Small-quantity lipid-based nutrient supplements (SQ-LNS) have been shown to improve growth, development, and survival among young children in low-resource settings. One hypothesized pathway is through improvements in intestinal health, including modulation of the gut microbiome and reductions in environmental enteric dysfunction (EED). This study examined the effects of SQ-LNS on the gut microbiome and markers of EED and systemic inflammation among young children in Lusaka, Zambia. We conducted intention-to-treat analyses of 302 children aged 27-35 months in a 2x2 cluster-randomized trial. Serum biomarkers of EED (soluble CD14, intestinal fatty acid binding protein) and inflammation (alpha-1-acid glycoprotein, C-reactive protein) were assessed in 240 children via the Multiple-Micronutrient and Environmental Enteric Dysfunction Assessment Tool (MEEDAT). Differences by SQ-LNS assignment were assessed using unadjusted and adjusted ordinary least squares regression models. Rectal swab samples from 299 children underwent 16S rRNA gene sequencing. Taxonomic profiles were visualized using stacked bar plots, alpha diversity was quantified using Shannon diversity indices, and beta diversity was assessed using non-metric multidimensional scaling based on Bray-Curtis dissimilarity matrices. We found that SQ-LNS had no significant effect on EED or inflammation biomarkers and was not associated with differences in gut microbiome alpha diversity, beta diversity, or overall microbial community composition. In exploratory analyses, Enterococcus abundance was lower among children receiving SQ-LNS. Overall, 18 months of SQ-LNS supplementation was not associated with broad changes in intestinal health among young Lusakan children. These findings suggest that the benefits of SQ-LNS operate through pathways other than intestinal health, such as improved nutrient availability.
Sponges, the oldest metazoans on the planet, have an evolutionary history shaped by symbiotic associations with microorganisms. Although well studied in marine sponges, these associations are poorly understood in freshwater species. This study explored the taxonomic diversity and functional potential of the microbiome of the freshwater sponge Metania sp. and its distinction from the surrounding water, using a metagenomic approach. The samples were collected in the Brazilian Cerrado. Taxonomic assignment identified 17 phyla, including bacterial and archaeal, with 19 sequence variants successfully assigned to the species level. Bacteria comprised 16 phyla, with a predominance of Pseudomonadota, Actinomycetota, and Bacteroidota in both microbiomes. The sponge microbiome is distinct from the water microbiome (PERMANOVA; F = 21.6, p = 0.04), sharing only 27% of the identified taxa. Functional prediction resulted in 7,201 KEGG Orthologs (KOs), assigned to 117 significantly enriched metabolic pathways. Although 95 pathways are shared, differential abundance analysis identified 1,024 KOs more abundant in the sponge microbiome and 1,275 in the water. The presence of bacterial defense systems such as CRISPR-Cas in the sponge microbiome suggests a crucial role in protecting against phages while maintaining symbiosis. In contrast, the water microbiota is enriched with pathways linked to environmental adaptation, such as secondary metabolite biosynthesis and pollutant degradation. Although the water microbiome harbored 1.3 times more biosynthetic gene clusters (BGCs), the sponge microbiome also demonstrated biotechnological potential for producing secondary metabolites, especially antimicrobial. These findings demonstrate that the freshwater sponge Metania sp. hosts a complex and functionally specialized microbial community that plays fundamental roles in adaptation, nutrition, and defense, highlighting the critical importance of symbiotic associations for the host.
The gut microbiome of cattle suppresses pathogens and aids host immunity. However, the gut microbiome of newborn calves is still developing; therefore, diarrhea caused by pathogen infection is common. Rapid changes in the gut microbiome due to diarrhea have a significant impact on the health and growth of calves. Until recently, there have been few studies on the changes in the gut microbiome following infection with major digestive pathogens that cause diarrhea in Hanwoo (Korean indigenous cattle) calves. Therefore, this study was conducted to identify viral digestive pathogens that cause severe diarrhea in Hanwoo calves. Seven normal calves without diarrhea and eight calves with diarrhea were selected, and their feces were collected to analyze pathogens and the gut microbiome. Bovine rotavirus (BRV) and bovine coronavirus (BCoV) were detected in the feces of the calves with diarrhea. There was no significant difference in the alpha diversity of the microbiome between normal calves and calves infected with viruses; however, a significant decrease in NPShannon and Shannon indices and a significant increase in Simpson index were observed in calves infected with BRV compared to calves infected with BCoV. In addition, beta diversity of the microbiome differed distinctly between normal calves and calves infected with BRV or BCoV. At the class level, BRV infection increased Gammaproteobacteria and Actinobacteria, whereas BCoV infection increased Clostridia and decreased Bacilli. In addition, the abundance of Lactobacillus was significantly reduced upon infection with BRV and BCoV. In this study, we confirmed the differences in the gut microbiome based on viral pathogens causing diarrhea in Hanwoo calves. The results of pathogen-targeting research are expected to be helpful in preventing common pathogens in calves.
