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Antibiotic resistance genes (ARGs) are widespread among bacteria. However, not all ARGs pose serious threats to public health, highlighting the importance of identifying those that are high-risk. Here, we developed an ‘omics-based’ framework to evaluate ARG risk considering human-associated-enrichment, gene mobility, and host pathogenicity. Our framework classifies human-associated, mobile ARGs (3.6% of all ARGs) as the highest risk, which we further differentiate as ‘current threats’ (Rank I; 3%) - already present among pathogens - and ‘future threats’ (Rank II; 0.6%) - novel resistance emerging from non-pathogens. Our framework identified 73 ‘current threat’ ARG families. Of these, 35 were among the 37 high-risk ARGs proposed by the World Health Organization and other literature; the remaining 38 were significantly enriched in hospital plasmids. By evaluating all pathogen genomes released since framework construction, we confirmed that ARGs that recently transferred into pathogens were significantly enriched in Rank II (‘future threats’). Lastly, we applied the framework to gut microbiome genomes from fecal microbiota transplantation donors. We found that although ARGs were widespread (73% of genomes), only 8.9% of genomes contained high-risk ARGs. Our framework provides an easy-to-implement approach to identify current and future antimicrobial resistance threats, with potential clinical applications including reducing risk of microbiome-based interventions. Antibiotic resistance genes are common but not all are of high risk to human health. Here, the authors develop an omics-based framework for ranking genes by risk that incorporates level of enrichment in human associated environments, gene mobility, and host pathogenicity.

Phase variation, the reversible alternation between genetic states, enables infection by pathogens and colonization by commensals. However, the diversity of phase variation remains underexplored. We developed the PhaseFinder algorithm to quantify DNA inversion–mediated phase variation. A systematic search of 54,875 bacterial genomes identified 4686 intergenic invertible DNA regions (invertons), revealing an enrichment in host-associated bacteria. Invertons containing promoters often regulate extracellular products, underscoring the importance of surface diversity for gut colonization. We found invertons containing promoters regulating antibiotic resistance genes that shift to the ON orientation after antibiotic treatment in human metagenomic data and in vitro, thereby mitigating the cost of antibiotic resistance. We observed that the orientations of some invertons diverge after fecal microbiota transplant, potentially as a result of individual-specific selective forces.

The Asiatic fruit fly Drosophila suzukii has recently invaded Europe and North and South America, causing severe damage to fruit production systems. Although agronomic host plants of that fly are now well documented, little is known about the suitability of wild and ornamental hosts in its exotic area. In order to study the potential trophic niche of D. suzukii with relation to fruit characteristics, fleshy fruits from 67 plant species were sampled in natural and anthropic ecosystems (forests, hedgerows, grasslands, coastal areas, gardens and urban areas) of the north of France and submitted to experimental infestations. A set of fruit traits (structure, colour, shape, skin texture, diameter and weight, phenology) potentially interacting with oviposition choices and development success of D. suzukii was measured. Almost half of the tested plant species belonging to 17 plant families allowed the full development of D. suzukii. This suggests that the extreme polyphagy of the fly and the very large reservoir of hosts producing fruits all year round ensure temporal continuity in resource availability and contribute to the persistence and the exceptional invasion success of D. suzukii in natural habitats and neighbouring cultivated systems. Nevertheless, this very plastic trophic niche is not systematically beneficial to the fly. Some of the tested plants attractive to D. suzukii gravid females stimulate oviposition but do not allow full larval development. Planted near sensitive crops, these \"trap plants\" may attract and lure D. suzukii, therefore contributing to the control of the invasive fly.

