We face major agricultural challenges that remain a threat for global food security. Soil microbes harbor enormous potentials to provide sustainable and economically favorable solutions that could introduce novel approaches to improve agricultural practices and, hence, crop productivity. In this review we give an overview regarding the current state-of-the-art of microbiome research by discussing new technologies and approaches. We also provide insights into fundamental microbiome research that aim to provide a deeper understanding of the dynamics within microbial communities, as well as their interactions with different plant hosts and the environment. We aim to connect all these approaches with potential applications and reflect how we can use microbial communities in modern agricultural systems to realize a more customized and sustainable use of valuable resources (e.g., soil).

Understanding how plants respond to nitrogen in their environment is crucial for determining how they use it and how the nitrogen use affects other processes related to plant growth and development. Under nitrogen limitation the activity and affinity of uptake systems is increased in roots, and lateral root formation is regulated in order to adapt to low nitrogen levels and scavenge from the soil. Plants in the legume family can form associations with rhizobial nitrogen-fixing bacteria, and this association is tightly regulated by nitrogen levels. The effect of nitrogen on nodulation has been extensively investigated, but the effects of nodulation on plant nitrogen responses remain largely unclear. In this study, we integrated molecular and phenotypic data in the legume Medicago truncatula and determined that genes controlling nitrogen influx are differently expressed depending on whether plants are mock or rhizobia inoculated. We found that a functional autoregulation of nodulation pathway is required for roots to perceive, take up, and mobilize nitrogen as well as for normal root development. Our results together revealed that autoregulation of nodulation, root development, and the location of nitrogen are processes balanced by the whole plant system as part of a resource-partitioning mechanism.

Understanding the variables that influence microbiome studies is critical for successful translational research. Inflammatory bowel disease (IBD) is a complex group of diseases that can present at multiple locations within the Gastrointestinal tract. Here, using the FAMISHED study cohort, we aimed to investigate the relationship between IBD condition, IBD disease location, and the microbiome. Signatures of the microbiome, including measures of diversity, taxonomy, and functionality, all significantly differed across the three different IBD conditions, Crohn’s disease (CD), ulcerative colitis (UC), and microscopic colitis (MC). Notably, when stratifying by disease location, patients with CD in the terminal ileum were more similar to healthy controls than patients with CD in the small bowel or colon, however no differences were observed at different disease locations across patients with UC. Change in taxonomic composition resulted in changes in function, with CD at each disease location, UC and MC all having unique functional dysbioses. CD patients in particular had deficiencies in Short-Chain Fatty Acid (SCFA) pathways. Our results demonstrate the complex relationship between IBD and the microbiome and highlight the need for consistent strategies for the stratification of clinical cohorts and downstream analysis to ensure results across microbiome studies and clinical trials are comparable.

Background Effective standardisation of the microbiome field is essential to facilitate global translational research and increase the reproducibility of microbiome studies. In this study, we describe the development and validation of a whole cell reference reagent specific to the gut microbiome by the UK National Institute for Biological Standards and Control. We also provide and test a two-step reporting framework to allow microbiome researchers to quickly and accurately validate choices of DNA extraction, sequencing, and bioinformatic pipelines. Results Using 20 strains that are commonly found in the gut, we developed a whole cell reference reagent (WC-Gut RR) for the evaluation of the DNA extraction protocols commonly used in microbiome pipelines. DNA was first analysed using the physicochemical measures of yield, integrity, and purity, which demonstrated kits widely differed in the quality of the DNA they produced. Importantly, the combination of the WC-Gut RR and the three physicochemical measures allowed us to differentiate clearly between kit performance. We next assessed the ability of WC-Gut RR to evaluate kit performance in the reconstitution of accurate taxonomic profiles. We applied a four-measure framework consisting of Sensitivity, false-positive relative abundance (FPRA), Diversity, and Similarity as previously described for DNA reagents. Using the WC-Gut RR and these four measures, we could reliably identify the DNA extraction kits’ biases when using with both 16S rRNA sequencing and shotgun sequencing. Moreover, when combining this with complementary DNA standards, we could estimate the relative bias contributions of DNA extraction kits vs bioinformatic analysis. Finally, we assessed WC-Gut RR alongside other commercially available reagents. The analysis here clearly demonstrates that reagents of lower complexity, not composed of anaerobic and hard-to-lyse strains from the gut, can artificially inflate the performance of microbiome DNA extraction kits and bioinformatic pipelines. Conclusions We produced a complex whole cell reagent that is specific for the gut microbiome and can be used to evaluate and benchmark DNA extractions in microbiome studies. Used alongside a DNA standard, the NIBSC DNA-Gut-Mix RR helps estimating where biases occur in microbiome pipelines. In the future, we aim to establish minimum thresholds for data quality through an interlaboratory collaborative study.

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The biocontrol agent Paenibacillus alvei K165 was previously shown to protect Arabidopsis thaliana plants against Verticillium dahliae. Here we show that K165 also confers inherited immune resistance against V. dahliae. By performing a histone acetyltransferases mutant screen, ChIP-assays and transcriptomic experiments we were able to show that histone acetylation significantly contributes to the K165 biocontrol activity and establishment of inheritable resistance against V. dahliae. K165 treatment primed the expression of immune-related marker genes and the cinnamyl alcohol dehydrogenases CAD3 through the function of histone acetyltransferases. Our results reveal that offspring of plants treated with K165 have primed immunity and enhanced lignification both contributing towards the K165-mediated inherited immune resistance. Thus, our study paves that way for the use of biocontrol agents for the establishment of inheritable resistance against agronomically important pathogens.

Microbiome therapies have the potential to revolutionise our approach to medicine, but until now, a lack of standardisation and regulation has hampered clinical development. Here, Chrysi Sergaki and Jack Hassall from the National Institute for Biological Standards and Control discuss how they are developing reference reagents to standardise analysis of microbiome samples, and how research is now moving towards the development of more targeted microbiome‐based therapeutics.

The advent of immune checkpoint inhibitor therapy was a significant step in the development of treatments for cancer. It is, however, a double-edged sword. Immune related adverse events are the result of unleashing brakes on the immune system and affect many patients undergoing checkpoint inhibitor therapy, often being debilitating and occasionally lethal. It has been shown both in mice and in humans that the presence of certain families, genera and species of bacteria are associated with improved responses to checkpoint inhibitor therapy, whereas in their absence the response to therapy is often poor. Recent studies have demonstrated that immune related adverse events to checkpoint inhibitor therapy can be perturbed and perhaps predicted based on the composition and functional capacity of the gut microbiota and parts of the immune system. In the case of colitis associated with immune checkpoint inhibitor therapy, one interesting avenue of investigation is based on the activity of secretory immunoglobulin A (SIgA). Produced by plasma cells, IgA is present in high concentrations at the gut mucosa and is involved in both the maturation and maintenance of the microbiota as well as the development of IBD. Here we summarise the current literature surrounding the interplay between the gut microbiota and response to CPI therapy. Additionally, we overview the colonic immune system, paying particular attention to IgA, as a key component of the microbiota-immune system interaction.