Neonatal fungi promote lifelong metabolic health through macrophage-dependent β cell development.

Loss of early-life microbial diversity is correlated with diabetes, yet mechanisms by which microbes influence disease remain elusive. We report a critical neonatal window in mice when microbiota disruption results in lifelong metabolic consequences stemming from reduced β cell development. We show evidence for the existence of a similar program in humans and identify specific fungi and bacteria that are sufficient for β cell growth.

A microRNA-regulated transcriptional state defines intratumoral CD8 T cells that respond to immunotherapy.

The rising incidence of advanced-stage colorectal cancer (CRC) and poor survival outcomes necessitate new and effective therapies. Immune checkpoint inhibitors (ICIs), specifically anti-PD-1 therapy, show promise, yet clinical determinants of a positive response are suboptimal. Here, we identify microRNA-155 (miR-155) as necessary for CD8 T cell-infiltrated tumors through an unbiased in vivo CRISPR-Cas9 screen identifying functional tumor antigen-specific CD8 T cell-expressed microRNAs.

The gut microbiome is associated with disease-free survival in stage I-III colorectal cancer patients.

Colorectal cancer (CRC) is the second overall leading cause of cancer death in the United States, with recurrence being a frequent cause of mortality. Approaches to improve disease-free survival (DFS) are urgently needed. The gut microbiome, reflected in fecal samples, is likely mechanistically linked to CRC progression and may serve as a non-invasive biomarker.

Clec12a controls colitis by tempering inflammation and restricting expansion of specific commensals.

Microbiota composition regulates colitis severity, yet the innate immune mechanisms that control commensal communities and prevent disease remain unclear. We show that the innate immune receptor, Clec12a, impacts colitis severity by regulating microbiota composition. Transplantation of microbiota from a Clec12a animal is sufficient to worsen colitis in wild-type mice.

Draft genome of a human gut-derived sp. that ameliorates colitis and colitis-associated sociability deficits in mice.

is a genus of anaerobic, gram-positive bacteria commonly found in mammalian gastrointestinal tracts. Yet, how variations among different strains can impact host health is poorly understood. We present a sp.

Draft sp. genome isolated from a spore-forming community in mice.

is a common mammalian gut commensal; however, very few genomes have been sequenced, and little is understood regarding its importance for host health. Here, we add a complete sp. genome isolated from a spore-forming community in mice.

Genomes of diverse Clostridia isolated from a spore forming community in mice that were associated with protection against metabolic syndrome and obesity.

Clostridia are common mammalian gut commensals with emerging roles in human health. Here, we describe 10 Clostridia genomes from a consortium of spore forming bacteria, shown to protect mice from metabolic syndrome. These genomes will provide valuable insight on the beneficial role of spore forming bacteria in the gut.

Draft genome of a human-derived that caused spontaneous disseminated infection in a mouse.

We present the draft genome of a novel human-derived strain isolated from a healthy control human microbiota that, when put into a mouse, spontaneously disseminated from the gut to the kidneys.

Colitis reduces active social engagement in mice and is ameliorated by supplementation with human microbiota members.

Multiple neurological disorders are associated with gastrointestinal (GI) symptoms, including autism spectrum disorder (ASD). However, it is unclear whether GI distress itself can modify aspects of behavior. Here, we show that mice that experience repeated colitis have impaired active social engagement, as measured by interactions with a foreign mouse, even though signs of colitis were no longer present.

Efficient encoding of large antigenic spaces by epitope prioritization with Dolphyn.

We investigate a relatively underexplored component of the gut-immune axis by profiling the antibody response to gut phages using Phage Immunoprecipitation Sequencing (PhIP-Seq). To cover large antigenic spaces, we develop Dolphyn, a method that uses machine learning to select peptides from protein sets and compresses the proteome through epitope-stitching. Dolphyn compresses the size of a peptide library by 78% compared to traditional tiling, increasing the antibody-reactive peptides from 10% to 31%.

Efficient encoding of large antigenic spaces by epitope prioritization with Dolphyn.

We investigated a relatively underexplored component of the gut-immune axis by profiling the antibody response to gut phages using Phage Immunoprecipitation Sequencing (PhIP-Seq). To enhance this approach, we developed Dolphyn, a novel method that uses machine learning to select peptides from protein sets and compresses the proteome through epitope-stitching. Dolphyn improves the fraction of gut phage library peptides bound by antibodies from 10% to 31% in healthy individuals, while also reducing the number of synthesized peptides by 78%.