Wastewater surveillance represents a complementary approach to clinical surveillance to measure the presence and prevalence of emerging infectious diseases like the novel coronavirus SARS-CoV-2. This innovative data source can improve the precision of epidemiological modeling to understand the penetrance of SARS-CoV-2 in specific vulnerable communities. Here, we tested wastewater collected at a major urban treatment facility in Massachusetts and detected SARS-CoV-2 RNA from the N gene at significant titers (57 to 303 copies per ml of sewage) in the period from 18 to 25 March 2020 using RT-qPCR. We validated detection of SARS-CoV-2 by Sanger sequencing the PCR product from the S gene. Viral titers observed were significantly higher than expected based on clinically confirmed cases in Massachusetts as of 25 March. Our approach is scalable and may be useful in modeling the SARS-CoV-2 pandemic and future outbreaks.IMPORTANCE Wastewater-based surveillance is a promising approach for proactive outbreak monitoring. SARS-CoV-2 is shed in stool early in the clinical course and infects a large asymptomatic population, making it an ideal target for wastewater-based monitoring. In this study, we develop a laboratory protocol to quantify viral titers in raw sewage via qPCR analysis and validate results with sequencing analysis. Our results suggest that the number of positive cases estimated from wastewater viral titers is orders of magnitude greater than the number of confirmed clinical cases and therefore may significantly impact efforts to understand the case fatality rate and progression of disease. These data may help inform decisions surrounding the advancement or scale-back of social distancing and quarantine efforts based on dynamic wastewater catchment-level estimations of prevalence.Wastewater surveillance represents a complementary approach to clinical surveillance to measure the presence and prevalence of emerging infectious diseases like the novel coronavirus SARS-CoV-2. This innovative data source can improve the precision of epidemiological modeling to understand the penetrance of SARS-CoV-2 in specific vulnerable communities. Here, we tested wastewater collected at a major urban treatment facility in Massachusetts and detected SARS-CoV-2 RNA from the N gene at significant titers (57 to 303 copies per ml of sewage) in the period from 18 to 25 March 2020 using RT-qPCR. We validated detection of SARS-CoV-2 by Sanger sequencing the PCR product from the S gene. Viral titers observed were significantly higher than expected based on clinically confirmed cases in Massachusetts as of 25 March. Our approach is scalable and may be useful in modeling the SARS-CoV-2 pandemic and future outbreaks.IMPORTANCE Wastewater-based surveillance is a promising approach for proactive outbreak monitoring. SARS-CoV-2 is shed in stool early in the clinical course and infects a large asymptomatic population, making it an ideal target for wastewater-based monitoring. In this study, we develop a laboratory protocol to quantify viral titers in raw sewage via qPCR analysis and validate results with sequencing analysis. Our results suggest that the number of positive cases estimated from wastewater viral titers is orders of magnitude greater than the number of confirmed clinical cases and therefore may significantly impact efforts to understand the case fatality rate and progression of disease. These data may help inform decisions surrounding the advancement or scale-back of social distancing and quarantine efforts based on dynamic wastewater catchment-level estimations of prevalence.

Antimicrobial resistance (AMR) poses a significant threat to global health. The indiscriminate use of antibiotics has accelerated the emergence and spread of drug-resistant bacteria, compromising our ability to treat infectious diseases. A One Health approach is essential to address this urgent issue, recognizing the interconnectedness of human, animal, and environmental health. This study investigated the prevalence and transmission of AMR in a temporary settlement in Kathmandu, Nepal. By employing shotgun metagenomics, we analyzed a diverse range of samples, including human fecal samples, avian fecal samples, and environmental samples. Our analysis revealed a complex interplay of pathogenic bacteria, virulence factors (VF), and antimicrobial resistance genes (ARGs) across these different domains. We identified a diverse range of bacterial species, including potential pathogens, in both human and animal samples. Notably, Prevotella spp. was the dominant gut bacterium in human samples. Additionally, we detected a wide range of phages and viruses, including Stx-2 converting phages, which can contribute to the virulence of Shiga toxin-producing E. coli (STEC) strains. Our analysis revealed the presence of 72 virulence factor genes and 53 ARG subtypes across the studied samples. Poultry samples exhibited the highest number of ARG subtypes, suggesting that the intensive use of antibiotics in poultry production may contribute to the dissemination of AMR. Furthermore, we observed frequent horizontal gene transfer (HGT) events, with gut microbiomes serving as key reservoirs for ARGs. This study underscores the critical role of a One Health approach in addressing AMR. By integrating human, animal, and environmental health perspectives, we can better understand the complex dynamics of AMR and develop effective strategies for prevention and control. Our findings highlight the urgent need for robust surveillance systems, judicious antibiotic use, and improved hygiene practices to mitigate the impact of AMR on public health.

There is increasing evidence of distinct gut microbiome compositions between populations living industrialized and non-industrialized lifestyles worldwide. However, whether populations of Malaysia exhibit variations in their microbiome, and to what extent host lifestyle correlates with these variations, remains unclear. Malaysia’s extensive geographical and sociocultural diversity provides a unique opportunity to explore how lifestyle and environmental exposures are associated with the human gut microbiome. Here, we characterized the gut microbiome of three populations in peninsular Malaysia, each representing different lifestyle contexts, and identified host factors associated with microbiome variation. Our findings suggest that lifestyle-related factors are strongly associated with differences in microbial community composition across populations. In particular, urban and rural individuals harbor gut microbiota with distinct community structures. We further identified specific taxa as potential microbial signatures of host lifestyle, with the genera Prevotella and Cryptobacteroides enriched in rural populations, while Phocaeicola, Vescimonas, and Megasphaera were more prevalent among urban individuals. In addition to lifestyle, demographic factors such as age, sex, and BMI were also associated with variation in the gut microbiome. This study highlights the influence of urbanization, lifestyle, and diet on the gut microbiome landscape of Malaysian populations and underscores the importance of considering sociocultural context in future microbiome research.

