilimandscharicum Guerke is a perennial woody shrub characterized by its essential oil, which predominantly contains camphor, along with linalool, limonene, eugenol, 1,8-cineole, and camphene. This review aims to provide current information on the taxonomy, botany, distribution, ethnomedicinal uses, phytochemistry, pharmacology, and toxicological profile of O. kilimandscharicum. The information presented was critically analyzed to understand the current research on this species and to explore potential future opportunities for this plant in pharmaceutical research. A comprehensive literature search was conducted and relevant information was collected through an extensive exploration of bibliographic databases, including Google Scholar, ScienceDirect, PubMed, Web of Science, Semantic Scholar, Europe PMC, and Scopus. The literature suggests that the plant contains a range of compounds that underpin its broad spectrum of pharmacological effects. These phytoconstituents have been widely employed in the treatment and management of numerous conditions. This review consolidates the latest information on its phytochemical and pharmacological activities, traditional applications, and scientific research. The review highlights the significant phytoconstituents of Ocimum kilimandscharicum Guerke and summarizes the evidence supporting its pharmacological potential. The findings suggest that the plant's diverse compounds contribute to its extensive use in traditional medicine and underscore its potential for therapeutic applications in various diseases.

Urinary biochemical ecology reveals microbiome-metabolite interactions and metabolic markers of recurrent urinary tract infection.

Recurrent urinary tract infections (rUTIs) are a major clinical challenge in postmenopausal women and their increasing prevalence underscores the need to define interactions between the host and the urinary microbiome that may underlie rUTI susceptibility. A body of work has identified the taxonomic profile of the female urinary microbiome associate with aging, menopause, and urinay disease. However, how this microbial community engages with the host niche, including the local biochemical environment of the urogenital tract, in health and disease is yet to be fully defined. This study directly assesses differences in the biochemical environment of the urine, or biochemical ecology, associated with recurrent urinary tract infection (UTI) and defines a microbe-metabolite association network of the female urinary microbiome. By integrating metagenomic and metabolomic data collected from a controlled cohort of women with rUTI, we find that distinct metabolites, such as methionine sulfoxide (Met-SO) and trimethylamine oxide (TMAO), are associated with differences in urinary microbiome diversity. We observe associations between microbial and biochemical beta diversity and unique metabolic networks of uropathogenic Escherichia coli and uroprotective Lactobacillus species, highlighting potential metabolite-driven ecological shifts that may influence UTI susceptibility. We identify a urinary lipid signature of active rUTI that can accurately distinguish (AUC = 0.987) cases controls. Finally, using time-to-relapse data we identify deoxycholic acid (DCA) as a new prognostic indicator for rUTI recurrence. Together these findings suggest that systemic metabolic processes may influence susceptibility, opening new avenues for therapeutic intervention and the development of more accurate diagnostic and prognostic to improve patient outcomes.

Effect of the 16S rRNA Gene Hypervariable Region on the Microbiome Taxonomic Profile and Diversity in the Endangered Fish Totoaba macdonaldi

Understanding the intricate dynamics of fish microbiota through 16S rRNA amplicon sequencing is pivotal for ecological insights and effective disease management. However, this approach faces challenges including the co-amplification of host mitochondrial sequences and the variability in bacterial composition influenced by the selected 16S rRNA gene regions. To overcome these limitations, we conducted a comprehensive investigation to identify the most suitable 16S rRNA region for bacterial microbial analysis in endangered fish Totoaba macdonaldi, an endemic species of significant ecological and economic importance in Mexico. Targeting four distinct hypervariable regions (V1–V2, V2–V3, V3–V4, and V5–V7) of the 16S rRNA gene, we determined the microbial composition within the distal intestine. A total of 40 microbiomes were sequenced. Our findings underscore the critical impact of region selection on the accuracy of microbiota analysis. The V3–V4 region detected the highest number of bacterial taxa and exhibited significantly higher alpha diversity indices, demonstrating the highest taxonomic resolution. This study emphasizes the necessity of meticulous 16S rRNA region selection for fish microbiota analysis, particularly in native species of ecological and economic significance such as the endangered T. macdonaldi, where information is limited. Such optimization enhances the reliability and applicability of microbiota studies in fisheries management and conservation efforts.

MIIST305 mitigates gastrointestinal acute radiation syndrome injury and ameliorates radiation-induced gut microbiome dysbiosis.

High-dose radiation exposure results in gastrointestinal (GI) acute radiation syndrome identified by the destruction of mucosal layer, intestinal epithelial barrier dysfunction, and aberrant inflammatory responses. In addition, radiation causes gut microbiome dysbiosis characterized by diminished microbial diversity, reduction in the abundance of beneficial commensal bacteria, and the spread of bacterial pathogens that trigger the recruitment of immune cells and the production of pro-inflammatory factors that lead to further GI tissue damage. Currently, there are no FDA- approved countermeasures that can treat radiation-induced GI injury. To meet this critical need, Synedgen Inc ., has developed a glycopolymer radiomitigator (MIIST305) that is specifically targeted to the GI tract which acts by intercalating into the mucus layer and the glycocalyx of intestinal epithelial cells that could potentially ameliorate the deleterious effects of radiation. Male C57BL/6J adult mice were exposed to 13 Gy total body X-irradiation with 5% bone marrow shielding and MIIST305 was administered on days 1, 3, and 5 post-irradiation. Approximately 85% of the animals survived the irradiation exposure and were apparently healthy until the end of the 30-day study period. In contrast, no control, vehicle-treated animals survived past day 10 at this radiation dose. We show that MIIST305 improved intestinal epithelial barrier function and suppressed systemic inflammatory response mediated by radiation-induced pro-inflammatory cytokines. Taxonomic profiling and community structure of the fecal and colonic mucosa microbiota demonstrated that MIIST305 treatment increased microbial diversity and restored abundance of beneficial commensal bacteria, including Lactobacillus and Bifidobacterium genera, while suppressing potentially pathogenic bacteria compared with vehicle-treated animals. In summary, MIIST305 is a novel GI-targeted therapeutic that greatly enhances survival in mice exposed to lethal radiation and protects the GI tract from injury by restoring a balanced gut microbiota and effectively reducing proinflammatory responses. Further development of this drug as an FDA-approved medical countermeasure will be of critical importance in the event of a radiation public health emergency.