Cell

The Medieval Ottonian dynasty had a lasting impact on European history. We obtained ancient genomic DNA from the purported remains of Otto I (912-973) and Heinrich (Henry) II (973-1024), the first and last emperors of this dynasty, preserved in the cathedrals of Magdeburg and Bamberg, respectively. Historical records attest that they were related as a great-uncle and a grandnephew via the paternal line. Whole-genome sequencing confirms such a relationship between the two individuals, as we identify a third-degree genetic relationship based on shared DNA segments and infer matching Y haplogroups. This genetic relatedness effectively identifies the remains of the two emperors. The authentication yields a valuable resource for refining and calibrating bio-archaeological methods. Because historical records provide the precise lifespans and dates of death of these individuals, their remains can serve as a "ground-truth" for methods such as radiocarbon dating and age-at-death estimates. They can provide calibration data to improve our understanding of the radiocarbon reservoir effects of Medieval elites. As the Ottonian lineage was closely linked to the mating networks of elites across Europe, the genomes of the two emperors are valuable resources for identifying other potential elite burials.

Northwest South America was a pivotal region for human dispersals and cultural exchange during the Holocene. The Altiplano Cundiboyacense, a high-altitude plateau in the Eastern Cordillera of the Northern Andes of Colombia, preserves one of the most continuous archaeological sequences in the Americas, spanning from late Pleistocene hunter-gatherer groups to final late Holocene Muisca chiefdoms. Increasing the regional ancient DNA sample size 11-fold, we report genome-wide data from 209 individuals who lived over a period of more than 7000 years. This includes hunter-gatherers from the early-middle (10,000-7000 BP) and middle (7000-4000 BP) Holocene, initial late Holocene people (4000-2500 BP) who have the first isotopic evidence of C-enriched diets (attributed to maize), and populations associated with increasing sedentism and food production in the Herrera (2200-1300 BP) and Muisca (1200-500 BP) Periods. Previous work identified a major population turnover distinguishing earlier groups from Herrera-Muisca Period populations, but the absence of individuals dating 6000-2000 BP in that study left unresolved whether this ancestry shift was gradual or abrupt and whether it accompanied the earliest isotopic evidence of dietary input from maize or coincided with the later emergence of Herrera culture. We show that individuals predating the Herrera Period form a lineage that persisted for over five millennia, with population structure driven by drift in small groups and no detectable external gene flow. Two individuals who lived [~]2800 years ago - one directly dated to 983-835 calBCE - exhibit genetic profiles entirely consistent with hunter-gatherer ancestry yet have isotopic values consistent with the incorporation of maize into their diets, indicating subsistence change without population replacement. The emergence of Herrera culture [~]2200 BP coincided with a sharp genetic break, reflecting the migration of people carrying ancestry diverged by up to ten millennia into the Sabana de Bogota and displacing previously established peoples. By co-analyzing ancient data with modern Native Americans, we show these later populations derived from a mixture [~]4000 years ago of groups related to Chibchan language speakers of lower Central America and ones related to present-day people at the Amazonian-Andean interface who may have lived along the Chibchan expansion route. In the Herrera and Muisca Periods, genetic substructure distinguishes people from the southern and northern Altiplano, consistent with the cultural differentiation of these regions in the archaeological record. IN BRIEFAncient DNA data from the eastern Colombian Andes reveal five millennia of population continuity during which C plants were incorporated into subsistence systems without population replacement, followed later by a major ancestry turnover involving a population with ancestry admixed between that found in Chibchan-related groups and at the Amazonian-Andean interface.

A complete transcriptome atlas of every cell type of a vertebrate could promote understanding of animal cell-type composition, organization, and evolution. The miniaturized, transparent, and regenerative teleost Danionella cerebrum brings whole-organism single-cell profiling experiments within experimental reach for adult vertebrate biology. We performed regionally stratified single-cell RNA sequencing experiments in adult Danionella to profile cells across the whole body and mapped cell types and gene expression spatially at single-cell resolution using whole-animal spatial transcriptomics. We delineated spatially distinct neural progenitor and neuronal cell types across the adult nervous system based on their regional gene expression signatures. The body-wide atlas uncovered paedomorphic features, allowed elucidation of cell types likely to harbor adult positional information, and revealed constitutive expression of conserved body region and appendage specification programs in adult connective tissue. Comparative analyses revealed conserved neural cell types over a large evolutionary distance, and neural regeneration datasets uncovered temporally resolved expression dynamics in neural progenitors for telencephalon regeneration. This whole-vertebrate transcriptome atlas yields a comprehensive resource for myriad questions in biology and neuroscience.