Microbiome research is a dynamic, rapidly growing, and interdisciplinary field that generates valuable insights across the human health, agricultural, and environmental sectors. Despite this growth, gaps remain in educational content and professional development opportunities specifically tailored for microbiome science rather than traditional microbiology. The National Microbiome Data Collaborative (NMDC) has developed a Microbiome Science Certificate Program aimed at undergraduates but available to any learner or researcher interested in this field. The curriculum includes 12 modules to further technical knowledge, as well as practical and professional skills. The modules each include prepared slide decks, recorded lectures, resource documents, expert interviews, reading assignments, knowledge assessments, and an overall glossary. The modular content can be readily applied within the classroom as a stand-alone semester-long course or as supplementary to existing curricula. An asynchronous, online, certificate-granting implementation of the content is available through the American Society for Microbiology. We have outlined future laboratory, workforce development, and data science "mini-modules" that can be further developed with the help of educators. Improvements will be made to the program content based on feedback from learners and educators. This program aims to promote practical skills to empower the next generation of microbiome researchers.
In hydroponic horticulture, where soil is replaced by a sterile artificial substrate, attention to microorganisms is primarily focused on the suppression of plant pathogens and the application of potentially beneficial organisms. This study examined the ecology of the root microbiome of tomato plants which were grown to maturity in a hydroponic rockwool system and then treated with a Trichoderma-based biocontrol product. The bacterial community was species-rich but was dominated by a small number of Alphaproteobacteria, Gammaproteobacteria and Bacteroidia species. The fungal community was less diverse and consisted almost exclusively of Ascomycota and Rozellomycota species. Biocontrol treatment did not have a significant effect on bacterial diversity, but the microbiome composition changed distinctly over the period of sampling in both treated and untreated plants. These results support the view that mineral substrates in a hydroponic system can support a complex and resilient root microbiome. Understanding the microorganisms that thrive in this unique environment may help identify effective biological treatments, and enable the development of rockwool-specific practices for monitoring, protecting and promoting plant health.
How do some human infants adapt to environmental challenges while others do not? We examined whether infant behavioral responses to maternal unpredictability predict early inhibitory control and are linked to gut microbial community composition and neuroactive metabolic potential. Maternal unpredictability, quantified as the entropy of sensory signal transitions during mother-infant interaction (N = 255; 2-6 months), predicted poorer infant inhibitory control at 19-28 months. However, infants who exhibited high visual orienting behavior (VOB) under high unpredictability showed later inhibitory control comparable to infants exposed to low unpredictability, suggesting an adaptive behavioral buffering strategy. In a subset of infants (n = 87), we tested whether infant age, sex, delivery mode, feeding, maternal education, and maternal unpredictability explained variation in gut microbial community diversity. Only feeding status and VOB were significantly associated with both taxonomic and functional microbial profiles. VOB was associated with taxonomic and functional variation along a Bifidobacterium breve and Bifidobacterium longum axis and enrichment of microbial tryptophan and glutamate synthesis genes. Although feeding groups differed in alpha diversity, VOB was not associated with feeding status, suggesting that feeding is not the primary driver of the observed VOB-microbiome signatures. Interaction models of neuroactive gene functions revealed that microbial signatures vary across combinations of VOB and maternal unpredictability, suggesting that the microbial support for deploying visual attentional strategies differs under distinct levels of environmental unpredictability. Together, these findings support a framework in which infant behavioral strategy is associated with variation in gut microbial composition and metabolic gene potential.
