Human-associated Microbes Research Articles

Response, resistance, and recovery of gut bacteria to human-targeted drug exposure

Survival strategies of human-associated microbes to drug exposure have been mainly studied in the context of bona fide pathogens exposed to antibiotics. Less well understood are the survival strategies of non-pathogenic microbes and host-associated commensal communities to the variety of drugs and xenobiotics to which humans are exposed. The lifestyle of microbial commensals within complex communities offers a variety of ways to adapt to different drug-induced stresses. Here, we review the responses and survival strategies employed by gut commensals when exposed to drugs-antibiotics and non-antibiotics-at the individual and community level. We also discuss the factors influencing the recovery and establishment of a new community structure following drug exposure. These survival strategies are key to the stability and resilience of the gut microbiome, ultimately influencing the overall health and well-being of the host.

Surprising diversity of new plasmids in bacteria isolated from hemorrhoid patients.

Hemorrhoids are common conditions at or around the anus, to which numerous people suffer worldwide. Previous research has suggested that microbes may play a role in the development of hemorrhoids, and the origins of these microbes have been preliminarily investigated. However, no detailed research on the microbes related to hemorrhoid patients has been conducted. This work aims to provide an initial investigation into the microbes related to hemorrhoid patients with high quality whole genome sequencing. Forty-nine bacterial strains were isolated from seven hemorrhoid patients. Third-generation nanopore sequencing was performed to obtain high quality whole genome sequences. The presence of plasmids, particularly new plasmids, along with antibiotic resistance genes, was investigated for these strains. Phylogenetic analysis and genome comparisons were performed. Out of the 31 plasmids found in the strains, 15 new plasmids that have not been observed previously were discovered. Further structural analysis revealed new multidrug-resistant conjugative plasmids, virulent plasmids, and small, high-copy mobile plasmids that may play significant functional roles. These plasmids were found to harbor numerous integrases, transposases, and recombinases, suggesting their ability to quickly obtain genes to change functions. Analysis of antibiotic resistance genes revealed the presence of antibiotic resistant-integrons. Together with the surprising number of new plasmids identified, as well as the finding of transmission and modification events for plasmids in this work, we came to the suggestion that plasmids play a major role in genetic plasticity. This study reveals that the diversity of plasmids in human-associated microbes has been underestimated. With the decreasing cost of whole-genome sequencing, monitoring plasmids deserves increased attention in future surveillance efforts.

Systematic mining of the human microbiome identifies antimicrobial peptides with diverse activity spectra.

Human-associated bacteria secrete modified peptides to control host physiology and remodel the microbiota species composition. Here we scanned 2,229 Human Microbiome Project genomes of species colonizing skin, gastrointestinal tract, urogenital tract, mouth and trachea for gene clusters encoding RiPPs (ribosomally synthesized and post-translationally modified peptides). We found 218 lanthipeptides and 25 lasso peptides, 70 of which were synthesized and expressed in E. coli and 23 could be purified and functionally characterized. They were tested for activity against bacteria associated with healthy human flora and pathogens. New antibiotics were identified against strains implicated in skin, nasal and vaginal dysbiosis as well as from oral strains selectively targeting those in the gut. Extended- and narrow-spectrum antibiotics were found against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci. Mining natural products produced by human-associated microbes will enable the elucidation of ecological relationships and may be a rich resource for antimicrobial discovery.

Molecular commensalism-how to investigate underappreciated health-associated polymicrobial communities.

The study of human commensal bacteria began with the first observation of prokaryotes >340 years ago. Since then, the study of human-associated microbes has been justifiably biased toward the study of infectious pathogens. However, the role of commensal microbes has in recent years begun to be understood with some appreciation of them as potential protectors of host health rather than bystanders. As our understanding of these valuable microbes grows, it highlights how much more remains to be learned about them and their roles in maintaining health. We note here that a thorough framework for the study of commensals, both in vivo and in vitro is overall lacking compared to well-developed methodologies for pathogens. The modification and application of methods for the study of pathogens can work well for the study of commensals but is not alone sufficient to properly characterize their relationships. This is because commensals live in homeostasis with the host and within complex communities. One difficulty is determining which commensals have a quantifiable impact on community structure and stability as well as host health, vs benign microbes that may indeed serve only as bystanders. Human microbiomes are composed of bacteria, archaea, fungi, and viruses. This review focuses particularly on oral bacteria, yet many of the principles of commensal impacts on host health observed in the mouth can translate well to other host sites. Here, we discuss the value of commensals, the shortcomings involved in model systems for their study, and some of the more notable impacts they have upon not only each other but host health.