The small intestine houses an array of immune cells that receive diverse inputs from food intake, microbiota, and other cues that vary by time of day. However, how diurnal variation influences intestinal immune cell proportions and functions is unclear. Here, we use flow cytometry and single cell RNA sequencing to establish an atlas of 815,073 mouse small intestine immune cells at four times across the day-night cycle. These data suggest possible temporal coordination of dendritic cell antigen processing and subsequent T cell antigen recognition. Most cells express circadian clock genes and have intrinsic oscillatory transcriptomes. However, differentiated antibody-producing plasma cells have minimal circadian gene expression and instead may receive extrinsic oscillatory cues from other cell types. Finally, certain populations of B cells are extremely dynamic, with broad transcriptional changes within a six hour time span. This dataset provides insight into the circadian dynamics of intestinal immunity. SummaryO_LIAn atlas of 815,073 small intestine immune cells across four time-points reveals a large proportion of naive B and T cells. C_LIO_LIGene expression profiles suggest coordination of antigen processing in dendritic cells prior to antigen recognition by T cells. C_LIO_LITh17 and innate lymphoid cells have high expression of circadian clock genes and most immune cells have rhythmic gene expression. C_LIO_LIPopulations of certain B cell subtypes, including transitional B cells and centrocytes, are extremely dynamic with large shifts over a six hour time frame. C_LIO_LITerminally differentiated antibody-producing plasma cells have minimal circadian gene expression and few oscillatory genes. C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=121 SRC="FIGDIR/small/701519v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@162f451org.highwire.dtl.DTLVardef@1960711org.highwire.dtl.DTLVardef@a9fd4aorg.highwire.dtl.DTLVardef@341f42_HPS_FORMAT_FIGEXP M_FIG C_FIG

Climatic oscillations in the Andes have repeatedly reshaped habitats over millions of years, yet their long-term genomic consequences for wide-ranging carnivores remain unclear. We generated whole-genome sequences from pumas (Puma concolor) across ecologically distinct regions of Ecuador to test how paleoclimate shaped population structure, demography, and genetic load. We show that northwestern forest pumas persisted in long-term isolation within humid refugia, whereas northern Andean and southern Pacific populations reconnected intermittently during warm interglacial periods. Southern coastal pumas maintained persistently small effective population sizes, leading to elevated runs of homozygosity and increased burdens of homozygous loss-of-function variants. In contrast, northern populations historically remained larger but exhibit early signs of inbreeding in one individual, marked by long runs of homozygosity and a kinked tail phenotype. Our findings indicate that recent fragmentation may be disrupting historical connectivity. Restoring corridors around the western foothills could reestablish gene flow and reduce inbreeding risk, while targeted genetic rescue may support chronically isolated southern populations. By integrating paleoclimate history with genome-wide data, we provide a framework for region-specific conservation strategies that balance connectivity restoration with the preservation of local adaptation.

Synthetic living constructs, which lack the long histories of selection in ecological contexts that shape behaviors of conventional organisms, offer an important complement to traditional studies of learning. Could novel biobots exhibit sensing and memory of experiences? Here, we investigated the effects of chemical stimuli on basal Xenobots - autonomously motile entities derived from Xenopus embryonic ectodermal explants (with no additional sculpting or bioengineering). We quantified and characterized the coordinated ciliary activity that generates fluid flow fields guiding the trajectory of Xenobot motion. We also show distinct and specific changes in Xenobot behavior after brief exposure to Xenopus embryonic cell extract and to ATP. These two experiences produced distinct, long-term, stimulus-specific memories, detectable through both transcriptional and physiological signatures. Exposure to specific environmental stimuli induced alterations in the spatiotemporal patterns of calcium signaling across Xenobots. Together, these data lay a foundation for characterizing the capabilities of synthetic cellular collectives to sense and discriminate among stimuli, as well as store functional information in a non-neural context. Understanding behavioral competencies in novel, non-neural systems have broad implications across evolutionary biology, behavioral science, bioengineering, and bio/hybrid robotics.

