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Individuals who are minoritized as a result of race, sexual identity, gender, or socioeconomic status experience a higher prevalence of many diseases. Understanding the biological processes that cause and maintain these socially driven health inequities is essential for addressing them. The gut microbiome is strongly shaped by host environments and affects host metabolic, immune, and neuroendocrine functions, making it an important pathway by which differences in experiences caused by social, political, and economic forces could contribute to health inequities. Nevertheless, few studies have directly integrated the gut microbiome into investigations of health inequities. Here, we argue that accounting for host-gut microbe interactions will improve understanding and management of health inequities, and that health policy must begin to consider the microbiome as an important pathway linking environments to population health.
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Microbioma Gastrointestinal , Disparidades nos Níveis de Saúde , Doença , Saúde , Humanos , Saúde Mental , PublicaçõesRESUMO
This essay, written by a biologist, a microbial ecologist, a biological anthropologist, and an anthropologist-historian, examines tensions and translations in microbiome research on animals in the laboratory and field. The authors trace how research questions and findings in the laboratory are extrapolated into the field and vice versa, and the shifting evidentiary standards that these research settings require. Showing how complexities of microbiomes challenge traditional standards of causation, the authors contend that these challenges require new approaches to inferences used in ecology, anthropology, and history. As social scientists incorporate investigations of microbial life into their human studies, microbiome researchers venture into field settings to develop mechanistic understandings about the functions of complex microbial communities. These efforts generate new possibilities for cross-fertilizations and inference frameworks to interpret microbiome findings. Microbiome research should integrate multiple scales, levels of variability, and other disciplinary approaches to tackle questions spanning conditions from the laboratory to the field.
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Pesquisa Interdisciplinar , Microbiota/fisiologia , Animais , Ecologia , Interações entre Hospedeiro e Microrganismos , Humanos , Modelos AnimaisRESUMO
Long-term dietary intake influences the structure and activity of the trillions of microorganisms residing in the human gut, but it remains unclear how rapidly and reproducibly the human gut microbiome responds to short-term macronutrient change. Here we show that the short-term consumption of diets composed entirely of animal or plant products alters microbial community structure and overwhelms inter-individual differences in microbial gene expression. The animal-based diet increased the abundance of bile-tolerant microorganisms (Alistipes, Bilophila and Bacteroides) and decreased the levels of Firmicutes that metabolize dietary plant polysaccharides (Roseburia, Eubacterium rectale and Ruminococcus bromii). Microbial activity mirrored differences between herbivorous and carnivorous mammals, reflecting trade-offs between carbohydrate and protein fermentation. Foodborne microbes from both diets transiently colonized the gut, including bacteria, fungi and even viruses. Finally, increases in the abundance and activity of Bilophila wadsworthia on the animal-based diet support a link between dietary fat, bile acids and the outgrowth of microorganisms capable of triggering inflammatory bowel disease. In concert, these results demonstrate that the gut microbiome can rapidly respond to altered diet, potentially facilitating the diversity of human dietary lifestyles.