Characterization of SARS-CoV-2 Distribution and Microbial Succession in a Clinical Microbiology Testing Facility during the SARS-CoV-2 Pandemic.

The exchange of microbes between humans and the built environment is a dynamic process that has significant impact on health. Most studies exploring the microbiome of the built environment have been predicated on improving our understanding of pathogen emergence, persistence, and transmission. Previous studies have demonstrated that SARS-CoV-2 presence significantly correlates with the proportional abundance of specific bacteria on surfaces in the built environment. However, in these studies, SARS-CoV-2 originated from infected patients. Here, we perform a similar assessment for a clinical microbiology lab while staff were handling SARS-CoV-2 infected samples. The goal of this study was to understand the distribution and dynamics of microbial population on various surfaces within different sections of a clinical microbiology lab during a short period of 2020 Coronavirus disease (COVID-19) pandemic. We sampled floors, benches, and sinks in 3 sections (bacteriology, molecular microbiology, and COVID) of an active clinical microbiology lab over a 3-month period. Although floor samples harbored SARS-CoV-2, it was rarely identified on other surfaces, and bacterial diversity was significantly greater on floors than sinks and benches. The floors were primarily colonized by bacteria common to natural environments (e.g., soils), and benchtops harbored a greater proportion of human-associated microbes, including Staphylococcus and Streptococcus. Finally, we show that the microbial composition of these surfaces did not change over time and remained stable. Despite finding viruses on the floors, no lab-acquired infections were reported during the study period, which suggests that lab safety protocols and sanitation practices were sufficient to prevent pathogen exposures. IMPORTANCE For decades, diagnostic clinical laboratories have been an integral part of the health care systems that perform diagnostic tests on patient's specimens in bulk on a regular basis. Understanding their microbiota should assist in designing and implementing disinfection, and cleaning regime in more effective way. To our knowledge, there is a lack of information on the composition and dynamics of microbiota in the clinical laboratory environments, and, through this study, we have tried to fill that gap. This study has wider implications as understanding the makeup of microbes on various surfaces within clinical laboratories could help identify any pathogenic bacterial taxa that could have colonized these surfaces, and might act as a potential source of laboratory-acquired infections. Mapping the microbial community within these built environments may also be critical in assessing the reliability of laboratory safety and sanitation practices to lower any potential risk of exposures to health care workers.

Contributions of Human-Associated Archaeal Metabolites to Tumor Microenvironment and Carcinogenesis.

ABSTRACTThere is increasing awareness that archaea are interrelated with human diseases (including cancer). Archaea utilize unique metabolic pathways to produce a variety of metabolites that serve as a direct link to host-microbe interactions. However, knowledge on the diversity of human-associated archaea is still extremely limited, and less is known about the pathological effects of their metabolites to the tumor microenvironment and carcinogenesis. In the present study, we performed a large-scale analysis of archaea and their cancer-related metabolites across different body sites using >44,000 contigs with length >1,000 bp. Taxonomy annotation revealed that the occurrence and diversity of archaea are higher in two body sites, the gut and the oral cavity. Unlike other human-associated microbes, the nonmetric multidimensional scaling (NMDS) and permutational multivariate analysis of variance (PERMANOVA) analyses have shown no difference of archaeal compositions between Easterners and Westerners. Likewise, protein annotation suggests that genes encoding cancer-related metabolites (e.g., short-chain fatty acids and polyamines) are more prevalent and diverse in gut and oral samples. Archaea carrying these metabolites are restricted to Euryarchaeota and the TACK superphylum (Thaumarchaeota, Aigarchaeota, Crenarchaeota, and Korarchaeota), especially methanogenic archaea, such as Methanobacteria.IMPORTANCE More evidence suggests that archaea are associated with human disease, including cancer. Here, we present the first framework of the diversity and distribution of human-associated archaea across human body sites, such as gut and oral cavity, using long contigs. Furthermore, we unveiled the potential archaeal metabolites linking to different lineages that might influence the tumor microenvironment and carcinogenesis. These results could open a new door to the guidance of diagnosing cancer and developing new treatment strategies.