Extracellular traps (ETs) were originally described in neutrophils as DNA-based structures that immobilize microbes and contribute to innate immunity. Subsequent studies revealed that ET formation occurs across diverse immune cell types and can proceed through non-lytic mechanisms involving mitochondrial DNA release. Whether ETosis also operates outside classical immune contexts and what its ancestral functions may be remain incompletely understood. Here, we show that vegetative, phagocytic cells of the social amoeba Dictyostelium discoideum, a professional bacterial predator with phagocytic mechanisms conserved with those of mammalian innate immune cells, deploy extracellular DNA traps in response to bacterial cues. ET formation is selectively induced by specific lipopolysaccharide variants, is not triggered by canonical neutrophil NET inducers, and occurs through a vital ETosis mechanism that preserves membrane integrity and feeding capacity. Ultrastructural analyses provide the first visualization of extracellular traps in Amoebozoa, revealing extracellular filamentous networks that physically capture bacteria. Molecular characterization demonstrates that amoeboid ETs are enriched in mitochondrial DNA and harbor a dynamic proteomic repertoire dominated by mitochondrial components, DNA-associated proteins, and multiple antibacterial effectors. Notably, ET composition varies with the bacterial stimulus, indicating that ETs are not static structures but rather responsive extracellular assemblies. Together, these findings establish ET formation as a regulated response in a unicellular phagocyte and suggest that extracellular traps may have originally functioned in microbial management during feeding, prior to their elaboration as immune effectors in multicellular organisms. HighlightsO_LIVegetative Dictyostelium discoideum cells deploy mitochondrial DNA-based extracellular traps in response to bacterial cues. C_LIO_LIET formation occurs through a vital, non-lytic mechanism that preserves membrane integrity and feeding capacity. C_LIO_LIExtracellular traps exhibit stimulus-dependent composition and are enriched in mitochondrial and antimicrobial proteins. C_LIO_LIETosis functions as an ancestral strategy for microbial containment and management beyond canonical immune contexts. C_LI

Ancient proteins provide a direct window into past diets by enabling the identification of consumed foods through the analysis of dental calculus. While previous studies have reliably detected animal-derived proteins such as milk, plant-derived proteins remain markedly underrepresented, leaving a significant gap in our understanding of the role of plants in past human diets. Here, we show how the reanalysis of open-access paleoproteomics datasets can reveal previously overlooked plant proteins by revisiting two archaeological dental calculus datasets spanning the Eneolithic to Iron Age from the Pontic-Caspian region and the Levantine coast (n = 63 individuals). We identify 60 unique peptides derived from 60 distinct proteins of broomcorn millet (Panicum miliaceum) in 39 individuals. All peptides are unique to Panicum miliaceum and their taxonomic assignment was confirmed using a stringent multi-tier validation strategy, providing the first paleoproteomics evidence of its consumption preserved in dental calculus and extending beyond current protein database annotations. Combined with existing radiocarbon chronologies, these findings represent the earliest paleoproteomics evidence of broomcorn millet consumption, substantially revising its chronology and geographic pathways of dispersal across Eurasia. More broadly, this study demonstrates the untapped potential of dental calculus proteomics and open-access data to directly trace plant consumption, opening new avenues for investigating crops that remain underrepresented in archaeological and proteomics research.

RNA viruses cause substantial global morbidity, yet their impact prior to the twentieth century remains obscured. While ancient DNA studies have transformed our understanding of past pathogens, ancient RNA (aRNA) isolation is largely restricted to exceptionally preserved samples. Here, we simultaneously recover aDNA and aRNA from non-formalin-fixed human lung specimens and reconstructed an 18th-century Human Rhinovirus (HRV) A genome--the oldest human RNA virus identified to date. The RNA is highly fragmented, with distinctive terminal misincorporations and coverage patterns consistent with double-stranded RNA. Phylogenetic analyses indicate that this historical HRV genome is an extinct lineage related to contemporary genotypes, providing a unique perspective on rhinovirus evolution. These findings demonstrate that centuries-old medical specimens can retain informative aRNA, expanding the temporal scope of paleovirology.