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Bactérias/genética , Bactérias/isolamento & purificação , Dieta , Trato Gastrointestinal/microbiologia , Metagenoma , Microbiota , Adulto , Bactérias/efeitos dos fármacos , Bacteroides/efeitos dos fármacos , Bacteroides/genética , Bacteroides/isolamento & purificação , Ácidos e Sais Biliares/análise , Ácidos e Sais Biliares/metabolismo , Bilophila/efeitos dos fármacos , Bilophila/genética , Bilophila/isolamento & purificação , Carnivoridade , Dieta/efeitos adversos , Dieta Vegetariana , Gorduras na Dieta/efeitos adversos , Gorduras na Dieta/farmacologia , Fezes/química , Fezes/microbiologia , Feminino , Fermentação/efeitos dos fármacos , Microbiologia de Alimentos , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/virologia , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Herbivoria , Humanos , Doenças Inflamatórias Intestinais/microbiologia , Masculino , Metagenoma/efeitos dos fármacos , Metagenoma/genética , Microbiota/efeitos dos fármacos , Microbiota/genética , Fatores de Tempo , Adulto JovemRESUMO
Systemic infection induces conserved physiological responses that include both resistance and 'tolerance of infection' mechanisms. Temporary anorexia associated with an infection is often beneficial, reallocating energy from food foraging towards resistance to infection or depriving pathogens of nutrients. However, it imposes a stress on intestinal commensals, as they also experience reduced substrate availability; this affects host fitness owing to the loss of caloric intake and colonization resistance (protection from additional infections). We hypothesized that the host might utilize internal resources to support the gut microbiota during the acute phase of the disease. Here we show that systemic exposure to Toll-like receptor (TLR) ligands causes rapid α(1,2)-fucosylation of small intestine epithelial cells (IECs) in mice, which requires the sensing of TLR agonists, as well as the production of interleukin (IL)-23 by dendritic cells, activation of innate lymphoid cells and expression of fucosyltransferase 2 (Fut2) by IL-22-stimulated IECs. Fucosylated proteins are shed into the lumen and fucose is liberated and metabolized by the gut microbiota, as shown by reporter bacteria and community-wide analysis of microbial gene expression. Fucose affects the expression of microbial metabolic pathways and reduces the expression of bacterial virulence genes. It also improves host tolerance of the mild pathogen Citrobacter rodentium. Thus, rapid IEC fucosylation appears to be a protective mechanism that utilizes the host's resources to maintain host-microbial interactions during pathogen-induced stress.
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Doença , Epitélio/metabolismo , Epitélio/microbiologia , Fucose/metabolismo , Intestino Delgado/metabolismo , Intestino Delgado/microbiologia , Simbiose , Animais , Anorexia/complicações , Anorexia/microbiologia , Bactérias/genética , Bactérias/metabolismo , Bactérias/patogenicidade , Citrobacter rodentium/imunologia , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Ingestão de Alimentos , Ácidos Graxos/química , Ácidos Graxos/metabolismo , Feminino , Fucosiltransferases/metabolismo , Regulação Bacteriana da Expressão Gênica , Glicosilação , Tolerância Imunológica , Imunidade Inata , Interleucinas/biossíntese , Interleucinas/imunologia , Ligantes , Masculino , Redes e Vias Metabólicas/genética , Camundongos , Microbiota/fisiologia , Fatores de Proteção , Receptores Toll-Like/agonistas , Receptores Toll-Like/imunologia , Receptores Toll-Like/metabolismo , Fatores de Virulência/genética , Interleucina 22 , Galactosídeo 2-alfa-L-FucosiltransferaseRESUMO
The human gut is an extremely active immunological site interfacing with the densest microbial community known to colonize the human body, the gut microbiota. Despite tremendous advances in our comprehension of how the gut microbiota is involved in human health and interacts with the mammalian immune system, most studies are incomplete as they typically do not consider bacteriophages. These bacterial viruses are estimated to be as numerous as their bacterial hosts, with tremendous and mostly uncharacterized genetic diversity. In addition, bacteriophages are not passive members of the gut microbiota, as highlighted by the recent evidence for their active involvement in human health. Yet, how bacteriophages interact with their bacterial hosts and the immune system in the human gut remains poorly described. Here, we aim to fill this gap by providing an overview of bacteriophage communities in the gut during human development, detailing recent findings for their bacterial-mediated effects on the immune response and summarizing the latest evidence for direct interactions between them and the immune system. The dramatic increase in antibiotic-resistant bacterial pathogens has spurred a renewed interest in using bacteriophages for therapy, despite the many unknowns about bacteriophages in the human body. Going forward, more studies encompassing the communities of bacteria, bacteriophages, and the immune system in diverse health and disease settings will provide invaluable insight into this dynamic trio essential for human health.