RNA Viromics of Southern California Wastewater and Detection of SARS-CoV-2 Single-Nucleotide Variants.

ABSTRACTMunicipal wastewater provides an integrated sample of a diversity of human-associated microbes across a sewershed, including viruses. Wastewater-based epidemiology (WBE) is a promising strategy to detect pathogens and may serve as an early warning system for disease outbreaks. Notably, WBE has garnered substantial interest during the coronavirus disease 2019 (COVID-19) pandemic to track disease burden through analyses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA. Throughout the COVID-19 outbreak, tracking SARS-CoV-2 in wastewater has been an important tool for understanding the spread of the virus. Unlike traditional sequencing of SARS-CoV-2 isolated from clinical samples, which adds testing burden to the health care system, in this study, metatranscriptomics was used to sequence virus directly from wastewater. Here, we present a study in which we explored RNA viral diversity through sequencing 94 wastewater influent samples across seven wastewater treatment plants (WTPs), collected from August 2020 to January 2021, representing approximately 16 million people in Southern California. Enriched viral libraries identified a wide diversity of RNA viruses that differed between WTPs and over time, with detected viruses including coronaviruses, influenza A, and noroviruses. Furthermore, single-nucleotide variants (SNVs) of SARS-CoV-2 were identified in wastewater, and we measured proportions of overall virus and SNVs across several months. We detected several SNVs that are markers for clinically important SARS-CoV-2 variants along with SNVs of unknown function, prevalence, or epidemiological consequence. Our study shows the potential of WBE to detect viruses in wastewater and to track the diversity and spread of viral variants in urban and suburban locations, which may aid public health efforts to monitor disease outbreaks.IMPORTANCE Wastewater-based epidemiology (WBE) can detect pathogens across sewersheds, which represents the collective waste of human populations. As there is a wide diversity of RNA viruses in wastewater, monitoring the presence of these viruses is useful for public health, industry, and ecological studies. Specific to public health, WBE has proven valuable during the coronavirus disease 2019 (COVID-19) pandemic to track the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) without adding burden to health care systems. In this study, we used metatranscriptomics and reverse transcription-droplet digital PCR (RT-ddPCR) to assay RNA viruses across Southern California wastewater from August 2020 to January 2021, representing approximately 16 million people from Los Angeles, Orange, and San Diego counties. We found that SARS-CoV-2 quantification in wastewater correlates well with county-wide COVID-19 case data, and that we can detect SARS-CoV-2 single-nucleotide variants through sequencing. Likewise, wastewater treatment plants (WTPs) harbored different viromes, and we detected other human pathogens, such as noroviruses and adenoviruses, furthering our understanding of wastewater viral ecology.

Gut-inhabiting Clostridia build human GPCR ligands by conjugating neurotransmitters with diet- and human-derived fatty acids.

Human physiology is regulated by endogenous signalling compounds, including fatty acid amides (FAAs), chemical mimics of which are made by bacteria. The molecules produced by human-associated microbes are difficult to identify because they may only be made in a local niche or they require a substrate sourced from the host, diet or other microbes. We identified a set of uncharacterized gene clusters in metagenomics data from the human gut microbiome. These clusters were discovered to make FAAs by fusing exogenous fatty acids with amines. Using an in vitro assay, we tested their ability to incorporate 25 fatty acids and 53 amines known to be present in the human gut, from which the production of six FAAs was deduced (oleoyl dopamine, oleoyl tyramine, lauroyl tryptamine, oleoyl aminovaleric acid, α-linolenoyl phenylethylamine and caproyl tryptamine). These molecules were screened against panels of human G-protein-coupled receptors to deduce their putative human targets. Lauroyl tryptamine is found to be an antagonist to the immunomodulatory receptor EBI2 against its native oxysterol ligand (0.98 μM half-maximal inhibitory concentration), is produced in culture by Eubacterium rectale and is present in human faecal samples. FAAs produced by Clostridia may serve as a mechanism to modulate their host by mimicking human signalling molecules.