Soil microbial communities underpin both soil health and agricultural productivity, yet genome-resolved resources from long-term field experiments remain limited. Here, we present a genome-resolved metagenomic dataset from the historic Morrow Plots long-term experiment in central USA, comprising 33 shotgun metagenomes collected across diverse crop rotation and fertilization treatments in year 149 of the experiment. Using a co-assembly, multi-binner workflow, we recovered 230 metagenome-assembled genomes (MAGs), including 44 archaeal and 186 bacterial genomes spanning multiple soil-associated phyla. Among these, 59 MAGs were linked to nitrogen-cycling functions, including ammonia- and nitrite-oxidizing lineages. The dataset also includes genome quality metrics, taxonomic classification, and treatment-resolved abundance patterns across different management regimes. Importantly, these nitrogen guild MAGs enable comparative analyses of nitrifier ecology, genome diversity, and functional variation linked to management in agricultural soils. Together, these resources establish a unique benchmark for studying how agricultural practices shape soil microbial communities at genome level, with associated long-term crop yield and soil fertility changes since the experiments inception in 1876.

Upon infection, arteriviruses, coronaviruses, and other nidoviruses transform endoplasmic reticulum membranes into viral replication organelles. These include large numbers of double-membrane vesicles (DMVs) whose interior is considered the primary site of viral RNA synthesis. Early studies characterized nidovirus DMVs as sealed compartments, leaving it unclear how newly synthesized viral RNA could be exported to the cytosol. The discovery of DMV-spanning pore complexes in coronavirus-infected cells provided a plausible solution for this topological challenge. However, their structural organization, functional features, and evolutionary conservation across the nidovirus order, have remained unclear. Here, we investigated the macromolecular architecture of DMVs induced by two prototypic arteriviruses using cellular cryo-electron tomography. Despite the substantial evolutionary distance separating arteriviruses and coronaviruses, we observed DMV-spanning pore complexes with striking structural similarities to those previously described in coronaviruses. These pores appear to facilitate both export and encapsidation of viral RNA. In the absence of viral RNA synthesis, ectopic expression of the arterivirus transmembrane nonstructural proteins nsp2 and nsp3 sufficed to induce the formation of pore-containing DMVs. Together, our findings reveal the conservation of key structural features of DMV pores across two distantly related nidovirus families and support a central role for these pores in nidovirus replication.

The fossil record of the Precambrian era preserves some of the earliest evidence of life, yet these ancient microfossils primarily reveal morphology rather than function, leaving unresolved questions about how early cells lived, replicated and evolved. The RNA world hypothesis proposes that primordial organisms relied on RNA for both information storage and catalysis, but direct living systems reflecting such biology remain poorly characterized. Here we describe cell-like entities isolated from mammalian tissues, measuring approximately 1-3 m in diameter and exhibiting morphological similarity to a range of Precambrian microfossils. Ultrastructural comparisons reveal a high degree of correspondence with fossil taxa spanning the Paleoproterozoic to Ediacaran intervals ([~]1.8 Ga to [~]551 Ma). In addition to these morphological features, the entities display biochemical characteristics, including RNA-dominant nucleic acid content and particle-associated reverse transcriptase activity. These observations indicate that the cell-like entities described are not inert, but represent biologically active systems. The combined ultrastructural and biochemical features raise the possibility that biologically active entities comparable to those observed in Precambrian microfossils may occur in contemporary biological contexts.

Invasion genetics presents a classic paradox: how do species successfully establish and spread despite severe population bottlenecks? The brown treesnake (Boiga irregularis) in Guam represents a striking example of this phenomenon, having been introduced with only a handful of individuals. We show that the population endured an extreme bottleneck and high levels of inbreeding, with roughly half of the genome exhibiting runs of homozygosity, comparable to species of conservation concern. Despite this, we uncovered extensive diversity in the form of nearly 19,000 genomic structural variants, which affect almost eight times more of the genome than single-nucleotide variants and provide material for rescuing the population from inbreeding-driven declines. This diversity is not randomly distributed across chromosomes but rather is enriched in genes vital for immunity and olfaction, suggesting genomic diversity in key chromosomal regions can rescue populations from inbreeding. This work has implications for invasion biology and conservation genetics practitioners. TEASERGenomic structural variants rescue a textbook biological invader from a population bottleneck and inbreeding