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Bacteriófagos/imunologia , Animais , Bactérias/metabolismo , Bactérias/virologia , Bacteriófagos/patogenicidade , Bacteriófagos/fisiologia , Microbioma Gastrointestinal/fisiologia , Humanos , Sistema Imunitário/metabolismo , MicrobiotaRESUMO
There is rapidly growing awareness of microbiome assembly and function in early-life gut health. Although many factors, such as antibiotic use and highly processed diets, impinge on this process, most research has focused on people residing in high-income countries. However, much of the world's population lives in low- and middle-income countries (LMICs), where, in addition to erratic antibiotic use and suboptimal diets, these groups experience unique challenges. Indeed, many children in LMICs are infected with intestinal helminths. Although helminth infections are strongly associated with diverse developmental co-morbidities and induce profound microbiome changes, few studies have directly examined whether intersecting pathways between these components of the holobiont shape health outcomes in early life. Here, we summarize microbial colonization within the first years of human life, how helminth-mediated changes to the gut microbiome may affect postnatal growth, and why more research on this relationship may improve health across the lifespan.
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Microbioma Gastrointestinal , Helmintíase , Helmintos , Animais , Humanos , Lactente , Helmintíase/microbiologia , Helmintos/fisiologia , Enteropatias ParasitáriasRESUMO
The composition of the intestinal bacterial community is well described, but recent research suggests that the metabolism of these bacteria plays a larger role in health than which species are present. One fundamental aspect of gut bacterial metabolism that remains understudied is bacterial replication. Indeed, there exist few techniques which can identify actively replicating gut bacteria. In this study, we aimed to address this gap by adapting 5-ethynyl-2'-deoxyuridine (EdU) click chemistry (EdU-click), a metabolic labeling method, coupled with fluorescence-activated cell sorting and sequencing (FACS-Seq) to characterize replicating gut bacteria. We first used EdU-click with human gut bacterial isolates and show that many of them are amenable to this technique. We then optimized EdU-click and FACS-Seq for murine fecal bacteria and reveal that Prevotella UCG-001 and Ileibacterium are enriched in the replicating fraction. Finally, we labeled the actively replicating murine gut bacteria during exposure to cell wall-specific antibiotics in vitro. We show that regardless of the antibiotic used, the actively replicating bacteria largely consist of Ileibacterium, suggesting the resistance of this taxon to perturbations. Overall, we demonstrate how combining EdU-click and FACSeq can identify the actively replicating gut bacteria and their link with the composition of the whole community in both homeostatic and perturbed conditions. This technique will be instrumental in elucidating in situ bacterial replication dynamics in a variety of other ecological states, including colonization and species invasion, as well as for investigating the relationship between the replication and abundance of bacteria in complex communities.
The bacteria that live in our guts are known to influence our intestinal and overall health. Though we know a lot about which kinds of bacteria are in our guts, we still don't know much about which bacteria are actually alive and growing. This is important to know, because bacteria that are growing, or replicating, are more likely to impact our health than bacteria which are not replicating. Our research group aimed to address this issue by developing a new technique that can identify which gut bacteria are actively replicating. We first tested this technique on specific gut bacteria, and then we made sure the technique worked when it was used on the gut bacteria of mice. By using this technique, we identified several types of mouse gut bacteria that were actively replicating. We also demonstrated one possible application of this technique by using it to identify mouse gut bacteria that were able to replicate after they were grown with antibiotics. Overall, we have introduced a new technique to identify replicating gut bacteria and show how it can be used to increase our knowledge on which bacteria are growing in the gut. This technique will help us identify which bacteria may be more important to our health due to their active growth.