To investigate whether secondhand smoke (SHS) exposure alters the ocular surface microbiome (OSM) in children and to explore potential functional consequences. 432 children aged 3-18 years were enrolled, including 111 SHS-exposed and 321 unexposed controls. Conjunctival swabs were collected and analyzed by 16S rRNA gene sequencing targeting the V3-V4 region. Sequencing data were processed with Qiime2 and DADA2, and taxonomic classification was based on the SILVA 138 database. Alpha diversity and beta diversity were compared using t-tests and PERMANOVA. Differentially abundant taxa were identified using LEfSe, and predicted functional pathways were analyzed using PICRUSt2 with MetaCyc and KEGG annotation. SHS-exposed children showed significantly altered alpha diversity (Chao1, Shannon, Simpson) and distinct beta diversity compared with controls. LEfSe analysis revealed enrichment of several phyla and genera, including Lactobacillus and Rubellimicrobium in controls, with no taxa enriched in SHS-exposed children. Functional prediction showed enrichment of metabolism pathways such as L-methionine salvage, biphenyl, heparin, and toluene degradation and immune-related pathways, including complement activation, T and B cell receptor signaling, MAPK, and TGF-beta pathways. SHS exposure in children is associated with significant alterations in ocular surface microbial diversity, community structure, and predicted functional pathways related to environmental stress and immune signaling. These findings highlight the sensitivity of the pediatric OSM to SHS exposure and underscore the importance of minimizing environmental tobacco smoke to protect children's ocular health.
Antimicrobial resistance (AMR) is a One Health challenge driven by clinical antibiotic use and environmental processes that shape microbial selection and genetic exchanges. Nature-based solutions (NbS), particularly constructed wetlands, are increasingly used to remove complex contaminant mixtures from aquatic systems. Although these systems often achieve considerable efficiencies, their effects on AMR dynamics remain unclear. This review synthesizes evidence on how aquatic rhizospheres function as microbiome-associated ecological reactors, in which contaminant mixtures, redox gradients and microbial interactions jointly influence resistance. We show that wetlands can function along a continuum between antimicrobial resistance attenuation, persistence, and dissemination, depending on the design, operation, and ecological context. Importantly, the removal of bioactive compounds does not necessarily translate to a reduced resistance risk, as selective pressures may persist within biofilms, sediments, and plant-associated compartments. We propose a microbiome-informed conceptual framework for interpreting AMR in nature-based systems. This perspective identifies potentially modifiable leverage points for understanding, interpreting, and potentially mitigating resistance-related risks and underscores the need for monitoring and risk assessment strategies that extend beyond conventional chemical metrics and incorporate the One Health exposure pathways. Together, these insights reposition wetlands as conditional solutions, whose sustainability depends on explicitly addressing antimicrobial resistance, alongside contaminant removal.
Phosphorus (P) utilization is a complex trait influenced by numerous genetic variants. The jejunum is the primary site of P absorption in poultry. Therefore, identifying the genetics that regulate transcription in jejunum may help uncover key regulators of P homeostasis. We performed a genome-wide association study using the expression of jejunal mucosa transcripts (88 miRNAs, 65 mRNAs). These transcripts were selected from our previous studies due to their association with P utilization and related pathways. In total, the trial comprised 400 laying hens from two high-yielding strains, Lohmann Brown (LB) and Lohmann Selected Leghorn (LSL), fed a diet lacking mineral P supplements and exogenous microbial phytase to stimulate adaptive mechanisms. In total, 114 miR-eQTLs (microRNA expression quantitative trait loci) were detected at a false discovery rate (FDR) of less than 5%, including 56 miR-eQTLs in the LB strain and 58 miR-eQTLs in the LSL strain. Lohmann Brown contained 23 cis and 35 trans loci, with the most significant cis-eQTL targeting miR-146b. In the LSL strain, a cis-eQTL cluster for miR-203a was present on chromosome 5. Similarly, 123 mRNA-eQTLs (94 in LB and 29 in LSL) were identified at the 5% FDR threshold. The genetic regulation of key genes involved in mineral binding and mineral transport, including CALB1 and SLC34A2, in LB hens was predominantly driven by strong cis-eQTL. In contrast, gene expression in LSL hens was largely modulated by trans-eQTLs, with CALM1 being the only gene under significant cis-regulation. Furthermore, correlation analysis with the gut microbiome revealed that the expression of cis-regulated CALB1 is significantly positively associated with the abundance of Lactobacillus species. Our findings reveal that LB and LSL hens exhibit distinct genetic architectures contributing to maintain mineral homeostasis. Genetic differences between the two strains influence the transcriptional response of key mineral transporter genes and miRNAs under a low-P diet. These divergent host genetic strategies are also associated with distinct gut microbiota profiles, highlighting interactions between host genetics, gene expression, and the microbiome in P utilization.
