RESUMEN
Surveillance data from wildlife and poultry was used to describe the spread of highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b in British Columbia (B.C.) and the Yukon, Canada from September 2022 - June 2023 compared to the first 'wave' of the outbreak in this region, which occurred April - August 2022, after the initial viral introduction. Although the number of HPAI-positive poultry farms and wildlife samples was greater in 'Wave 2', cases were more tightly clustered in southwestern B.C. and the most commonly affected species differed, likely due to an influx of overwintering waterfowl in the area. Eight HPAI genetic clusters, representing seven genotypes and two inter-continental viral incursions, were detected, with significant variation in the relative abundance of each cluster between the waves. Phylogenetic data suggests multiple spillover events from wild birds to poultry and mammals but could not rule out transmission among farms and among mammals.
RESUMEN
The SARS-CoV-2 variant Omicron emerged in late 2021. In British Columbia (BC), Canada, and globally, three genetically distinct subvariants of Omicron, BA.1, BA.2, and BA.5, emerged and became dominant successively within an 8-month period. SARS-CoV-2 subvariants continue to circulate in the population, acquiring new mutations that have the potential to alter infectivity, immunity, and disease severity. Here, we report a propensity-matched severity analysis from residents of BC over the course of the Omicron wave, including 39,237 individuals infected with BA.1, BA.2, or BA.5 based on paired high-quality sequence data and linked to comprehensive clinical outcomes data between December 23, 2021 and August 31, 2022. Relative to BA.1, BA.2 cases were associated with a 15% and 28% lower risk of hospitalization and intensive care unit (ICU) admission (aHRhospital = 1.17; 95% confidence interval [CI] = 1.096-1.252; aHRICU = 1.368; 95% CI = 1.152-1.624), whereas BA.5 infections were associated with an 18% higher risk of hospitalization (aHRhospital = 1.18; 95% CI = 1.133-1.224) after accounting for age, sex, comorbidities, vaccination status, geography, and social determinants of health. Phylogenetic analysis revealed no specific subclades associated with more severe clinical outcomes for any Omicron subvariant. In summary, BA.1, BA.2, and BA.5 subvariants were associated with differences in clinical severity, emphasizing how variant-specific monitoring programs remain critical components of patient and population-level public health responses as the pandemic continues.
Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , Colombia Británica/epidemiología , SARS-CoV-2/genética , Estudios de Cohortes , Filogenia , COVID-19/epidemiologíaRESUMEN
BACKGROUND: Investigating antibody titers in individuals who have been both naturally infected with SARS-CoV-2 and vaccinated can provide insight into antibody dynamics and correlates of protection over time. METHODS: Human coronavirus (HCoV) IgG antibodies were measured longitudinally in a prospective cohort of qPCR-confirmed, COVID-19 recovered individuals (k = 57) in British Columbia pre- and post-vaccination. SARS-CoV-2 and endemic HCoV antibodies were measured in serum collected between Nov. 2020 and Sept. 2021 (n = 341). Primary analysis used a linear mixed-effects model to understand the effect of single dose vaccination on antibody concentrations adjusting for biological sex, age, time from infection and vaccination. Secondary analysis investigated the cumulative incidence of high SARS-CoV-2 anti-spike IgG seroreactivity equal to or greater than 5.5 log10 AU/mL up to 105 days post-vaccination. No re-infections were detected in vaccinated participants, post-vaccination by qPCR performed on self-collected nasopharyngeal specimens. RESULTS: Bivariate analysis (complete data for 42 participants, 270 samples over 472 days) found SARS-CoV-2 spike and RBD antibodies increased 14-56 days post-vaccination (p < 0.001) and vaccination prevented waning (regression coefficient, B = 1.66 [95%CI: 1.45-3.46]); while decline of nucleocapsid antibodies over time was observed (regression coefficient, B = -0.24 [95%CI: -1.2-(-0.12)]). A positive association was found between COVID-19 vaccination and endemic human ß-coronavirus IgG titer 14-56 days post vaccination (OC43, p = 0.02 & HKU1, p = 0.02). On average, SARS-CoV-2 anti-spike IgG concentration increased in participants who received one vaccine dose by 2.06 log10 AU/mL (95%CI: 1.45-3.46) adjusting for age, biological sex, and time since infection. Cumulative incidence of high SARS-CoV-2 spike antibodies (>5.5 log10 AU/mL) was 83% greater in vaccinated compared to unvaccinated individuals. CONCLUSIONS: Our study confirms that vaccination post-SARS-CoV-2 infection provides multiple benefits, such as increasing anti-spike IgG titers and preventing decay up to 85 days post-vaccination.