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Química Click , Microbioma Gastrointestinal , Humanos , Camundongos , Animais , Química Click/métodos , Desoxiuridina/química , Desoxiuridina/metabolismo , Bactérias/metabolismoRESUMO
Bacteriophages, viruses specific to bacteria, coexist with their bacterial hosts with limited diversity fluctuations in the guts of healthy individuals where they replicate mostly via lysogenic replication. This favors 'piggy-back-the-winner' over 'kill-the-winner' dynamics which are driven by lytic bacteriophage replication. Revisiting the deep-viral sequencing data of a healthy individual sampled over 2.4 years, we explore how these dynamics occur. Prophages found in assembled bacterial metagenomes were also found extra-cellularly, as induced phage particles (iPPs), likely derived from prophage activation. These iPPs were diverse and continually present in low abundance, relative to the highly abundant but less diverse lytic phage population. The continuous detection of low levels of iPPs suggests that spontaneous induction regularly occurs in this healthy individual, possibly allowing prophages to maintain their ability to replicate and avoiding degradation and loss from the gut microbiota.
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The composition and metabolism of the human gut microbiota are strongly influenced by dietary complex glycans, which cause downstream effects on the physiology and health of hosts. Despite recent advances in our understanding of glycan metabolism by human gut bacteria, we still need methods to link glycans to their consuming bacteria. Here, we use a functional assay to identify and isolate gut bacteria from healthy human volunteers that take up different glycans. The method combines metabolic labeling using fluorescent oligosaccharides with fluorescence-activated cell sorting (FACS), followed by amplicon sequencing or culturomics. Our results demonstrate metabolic labeling in various taxa, such as Prevotella copri, Collinsella aerofaciens and Blautia wexlerae. In vitro validation confirms the ability of most, but not all, labeled species to consume the glycan of interest for growth. In parallel, we show that glycan consumers spanning three major phyla can be isolated from cultures of sorted labeled cells. By linking bacteria to the glycans they consume, this approach increases our basic understanding of glycan metabolism by gut bacteria. Going forward, it could be used to provide insight into the mechanism of prebiotic approaches, where glycans are used to manipulate the gut microbiota composition.
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Microbioma Gastrointestinal , Humanos , Microbioma Gastrointestinal/fisiologia , Citometria de Fluxo , Polissacarídeos/metabolismo , Prebióticos , Oligossacarídeos , Carboidratos da Dieta/metabolismoRESUMO
In vitro fermentation systems allow for the investigation of gut microbial communities with precise control of various physiological parameters while decoupling confounding factors from the human host. Current systems, such as the SHIME and Robogut, are large in footprint, lack multiplexing, and have low experimental throughput. Alternatives which address these shortcomings, such as the Mini Bioreactor Array system, are often reliant on expensive specialized equipment, which hinders wide replication across labs. Here, we present the Mini Colon Model (MiCoMo), a low-cost, benchtop multi-bioreactor system that simulates the human colon environment with physiologically relevant conditions. The device consists of triplicate bioreactors working independently of an anaerobic chamber and equipped with automated pH, temperature, and fluidic control. We conducted 14-d experiments and found that MiCoMo was able to support a stable complex microbiota community with a Shannon Index of 3.17 ± 0.65, from individual fecal samples after only 3-5 d of inoculation. MiCoMo also retained inter-sample microbial differences by developing closely related communities unique to each donor, while maintaining both minimal variations between replicate reactors (average Bray-Curtis similarity 0.72 ± 0.13) andday-to-day variations (average Bray-Curtis similarity 0.81±0.10) after this short stabilization period. Together, these results establish MiCoMo as an accessible system for studying gut microbial communities with high throughput and multiplexing capabilities.
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Microbioma Gastrointestinal , Microbiota , Reatores Biológicos , Colo , Fezes , Humanos , RNA Ribossômico 16SRESUMO
In the original publication [...].