Glycan-microbe interactions are central to gut colonization and host-microbiota communication. Here, we apply a DNA-encoded Liquid Glycan Array (LiGA) to quantify interactions between live gut bacteria and multivalent natural or mirror glycans. LiGA comprises glycosylated M13 bacteriophage bearing silent DNA barcodes that encode glycan identity and density. Using LiGA, we profiled glycan binding across 16 Limosilactobacillus reuteri strains isolated from murine, porcine, poultry, and human hosts, and then extended the approach to profile glycan binding of taxonomically diverse bacteria from three phyla Bacillota, Bacteroidota, Pseudomonadota consisting of nine different species. Recent discussion of mirror-image microorganisms raise a question whether these microorganisms could interact with present-day life by engaging naturally chiral glycans. We demonstrated that this question can be assessed by testing the binding of mirror-image glycans to natural bacteria. Evaluation of enantiomers of common glycan revealed cross-chiral recognition by Escherichia coli and L. reuteri, indicating that these bacteria can used mirror-image glycans to engage for adhesion and potential colonization. By symmetry the same arguments extends to mirror microorganisms and glycans of naturally chirality. We established that LiGA enables efficient characterization of bacterial glycan binding and provides new insights into intestinal microbial ecology.

The common marmoset is a New World monkey (NWM) commonly used as a model organism to investigate questions in primate evolution and human disease, including Alzheimers and other neurodegenerative diseases, as well as neuropsychiatric disorders. Here we present the first telomere-to-telomere (T2T) reference genome for the common marmoset, adding over 88 Mb of sequence and resolving challenging genomic regions. An additional near-T2T assembly from a second unrelated individual yields a total of four high-quality haplotypes for analysis. The improved contiguity and accuracy of these assemblies enable unprecedented insights into complex and rapidly evolving genomic regions such as centromeres, sex chromosomes, ribosomal DNA (rDNA) structure, and the major histocompatibility complex (MHC). We fully resolved all marmoset centromeres, uncovering dimeric alpha satellites with chromosomal specificity and stratified inactive layers documenting ancestral centromere turnover. We assembled six acrocentric autosomes with gene-poor, satellite-rich short arms and provide evidence that most of them can harbor rDNA and all of them share large pseudo-homologous regions (PHRs). The Y chromosome, but not the X chromosome, carries active rDNA and PHRs, and the rDNA copy number is sexually dimorphic. Chromosomes that share PHRs also share closely related centromeric satellite DNA, supporting a model of ongoing recombinational exchange between heterologous chromosomes facilitated by rDNA. We discovered multiple novel, marmoset-specific MHC genes that are predicted to protect against pathogens encountered in its environment. Leveraging this complete reference, we further identified over 500 transcribed genes with transcript models or expansions specific to the marmoset lineage. Together with additional long-read marmoset assemblies, these genomes were used to construct a marmoset pangenome, providing a robust reference framework for short-read mapping across diverse individuals. This resource will improve the utility of the common marmoset as a biomedical model organism and fill key gaps in our understanding of primate evolution.

The ascidian Ciona provides a key model for understanding the evolutionary origin of the vertebrate brain. While the larval nervous system has been extensively characterized, the molecular and cellular organization of the adult neural complex remains poorly defined. Here, we generated spatial transcriptomic maps of the adult Ciona neural complex from three individuals, with four serial sections per donor, using the 10x Visium platform. Clustering-based analysis identified five major tissue domains, including the cerebral ganglion, neural gland, ciliated funnel, neural gland duct/dorsal strand, and body wall muscle. To further refine spatial resolution, we computationally reconstructed approximately 980 super-resolution gene expression maps by integrating transcriptomic measurements with histological image features. The super-resolution maps enabled precise delineation of molecular territories within the neural complex. In the cerebral ganglion, high-resolution reconstruction revealed clear molecular zonation, distinguishing the cortex and medulla. Within the cortex, the central region facing the neural gland and anteroposterior distal regions showed distinct molecular properties. In the neural gland, we identified coordinated enrichment of cell-cell interaction- and extracellular matrix-related genes, suggesting specialized structural and physiological properties. We propose that the neural gland play a pivotal role for the cerebral ganglion in maintaining homeostasis, supporting development, and providing a signaling interface, which is reminiscent of a primitive form of the choroid plexus and meninges found in vertebrates. Together, this study provides the first spatially resolved transcriptomic atlas of the adult Ciona neural complex and establishes a molecular framework for investigating functional regionalization and brain evolution in chordates.

