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767300.9885Effects of ex situ conservation on diversity and function of the gut microbiota of the Tibetan wild ass (Equus kiang). Ex situ conservation is the main method for the protection of endangered wildlife. To explore the effect of ex situ conservation on the gut microbiota of the kiang (Equus kiang), metagenomic sequencing combined with bioinformatics analysis was used to investigate the composition and function of the gut microbiota of the kiang. The results showed that ex situ conservation not only protected wildlife, but also affected the composition and function of gut microbiota, as well as the health of animals. In the zoo, the ratio of the relative abundance of Firmicutes to that of Bacteroidetes (F/B) is higher, clusters of potentially pathogenic bacteria (such as Catonella, Catonella, and Mycoplasma) are more numerous, the abundance of resistance genes is higher, and the abundance of metabolic functions is increased. The dynamic changes of the gut microbiota also played an important role in the nutritional absorption, energy metabolism, and environmental adaptation of the kiang. Improving the rearing environment and increasing food diversity play important roles for increasing the diversity of gut microbiota, reducing the spread of potentially pathogenic bacteria, and reducing diseases. In the wild, especially in winter and in food-deficient areas, food supplementation can enhance the gut microbial homeostasis of wild animals and reduce the impact of crises. In depth studies of the gut microbial function of wildlife have important implications for improving ex situ conservation.202337231976
767210.9879Multiple micronutrient deficiencies in early life cause multi-kingdom alterations in the gut microbiome and intrinsic antibiotic resistance genes in mice. Globally, ~340 million children suffer from multiple micronutrient deficiencies, accompanied by high pathogenic burden and death due to multidrug-resistant bacteria. The microbiome is a reservoir of antimicrobial resistance (AMR), but the implications of undernutrition on the resistome is unclear. Here we used a postnatal mouse model that is deficient in multiple micronutrients (that is, zinc, folate, iron, vitamin A and vitamin B12 deficient) and shotgun metagenomic sequencing of faecal samples to characterize gut microbiome structure and functional potential, and the resistome. Enterobacteriaceae were enriched in micronutrient-deficient mice compared with mice fed an isocaloric experimental control diet. The mycobiome and virome were also altered with multiple micronutrient deficiencies including increased fungal pathogens such as Candida dubliniensis and bacteriophages. Despite being antibiotic naïve, micronutrient deficiency was associated with increased enrichment of genes and gene networks encoded by pathogenic bacteria that are directly or indirectly associated with intrinsic antibiotic resistance. Bacterial oxidative stress was associated with intrinsic antibiotic resistance in these mice. This analysis reveals multi-kingdom alterations in the gut microbiome as a result of co-occurring multiple micronutrient deficiencies and the implications for antibiotic resistance.202337973864
865820.9876Microplastic exposure reshapes the virome and virus-bacteria networks with implications for immune regulation in Mytilus coruscus. Microplastic pollution has emerged as a critical environmental concern, yet its impacts on host-associated viral communities and immune balance in marine bivalves remain largely unexplored. In this study, Mytilus coruscus individuals were exposed to microplastics in situ for seven days. Virome sequencing and bioinformatic analyses revealed that microplastic exposure induced divergent responses in DNA and RNA viral communities. DNA viromes exhibited suppressed diversity and downregulation of core viral metabolic pathways, potentially reflecting reduced viral replication capacity under host immune stress. In contrast, RNA viromes displayed metabolic activation and functional shifts, including enriched glycan and nucleotide metabolism, possibly linked to enhanced viral activity or immune evasion. Phage-bacteria interaction networks were also restructured, showing increased associations with opportunistic pathogens such as Vibrio cholerae and Enterobacter, potentially affecting immune surveillance. Furthermore, the expression of antibiotic resistance genes (ARGs) in viral genomes was differentially regulated, suggesting pollutant-induced microbial selection that may challenge host immune resilience. These findings suggest that microplastics not only reshape virome composition and metabolic functions but also influence virus-mediated immune interactions, with important implications for disease susceptibility and immune homeostasis in filter-feeding shellfish.202541056669
644830.9875The resistance within: Antibiotic disruption of the gut microbiome and resistome dynamics in infancy. Intestinal host-microbiota interactions during the first year of life are critical for infant development. Early-life antibiotic exposures disrupt stereotypical gut microbiota maturation and adversely affect childhood health. Furthermore, antibiotics increase the abundance of resistant bacteria and enrich the resistome-the compendium of antibiotic resistance genes-within the gut microbiota. Here, we discuss acute and persistent impacts of antibiotic exposure during infancy on pediatric health, the gut microbiome, and, particularly, the resistome. Reviewing our current understanding of antibiotic resistance acquisition and dissemination within and between microbiomes, we highlight open questions, which are imperative to resolve in the face of rising bacterial resistance.202235550670