Asunto(s)
COVID-19 , Humanos , COVID-19/prevención & control , Formación de Anticuerpos , SARS-CoV-2 , Estudios Prospectivos , Vacunas contra la COVID-19 , Anticuerpos Antivirales , Vacunación , Inmunoglobulina GRESUMEN
The ubiquitous gasotransmitter hydrogen sulfide (H2S) has been recognized to play a crucial role in human health. Using cystathionine γ-lyase (CSE)-deficient mice, we demonstrate an unexpected role of H2S in Mycobacterium tuberculosis (Mtb) pathogenesis. We showed that Mtb-infected CSE-/- mice survive longer than WT mice, and support reduced pathology and lower bacterial burdens in the lung, spleen, and liver. Similarly, in vitro Mtb infection of macrophages resulted in reduced colony forming units in CSE-/- cells. Chemical complementation of infected WT and CSE-/- macrophages using the slow H2S releaser GYY3147 and the CSE inhibitor DL-propargylglycine demonstrated that H2S is the effector molecule regulating Mtb survival in macrophages. Furthermore, we demonstrate that CSE promotes an excessive innate immune response, suppresses the adaptive immune response, and reduces circulating IL-1ß, IL-6, TNF-α, and IFN-γ levels in response to Mtb infection. Notably, Mtb infected CSE-/- macrophages show increased flux through glycolysis and the pentose phosphate pathway, thereby establishing a critical link between H2S and central metabolism. Our data suggest that excessive H2S produced by the infected WT mice reduce HIF-1α levels, thereby suppressing glycolysis and production of IL-1ß, IL-6, and IL-12, and increasing bacterial burden. Clinical relevance was demonstrated by the spatial distribution of H2S-producing enzymes in human necrotic, nonnecrotic, and cavitary pulmonary tuberculosis (TB) lesions. In summary, CSE exacerbates TB pathogenesis by altering immunometabolism in mice and inhibiting CSE or modulating glycolysis are potential targets for host-directed TB control.
Asunto(s)
Carbono/metabolismo , Cistationina gamma-Liasa/fisiología , Sulfuro de Hidrógeno/toxicidad , Mycobacterium tuberculosis/inmunología , Tuberculosis Pulmonar/etiología , Alquinos/farmacología , Animales , Cistationina gamma-Liasa/antagonistas & inhibidores , Citocinas/metabolismo , Inhibidores Enzimáticos/farmacología , Glicina/análogos & derivados , Glicina/farmacología , Glucólisis , Sulfuro de Hidrógeno/metabolismo , Linfocitos/efectos de los fármacos , Linfocitos/inmunología , Linfocitos/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Macrófagos/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Mycobacterium tuberculosis/efectos de los fármacos , Células Mieloides/efectos de los fármacos , Células Mieloides/inmunología , Células Mieloides/metabolismo , Transducción de Señal , Tuberculosis Pulmonar/metabolismo , Tuberculosis Pulmonar/patologíaRESUMEN
The immunometabolic mechanisms underlying suboptimal T cell immunity in tuberculosis remain undefined. Here, we examine how chronic Mycobacterium tuberculosis (Mtb) and M. bovis BCG infections rewire metabolic circuits and alter effector functions in lung CD8+ T cells. As Mtb infection progresses, mitochondrial metabolism deteriorates in CD8+ T cells, resulting in an increased dependency on glycolysis that potentiates inflammatory cytokine production. Over time, these cells develop bioenergetic deficiencies that reflect metabolic "quiescence." This bioenergetic signature coincides with increased mitochondrial dysfunction and inhibitory receptor expression and was not observed in BCG infection. Remarkably, the Mtb-triggered decline in T cell bioenergetics can be reinvigorated by metformin, giving rise to an Mtb-specific CD8+ T cell population with improved metabolism. These findings provide insights into Mtb pathogenesis whereby glycolytic reprogramming and compromised mitochondrial function contribute to the breakdown of CD8+ T cell immunity during chronic disease, highlighting opportunities to reinvigorate immunity with metabolically targeted pharmacologic agents.