Environmental pollution resulting from heavy metals constitutes a critical global issue. Remediation technologies offer potential solutions, particularly through the innovative use of endophytic microbes, either independently or in conjunction with plants. This solution is based on the ability of certain endophytic bacteria to produce metallophores, which are low-molecular-weight compounds capable of chelating various heavy metals. This study investigates ten bacterial endophytes isolated from the medicinal plant Galium aparine L. belonging to the Bacillus, Priestia, and Peribacillus genera. We tested different media to efficiently induce their production and assessed their ability to chelate various heavy metals, including highly toxic Pb2+, Cd2+ and Hg2+. Moreover, we examined in detail of their metallophore gene clusters, their organization, diversity and prevalence, by broad homology search. All strains exhibited moderate to high metallophore production ability, with few strains capable of chelating more metals than iron. Among them, Priestia sp. GS2 was identified as promising producer, reaching up to 60% SU, with binding activity also towards Co2+, Mn2+, Zn2+, Ni2+ or Cu2+. Also, Peribacillus frigoritolerans GR2 exhibits a remarkable ability to chelate Pb2+, Hg2+ and Cd2+. An in-depth analysis of the biosynthetic gene clusters and enzymes involved in metallophore biosynthesis revealed homologous clusters within previously deposited genomes, highlighting their distribution and potential evolutionary conservation. The strains demonstrated capacity for metallophore production and heavy metal chelation, which makes them promising candidates for the development of advanced microbial solutions. A genome-guided selection approach can guide the selection of strains for agricultural applications, where they enhance plant nutrient uptake, suppress soil pathogens, and support sustainable fertilization strategies beyond sequestering crucial metals. Apart from agriculture, purified metallophores can aid bioremediation and mobilization of heavy metals from various environments and matrices.
Living entities, inlcuding laboratory animals, are composed of the host and its associated microbial communities and defined as holobionts. The host genotype and its microbiome drive together as a metagenome, the holobiont phenotype, with the microbiome itself as a well-recognized source of phenotypic variation. Multiple environmental (diet, light/dark cycles, etc.) as well as host-related factors (genotype, maternal effect, etc.) not only influence the animal experimental phenotype but also contribute to the shaping of the microbiome, raising the question of whether the microbiome of experimental animals represents an extrinsic, intrinsic, or intermediate influence. Currently, there is sufficient evidence that microbial communities at different body sites are shaped by distinct endogenous and exogenous factors, indicating that the host does not leave its microbial status to chance but instead actively modulates it through host-specific mechanisms, despite extrinsic influences. This leads to a microbiome that reflects a 'fingerprint' of its own endogenous and exogenous influences. This suggests that the microbiome of experimental animals is an intermediate factor with both intrinsic and extrinsic components and underscores the importance of refining the selection of the appropriate metagenome for each specific rodent experiment.
Silkworm (Bombyx mori) excrement accumulates in large quantities and causes severe environmental pollution, with highly crystalline cellulose limiting efficient resource utilization. The development of effective cellulose-degrading bacterial technologies is crucial for advancing biotechnological applications. This study investigated the effects of exogenous microbial agents and housefly larvae composting on cellulose biodegradation in silkworm excrement. After six days, the cellulose content decreased by 52.6%, 58.2%, and 64.0% in the treatment groups, respectively, which was significantly greater than the 39.41% reduction in the control group without exogenous agents. The combination of exogenous microbial agents and housefly larvae reshaped the bacterial community, increasing the relative abundance of cellulose-degrading taxa. Specifically, Firmicutes and Actinobacteria were enriched, and the abundances of Bacillus, Pseudomonas, and Cellulosimicrobium increased. Functional predictions via PICRUSt indicated that carbohydrate metabolism was predicted to dominate bacterial activity, while Tax4Fun analysis suggested that exogenous agents were associated with increased predicted abundances of endo-β-1,4-glucanase and exo-β-1,4-glucanase genes in excrement, which may relate to accelerated cellulose degradation. This study suggests that the combination of exogenous microbial agents and housefly larvae could promote cellulose-degrading bacterial populations and the genetic potential for cellulase activity, representing a possible strategy for silkworm excrement bioconversion.
