In vivo antiviral host transcriptional response to SARS-CoV-2 by viral load, sex, and age

Abstract Despite limited genomic diversity, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has shown a wide range of clinical manifestations in different patient populations. The mechanisms behind these host differences are still unclear. Here, we examined host response gene expression across infection status, viral load, age, and sex among shotgun RNA sequencing profiles of nasopharyngeal […]


Microbial metabolite protects against infection

Abstract Intestinal dysbiosis is associated with an increased susceptibility to disseminated bacterial infections and sepsis. Kupffer cells, the resident macrophages of the liver that reside within the hepatic vasculature, protect the organ from pathogens and are the first liver cells to come into contact with the blood that is delivered directly to this organ from […]


Gut microorganisms act together to exacerbate inflammation in spinal cords

Abstract Accumulating evidence indicates that gut microorganisms have a pathogenic role in autoimmune diseases, including in multiple sclerosis1. Studies of experimental autoimmune encephalomyelitis (an animal model of multiple sclerosis)2,3, as well as human studies4,5,6, have implicated gut microorganisms in the development or severity of multiple sclerosis. However, it remains unclear how gut microorganisms act on […]


Glycan cross-feeding supports mutualism between Fusobacterium and the vaginal microbiota

Abstract Women with bacterial vaginosis (BV), an imbalance of the vaginal microbiome, are more likely to be colonized by potential pathogens such as Fusobacterium nucleatum, a bacterium linked with intrauterine infection and preterm birth. However, the conditions and mechanisms supporting pathogen colonization during vaginal dysbiosis remain obscure. We demonstrate that sialidase activity, a diagnostic feature […]


Microbiome-derived inosine modulates response to checkpoint inhibitor immunotherapy

Abstract Several species of intestinal bacteria have been associated with enhanced efficacy of checkpoint blockade immunotherapy, but the underlying mechanisms by which the microbiome enhances anti-tumor immunity is unclear. Here, we isolated three bacterial species, including Bifidobacterium pseudolongum, Lactobacillus johnsonii and Olsenella species, that significantly enhanced efficacy of immune checkpoint inhibitors in four mouse models […]


Lung and gut microbiota are altered by hyperoxia and contribute to oxygen-induced lung injury in mice

Abstract Inhaled oxygen, although commonly administered to patients with respiratory disease, causes severe lung injury in animals and is associated with poor clinical outcomes in humans. The relationship between hyperoxia, lung and gut microbiota, and lung injury is unknown. Here, we show that hyperoxia conferred a selective relative growth advantage on oxygen-tolerant respiratory microbial species […]


Microbiota-derived metabolite promotes HDAC3 activity in the gut

Abstract The coevolution of mammalian hosts and their beneficial commensal microbes has led to development of a symbiotic host-microbiota relationship. Epigenetic machinery permits mammalian cells to integrate environmental signals, however, how these pathways are finely tuned by diverse cues from commensal bacteria is not well understood. Here, we reveal a highly selective pathway through which […]


Colonization of Germ-free Transgenic Mice with Genotyped Helicobacter pylori Strains from a Case-Control Study of Gastric Cancer Reveals a Correlation between Host Responses and HsdS Components of Type I Restriction-Modification Systems

Abstract Helicobacter pylori infects the stomachs of half of all humans. It has a relatively benign relationship with most hosts but produces severe pathology, including gastric cancer, in others. Identifying the relative contributions of host, microbial, and environmental factors to the outcome of infection has been challenging. Here we describe one approach for identifying microbial […]


Neonatal Exposure to Commensal-Bacteria-Derived Antigens Directs Polysaccharide-Specific B-1 B Cell Repertoire Development

Summary B-1 B cells derive from a developmental program distinct from that of conventional B cells, through B cell receptor (BCR)-dependent positive selection of fetally derived precursors. Here, we used direct labeling of B cells reactive with the N-acetyl-D-glucosamine (GlcNAc)-containing Lancefield group A carbohydrate of Streptococcus pyogenes to study the effects of bacterial antigens on […]


Microbiota modulate sympathetic neurons via a gut–brain circuit

Abstract Connections between the gut and brain monitor the intestinal tissue and its microbial and dietary content1, regulating both physiological intestinal functions such as nutrient absorption and motility2,3, and brain-wired feeding behaviour2. It is therefore plausible that circuits exist to detect gut microorganisms and relay this information to areas of the central nervous system that, […]