Asunto(s)
Linfocitos T CD8-positivos/metabolismo , Citocinas/metabolismo , Glucólisis , Tuberculosis Latente/inmunología , Mitocondrias/metabolismo , Animales , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/inmunología , Células Cultivadas , Femenino , Hipoglucemiantes/farmacología , Tuberculosis Latente/microbiología , Metformina/farmacología , Ratones , Ratones Endogámicos C57BL , Mycobacterium bovis/patogenicidad , Mycobacterium tuberculosis/patogenicidadRESUMEN
The Mycobacterium tuberculosis (Mtb) electron transport chain (ETC) has received significant attention as a drug target, however its vulnerability may be affected by its flexibility in response to disruption. Here we determine the effect of the ETC inhibitors bedaquiline, Q203 and clofazimine on the Mtb ETC, and the value of the ETC as a drug target, by measuring Mtb's respiration using extracellular flux technology. We find that Mtb's ETC rapidly reroutes around inhibition by these drugs and increases total respiration to maintain ATP levels. Rerouting is possible because Mtb rapidly switches between terminal oxidases, and, unlike eukaryotes, is not susceptible to back pressure. Increased ETC activity potentiates clofazimine's production of reactive oxygen species, causing rapid killing in vitro and in a macrophage model. Our results indicate that combination therapy targeting the ETC can be exploited to enhance killing of Mtb.
Asunto(s)
Antituberculosos/farmacología , Proteínas del Complejo de Cadena de Transporte de Electrón/antagonistas & inhibidores , Mycobacterium tuberculosis/fisiología , Especies Reactivas de Oxígeno/metabolismo , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Adenosina Trifosfato/metabolismo , Animales , Antituberculosos/uso terapéutico , Clofazimina/farmacología , Clofazimina/uso terapéutico , Diarilquinolinas/farmacología , Diarilquinolinas/uso terapéutico , Quimioterapia Combinada/métodos , Células Hep G2 , Humanos , Imidazoles/síntesis química , Imidazoles/farmacología , Imidazoles/uso terapéutico , Concentración 50 Inhibidora , Macrófagos/microbiología , Ratones , Mutación , Mycobacterium tuberculosis/efectos de los fármacos , Piperidinas/síntesis química , Piperidinas/farmacología , Piperidinas/uso terapéutico , Piridinas/síntesis química , Piridinas/farmacología , Piridinas/uso terapéutico , Células RAW 264.7 , Tuberculosis Resistente a Múltiples Medicamentos/microbiologíaRESUMEN
There is increasing evidence for a role of early life gut microbiota in later development of asthma in children. In our recent study, children with reduced abundance of the bacterial genera Lachnospira, Veillonella, Faecalibacterium, and Rothia had an increased risk of development of asthma and addition of these bacteria in a humanized mouse model reduced airway inflammation. In this Addendum, we provide additional data on the use of a humanized gut microbiota mouse model to study the development of asthma in children, highlighting the differences in immune development between germ-free mice colonized with human microbes compared to those colonized with mouse gut microbiota. We also demonstrate that there is no association between the composition of the gut microbiota in older children and the diagnosis of asthma, further suggesting the importance of the gut microbiota-immune system axis in the first 3 months of life.
Asunto(s)
Bacterias/aislamiento & purificación , Microbioma Gastrointestinal , Tracto Gastrointestinal/microbiología , Neumonía/microbiología , Animales , Bacterias/clasificación , Bacterias/genética , Modelos Animales de Enfermedad , Femenino , Tracto Gastrointestinal/inmunología , Vida Libre de Gérmenes , Humanos , Masculino , Ratones , Ovalbúmina/efectos adversos , Neumonía/etiología , Neumonía/genética , Neumonía/inmunologíaRESUMEN
BACKGROUND: Resident gut microbiota are now recognized as potent modifiers of host immune responses in various scenarios. Recently, we demonstrated that perinatal exposure to vancomycin, but not streptomycin, profoundly alters gut microbiota and enhances susceptibility to a TH2 model of allergic asthma. OBJECTIVE: Here we sought to further clarify the etiology of these changes by determining whether perinatal antibiotic treatment has a similar effect on the TH1/TH17-mediated lung disease, hypersensitivity pneumonitis. METHODS: Hypersensitivity pneumonitis was induced in C57BL/6 wild-type or recombination-activating gene 1-deficient mice treated perinatally with vancomycin or streptomycin by repeated intranasal administration of Saccharopolyspora rectivirgula antigen. Disease severity was assessed by measuring lung inflammation, pathology, cytokine responses, and serum antibodies. Microbial community analyses were performed on stool samples via 16S ribosomal RNA pyrosequencing and correlations between disease severity and specific bacterial taxa were identified. RESULTS: Surprisingly, in contrast to our findings in an allergic asthma model, we found that the severity of hypersensitivity pneumonitis was unaffected by vancomycin, but increased dramatically after streptomycin treatment. This likely reflects an effect on the adaptive, rather than innate, immune response because the effects of streptomycin were not observed during the early phases of disease and were abrogated in recombination-activating gene 1-deficient mice. Interestingly, Bacteroidetes dominated the intestinal microbiota of streptomycin-treated animals, while vancomycin promoted the expansion of the Firmicutes. CONCLUSIONS: Perinatal antibiotics exert highly selective effects on resident gut flora, which, in turn, lead to very specific alterations in susceptibility to TH2- or TH1/TH17-driven lung inflammatory disease.