644240.9874A systematic review of antibiotic resistance driven by metal-based nanoparticles: Mechanisms and a call for risk mitigation. Elevations in antibiotic resistance genes (ARGs) are due not only to the antibiotic burden, but also to numerous environmental pressures (e.g., pesticides, metal ions, or psychotropic pharmaceuticals), which have led to an international public health emergency. Metal-based nanoparticles (MNPs) poison bacteria while propelling nanoresistance at ambient or sub-lethal concentrations, acting as a wide spectrum germicidal agent. Awareness of MNPs driven antibiotic resistance has created a surge of investigation into the molecule mechanisms of evolving and spreading environmental antibiotic resistome. Co-occurrence of MNPs resistance and antibiotic resistance emerge in environmental pathogens and benign microbes may entail a crucial outcome for human health. In this review we expound on the systematic mechanism of ARGs proliferation under the stress of MNPs, including reactive oxygen species (ROS) induced mutation, horizontal gene transfer (HGT) relevant genes regulation, nano-property, quorum sensing, and biofilm formation and highlighting on the momentous contribution of nanoparticle released ion. As antibiotic resistance pattern alteration is closely knit with the mediate activation of nanoparticle in water, soil, manure, or sludge habitats, we have proposed a virulence and evolution based antibiotic resistance risk assessment strategy for MNP contaminated areas and discussed practicable approaches that call for risk management in critical environmental compartments.202438220012
664750.9874Potential Elimination of Human Gut Resistome by Exploiting the Benefits of Functional Foods. Recent advances in technology over the last decades have strived to elucidate the diverse and abundant ecosystem of the human microbiome. The intestinal microbiota represents a densely inhabited environment that offers a plethora of beneficial effects to the host's wellbeing. On the other hand, it can serve as a potential reservoir of Multi-Drug Resistant (MDR) bacteria and their antibiotic-resistant genes (ARgenes), which comprise the "gut resistome." ARgenes, like antibiotics, have been omnipresent in the environment for billions of years. In the context of the gut microbiome, these genes may conflate into exogenous MDR or emerge in commensals due to mutations or gene transfers. It is currently generally accepted that Antimicrobial Resistance (AMR) poses a serious threat to public health worldwide. It is of paramount importance that researchers focus on, amongst other parameters, elaborating strategies to manage the gut resistome, particularly focusing on the diminution of AMR. Potential interventions in the gut microbiome field by Fecal Microbiota Transplant (FMT) or functional foods are newly emerged candidates for the uprooting of MDR strains and restoring dysbiosis and resilience. Probiotic nutrition is thought to diminish gut colonization from pathobionts. Yet only a few studies have explored the effects of antibiotics use on the reservoir of AR genes and the demanding time for return to normal by gut microbiota-targeted strategies. Regular administration of probiotic bacteria has recently been linked to restoration of the gut ecosystem and decrease of the gut resistome and AR genes carriers. This review summarizes the latest information about the intestinal resistome and the intriguing methods of fighting against AMR through probiotic-based methods and gut microbial shifts that have been proposed. This study contains some key messages: (1) AMR currently poses a lethal threat to global health, and it is pivotal for the scientific community to do its utmost in fighting against it; (2) human gut microbiome research, within the last decade especially, seems to be preoccupied with the interface of numerous diseases and identifying a potential target for a variety of interventions; (3) the gut resistome, comprised of AR genesis, presents very early on in life and is prone to shifts due to the use of antibiotics or dietary supplements; and (4) future strategies involving functional foods seem promising for the battle against AMR through intestinal resistome diminution.202032117102
957760.9872Doxycycline post-exposure prophylaxis and off-target antimicrobial resistance: potential amplification within sexual networks. Doxycycline post-exposure prophylaxis (doxyPEP) is now included in many clinical guidelines, yet concerns remain regarding antimicrobial resistance (AMR), particularly off-target effects on commensal bacteria in the oropharynx, with intimate behaviours potentially facilitating resistance transmission within sexual networks.202540830028