The oral microbiome has been shown to be associated with respiratory health, primarily in adult case studies or among children. This relationship has been scarcely investigated in adult population-based cohorts. To investigate the association between oral microbiome and respiratory health, more specifically asthma, chronic rhinosinusitis (CRS), lung function and fractional exhaled nitric oxide (FeNO) in a population-based cross-continental multicentre study among adults. Subgingival samples from 355 adult European Community Respiratory Health Survey participants from Norway, Australia and Estonia underwent metagenomic sequencing. Respiratory disease was defined from questionnaires and sensitisation from specific immunoglobulin E (IgE)/skin prick tests. Spirometry and FeNO were measured. The associations between alpha diversity and disease status were evaluated in cross-sectional analyses using logistic regression adjusting for sex, smoking and study centre. Differential abundance analyses were performed using analysis of compositions of microbiomes with bias correction. Alpha diversity differed by study centre and sensitisation status and was associated with non-allergic CRS (richness: 1.12, 95% CI 1.03 to 1.22). A similar though not statistically significant pattern was seen for forced vital capacity (FVC) below the lower limit of normal (LLN). Lachnospiraceae and Xanthomonas were more abundant in the oral microbiome of non-asthmatics and individuals without CRS, respectively, as compared with asthmatics and CRS patients. Several functional genes (1477-3391) and genera (54-98) were only present in the non-case groups, whereas individuals with affected respiratory health had 0-74 unique functional genes, but no unique genera present only in their respective groups. Increased alpha diversity was associated with non-allergic CRS and a similar trend was seen for FVC below LLN. Bacterial composition and functional profiles of the oral microbiome differed by respiratory health status. This study is novel in exploring functional gene profiling in relation to asthma and FeNO.
Cryospheric ecosystems in the high Arctic harbor largely unexplored microbiomes with significant biotechnological potential. The present study evaluates the biohydrogen production capabilities of the indigenous microbiome of Ny-Ålesund, Svalbard, using glacial ice and surface water samples. Dark fermentation batch assays were performed at 4 °C and 20 °C with 2-bromoethanesulfonate (BES), a methanogenic inhibitor, to track the succession of metabolic and taxonomic diversity. Metagenomic and functional analyses revealed that under 20 °C and BES conditions, psychrotolerant microbial communities maximize biohydrogen production to 85% of the total biogas produced, with an acetate-dominant fermentation pathway, as inferred from volatile fatty acid (VFA) analysis. This evolves into a highly coordinated system utilizing a coupled Rnf-nitrogenase route alongside Formate Hydrogenlyase and [FeFe]-hydrogenase pathways. Kinetic modelling using the Modified Gompertz equation, along with Q10 temperature-sensitivity indices, demonstrated a very high latent catalytic potential in these cold-adapted microbiomes. This study indicates that Arctic microbiomes are highly elastic thermodynamically and could serve as highly efficient, manipulatable biocatalysts for the environmental recovery of bioenergy through engineered low-temperature systems.
The human gut microbiome represents a dynamic microbial ecosystem profoundly influencing host physiology, immune development, and disease susceptibility. While metagenomic approaches have advanced our understanding of microbial composition and functional potential, they remain insufficient to capture the real-time molecular events governing host‒microbe interactions. Taxonomic abundance and genomic content alone do not reflect active gene expression or phenotypic output, and functional roles cannot be reliably inferred from phylogenetic identity, given the substantial heterogeneity observed even within species. Central to bridging this gap is the concept of bacterial functional plasticity, with a focus on phase-mediated functional plasticity, the intrinsic capacity of microbes to rapidly remodel their activity and phenotype in response to environmental and host-derived cues. This review highlights phase variation as a prominent and evolutionarily conserved mechanism underlying plasticity, encompassing DNA inversions, short-sequence repeat modifications, and broader structural genomic variation. Emerging evidence demonstrates not only the prevalence of phase-variable mechanisms across diverse gut taxa but also their significant regulatory, ecological, and immunological consequences. These findings reframe the microbiome from a static consortium of species to a functionally dynamic system capable of rapid rewiring in response to environmental pressures. By integrating genomic, ecological, and host-response data, this review lays the groundwork for mechanistic frameworks that could explain how flexible microbial strategies influence bacterial behavior and host outcomes. Moving beyond cataloging microbial composition toward deciphering the logic of functional adaptation will be essential for translating microbiome research into predictive, diagnostic, and therapeutic applications.