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BACKGROUND: Inflammatory bowel diseases (IBDs) including Crohn's disease (CD) and ulcerative colitis (UC) are characterized by chronic and debilitating gut inflammation. Altered bacterial communities of the intestine are strongly associated with IBD initiation and progression. The gut virome, which is primarily composed of bacterial viruses (bacteriophages, phages), is thought to be an important factor regulating and shaping microbial communities in the gut. While alterations in the gut virome have been observed in IBD patients, the contribution of these viruses to alterations in the bacterial community and heightened inflammatory responses associated with IBD patients remains largely unknown. RESULTS: Here, we performed in vivo microbial cross-infection experiments to follow the effects of fecal virus-like particles (VLPs) isolated from UC patients and healthy controls on bacterial diversity and severity of experimental colitis in human microbiota-associated (HMA) mice. Shotgun metagenomics confirmed that several phages were transferred to HMA mice, resulting in treatment-specific alterations in the gut virome. VLPs from healthy and UC patients also shifted gut bacterial diversity of these mice, an effect that was amplified during experimental colitis. VLPs isolated from UC patients specifically altered the relative abundance of several bacterial taxa previously implicated in IBD progression. Additionally, UC VLP administration heightened colitis severity in HMA mice, as indicated by shortened colon length and increased pro-inflammatory cytokine production. Importantly, this effect was dependent on intact VLPs. CONCLUSIONS: Our findings build on recent literature indicating that phages are dynamic regulators of bacterial communities in the gut and implicate the intestinal virome in modulating intestinal inflammation and disease. Video Abstract.
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Bacteriófagos , Colite Ulcerativa , Colite , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Animais , Bactérias/genética , Bacteriófagos/genética , Colite/terapia , Colite Ulcerativa/microbiologia , Colite Ulcerativa/terapia , Inflamação , Doenças Inflamatórias Intestinais/microbiologia , CamundongosRESUMO
Culture studies of phage-host systems have shown that phage proliferation strongly depends on the physiological state of the host, but it is still unclear to what extent this holds true within aquatic ecosystems. We used a combination of flow sorting and electron microscopy to explore how the frequency of bacterial cells with attached viruses (FCAV), of visibly infected cells, and the number of intracellular viruses are distributed within five physiologic categories: cells with high (HNA) and low (LNA) nucleic acid content, with a compromised membrane, in division, and with an intact-looking morphology. FCAV was not different between the cellular physiologic categories, suggesting low influence of host physiology on viral adsorption. Infected cells were found within all the physiologic categories, besides the dividing cells, but showed different levels of new virion production, with the abundance of intracellular viruses ranked as follows: HNA > intact-looking cells > LNA > compromised membrane cells. These results favor the physiological control hypothesis of viral progeny production. The calculation of viral production rate of the HNA and LNA cells show that viral infection of HNA cells likely accounts for the majority of viral production. It also show that cells considered as less active can still act as resources for phages, although they contain much less intracellular phage particles.
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Bactérias/virologia , Bacteriófagos/fisiologia , Microbiologia da Água , Adsorção , Bactérias/citologia , Bactérias/ultraestrutura , Membrana Celular/ultraestrutura , Água Doce/microbiologia , Água Doce/virologia , Ácidos Nucleicos/análise , Água do Mar/microbiologia , Água do Mar/virologia , Vírion/fisiologia , Ligação ViralRESUMO
Introduction: Bacteriophage plaque enumeration is a critical step in a wide array of protocols. The current gold standard for plaque enumeration on Petri dishes is through manual counting. However, this approach is not only time-consuming and prone to human error but also limited to Petri dishes with countable number of plaques resulting in low throughput. Materials and Methods: We present OnePetri, a collection of trained machine learning models and open-source mobile application for the rapid enumeration of bacteriophage plaques on circular Petri dishes. Results: When compared against the current gold standard of manual counting, OnePetri was â¼30 × faster. Compared against other similar tools, OnePetri had lower relative error (â¼13%) than Plaque Size Tool (PST) (â¼86%) and CFU.AI (â¼19%), while also having significantly reduced detection times over PST (1.7 × faster). Conclusions: The OnePetri application is a user-friendly platform that can rapidly enumerate phage plaques on circular Petri dishes with high precision and recall.
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The human gut virome has become increasingly associated with health and disease. In this issue of Cell Host & Microbe, Mangalea et al. (2021) find differences in viromes of individuals at risk for rheumatoid arthritis (RA), suggesting that phages may play a role in RA and provide a path for biomarker development.