Asunto(s)
Alveolitis Alérgica Extrínseca/inmunología , Alveolitis Alérgica Extrínseca/microbiología , Antibacterianos/efectos adversos , Tracto Gastrointestinal/microbiología , Microbiota , Estreptomicina/efectos adversos , Alveolitis Alérgica Extrínseca/sangre , Alveolitis Alérgica Extrínseca/patología , Animales , Animales Recién Nacidos , Citocinas/inmunología , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Pulmón/inmunología , Pulmón/patología , Ratones Endogámicos C57BL , Saccharopolyspora , Índice de Severidad de la Enfermedad , Vancomicina/farmacologíaRESUMEN
15-deoxy-Δ(12,14)-prostaglandin J2 (15d-PGJ2) is an anti-inflammatory downstream product of the cyclooxygenase enzymes. It has been implicated to play a protective role in a variety of inflammatory mediated diseases, including rheumatoid arthritis, neural damage, and myocardial infarctions. Here we show that 15d-PGJ2 also plays a role in Salmonella infection. Salmonella enterica Typhimurium is a Gram-negative facultative intracellular pathogen that is able to survive and replicate inside phagocytic immune cells, allowing for bacterial dissemination to systemic sites. Salmonella species cause a wide range of morbidity and mortality due to gastroenteritis and typhoid fever. Previously we have shown that in mouse models of typhoid fever, Salmonella infection causes a major perturbation in the prostaglandin pathway. Specifically, we saw that 15d-PGJ2 production was significantly increased in both liver and feces. In this work we show that 15d-PGJ2 production is also significantly increased in macrophages infected with Salmonella. Furthermore, we show that the addition of 15d-PGJ2 to Salmonella infected RAW264.7, J774, and bone marrow derived macrophages is sufficient to significantly reduce bacterial colonization. We also show evidence that 15d-PGJ2 is reducing bacterial uptake by macrophages. 15d-PGJ2 reduces the inflammatory response of these infected macrophages, as evidenced by a reduction in the production of cytokines and reactive nitrogen species. The inflammatory response of the macrophage is important for full Salmonella virulence, as it can give the bacteria cues for virulence. The reduction in bacterial colonization is independent of the expression of Salmonella virulence genes SPI1 and SPI2, and is independent of the 15d-PGJ2 ligand PPAR-γ. 15d-PGJ2 also causes an increase in ERK1/2 phosphorylation in infected macrophages. In conclusion, we show here that 15d-PGJ2 mediates the outcome of bacterial infection, a previously unidentified role for this prostaglandin.
Asunto(s)
Macrófagos/efectos de los fármacos , Macrófagos/microbiología , Prostaglandina D2/análogos & derivados , Salmonella typhimurium/crecimiento & desarrollo , Animales , Ácido Araquidónico/metabolismo , Recuento de Colonia Microbiana , Citocinas/biosíntesis , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Femenino , Regulación Bacteriana de la Expresión Génica/efectos de los fármacos , Genes Bacterianos/genética , Células HeLa , Interacciones Huésped-Patógeno/efectos de los fármacos , Humanos , Inmunidad/efectos de los fármacos , Macrófagos/enzimología , Macrófagos/inmunología , Ratones , Ratones Endogámicos C57BL , PPAR gamma/metabolismo , Fosforilación/efectos de los fármacos , Prostaglandina D2/farmacología , Especies de Nitrógeno Reactivo/metabolismo , Infecciones por Salmonella/microbiología , Infecciones por Salmonella/patología , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/genética , Salmonella typhimurium/patogenicidad , Virulencia/efectos de los fármacos , Virulencia/genéticaRESUMEN
There is convincing evidence from recent human and animal studies that suggests the intestinal microbiota plays an important role in regulating immune responses associated with the development of allergic asthma, particularly during early infancy. Although identifying the mechanistic link between host-microbe interactions in the gut and lung mucosal tissues has proved challenging, several very recent studies are now providing significant insights. We have shown that administering vancomycin to mice early in life shifts resident gut flora and enhances future susceptibility to allergic asthma. This effect was not observed in mice given another antibiotic, streptomycin, nor when either antibiotic was administered to adult mice. In this addendum, we further analyze the link between early life administration of vancomycin and future susceptibility to asthma and describe how specific immune cell populations, which have been implicated in other asthma-related microbiota studies, are affected. We propose that shifts in gut microbiota exacerbate asthma-related immune responses when they occur shortly after birth and before weaning (perinatal period), and suggest that these effects may be mediated, at least in the case of vancomycin, by elevated serum IgE and reduced regulatory T cell populations.