In plants and insects, social immunity enables individuals to detect infection in neighbors and mount protective, community-level responses. Whether mammals possess analogous mechanisms remains unknown. Here, we asked how the presence of sick cage-mates influences the physiology of uninfected neighbors. We found that healthy mice co-housed with conspecifics infected with the non-communicable murine pathogen Toxoplasma gondii undergo a shift in peripheral immune responses that establishes a primed immune state. This exposure-induced priming conferred physiological resilience to a sublethal lipopolysaccharide (LPS)-inflammatory challenge and was mediated by increased myeloid-derived IL-10 production. Blocking IL-10 signaling abrogated exposure-induced protection against a subsequent immune challenge. Thus, our findings show that immune state in healthy mammals can be shaped by exposure to infected conspecifics, hinting at social immunity-based protective mechanisms in mammals. One sentence summaryImmune responses in healthy mammals are shaped by exposure to infected conspecifics.

Horizontal Gene Transfer (HGT) contributes to eukaryotic evolution, potentially bringing phenotypic novelties to the recipient organisms. Ticks pose a severe threat to human health as vectors of various pathogens, including viruses, bacteria and protozoa, while stably hosting endosymbiotic bacteria. As such, these obligate blood-feeding parasites have been and continue to be exposed to HGT from a broad range of donors. To determine whether bacterial-to-tick HGT has contributed to important tick traits, we surveyed Ixodes tick genomes for HGT events. We revealed duplications of the known bacteria-derived gene dae2 and discovered two novel cases of bacterial HGT, the most remarkable of which involves a bacterial peptidoglycan metabolic gene (anmK) acquired by the common ancestor of ticks. The acquisition of an intron demonstrates "eukaryotization" of anmK within tick genomes. Transcript profiling revealed that anmK expression is upregulated during blood feeding, peaking in female ovaries, a niche occupied by horizontally acquired endosymbionts. Biochemical analysis confirmed that, to some extent, recombinant AnmK retains kinase activity on its cognate substrate - the bacterial cell wall component 1,6-anhydro-N-acetylmuramic acid. Immunolocalization showed that the enzyme is predominantly localized towards outer layers of the vitellogenic oocytes. Silencing of anmK in different tick species compromised blood-feeding and reproduction, demonstrating that this domesticated bacterial enzyme underpins reproductive fitness across tick species. Our findings exemplify the ability of horizontally acquired genes to integrate into the host biology and thereby shape host life history.

A year-long sequencing analysis of bacterial commensals sampled from infants during periods in which they were healthy or suffering recurrent ear infections [otitis media (OM)] identified several species of bacterial commensals that correlate with health and absence of ear infections. Here we consider and test the possibility of a causal relationship between a group of commensals and periods of health. We assemble a set of five health-associated bacterial species into a nasopharyngeal commensal consortium (NPCC) and test whether these organisms can effectively colonize the respiratory tracts of mice so that their effects on invading pathogens could be evaluated. We observed that NPCC efficiently colonize mice and that they provide substantial protection against the otopathogens, Streptococcus pneumoniae and Bordetella pertussis, reducing numbers of each in the middle ears by 99 to 99.9%. The NPCC also affected colonization/growth of these pathogens within the lower respiratory tract, suggesting complexity in these interactions. Together these data demonstrate a profound effect of commensals on invading otopathogens and describe a powerful experimental system in which the important interactions between the healthy infant microbiota and invading pathogens can be studied mechanistically.

Metabolites produced by the gut microbiome influence host metabolic health, but how this occurs remains incompletely defined. Here, we report that a common human gut commensal, Blautia wexlerae, converts dietary fats into bioactive metabolites that induce gut hormone production to affect glucose metabolism and suppress appetite. We found that colonization with Blautia wexlerae correlated with healthier eating behaviors in humans. Blautia wexlerae encodes a unique acyl transferase and is capable of producing acyl amines from nutrient substrates. These Blautia acyl amines stimulated human enteroendocrine cells to secrete GLP-1 and other gut peptide hormones more potently than endogenously produced acyl amines. When fed to mice, acyl amines improved glycemic control and decreased appetite. In humans, higher stool levels of Blautia DNA encoding acyl amine synthesis genes correlated with leanness and decreased dietary fat intake. These results define a mechanism of action for how Blautia wexlerae affects host metabolic control.