Extreme environments such as acid mine drainage (AMD) host highly specialized microbial communities that drive profound biogeochemical cycles. Within these ecosystems, iron- and sulfur-metabolizing taxa catalyze mineral weathering, generating intense acidity and mobilizing heavy metals. However, more than 97% of these microorganisms remain uncultured "microbial dark matter," heavily restricting our understanding of extremophile metabolism and adaptation. Here we present the Microbial Biobank of AMD (mbAMD), a culturomics-derived collection of 652 isolates spanning 42 species-including 21 novel taxa-that achieves 86.7% coverage of the global AMD core microbiome. Functional validation demonstrates that 36 of these taxa possess active iron or sulfur metabolic capacities, including the discovery of the first pure cultures of acid-tolerant sulfate reducers. Comparative genomic analyses across these isolates reveal that extreme environmental adaptation is predominantly driven by pervasive horizontal gene transfer. Specifically, extremophiles preferentially acquire adaptive genes governing acid tolerance and metal resistance from phylogenetically proximal relatives rather than distant donors. These findings elucidate the modular evolutionary strategies of extremophiles and provide critical functional resources for advancing biohydrometallurgy and environmental bioremediation. This mbAMD resource will accelerate biohydrometallurgical process optimization and environmental bioremediation strategies while advancing evolutionary microbial ecology research.
The gut microbiota plays a critical role in mammalian health, yet remains poorly understood in wild Asian elephants (Elephas maximus). This study characterized the gut microbiome of wild elephants using 16S rRNA sequencing of fecal samples collected from five natural habitats in Thailand: Doi Pha Mueang Wildlife Sanctuary (DPM), Khao Ang Rue Nai Wildlife Sanctuary (KARN), Khao Yai National Park (KY), Phuluang Wildlife Sanctuary (PL), and Sublangka Wildlife Sanctuary (SLK), representing distinct geographic regions. Across all sites, Thai wild elephants shared a core gut microbiota dominated by fiber-degrading bacteria. Firmicutes was the most abundant phylum, followed by Bacteroidota, Actinobacteriota, and Proteobacteria. At the family level, Lachnospiraceae predominated, followed by Oscillospiraceae, Anaerovoracaceae, and Christensenellaceae. Environmental variable, including geographic coordinates and minimum elevation, significantly influenced microbial community composition and explained patterns of beta diversity, indicating distinct gut microbiota profiles among elephant populations from different forest regions. These findings establish baseline gut microbiome data for wild Asian elephants and provide a foundation for future ecological and conservation-focused microbiome studies.
The gut microbiome undergoes natural selection pressure, likely because it can affect infection resistance by stimulating natural antibody (NAb) production, notably against the glycan Galα1-3Galβ1-4GlcNAc-R (α-Gal). In our study, we explored whether particular glycans, such as α-Gal, from specific host microbiota components could trigger NAbs that, once ingested by Ixodes ricinus ticks during the blood meal, are capable of cross-reacting with bacterial strains in the tick microbiota that share these glycans. Such interactions might alter the tick microbiota and reduce Borrelia afzelii colonization in ticks. When mice were orally administered various Escherichia coli strains, it triggered the stimulation of NAbs and resulted in strain-specific alterations in the tick microbiota. These changes effectively decreased Borrelia colonization in the tick vector. Additionally, vaccination with the glycan α-Gal induced notable shifts in the tick microbiota and similarly reduced Borrelia colonization. Reduced Borrelia colonization was associated with shifts in bacterial diversity, abundance, and microbial network properties. The study provides evidence that natural mechanisms, such as the production of NAb in response to the host gut microbiome, can modulate the microbiota of disease vectors and reduce pathogen colonization within the vector. These findings offer new insights into potential strategies for reducing the transmission of vector-borne diseases through modulation of the host gut microbiome.