Real-Time Culture-Independent Microbial Profiling Onboard the International Space Station Using Nanopore Sequencing

For the past two decades, microbial monitoring of the International Space Station (ISS) has relied on culture-dependent methods that require return to Earth for analysis. This has a number of limitations, with the most significant being bias towards the detection of culturable organisms and the inherent delay between sample collection and ground-based analysis. In recent years, portable and easy-to-use molecular-based tools, such as Oxford Nanopore Technologies’ MinION™ sequencer and miniPCR bio’s miniPCR™ thermal cycler, have been validated onboard the ISS. Here, we report on the development, validation, and implementation of a swab-to-sequencer method that provides a culture-independent solution to real-time microbial profiling onboard the ISS. Method development focused on analysis of swabs collected in a low-biomass environment with limited facility resources and stringent controls on allowed processes and reagents. ISS-optimized procedures included enzymatic DNA extraction from a swab tip, bead-based purifications, altered buffers, and the use of miniPCR and the MinION. Validation was conducted through extensive ground-based assessments comparing current standard culture-dependent and newly developed culture-independent methods. Similar microbial distributions were observed between the two methods; however, as expected, the culture-independent data revealed microbial profiles with greater diversity. Protocol optimization and verification was established during NASA Extreme Environment Mission Operations (NEEMO) analog missions 21 and 22, respectively. Unique microbial profiles obtained from analog testing validated the swab-to-sequencer method in an extreme environment. Finally, four independent swab-to-sequencer experiments were conducted onboard the ISS by two crewmembers. Microorganisms identified from ISS swabs were consistent with historical culture-based data, and primarily consisted of commonly observed human-associated microbes. This simplified method has been streamlined for high ease-of-use for a non-trained crew to complete in an extreme environment, thereby enabling environmental and human health diagnostics in real-time as future missions take us beyond low-Earth orbit.

Automated Prediction and Annotation of Small Open Reading Frames in Microbial Genomes

Small open reading frames (smORFs) and their encoded microproteins play central roles in microbes. However, there is a vast unexplored space of smORFs within human-associated microbes. A recent bioinformatic analysis used evolutionary conservation signals to enhance prediction of small protein families. To facilitate the annotation of specific smORFs, we introduce SmORFinder. This tool combines profile hidden Markov models of each smORF family and deep learning models that better generalize to smORF families not seen in the training set, resulting in predictions enriched for Ribo-seq translation signals. Feature importance analysis reveals that the deep learning models learn to identify Shine-Dalgarno sequences, deprioritize the wobble position in each codon, and group codon synonyms found in the codon table. A core-genome analysis of 26 bacterial species identifies several core smORFs of unknown function. We pre-compute smORF annotations for thousands of RefSeq isolate genomes and Human Microbiome Project metagenomes and provide these data through a public web portal.

Intestinal microbiota in patients with acute leukemia (AL) and allogeneic hematopoietics stem cell transplantation (allo-HSCT).