642570.9872Freshwater plastisphere: a review on biodiversity, risks, and biodegradation potential with implications for the aquatic ecosystem health. The plastisphere, a unique microbial biofilm community colonizing plastic debris and microplastics (MPs) in aquatic environments, has attracted increasing attention owing to its ecological and public health implications. This review consolidates current state of knowledge on freshwater plastisphere, focussing on its biodiversity, community assembly, and interactions with environmental factors. Current biomolecular approaches revealed a variety of prokaryotic and eukaryotic taxa associated with plastic surfaces. Despite their ecological importance, the presence of potentially pathogenic bacteria and mobile genetic elements (i.e., antibiotic resistance genes) raises concerns for ecosystem and human health. However, the extent of these risks and their implications remain unclear. Advanced sequencing technologies are promising for elucidating the functions of plastisphere, particularly in plastic biodegradation processes. Overall, this review emphasizes the need for comprehensive studies to understand plastisphere dynamics in freshwater and to support effective management strategies to mitigate the impact of plastic pollution on freshwater resources.202438699475
937080.9871'Blooming' in the gut: how dysbiosis might contribute to pathogen evolution. Hundreds of bacterial species make up the mammalian intestinal microbiota. Following perturbations by antibiotics, diet, immune deficiency or infection, this ecosystem can shift to a state of dysbiosis. This can involve overgrowth (blooming) of otherwise under-represented or potentially harmful bacteria (for example, pathobionts). Here, we present evidence suggesting that dysbiosis fuels horizontal gene transfer between members of this ecosystem, facilitating the transfer of virulence and antibiotic resistance genes and thereby promoting pathogen evolution.201323474681
768090.9871Unveiling the Gut Microbiota and Resistome of Wild Cotton Mice, Peromyscus gossypinus, from Heavy Metal- and Radionuclide-Contaminated Sites in the Southeastern United States. The prevalence of antibiotic resistance genes (ARGs) can be driven by direct selection from antibiotic use and indirect selection from substances such as heavy metals (HMs). While significant progress has been made to characterize the influence of HMs on the enrichment and dissemination of ARGs in the environment, there is still much we do not know. To fill this knowledge gap, we present a comprehensive analysis of gut bacteria associated with wild cotton mice (Peromyscus gossypinus) trapped from several areas affected by legacies of HM and radionuclide contamination. We explore how these contaminants affect gut microbial community (GMC) composition and diversity and the enrichment of antibiotic, biocide, and metal resistance genes. Although we were able to identify that a myriad of co-occurring antimicrobial and HM resistance genes appear in mice from all areas, including those without a history of contamination, the proportions of co-occurring ARGs and metal resistance genes (MRGs) are higher in sites with radionuclide contamination. These results support those from several previous studies and enhance our understanding of the coselection process, while providing new insights into the ubiquity of antimicrobial resistance in the resistome of wild animals. IMPORTANCE Antimicrobial resistance is a serious global public health concern because of its prevalence and ubiquitous distribution. The rapid dissemination of antibiotic resistance genes is thought to be the result of the massive overuse of antibiotics in agriculture and therapeutics. However, previous studies have demonstrated that the spread of antibiotic resistance genes can also be influenced by heavy metal contamination. This coselection phenomenon, whereby different resistance determinants are genetically linked on the same genetic element (coresistance) or a single genetic element provides resistance to multiple antimicrobial agents (cross-resistance), has profound clinical and environmental implications. In contrast to antibiotics, heavy metals can persist in the environment as a selection pressure for long periods of time. Thus, it is important to understand how antibiotic resistance genes are distributed in the environment and to what extent heavy metal contaminants may be driving their selection, which we have done in one environmental setting.202134431703
6796100.9870Assessing the pig microbial health impacts of smallholder farming. The livestock industry has long been a hotspot environment for antibiotic resistance genes, with smallholder farming still holding a significant position in pig farming. However, the microbial antibiotic resistance and pathogen risks in pigs under the smallholder farming model remain unclear. We systematically analyzed the antibiotic resistance and microbial composition of pig feces from smallholder and large-scale farming models in Sichuan. The results indicated a lower abundance of antibiotic resistance genes (ARGs) and similar microbial composition in smallholder farming compared to large-scale farming. Beneficial bacteria were more abundant in small-scale farming, whereas large-scale farming exhibited more ARGs, virulence genes, and human pathogenic bacteria (HPBs), including ESBL Escherichia coli strains closely related to human strains, indicating higher zoonotic risk. The findings suggest that smallholder farming presents a relatively better microbial composition and resistance profile, highlighting its advantages over large-scale farming in terms of pig and human health. It is noteworthy that a considerable proportion of HPBs carrying ARGs still exist in the feces from smallholder farming, and given the openness of fecal handling, there remains a high risk of transmitting ARGs and pathogens to humans.202439454358