Asunto(s)
Antibacterianos/administración & dosificación , Asma/inmunología , Asma/microbiología , Tracto Gastrointestinal/microbiología , Metagenoma/efectos de los fármacos , Metagenoma/inmunología , Animales , Inmunoglobulina E/sangre , Ratones , Estreptomicina/administración & dosificación , Linfocitos T Reguladores/inmunología , Vancomicina/administración & dosificaciónRESUMEN
PURPOSE OF REVIEW: The prevalence of allergic diseases continues to rise globally in developed countries. Since the initial proposal of the hygiene hypothesis, there has been increasing evidence to suggest that the intestinal microbiota, particularly during early infancy, plays a critical role in regulating immune responses associated with the development of atopy. This review evaluates the key epidemiologic and mechanistic data published to date. RECENT FINDINGS: Epidemiological data have provided the framework for animal studies investigating the importance of gut commensals in allergy development. These studies provide new insights about the microbial regulation of mucosal immune responses inside and outside the gut, and how these effects may drive allergic inflammation in susceptible individuals. Specific immune cells have been identified as mediators of these microbiota-regulated allergic responses. SUMMARY: In the last year, technological advances have provided us with a better understanding of the gut microbiome in healthy and allergic individuals. Recent studies have identified the associations between particular gut microbes and different disease phenotypes, as well as identified immune cells and their mediators involved in allergy development. This research has provided a number of host and microbe targets that may be used to develop novel therapies suitable for the treatment or prevention of allergic diseases.
Asunto(s)
Hipersensibilidad/microbiología , Intestinos/microbiología , Metagenoma/inmunología , Animales , Asma/epidemiología , Asma/inmunología , Modelos Animales de Enfermedad , Humanos , Hipótesis de la Higiene , Hipersensibilidad/epidemiología , Hipersensibilidad/inmunología , Inmunidad Mucosa , Intestinos/inmunología , Membrana Mucosa/inmunologíaRESUMEN
Allergic asthma rates have increased steadily in developed countries, arguing for an environmental aetiology. To assess the influence of gut microbiota on experimental murine allergic asthma, we treated neonatal mice with clinical doses of two widely used antibiotics--streptomycin and vancomycin--and evaluated resulting shifts in resident flora and subsequent susceptibility to allergic asthma. Streptomycin treatment had little effect on the microbiota and on disease, whereas vancomycin reduced microbial diversity, shifted the composition of the bacterial population and enhanced disease severity. Neither antibiotic had a significant effect when administered to adult mice. Consistent with the 'hygiene hypothesis', our data support a neonatal, microbiota-driven, specific increase in susceptibility to experimental murine allergic asthma.
