RESUMO
We show how metagenomic analysis of the human gut antibiotic resistome, compared across large populations and against environmental or agricultural resistomes, suggests a strong anthropogenic cause behind increasing antibiotic resistance in bacteria. This area has been the subject of intense and polarized debate driven by economic and political concerns; therefore such recently available insights address an important need. We derive and compare antibiotic resistomes of human gut microbes from 832 individuals from ten different countries. We observe and describe significant differences between samples from these countries in the gut resistance potential, in line with expectations from antibiotic usage and exposure in medical and food production contexts. Our results imply roles for both of these sources in increased resistance among pathogens in recent history. In contrast, other available metadata such as age, body mass index, sex, or health status have little effect on the antibiotic resistance potential of human gut microbes. Also watch the Video Abstract.
Assuntos
Resistência Microbiana a Medicamentos/genética , Trato Gastrointestinal/microbiologia , Metagenômica/métodos , Evolução Biológica , HumanosRESUMO
The gastrointestinal tract is abundantly colonized by microbes, yet the translocation of oral species to the intestine is considered a rare aberrant event, and a hallmark of disease. By studying salivary and fecal microbial strain populations of 310 species in 470 individuals from five countries, we found that transmission to, and subsequent colonization of, the large intestine by oral microbes is common and extensive among healthy individuals. We found evidence for a vast majority of oral species to be transferable, with increased levels of transmission in colorectal cancer and rheumatoid arthritis patients and, more generally, for species described as opportunistic pathogens. This establishes the oral cavity as an endogenous reservoir for gut microbial strains, and oral-fecal transmission as an important process that shapes the gastrointestinal microbiome in health and disease.
Assuntos
Bactérias/classificação , Bactérias/genética , Intestino Grosso/microbiologia , Microbiota , Boca/microbiologia , Análise por Conglomerados , Fezes/microbiologia , Humanos , Metagenômica , Saliva/microbiologiaRESUMO
Before they infect red blood cells and cause malaria, Plasmodium parasites undergo an obligate and clinically silent expansion phase in the liver that is supposedly undetected by the host. Here, we demonstrate the engagement of a type I interferon (IFN) response during Plasmodium replication in the liver. We identified Plasmodium RNA as a previously unrecognized pathogen-associated molecular pattern (PAMP) capable of activating a type I IFN response via the cytosolic pattern recognition receptor Mda5. This response, initiated by liver-resident cells through the adaptor molecule for cytosolic RNA sensors, Mavs, and the transcription factors Irf3 and Irf7, is propagated by hepatocytes in an interferon-α/ß receptor-dependent manner. This signaling pathway is critical for immune cell-mediated host resistance to liver-stage Plasmodium infection, which we find can be primed with other PAMPs, including hepatitis C virus RNA. Together, our results show that the liver has sensor mechanisms for Plasmodium that mediate a functional antiparasite response driven by type I IFN.