7674110.9870Insights into gut microbiomes in stem cell transplantation by comprehensive shotgun long-read sequencing. The gut microbiome is a diverse ecosystem, dominated by bacteria; however, fungi, phages/viruses, archaea, and protozoa are also important members of the gut microbiota. Exploration of taxonomic compositions beyond bacteria as well as an understanding of the interaction between the bacteriome with the other members is limited using 16S rDNA sequencing. Here, we developed a pipeline enabling the simultaneous interrogation of the gut microbiome (bacteriome, mycobiome, archaeome, eukaryome, DNA virome) and of antibiotic resistance genes based on optimized long-read shotgun metagenomics protocols and custom bioinformatics. Using our pipeline we investigated the longitudinal composition of the gut microbiome in an exploratory clinical study in patients undergoing allogeneic hematopoietic stem cell transplantation (alloHSCT; n = 31). Pre-transplantation microbiomes exhibited a 3-cluster structure, characterized by Bacteroides spp. /Phocaeicola spp., mixed composition and Enterococcus abundances. We revealed substantial inter-individual and temporal variabilities of microbial domain compositions, human DNA, and antibiotic resistance genes during the course of alloHSCT. Interestingly, viruses and fungi accounted for substantial proportions of microbiome content in individual samples. In the course of HSCT, bacterial strains were stable or newly acquired. Our results demonstrate the disruptive potential of alloHSCTon the gut microbiome and pave the way for future comprehensive microbiome studies based on long-read metagenomics.202438374282
7688120.9869The microbiome of uncontacted Amerindians. Most studies of the human microbiome have focused on westernized people with life-style practices that decrease microbial survival and transmission, or on traditional societies that are currently in transition to westernization. We characterize the fecal, oral, and skin bacterial microbiome and resistome of members of an isolated Yanomami Amerindian village with no documented previous contact with Western people. These Yanomami harbor a microbiome with the highest diversity of bacteria and genetic functions ever reported in a human group. Despite their isolation, presumably for >11,000 years since their ancestors arrived in South America, and no known exposure to antibiotics, they harbor bacteria that carry functional antibiotic resistance (AR) genes, including those that confer resistance to synthetic antibiotics and are syntenic with mobilization elements. These results suggest that westernization significantly affects human microbiome diversity and that functional AR genes appear to be a feature of the human microbiome even in the absence of exposure to commercial antibiotics. AR genes are likely poised for mobilization and enrichment upon exposure to pharmacological levels of antibiotics. Our findings emphasize the need for extensive characterization of the function of the microbiome and resistome in remote nonwesternized populations before globalization of modern practices affects potentially beneficial bacteria harbored in the human body.201526229982
8599130.9869Artificial sweeteners stimulate horizontal transfer of extracellular antibiotic resistance genes through natural transformation. Antimicrobial resistance has emerged as a global threat to human health. Natural transformation is an important pathway for horizontal gene transfer, which facilitates the dissemination of antibiotic resistance genes (ARGs) among bacteria. Although it is suspected that artificial sweeteners could exert antimicrobial effects, little is known whether artificial sweeteners would also affect horizontal transfer of ARGs via transformation. Here we demonstrate that four commonly used artificial sweeteners (saccharin, sucralose, aspartame, and acesulfame potassium) promote transfer of ARGs via natural transformation in Acinetobacter baylyi ADP1, a model organism for studying competence and transformation. Such phenomenon was also found in a Gram-positive human pathogen Bacillus subtilis and mice faecal microbiome. We reveal that exposure to these sweeteners increases cell envelope permeability and results in an upregulation of genes encoding DNA uptake and translocation (Com) machinery. In addition, we find that artificial sweeteners induce an increase in plasmid persistence in transformants. We propose a mathematical model established to predict the long-term effects on transformation dynamics under exposure to these sweeteners. Collectively, our findings offer insights into natural transformation promoted by artificial sweeteners and highlight the need to evaluate these environmental contaminants for their antibiotic-like side effects.202234465899