Non-biting synanthropic flies from the order Diptera have long been implicated as mechanical vectors to several human and animal pathogens, yet their microbiome variations across different regions remain poorly understood. Here, we compared the abundance of gut microbial composition in four species (Chrysomya megacephala, Lucilia cuprina, Musca domestica, and Physiphora clausa of non-biting synanthropic flies from two countries (The Gambia and China), providing insights into the potential pathogenic bacterial taxa they harbor. This study was conducted in Kanifing Municipal Council, The Gambia, and Changsha city, China, with sampling occurring between August and November 2023. Illumina NovaSeq6000 sequencing was used to amplify the V3-V4 region of the 16S rDNA from the midgut of these flies, which were pooled (n = 20 per sample) into 21 samples comprising Chrysomya megacephala, Lucilia cuprina, Musca domestica (from both cities), and Physiphora clausa (from KMC). Alpha and beta diversity indices were used to compare bacterial composition in the midguts of these flies. All bioinformatics and statistical analyses were performed using the BMKCloud online platform (http://www.biocloud.net). Taxonomic classification was annotated into 2 kingdoms, 44 phyla, and 2,379 species. Proteobacteria (41.14%) and Firmicutes (39.51%) dominated across all the samples. Significant geographic differences were observed. Shannon Alpha diversity analyses differed significantly between countries (P = 0.023), and Bray-Curtis-based PERMANOVA confirmed distinct bacterial compositions (R²=0.201, P = 0.001). Gambian flies harbored more Wohlfahrtiimonas chitiniclastica (13.79%), while Changsha samples contained higher Pseudomonas (3.99%). To the best of our knowledge, this is the first description of the gut microbiome of P. clausa, which was dominated by Corynebacterium (15.82%). These geographic and species-specific patterns highlight flies as reservoirs for regionally relevant pathogens. This study highlights the geographic variability in gut microbiota of non-biting synanthropic flies as potential carriers of regionally relevant bacterial taxa and motivates further investigation into fly-borne pathogen transmission in both regions. This study also provides, to the best of our knowledge, the first description of the gut microbiome of P. clausa.
Ulcerative colitis (UC) is a chronic, relapsing, immune-mediated inflammatory disease of the colonic mucosa that imposes a substantial and growing global health burden. The pathophysiological basis of UC encompasses a multifactorial interplay among genetic predisposition, dysregulated innate and adaptive immune responses, gut microbiome dysbiosis, epithelial barrier dysfunction, and environmental triggers. Despite considerable advances in therapeutic strategies over the past two decades ranging from aminosalicylates and corticosteroids to biologic agents targeting TNF-α, integrins, and the IL-12/23 axis, as well as small molecule modulators such as JAK inhibitors and sphingosine-1-phosphate receptor agonists-a substantial proportion of patients either fail to achieve remission or experience loss of response over time, underscoring the continued need for novel therapeutic approaches. This comprehensive review systematically addresses the definition, epidemiology, socioeconomic burden, and unmet clinical needs in UC. The molecular and cellular underpinnings of the disease are discussed in depth, including the roles of key signaling pathways, pattern recognition receptors, cytokine networks, and the gut-immune interface. Clinical features, diagnostic criteria, endoscopic and histological scoring systems, and validated disease activity indices are also described. Current pharmacological therapies are reviewed with regard to mechanisms of action, pivotal clinical trial data, and safety profiles. Emerging investigational strategies including precision biologic agents, next-generation small molecules, microbiome-based therapeutics, and cell and gene therapy approaches are evaluated within a translational framework. A curated synthesis of experimental models of UC induction in rodents is presented, followed by structured tabular summaries of selected naturally derived bioactive compounds and pharmacological drug candidates that have demonstrated protective efficacy in preclinical models of UC. Compounds were selected for tabular inclusion on the basis of three prespecified criteria: (i) availability of at least one peer-reviewed in vivo study conducted in a validated experimental colitis model (DSS, TNBS, and acetic acid); (ii) a clearly described and mechanistically plausible basis of action relevant to UC pathophysiology; and (iii) representation across the principal mechanistic clusters identified in this review. Application of these criteria to the studies included in the final review yielded 29 naturally derived bioactive compounds (Table 1) and 26 pharmacological drug candidates (Table 2) for structured synthesis.