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 […]


Intratumoral accumulation of gut microbiota facilitates CD47-based immunotherapy via STING signaling

Most studies focus on how intestinal microbiota influence cancer immunotherapy through activating gut immunity. However, immunotherapies related to innate responses such as CD47 blockade rely on the rapid immune responses within the tumor microenvironment. Using one defined anaerobic gut microbiota to track whether microbiota interact with host immunity, we observed that Bifidobacterium facilitates local anti-CD47 […]


It’s the fiber, not the fat: significant effects of dietary challenge on the gut microbiome

Abstract Background Dietary effects on the gut microbiome play key roles in the pathophysiology of inflammatory disorders, metabolic syndrome, obesity, and behavioral dysregulation. Often overlooked in such studies is the consideration that experimental diets vary significantly in the proportion and source of their dietary fiber. Commonly, treatment comparisons are made between animals fed a purchased […]


Germ‐Free and Microbiota‐Associated Mice yield Small Intestinal Epithelial Organoids with Equivalent and Robust Transcriptome/Proteome Expression Phenotypes

Abstract Intestinal epithelial organoids established from gut tissue have become a widely used research tool. However, it remains unclear how environmental cues, divergent microbiota composition and other sources of variation before, during and after establishment confound organoid properties, and how these properties relate to the original tissue. While environmental influences cannot be easily addressed in […]


Self-reinoculation with fecal flora changes microbiota density and composition leading to an altered bile-acid profile in the mouse small intestine

ABSTRACT Background The upper gastrointestinal tract plays a prominent role in human physiology as the primary site for enzymatic digestion and nutrient absorption, immune sampling, and drug uptake. Alterations to the small intestine microbiome have been implicated in various human diseases, such as non-alcoholic steatohepatitis and inflammatory bowel conditions. Yet, the physiological and functional roles […]


Gut microbiota mediates intermittent-fasting alleviation of diabetes-induced cognitive impairment

ABSTRACT Cognitive decline is one of the complications of type 2 diabetes (T2D). Intermittent fasting (IF) is a promising dietary intervention for alleviating T2D symptoms, but its protective effect on diabetes-driven cognitive dysfunction remains elusive. Here, we find that a 28-day IF regimen for diabetic mice improves behavioral impairment via a microbiota-metabolites-brain axis: IF enhances […]


Ursolic acid improves the bacterial community mapping of the intestinal tract in liver fibrosis mice

ABSTRACT Liver fibrosis often appears in chronic liver disease, with extracellular matrix (ECM) deposition as the main feature. Due to the presence of the liver-gut axis, the destruction of intestinal homeostasis is often accompanied by the development of liver fibrosis. The inconsistent ecological environment of different intestinal sites may lead to differences in the microbiota. […]


Gastric bypass surgery in a rat model alters the community structure and functional composition of the intestinal microbiota independently of weight loss

Abstract Background Roux-en-Y gastric bypass (RYGB) surgery is a last-resort treatment to induce substantial and sustained weight loss in cases of severe obesity. This anatomical rearrangement affects the intestinal microbiota, but so far, little information is available on how it interferes with microbial functionality and microbial-host interactions independently of weight loss. Methods A rat model […]


Time of Feeding Alters Obesity-Associated Parameters and Gut Bacterial Communities, but Not Fungal Populations, in C57BL/6 Male Mice

ABSTRACT Background Fasting and timed feeding strategies normalize obesity parameters even under high-fat dietary intake. Although previous work demonstrated that these dietary strategies reduce adiposity and improve metabolic health, limited work has examined intestinal microbial communities. Objectives We determined whether timed feeding modifies the composition of the intestinal microbiome and mycobiome (yeast and fungi). Methods […]


Degeneration of the intestinal microbial community in PI3Kγ-knockout mice

Abstract Background and aim PI3Kγ is closely related to inflammation and cardiovascular diseases and thus, PI3Kγ inhibitors are candidate drugs for the treatment of these disorders. Considering the potential effect of the intestinal microbiome on inflammation and cardiovascular diseases, this study aimed to identify characteristics of the intestinal microbial community under PI3Kγ deficiency, to help […]


Prenatal exposure to glufosinate ammonium disturbs gut microbiome and induces behavioral abnormalities in mice

ABSTRACT Glufosinate ammonium (GLA) is a widely used organophosphate herbicide, which could be commonly detected in body fluids of both pregnant women and newborns. Existing evidences indicate that GLA has reproductive toxicity, while data concerning the effects of prenatal GLA exposure on neurodevelopment is rather limited. Here we employed a mouse model exposed to GLA […]


Effect of probiotic administration on gut microbiota and depressive behaviors in mice

Abstract Background The gut microbiota is closely associated with the bidirectional gut-brain axis that modulates neuropsychological functions of the central nervous system, thereby affecting mental disorders such as depression. Although it is known that probiotics affect brain functions, the impact of probiotics on the regulation of the prevalence and composition of gut microbiota, leading to […]


Establishing or Exaggerating Causality for the Gut Microbiome: Lessons from Human Microbiota-Associated Rodents

ABSTRACT Human diseases are increasingly linked with an altered or “dysbiotic” gut microbiota, but whether such changes are causal, consequential, or bystanders to disease is, for the most part, unresolved. Human microbiota-associated (HMA) rodents have become a cornerstone of microbiome science for addressing causal relationships between altered microbiomes and host pathology. In a systematic review, […]






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