The transition from a rural or non-industrialized lifestyle to urbanization and industrialization has been linked to changes in the structure and function of the human gut microbiome. Understanding how the gut microbiomes changes over time is crucial to define healthy states and to grasp how the gut microbiome interacts with the host environment. Here, we investigate the temporal dynamics of gut microbiomes from an urban and non-industrialized population in the Amazon, as well as metagenomic data sets from urban United States and rural Tanzania. We showed that healthy non-industrialized microbiomes experience greater compositional shifts over time compared to industrialized individuals. Furthermore, bacterial strain populations are more frequently replaced in non-industrialized microbiomes, and most non-synonymous mutations accumulate in genes associated with the degradation of host dietary components. This indicates that microbiome stability is affected by transitions to industrialization, and that strain tracking can elucidate the ecological dynamics behind such transitions.

Urban populations from highly industrialized countries are characterized by a lower gut bacterial diversity as well as by changes in composition compared to rural populations from less industrialized countries. to unveil the mechanisms and factors leading to this diversity loss, it is necessary to identify the factors associated with urbanization-induced shifts at a smaller geographical scale, especially in less industrialized countries. to do so, we investigated potential associations between a variety of dietary, medical, parasitological and socio-cultural factors and the gut and saliva microbiomes of 147 individuals from three populations along an urbanization gradient in cameroon. We found that the presence of Entamoeba sp., a commensal gut protozoan, followed by stool consistency, were major determinants of the gut microbiome diversity and composition. interestingly, urban individuals have retained most of their gut eukaryotic and bacterial diversity despite significant changes in diet compared to the rural areas, suggesting that the loss of bacterial microbiome diversity observed in industrialized areas is likely associated with medication. finally, we observed a weak positive correlation between the gut and the saliva microbiome diversity and composition, even though the saliva microbiome is mainly shaped by habitat-related factors.

Crohn's disease (CD) is a clinical subset of inflammatory bowel disease that is characterized by patchy transmural inflammation across the gastrointestinal tract. Although the exact etiology remains unknown, recent findings suggest that it is a complex multifactorial disease with contributions from the host genetics and environmental factors such as the microbiome. We have previously shown that the T cell repertoire of individuals with CD harbors a group of highly expanded T cells which hints toward an antigen-mediated pathology. We simultaneously profiled the αβ and γδ T cell repertoire in addition to the B cell repertoire of both the blood and the colonic mucosa of 27 treatment-naïve individuals with CD and 27 age-matched symptomatic controls. Regardless of disease status, we observed multiple physiological differences between the immune repertoire of blood and colonic mucosa. Additionally, by comparing the repertoire of individuals with CD relative to controls, we observed different alterations that were only detected in the blood or colonic mucosa. These include a depletion of mucosal-associated invariant T (MAIT) cells and an expansion of clonotypes in the blood repertoire of individuals with CD. Also, a significant depletion of multiple and clonotypes in the blood and gut IGH repertoire of individuals with CD. Our findings highlight the importance of studying the immune repertoire in a tissue-specific manner and the need to profile the T and B cell immune repertoire of gut tissues as not all disease-induced alterations will be detected in the blood.

Crosstalk of microbes with human gut epithelia and immune cells is crucial for gut health. However, there is no existing system for a long-term co-culture of human innate immune cells with epithelium and oxygen-intolerant commensal microbes, hindering the understanding of microbe-immune interactions in a controlled manner. Here, we established a gut epithelium-microbe-immune (GuMI) microphysiological system to maintain the long-term continuous co-culture of Faecalibacterium prausnitzii/Faecalibacterium duncaniae with colonic epithelium, antigen-presenting cells (APCs, herein dendritic cells and macrophages), and CD4+ naive T cells circulating underneath the colonic epithelium. In GuMI-APC condition, multiplex cytokine assays suggested that APCs contribute to the elevated level of cytokines and chemokines secreted into both apical and basolateral compartments compared to GuMI condition that lacks APC. In GuMI-APC with F. prausnitzii (GuMI-APC-FP), F. prausnitzii increased the transcription of pro-inflammatory genes such as toll-like receptor 1 (TLR1) and interferon alpha 1 (IFNA1) in the colonic epithelium, without a significant effect on cytokine secretion, compared to the GuMI-APC without bacteria (GuMI-APC-NB). In contrast, in the presence of CD4+ naive T cells (GuMI-APCT-FP), TLR1, IFNA1, and IDO1 transcription levels decreased with a simultaneous increase in F. prausnitzii-induced secretion of pro-inflammatory cytokines (e.g., IL8) compared to GuMI-APC-FP that lacks T cells. These results highlight the contribution of individual innate immune cells in regulating the immune response triggered by the gut commensal F. prausnitzii. The integration of defined populations of immune cells in the gut microphysiological system demonstrated the usefulness of GuMI physiomimetic platform to study microbe-epithelial-immune interactions in healthy and disease conditions.