e19518 Background: Microbiome is a challenging study area due to its influence on the multiple host functions. The majority of human-associated microbes reside within the colon. Our understanding about the complex interplay between host and environmental factors to shaping the microbiota is evolving rapidly AL is an unfavorable prognosis disease whose only cure possibility is the allo-HSCT. This procedure uses high doses of chemotherapy and multiple drugs such as antibiotics, antiviral, antifungals, and immunosuppressants that damage the mucous membranes and alter the intestinal microbiome balance. These events have been linked to bacterial resistance, relapse risk, Graft Versus Host Disease (GVHD), and poor Overall Survival (OS). The present study’s objective was to identify the intestinal microbiome bacteria groups during allo-HSCT and to evaluate their impact on patients outcome. Methods: Observational and prospective study was performed. Eleven patients with acute leukemia under alloHSCT and 11 health control (relatives) were enrolled. Gut faecal samples were collected in both groups; three for patients (at income day (ID), neutropenic period (N) and 30 days after discharge (+30D) and one in healthy donor (HD) at income day of their relatives. Bacterial 16S rRNA gene sequences were characterized by illumina and QUIIME 2. Biodiversity of microbiome was evaluated by OTUS, Shannon index and dominance. This proyect was supported by CONACyT. Results: We analyze 11 patients, 55% were male, with a median of 25 years-old at allo-HSCT. 7/10 received a HLA-identical and 4/10 an haploidentical HSCT. 82% had GVHD (I-IV), 1/11 died (two due to infections-GVHD and one of disease relapse). We analyzed 44 samples. There are no difference between healthy control group and income day patients’ samples. Statistical differences in the patients’ microbiome were identified among HSCT moments. According OTUS and Shannon Index the biodiversity decrease at neutropenia, and increase at day +30 outcome but it doesn’t represent a complete recovery. Greater bacterial dominance was observed in neutropenia period. (Table). 3/10 patients who died didn’t recovery biodiversity at day +30. Conclusions: Our results suggest that poor microbiome biodiversity recovery could be a worst prognostic [Table: see text]

Microbial genomes from non-human primate gut metagenomes expand the primate-associated bacterial tree of life with over 1000 novel species

BackgroundHumans have coevolved with microbial communities to establish a mutually advantageous relationship that is still poorly characterized and can provide a better understanding of the human microbiome. Comparative metagenomic analysis of human and non-human primate (NHP) microbiomes offers a promising approach to study this symbiosis. Very few microbial species have been characterized in NHP microbiomes due to their poor representation in the available cataloged microbial diversity, thus limiting the potential of such comparative approaches.ResultsWe reconstruct over 1000 previously uncharacterized microbial species from 6 available NHP metagenomic cohorts, resulting in an increase of the mappable fraction of metagenomic reads by 600%. These novel species highlight that almost 90% of the microbial diversity associated with NHPs has been overlooked. Comparative analysis of this new catalog of taxa with the collection of over 150,000 genomes from human metagenomes points at a limited species-level overlap, with only 20% of microbial candidate species in NHPs also found in the human microbiome. This overlap occurs mainly between NHPs and non-Westernized human populations and NHPs living in captivity, suggesting that host lifestyle plays a role comparable to host speciation in shaping the primate intestinal microbiome. Several NHP-specific species are phylogenetically related to human-associated microbes, such as Elusimicrobia and Treponema, and could be the consequence of host-dependent evolutionary trajectories.ConclusionsThe newly reconstructed species greatly expand the microbial diversity associated with NHPs, thus enabling better interrogation of the primate microbiome and empowering in-depth human and non-human comparative and co-diversification studies.

Extensive Unexplored Human Microbiome Diversity Revealed by Over 150,000 Genomes from Metagenomes Spanning Age, Geography, and Lifestyle

SummaryThe body-wide human microbiome plays a role in health, but its full diversity remains uncharacterized, particularly outside of the gut and in international populations. We leveraged 9,428 metagenomes to reconstruct 154,723 microbial genomes (45% of high quality) spanning body sites, ages, countries, and lifestyles. We recapitulated 4,930 species-level genome bins (SGBs), 77% without genomes in public repositories (unknown SGBs [uSGBs]). uSGBs are prevalent (in 93% of well-assembled samples), expand underrepresented phyla, and are enriched in non-Westernized populations (40% of the total SGBs). We annotated 2.85 M genes in SGBs, many associated with conditions including infant development (94,000) or Westernization (106,000). SGBs and uSGBs permit deeper microbiome analyses and increase the average mappability of metagenomic reads from 67.76% to 87.51% in the gut (median 94.26%) and 65.14% to 82.34% in the mouth. We thus identify thousands of microbial genomes from yet-to-be-named species, expand the pangenomes of human-associated microbes, and allow better exploitation of metagenomic technologies.