8666140.9869Decoding the genetic drivers of marine bacterial blooms through comparative genomics. BACKGROUND: While oligotrophic bacteria are known to dominate most marine microbial habitats, under certain conditions, such as during phytoplankton blooms, copiotrophs can dramatically increase in abundance and reach towering proportions of the bacterial communities. We are uncertain whether the bacteria exhibiting this capacity, which we denote as "bloomers," have specific functional characteristics or if, instead, they are randomly selected from the broader pool of copiotrophs. To explore the genomic determinants of this ecological trait, we conducted a comparative genomic analysis of bacterial genomes from microcosm experiments where grazer and viral presence was reduced and nutrient availability was increased, conditions that triggered bacterial blooms. RESULTS: We tested which functional genes were overrepresented in the bacteria that responded to the treatments, examining a total of 305 genomes from isolates and metagenome-assembled genomes (MAGs) that were categorized as copiotrophs or oligotrophs according to their codon usage bias (CUB). The responsive bacteria were enriched in genes related to transcriptional regulation in response to stimuli (mostly via two-component systems), transport, secretion, cell protection, catabolism of sugars and amino acids, and membrane/cell wall biosynthesis. These genes confer on them capabilities for adhesion, biofilm formation, resistance to stress, quorum sensing, chemotaxis, nutrient uptake, and fast replication. They were overrepresented mainly in copiotrophic genomes from the families Alteromonadaceae, Vibrionaceae, Rhodobacteraceae, Sphingomonadaceae, and Flavobacteriaceae. Additionally, we found that these responsive bacteria, when abundant, could affect biogeochemical cycling, particularly the phosphorus cycle. CONCLUSIONS: In this study, we provide insights into the functional characteristics that enable certain bacteria to rapidly respond to changes in the environment and bloom. We also hint at the ecological meaning and implications of these phenomena that could affect biogeochemical cycles in the oceans. Video Abstract.202541029845
8624150.9869Antidepressant drugs promote the spread of broad-host-range plasmid in mouse and human gut microbiota. Antibiotic resistance is a global public health challenge. The gut microbiota serves as a reservoir for antibiotic resistance genes (ARGs), facilitating their transfer between bacteria. With the rising incidence of major depressive disorders (MDD), antidepressant prescriptions have surged. Previous pure-culture studies suggest that antidepressants exhibit antibiotic-like side effects, but their impact on gene transfer in microbial communities remains unclear. Here, we report that clinically relevant doses of antidepressants duloxetine and sertraline enhance the transfer of a broad-host range conjugative plasmid across bacterial phyla from mice gut microbiota. Tests in human gut simulators confirmed that duloxetine facilitates plasmid transfer in human gut microbiota. Mechanistic analyses revealed that antidepressants increase reactive oxygen species levels and alter bacterial cell membrane permeability. Using fluorescence-activated cell sorting and 16S rRNA gene sequencing, we discovered that antidepressants alter plasmid transfer patterns at both phylum and genus levels, driving ARG exchange among opportunistic pathogens. Our findings suggest that antidepressant use may promote the spread of antibiotic resistance between commensal and pathogenic bacteria, raising important public health concerns.202540462285
6461160.9869Implications of indoor microbial ecology and evolution on antibiotic resistance. The indoor environment is an important source of microbial exposures for its human occupants. While we naturally want to favor positive health outcomes, built environment design and operation may counter-intuitively favor negative health outcomes, particularly with regard to antibiotic resistance. Indoor environments contain microbes from both human and non-human origins, providing a unique venue for microbial interactions, including horizontal gene transfer. Furthermore, stressors present in the built environment could favor the exchange of genetic material in general and the retention of antibiotic resistance genes in particular. Intrinsic and acquired antibiotic resistance both pose a potential threat to human health; these phenomena need to be considered and controlled separately. The presence of both environmental and human-associated microbes, along with their associated antibiotic resistance genes, in the face of stressors, including antimicrobial chemicals, creates a unique opportunity for the undesirable spread of antibiotic resistance. In this review, we summarize studies and findings related to various interactions between human-associated bacteria, environmental bacteria, and built environment conditions, and particularly their relation to antibiotic resistance, aiming to guide "healthy" building design.202031591493