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Artrite Reumatoide , Bacteriófagos , HumanosRESUMO
While the diversity of the human gut microbiota is becoming increasingly well characterized, bacterial physiology is still a critical missing link in understanding how the gut microbiota may be implicated in disease. The current best practice for studying bacterial physiology involves the immediate storage of fecal samples in an anaerobic chamber. This reliance on immediate access to anaerobic chambers greatly limits the scope of sample populations that can be studied. Here, we assess the effects of short-term oxygen exposure on gut bacterial physiology and diversity. We use relative nucleic acid content and membrane integrity as markers of bacterial physiology, and 16S rRNA gene amplicon sequencing to measure bacterial diversity. Samples were stored for up to 6 h in either ambient conditions or in anoxic environments created with gas packs or in an anaerobic chamber. Our data indicate that AnaeroGen sachets preserve bacterial membrane integrity and nucleic acid content over the course of 6 h similar to storage in an anaerobic chamber. Short-term oxygen exposure increases bacterial membrane permeability, without exceeding inter-individual differences. As oxygen exposure remains an important experimental consideration for bacterial metabolism, our data suggest that AnaeroGen sachets are a valid alternative limiting loss of membrane integrity for short-term storage of samples from harder-to-access populations.
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Changes in bacterial diversity in the human gut have been associated with many conditions, despite not always reflecting changes in bacterial activity. Methods linking bacterial identity to function are needed for improved understanding of how bacterial communities adapt and respond to their environment, including the gut. Here, we optimized bioorthogonal non-canonical amino acid tagging (BONCAT) for the gut microbiota and combined it with fluorescently activated cell sorting and sequencing (FACS-Seq) to identify the translationally active members of the community. We then used this novel technique to compare with other bulk community measurements of activity and viability: relative nucleic acid content and membrane damage. The translationally active bacteria represent about half of the gut microbiota, and are not distinct from the whole community. The high nucleic acid content bacteria also represent half of the gut microbiota, but are distinct from the whole community and correlate with the damaged subset. Perturbing the community with xenobiotics previously shown to alter bacterial activity but not diversity resulted in stronger changes in the distinct physiological fractions than in the whole community. BONCAT is a suitable method to probe the translationally active members of the gut microbiota, and combined with FACS-Seq, allows for their identification. The high nucleic acid content bacteria are not necessarily the protein-producing bacteria in the community; thus, further work is needed to understand the relationship between nucleic acid content and bacterial metabolism in the human gut. Considering physiologically distinct subsets of the gut microbiota may be more informative than whole-community profiling.
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Aminoácidos/metabolismo , Bactérias/metabolismo , Microbioma Gastrointestinal , Ácidos Nucleicos/metabolismo , Biossíntese de Proteínas , Bactérias/classificação , Fenômenos Fisiológicos Bacterianos , Biodiversidade , DNA Bacteriano , Fezes/microbiologia , Citometria de Fluxo/métodos , Humanos , RNA Ribossômico 16S , Análise de Sequência de DNA , Análise de Célula ÚnicaRESUMO
Many bacteria carry bacteriophages (bacterial viruses) integrated in their genomes in the form of prophages, which replicate passively alongside their bacterial host. Environmental conditions can lead to prophage induction; the switching from prophage replication to lytic replication, that results in new bacteriophage progeny and the lysis of the bacterial host. Despite their abundance in the gut, little is known about what could be inducing these prophages. We show that several medications, at concentrations predicted in the gut, lead to prophage induction of bacterial isolates from the human gut. We tested five medication classes (non-steroidal anti-inflammatory, chemotherapy, mild analgesic, cardiac, and antibiotic) for antimicrobial activity against eight prophage-carrying human gut bacterial representative isolates in vitro. Seven out of eight bacteria showed signs of growth inhibition in response to at least one medication. All medications led to growth inhibition of at least one bacterial isolate. Prophage induction was confirmed in half of the treatments showing antimicrobial activity. Unlike antibiotics, host-targeted medications led to a species-specific induction of Clostridium beijerinckii, Bacteroides caccae, and to a lesser extent Bacteroides eggerthii. These results show how common medication consumption can lead to phage-mediated effects, which in turn would alter the human gut microbiome through increased prophage induction.