Asunto(s)
Antibacterianos/efectos adversos , Asma/inducido químicamente , Biología Computacional/métodos , Susceptibilidad a Enfermedades/inducido químicamente , Metagenoma/efectos de los fármacos , Estreptomicina/efectos adversos , Vancomicina/efectos adversos , Animales , Asma/microbiología , Femenino , Citometría de Flujo , Ratones , Ratones Endogámicos C57BLRESUMEN
The intestinal microbiota is composed of hundreds of species of bacteria, fungi and protozoa and is critical for numerous biological processes, such as nutrient acquisition, vitamin production, and colonization resistance against bacterial pathogens. We studied the role of the intestinal microbiota on host resistance to Salmonella enterica serovar Typhimurium-induced colitis. Using multiple antibiotic treatments in 129S1/SvImJ mice, we showed that disruption of the intestinal microbiota alters host susceptibility to infection. Although all antibiotic treatments caused similar increases in pathogen colonization, the development of enterocolitis was seen only when streptomycin or vancomycin was used; no significant pathology was observed with the use of metronidazole. Interestingly, metronidazole-treated and infected C57BL/6 mice developed severe pathology. We hypothesized that the intestinal microbiota confers resistance to infectious colitis without affecting the ability of S. Typhimurium to colonize the intestine. Indeed, different antibiotic treatments caused distinct shifts in the intestinal microbiota prior to infection. Through fluorescence in situ hybridization, terminal restriction fragment length polymorphism, and real-time PCR, we showed that there is a strong correlation between the intestinal microbiota composition before infection and susceptibility to Salmonella-induced colitis. Members of the Bacteroidetes phylum were present at significantly higher levels in mice resistant to colitis. Further analysis revealed that Porphyromonadaceae levels were also increased in these mice. Conversely, there was a positive correlation between the abundance of Lactobacillus sp. and predisposition to colitis. Our data suggests that different members of the microbiota might be associated with S. Typhimurium colonization and colitis. Dissecting the mechanisms involved in resistance to infection and inflammation will be critical for the development of therapeutic and preventative measures against enteric pathogens.
Asunto(s)
Enterocolitis/microbiología , Intestinos/microbiología , Salmonelosis Animal/microbiología , Salmonella typhimurium/fisiología , Animales , Antiinfecciosos/farmacología , Bacterias/clasificación , Bacterias/efectos de los fármacos , Bacterias/genética , Proteínas de Transporte de Catión/deficiencia , Proteínas de Transporte de Catión/genética , Ecosistema , Heces/microbiología , Interacciones Huésped-Patógeno , Hibridación Fluorescente in Situ , Intestinos/efectos de los fármacos , Intestinos/patología , Metagenoma/efectos de los fármacos , Metagenoma/genética , Metronidazol/farmacología , Ratones , Ratones de la Cepa 129 , Ratones Endogámicos C57BL , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/genética , Especificidad de la Especie , Estreptomicina/farmacología , Vancomicina/farmacologíaRESUMEN
Antibiotics have been used effectively as a means to treat bacterial infections in humans and animals for over half a century. However, through their use, lasting alterations are being made to a mutualistic relationship that has taken millennia to evolve: the relationship between the host and its microbiota. Host-microbiota interactions are dynamic; therefore, changes in the microbiota as a consequence of antibiotic treatment can result in the dysregulation of host immune homeostasis and an increased susceptibility to disease. A better understanding of both the changes in the microbiota as a result of antibiotic treatment and the consequential changes in host immune homeostasis is imperative, so that these effects can be mitigated.
Asunto(s)
Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Infecciones Bacterianas/tratamiento farmacológico , Tracto Gastrointestinal/efectos de los fármacos , Interacciones Huésped-Patógeno/efectos de los fármacos , Inmunidad Mucosa , Metagenoma/efectos de los fármacos , Interacciones Microbianas/efectos de los fármacos , Animales , Antibacterianos/uso terapéutico , Bacterias/metabolismo , Infecciones Bacterianas/microbiología , Biomasa , Susceptibilidad a Enfermedades , Enterocolitis Seudomembranosa/etiología , Ácidos Grasos Volátiles/metabolismo , Tracto Gastrointestinal/inmunología , Tracto Gastrointestinal/microbiología , Homeostasis/efectos de los fármacos , HumanosRESUMEN
Gut microbiota is an assortment of microorganisms inhabiting the length and width of the mammalian gastrointestinal tract. The composition of this microbial community is host specific, evolving throughout an individual's lifetime and susceptible to both exogenous and endogenous modifications. Recent renewed interest in the structure and function of this "organ" has illuminated its central position in health and disease. The microbiota is intimately involved in numerous aspects of normal host physiology, from nutritional status to behavior and stress response. Additionally, they can be a central or a contributing cause of many diseases, affecting both near and far organ systems. The overall balance in the composition of the gut microbial community, as well as the presence or absence of key species capable of effecting specific responses, is important in ensuring homeostasis or lack thereof at the intestinal mucosa and beyond. The mechanisms through which microbiota exerts its beneficial or detrimental influences remain largely undefined, but include elaboration of signaling molecules and recognition of bacterial epitopes by both intestinal epithelial and mucosal immune cells. The advances in modeling and analysis of gut microbiota will further our knowledge of their role in health and disease, allowing customization of existing and future therapeutic and prophylactic modalities.