Developing standards for the microbiome field

Abstract Background Effective standardisation of methodologies to analyse the microbiome is essential to the entire microbiome community. Despite the microbiome field being established for over a decade, there are no accredited or certified reference materials available to the wider community. In this study, we describe the development of the first reference reagents produced by the […]


A Humanized Diet Profile May Facilitate Colonization and Immune Stimulation in Human Microbiota-Colonized Mice

Background: In spite of the importance of the use of gnotobiotic mice for human fecal transfer, colonization efficiency and immune stimulation after human microbiota inoculation in mice are poorly studied compared to mouse microbiota inoculation. We tested the colonization efficiency and immune responses in mice bred for one additional generation after inoculating the parent generation […]


C9orf72 suppresses systemic and neural inflammation induced by gut bacteria

Abstract A hexanucleotide-repeat expansion in C9ORF72 is the most common genetic variant that contributes to amyotrophic lateral sclerosis and frontotemporal dementia1,2. The C9ORF72 mutation acts through gain- and loss-of-function mechanisms to induce pathways that are implicated in neural degeneration3,4,5,6,7,8,9. The expansion is transcribed into a long repetitive RNA, which negatively sequesters RNA-binding proteins5 before its […]


Genetic and metabolic links between the murine microbiome and memory

Abstract Background Recent evidence has linked the gut microbiome to host behavior via the gut–brain axis [1,2,3]; however, the underlying mechanisms remain unexplored. Here, we determined the links between host genetics, the gut microbiome and memory using the genetically defined Collaborative Cross (CC) mouse cohort, complemented with microbiome and metabolomic analyses in conventional and germ-free […]


Gut Microbiota Modulate CD8 T Cell Responses to Influence Colitis-Associated Tumorigenesis

Summary There is increasing evidence that gut microbiome perturbations, also known as dysbiosis, can influence colorectal cancer development. To understand the mechanisms by which the gut microbiome modulates cancer susceptibility, we examine two wild-type mouse colonies with distinct gut microbial communities that develop significantly different tumor numbers using a mouse model of inflammation-associated tumorigenesis. We […]


Gut-Resident Lactobacilli Activate Hepatic Nrf2 and Protect Against Oxidative Liver Injury

Summary Many studies have suggested a role for gut-resident microbes (the “gut microbiome”) in modulating host health; however, the mechanisms by which they impact systemic physiology remain largely unknown. In this study, metabolomic and transcriptional profiling of germ-free and conventionalized mouse liver revealed an upregulation of the Nrf2 antioxidant and xenobiotic response in microbiome-replete animals. […]


Variations in microbiota composition of laboratory mice influence Citrobacter rodentium infection via variable short-chain fatty acid production

Author summary The distinct composition of the gut microbiota in each individual results in variable metabolic activity and output of these communities, which influences the host, including resistance to enteric pathogens. Lack of reproducibility in biomedical research is nowadays frequently attributed to the microbiota, but little is known about which specific members and metabolites contribute […]


Commensal Microbiota Regulation of Metabolic Networks During Olfactory Dysfunction in Mice

Introduction: Recently, an increasing number of studies have focused on commensal microbiota. These microorganisms have been suggested to impact human health and disease. However, only a small amount of data exists to support the assessment of the influences that commensal microbiota exert on olfactory function. Methods: We used a buried food pellet test (BFPT) to […]


A purified membrane protein from Akkermansia muciniphila or the pasteurised bacterium blunts colitis associated tumourigenesis by modulation of CD8+ T cells in mice

Abstract Objective Gut microbiota have been linked to inflammatory bowel disease (IBD) and colorectal cancer (CRC). Akkermansia muciniphila (A. muciniphila) is a gram-negative anaerobic bacterium that is selectively decreased in the faecal microbiota of patients with IBD, but its causative role and molecular mechanism in blunting colitis-associated colorectal cancer (CAC) remain inconclusive. This study investigates […]


Gut microbiota manipulation during the prepubertal period shapes behavioral abnormalities in a mouse neurodevelopmental disorder model

Abstract Previous studies demonstrate an association between activation of the maternal immune system during pregnancy and increased risk of neurodevelopmental psychiatric conditions, such as schizophrenia and autism, in the offspring. Relatively recent findings also suggest that the gut microbiota plays an important role in shaping brain development and behavior. Here we show that maternal immune […]






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