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Bactérias/crescimento & desenvolvimento , Bactérias/virologia , Bacteriófagos/crescimento & desenvolvimento , Lisogenia/efeitos dos fármacos , Preparações Farmacêuticas/administração & dosagem , Ativação Viral/efeitos dos fármacos , Bactérias/efeitos dos fármacos , Bactérias/genética , Bacteriófagos/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , HumanosRESUMO
Antibiotic resistance causes around 700,000 deaths a year worldwide. Without immediate action, we are fast approaching a post-antibiotic era in which common infections can result in death. Pseudomonas aeruginosa is the leading cause of nosocomial infection and is also one of the three bacterial pathogens in the WHO list of priority bacteria for developing new antibiotics against. A viable alternative to antibiotics is to use phages, which are bacterial viruses. Yet, the isolation of phages that efficiently kill their target bacteria has proven difficult. Using a combination of phages and antibiotics might increase treatment efficacy and prevent the development of resistance against phages and/or antibiotics, as evidenced by previous studies. Here, in vitro populations of a Pseudomonas aeruginosa strain isolated from a burn patient were treated with a single phage, a mixture of two phages (used simultaneously and sequentially), and the combination of phages and antibiotics (at sub-minimum inhibitory concentration (MIC) and MIC levels). In addition, we tested the stability of these phages at different temperatures, pH values, and in two burn ointments. Our results show that the two-phages-one-antibiotic combination had the highest killing efficiency against the P. aeruginosa strain. The phages tested showed low stability at high temperatures, acidic pH values, and in the two ointments. This work provides additional support for the potential of using combinations of phage-antibiotic cocktails at sub-MIC levels for the treatment of multidrug-resistant P. aeruginosa infections.
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Antibacterianos/uso terapêutico , Queimaduras/tratamento farmacológico , Infecções por Pseudomonas/terapia , Fagos de Pseudomonas/fisiologia , Pseudomonas aeruginosa/virologia , Queimaduras/microbiologia , Humanos , Testes de Sensibilidade Microbiana , Terapia por Fagos , Filogenia , Infecções por Pseudomonas/microbiologia , Fagos de Pseudomonas/classificação , Fagos de Pseudomonas/genética , Fagos de Pseudomonas/isolamento & purificação , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/fisiologia , Rios/virologia , Esgotos/virologiaRESUMO
Gut microbiota composition can modulate neuroendocrine function, inflammation, and cellular and immunological responses against different pathogens, including viruses. Zika virus (ZIKV) can infect adult immunocompetent individuals and trigger brain damage and antiviral responses. However, it is not known whether ZIKV infection could impact the gut microbiome from adult immunocompetent mice. Here, we investigated modifications induced by ZIKV infection in the gut microbiome of immunocompetent C57BL/6J mice. Adult C57BL/6J mice were infected with ZIKV and the gut microbiota composition was analyzed by next-generation sequencing of the V4 hypervariable region present in the bacterial 16S rDNA gene. Our data showed that ZIKV infection triggered a significant decrease in the bacteria belonging to Actinobacteria and Firmicutes phyla, and increased Deferribacteres and Spirochaetes phyla components compared to uninfected mice. Interestingly, ZIKV infection triggered a significant increase in the abundance of bacteria from the Spirochaetaceae family in the gut microbiota. Lastly, we demonstrated that modulation of microbiota induced by ZIKV infection may lead to intestinal epithelium damage and intense leukocyte recruitment to the intestinal mucosa. Taken together, our data demonstrate that ZIKV infection can impact the gut microbiota composition and colon tissue homeostasis in adult immunocompetent mice.