The gut microbiome: Relationships with disease and opportunities for therapy.

Over the past decade, our view of human-associated microbes has expanded beyond that of a few species toward an appreciation of the diverse and niche-specialized microbial communities that develop in the human host with chronological age. The largest reservoir of microbes exists in the distal gastrointestinal tract, both in the lumen, where microbes facilitate primary and secondary metabolism, and on mucosal surfaces, where they interact with host immune cell populations. While local microbial-driven immunomodulation in the gut is well described, more recent studies have demonstrated a role for the gut microbiome in influencing remote organs and mucosal and hematopoietic immune function. Unsurprisingly, therefore, perturbation to the composition and function of the gut microbiota has been associated with chronic diseases ranging from gastrointestinal inflammatory and metabolic conditions to neurological, cardiovascular, and respiratory illnesses. Considerable effort is currently focused on understanding the natural history of microbiome development in humans in the context of health outcomes, in parallel with improving our knowledge of microbiome-host molecular interactions. These efforts ultimately aim to develop effective approaches to rehabilitate perturbed human microbial ecosystems as a means to restore health or prevent disease. This review details the role of the gut microbiome in modulating host health with a focus on immunomodulation and discusses strategies for manipulating the gut microbiome for the management or prevention of chronic inflammatory conditions.

Links between environment, diet, and the hunter-gatherer microbiome

ABSTRACTThe study of traditional populations provides a view of human-associated microbes unperturbed by industrialization, as well as a window into the microbiota that co-evolved with humans. Here we discuss our recent work characterizing the microbiota from the Hadza hunter-gatherers of Tanzania. We found seasonal shifts in bacterial taxa, diversity, and carbohydrate utilization by the microbiota. When compared to the microbiota composition from other populations around the world, the Hadza microbiota shares bacterial families with other traditional societies that are rare or absent from microbiotas of industrialized nations. We present additional observations from the Hadza microbiota and their lifestyle and environment, including microbes detected on hands, water, and animal sources, how the microbiota varies with sex and age, and the short-term effects of introducing agricultural products into the diet. In the context of our previously published findings and of these additional observations, we discuss a path forward for future work.

Bacterial communities on facial skin of teenage and elderly Thai females.

The Human Microbiome Project was first established to understand the roles of human-associated microbes to human health and disease. This study presents preliminary findings of Thai female facial skin microbiome using three pooled samples from groups of skin microbiome profiles, namely (1) healthy and (2) acne-prone young adults (teenage.hea and teenage.acn) and (3) healthy elderly adults (elderly.hea) based on standard dermatological criteria. These samples were sequenced using 454-pyrosequencing targeting 16S rRNA (V3-V4 regions). Good's coverage index of greater than 92% shows sufficient sampling of our data for each group. Three unique OTUs for each microbiome profile (43, 258 and 59 for teenage.hea, teenage.acn and ederly.hea, respectively) were obtained with 134 shared OTUs among the three datasets. Based on Morisita-Horn similarity coefficient, age is the major factor that brings the community relationship factor closer. The comparison among the three datasets reveal majority of Gemmatimonadetes, Planctomycetes and Nitrospirae in the teenage.hea, whereas Firmicutes are more prevalent in teenage.acn and elderly.hea skin types. In addition, when comparing Thai facial microbial diversity with the 16S data from U.S. forehead female database, significant differences were found among orders of bacteria, pointing to possible differences in human ecto-flora.