6430170.9868Plastic leachate exposure drives antibiotic resistance and virulence in marine bacterial communities. Plastic pollution is a serious global problem, with more than 12 million tonnes of plastic waste entering the oceans every year. Plastic debris can have considerable impacts on microbial community structure and functions in marine environments, and has been associated with an enrichment in pathogenic bacteria and antimicrobial resistance (AMR) genes. However, our understanding of these impacts is largely restricted to microbial assemblages on plastic surfaces. It is therefore unclear whether these effects are driven by the surface properties of plastics, providing an additional niche for certain microbes residing in biofilms, and/or chemicals leached from plastics, the effects of which could extend to surrounding planktonic bacteria. Here, we examine the effects of polyvinyl chloride (PVC) plastic leachate exposure on the relative abundance of genes associated with bacterial pathogenicity and AMR within a seawater microcosm community. We show that PVC leachate, in the absence of plastic surfaces, drives an enrichment in AMR and virulence genes. In particular, leachate exposure significantly enriches AMR genes that confer multidrug, aminoglycoside and peptide antibiotic resistance. Additionally, enrichment of genes involved in the extracellular secretion of virulence proteins was observed among pathogens of marine organisms. This study provides the first evidence that chemicals leached from plastic particles alone can enrich genes related to microbial pathogenesis within a bacterial community, expanding our knowledge of the environmental impacts of plastic pollution with potential consequences for human and ecosystem health.202337019264
8665180.9868A Glyphosate-Based Herbicide Cross-Selects for Antibiotic Resistance Genes in Bacterioplankton Communities. Agrochemicals often contaminate freshwater bodies, affecting microbial communities that underlie aquatic food webs. For example, the herbicide glyphosate has the potential to indirectly select for antibiotic-resistant bacteria. Such cross-selection could occur if the same genes (encoding efflux pumps, for example) confer resistance to both glyphosate and antibiotics. To test for cross-resistance in natural aquatic bacterial communities, we added a glyphosate-based herbicide (GBH) to 1,000-liter mesocosms filled with water from a pristine lake. Over 57 days, we tracked changes in bacterial communities with shotgun metagenomic sequencing and annotated metagenome-assembled genomes (MAGs) for the presence of known antibiotic resistance genes (ARGs), plasmids, and resistance mutations in the enzyme targeted by glyphosate (enolpyruvyl-shikimate-3-phosphate synthase; EPSPS). We found that high doses of GBH significantly increased ARG frequency and selected for multidrug efflux pumps in particular. The relative abundance of MAGs after a high dose of GBH was predictable based on the number of ARGs in their genomes (17% of variation explained) and, to a lesser extent, by resistance mutations in EPSPS. Together, these results indicate that GBHs can cross-select for antibiotic resistance in natural freshwater bacteria. IMPORTANCE Glyphosate-based herbicides (GBHs) such as Roundup formulations may have the unintended consequence of selecting for antibiotic resistance genes (ARGs), as demonstrated in previous experiments. However, the effects of GBHs on ARGs remain unknown in natural aquatic communities, which are often contaminated with pesticides from agricultural runoff. Moreover, the resistance provided by ARGs compared to canonical mutations in the glyphosate target enzyme, EPSPS, remains unclear. Here, we performed a freshwater mesocosm experiment showing that a GBH strongly selects for ARGs, particularly multidrug efflux pumps. These selective effects were evident after just a few days, and the ability of bacteria to survive and thrive after GBH stress was predictable by the number of ARGs in their genomes and, to a lesser extent, by mutations in EPSPS. Intensive GBH application may therefore have the unintended consequence of selecting for ARGs in natural freshwater communities.202235266795
6453190.9868Bacteriophages in sewage: abundance, roles, and applications. The raw sewage that flows through sewage systems contains a complex microbial community whose main source is the human gut microbiome, with bacteriophages being as abundant as bacteria or even more so. Phages that infect common strains of the human gut bacteriome and transient bacterial pathogens have been isolated in raw sewage, as have other phages corresponding to non-sewage inputs. Although human gut phages do not seem to replicate during their transit through the sewers, they predominate at the entrance of wastewater treatment plants, inside which the dominant populations of bacteria and phages undergo a swift change. The sheer abundance of phages in the sewage virome prompts several questions, some of which are addressed in this review. There is growing concern about their potential role in the horizontal transfer of genes, including those related with bacterial pathogenicity and antibiotic resistance. On the other hand, some phages that infect human gut bacteria are being used as indicators of fecal/viral water pollution and as source tracking markers and have been introduced in water quality legislation. Other potential applications of enteric phages to control bacterial pathogens in sewage or undesirable bacteria that impede the efficacy of wastewater treatments, including biofilm formation on membranes, are still being researched.202237332509