Highlights d Mice harboring human ASD, but not TD, microbiomes exhibit ASD-like behaviors d ASD and TD microbiota produce differential metabolome profiles in mice d Extensive alternative splicing of risk genes in brains of mice with ASD microbiota d BTBR mice treated with 5AV or taurine improved repetitive and social behaviors

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In systems biology studies, the integration of multiple omics measurements (i.e., genomics, transcriptomics, proteomics, metabolomics, and lipidomics) has been shown to provide a more complete and informative view of biological pathways. Thus, the prospect of extracting different types of molecules (e.g., DNAs, RNAs, proteins, and metabolites) and performing multiple omics measurements on single samples is very attractive, but such studies are challenging due to the fact that the extraction conditions differ according to the molecule type. Here, we adapted an organic solvent-based extraction method that demonstrated broad applicability and robustness, which enabled comprehensive proteomics, metabolomics, and lipidomics analyses from the same sample.

Genome-scale metabolic network reconstruction and analysis of the murine leukemic macrophage cell line RAW 264.7 reveal a complementary relationship between how known metabolic immunomodulators are biochemically processed and their role in macrophage activation.

Microbial autotroph-heterotroph interactions influence biogeochemical cycles on a global scale, but the diversity and complexity of natural systems and their intractability to in situ manipulation make it challenging to elucidate the principles governing these interactions. The study of assembling phototrophic biofilm communities provides a robust means to identify such interactions and evaluate their contributions to the recruitment and maintenance of phylogenetic and functional diversity over time. To examine primary succession in phototrophic communities, we isolated two unicyanobacterial consortia from the microbial mat in Hot Lake, Washington, characterizing the membership and metabolic function of each consortium. We then analyzed the spatial structures and quantified the community compositions of their assembling biofilms. The consortia retained the same suite of heterotrophic species, identified as abundant members of the mat and assigned to Alphaproteobacteria, Gammaproteobacteria, and Bacteroidetes. Autotroph growth rates dominated early in assembly, yielding to increasing heterotroph growth rates late in succession. The two consortia exhibited similar assembly patterns, with increasing relative abundances of members from Bacteroidetes and Alphaproteobacteria concurrent with decreasing relative abundances of those from Gammaproteobacteria. Despite these similarities at higher taxonomic levels, the relative abundances of individual heterotrophic species were substantially different in the developing consortial biofilms. This suggests that, although similar niches are created by the cyanobacterial metabolisms, the resulting webs of autotroph-heterotroph and heterotroph-heterotroph interactions are specific to each primary producer. The relative simplicity and tractability of the Hot Lake unicyanobacterial consortia make them useful model systems for deciphering interspecies interactions and assembly principles relevant to natural microbial communities.

Genes encoding the virulence-promoting type III secretion system (T3SS) in phytopathogenic bacteria are induced at the start of infection, indicating that recognition of signals from the host plant initiates this response. However, the precise nature of these signals and whether their concentrations can be altered to affect the biological outcome of host-pathogen interactions remain speculative. Here we use a metabolomic comparison of resistant and susceptible genotypes to identify plant-derived metabolites that induce T3SS genes in Pseudomonas syringae pv tomato DC3000 and report that mapk phosphatase 1 (mkp1), an Arabidopsis mutant that is more resistant to bacterial infection, produces decreased levels of these bioactive compounds. Consistent with these observations, T3SS effector expression and delivery by DC3000 was impaired when infecting the mkp1 mutant. The addition of bioactive metabolites fully restored T3SS effector delivery and suppressed the enhanced resistance in the mkp1 mutant. Pretreatment of plants with pathogen-associated molecular patterns (PAMPs) to induce PAMPtriggered immunity (PTI) also restricts T3SS effector delivery and enhances resistance by unknown mechanisms, and the addition of the bioactive metabolites similarly suppressed both aspects of PTI.Together, these results demonstrate that DC3000 perceives multiple signals derived from plants to initiate its T3SS and that the level of these host-derived signals impacts bacterial pathogenesis. P lants evoke resistance against invading bacteria using plasma membrane-localized pattern recognition receptors (PRRs) to detect the presence of pathogen-associated molecular patterns (PAMPs) in the extracellular space (1). Activation of PRRs by PAMPs results in numerous defense responses that limit bacterial growth (1). However, the actual mechanisms by which plants suppress virulence and restrict bacterial growth remain unclear. Pseudomonas syringae is a model bacterial pathogen that infects a wide range of economically important crops as well as the laboratory model plant Arabidopsis (2). P. syringae uses several different virulence strategies to suppress host defenses, including a type III secretion system (T3SS) that secretes up to 30 effector proteins into plant cells (3, 4). Many effectors function to suppress PRR-induced signaling, thereby allowing the bacteria to avoid detection and proliferate (4). Mutants of P. syringae lacking a functional T3SS are not fully virulent, demonstrating that this system is essential for a successful infection (5, 6). Moreover, recent studies have revealed that PAMP-triggered immunity (PTI) leads to a restriction in the delivery of type III effectors into host cells, suggesting that plants possess an unknown mechanism(s) to block type III secretion (7,8).Despite the critical role of the T3SS in P. syringae virulence, T3SS structural components and effectors are not constitutively present but are produced at the onset of infection (9, 10). Early attempts to identify plant signals perceived by P. syringae revea...

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SUMMARY The pathogenesis of Human Ebola virus disease (EVD) is complex. EVD is characterized by high levels of virus replication and dissemination, dysregulated immune responses, extensive virus- and host-mediated tissue damage, and disordered coagulation. To clarify how host responses contribute to EVD pathophysiology, we performed multi-platform ‘omics analysis of peripheral blood mononuclear cells and plasma from EVD patients. Our results indicate that EVD molecular signatures overlap with those of sepsis, imply that pancreatic enzymes contribute to tissue damage in fatal EVD, and suggest that EBOV infection may induce aberrant neutrophils whose activity could explain hallmarks of fatal EVD. Moreover, integrated biomarker prediction identified putative biomarkers from different data platforms that differentiated survivors and fatalities early after infection. This work reveals insight into EVD pathogenesis, suggests an effective approach for biomarker identification, and provides an important community resource for further analysis of human EVD severity.