Commensal fungi in intestinal health and disease.

The microbiota is known to influence several facets of mammalian development, digestion and disease. Most studies of the microbiota have focused on the bacterial component, but the importance of commensal fungi in health and disease is becoming increasingly clear. Although fungi account for a smaller proportion of the microbiota than bacteria by number, they are much larger and therefore account for a substantial proportion of the biomass.

Associations of combined physical activity and body mass index groups with colorectal cancer survival outcomes.

Background: Physical activity and BMI have been individually associated with cancer survivorship but have not yet been studied in combinations in colorectal cancer patients. Here, we investigate individual and combined associations of physical activity and BMI groups with colorectal cancer survival outcomes.

Methods: Self-reported physical activity levels (MET hrs/wk) were assessed using an adapted version of the International Physical Activity Questionnaire (IPAQ) at baseline in 931 patients with stage I-III colorectal cancer and classified into 'highly active' and'not-highly active'(≥ / < 18 MET hrs/wk).

Clec12a tempers inflammation while restricting expansion of a colitogenic commensal.

Regulation of the microbiota is critical to intestinal health yet the mechanisms employed by innate immunity remain unclear. Here we show that mice deficient in the C-Type-lectin receptor, Clec12a developed severe colitis, which was dependent on the microbiota. Fecal-microbiota-transplantation (FMT) studies into germfree mice revealed a colitogenic microbiota formed within Clec12a mice that was marked by expansion of the gram-positive organism, .

MicroRNA-155 Plays Selective Cell-Intrinsic Roles in Brain-Infiltrating Immune Cell Populations during Neuroinflammation.

The proinflammatory microRNA-155 (miR-155) is highly expressed in the serum and CNS lesions of patients with multiple sclerosis (MS). Global knockout (KO) of miR-155 in mice confers resistance to a mouse model of MS, experimental autoimmune encephalomyelitis (EAE), by reducing the encephalogenic potential of CNS-infiltrating Th17 T cells. However, cell-intrinsic roles for miR-155 during EAE have not been formally determined.

Differences in the gut microbiome by physical activity and BMI among colorectal cancer patients.

Associations of energy balance components, including physical activity and obesity, with colorectal cancer risk and mortality are well established. However, the gut microbiome has not been investigated as underlying mechanism. We investigated associations of physical activity, BMI, and combinations of physical activity/BMI with gut microbiome diversity and differential abundances among colorectal cancer patients.

BefA, a microbiota-secreted membrane disrupter, disseminates to the pancreas and increases β cell mass.

Microbiome dysbiosis is a feature of diabetes, but how microbial products influence insulin production is poorly understood. We report the mechanism of BefA, a microbiome-derived protein that increases proliferation of insulin-producing β cells during development in gnotobiotic zebrafish and mice. BefA disseminates systemically by multiple anatomic routes to act directly on pancreatic islets.

CD11c+ myeloid cell exosomes reduce intestinal inflammation during colitis.

Intercellular communication is critical for homeostasis in mammalian systems, including the gastrointestinal (GI) tract. Exosomes are nanoscale lipid extracellular vesicles that mediate communication between many cell types. Notably, the roles of immune cell exosomes in regulating GI homeostasis and inflammation are largely uncharacterized.

Human differentiated eosinophils release IL-13 in response to IL-33 stimulation.

Objective: Eosinophils are hallmarks in allergic type 2 inflammation and are known to release cytotoxic granule proteins that contribute to inflammation. Eosinophils develop in the bone marrow from hematopoietic stem cells and once mature, have a limited lifespan in culture, making them difficult to study . IL-33 has increasingly been shown as a key regulator of type 2 inflammation signaling through its receptor, ST2.

Associations of Individual and Combined Physical Activity and Body Mass Index Groups with Proinflammatory Biomarkers among Colorectal Cancer Patients.

Background: Physical activity and obesity are well-established factors of colorectal cancer risk and prognosis. Here, we investigate associations of individual and combined physical activity and body mass index (BMI) groups with proinflammatory biomarkers in colorectal cancer patients.

Methods: Self-reported physical activity levels were classified as "active" (≥8.