Stable isotope profiles reveal active production of VOCs from human-associated microbes

Volatile organic compounds (VOCs) measured from exhaled breath have great promise for the diagnosis of bacterial infections. However, determining human or microbial origin of VOCs detected in breath remains a great challenge. For example, the microbial fermentation product 2,3-butanedione was recently found in the breath of Cystic Fibrosis (CF) patients; parallel culture-independent metagenomic sequencing of the same samples revealed that Streptococcus and Rothia spp. have the genetic capacity to produce 2,3-butanedione. To investigate whether the genetic capacity found in metagenomes translates to bacterial production of a VOC of interest such as 2,3-butanedione, we fed stable isotopes to three bacterial strains isolated from patients: two gram-positive bacteria, Rothia mucilaginosa and Streptococcus salivarius, and a dominant opportunistic gram-negative pathogen, Pseudomonas aeruginosa. Culture headspaces were collected and analyzed using a gas chromatographic system to quantify the abundance of VOCs of interest; mass spectroscopy was used to determine whether the stable isotope label had been incorporated. Our results show that R. mucilaginosa and S. salivarius consumed D-Glucose-13C6 to produce labeled 2,3-butanedione. R. mucilaginosa and S. salivarius also produced labeled acetaldehyde and ethanol when grown with 2H2O. Additionally, we find that P. aeruginosa growth and dimethyl sulfide production are increased when exposed to lactic acid in culture. These results highlight the importance VOCs produced by P. aeruginosa, R. mucilaginosa, and S. salivarius as nutrients and signals in microbial communities, and as potential biomarkers in a CF infection.

The effects of antibiotics on the microbiome throughout development and alternative approaches for therapeutic modulation.

The widespread use of antibiotics in the past 80 years has saved millions of human lives, facilitated technological progress and killed incalculable numbers of microbes, both pathogenic and commensal. Human-associated microbes perform an array of important functions, and we are now just beginning to understand the ways in which antibiotics have reshaped their ecology and the functional consequences of these changes. Mounting evidence shows that antibiotics influence the function of the immune system, our ability to resist infection, and our capacity for processing food. Therefore, it is now more important than ever to revisit how we use antibiotics. This review summarizes current research on the short-term and long-term consequences of antibiotic use on the human microbiome, from early life to adulthood, and its effect on diseases such as malnutrition, obesity, diabetes, and Clostridium difficile infection. Motivated by the consequences of inappropriate antibiotic use, we explore recent progress in the development of antivirulence approaches for resisting infection while minimizing resistance to therapy. We close the article by discussing probiotics and fecal microbiota transplants, which promise to restore the microbiota after damage of the microbiome. Together, the results of studies in this field emphasize the importance of developing a mechanistic understanding of gut ecology to enable the development of new therapeutic strategies and to rationally limit the use of antibiotic compounds.

Editorial on "Cancer and the microbiota" published in Science.

In recent years, improved sequencing technologies have resulted in a surge of information that has clarified the interactions between microorganisms and their environment. Most notably, examination of human-associated microbes has revealed their important role in the prevention and development of specific diseases. In particular, we now have a deeper understanding of how the microbiota can influence cancer development and progression as well as their potential application in cancer therapeutics. Dr. Wendy Garrett highlights these recent advances in her review “Cancer and the microbiota” which was published in April 2015 in Science . This is the most recent review of a relatively large number that cover this topic, but Dr. Garrett’s review stands out in its coverage of the therapeutic potential of microorganisms for cancer prevention. Here we provide an overview of Dr. Garrett’s manuscript in the context of the larger body of work on this topic.

A new era in palaeomicrobiology: prospects for ancient dental calculus as a long-term record of the human oral microbiome.

The field of palaeomicrobiology is dramatically expanding thanks to recent advances in high-throughput biomolecular sequencing, which allows unprecedented access to the evolutionary history and ecology of human-associated and environmental microbes. Recently, human dental calculus has been shown to be an abundant, nearly ubiquitous, and long-term reservoir of the ancient oral microbiome, preserving not only microbial and host biomolecules but also dietary and environmental debris. Modern investigations of native human microbiota have demonstrated that the human microbiome plays a central role in health and chronic disease, raising questions about changes in microbial ecology, diversity and function through time. This paper explores the current state of ancient oral microbiome research and discusses successful applications, methodological challenges and future possibilities in elucidating the intimate evolutionary relationship between humans and their microbes.