Anne-Marie Cassard-Doulcier

French Institute of Health and Medical Research, INSERM · UMR-S 996 , inflammation, chemokines and immunopathology

Enterococcus faecalis is a bacterial species present at a subdominant level in the human gut microbiota. This commensal turns into an opportunistic pathogen under specific conditions involving dysbiosis and host immune deficiency. E. faecalis is one of the rare pathobionts identified to date as contributing to liver damage in alcoholic liver diseas...

Alterations in the composition of the gut microbiota (dysbiosis) are observed in nutritional liver diseases, including non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) and have been shown to be associated with the severity of both. Editing the composition of the microbiota by fecal microbiota transfer or by application of...

We have previously showed that plasma membrane cholesterol and GM1 ganglioside content are responsible for the opposite sensitivity of mouse leukemic T cells to ATP. We also reported that the sensitivity of CD4+ and CD8+ T cells to ATP depends on their stage of differentiation. Here, we show that CD4+ and CD8+ T cells from B6 mice express different...

Reshaping the intestinal microbiota by the ingestion of fiber, such as pectin, improves alcohol-induced liver lesions in mice by modulating bacterial metabolites, including indoles, as well as bile acids (BAs). In this context, we aimed to elucidate how oral supplementation of pectin affects BA metabolism in alcohol-challenged mice receiving feces...

Introduction: Patients with alcoholic hepatitis have an increase in cytolysin-producing Enterococcus faecalis that correlates with disease severity and mortality. Aim: To determine whether patients with chronic alcoholic pancreatitis have an elevated abundance of cytolysin-producing E. faecalis. Methods: Quantification by qPCR of cytolysin-producin...

Pectin, a soluble fiber, improves non-alcoholic fatty-liver disease (NAFLD), but its mechanisms are unclear. We aimed to investigate the role of pectin-induced changes in intestinal microbiota (IM) in NAFLD. We recovered the IM from mice fed a high-fat diet, treated or not with pectin, to perform a fecal microbiota transfer (FMT). Mice fed a high-f...

Enterococcus faecalis is a bacterial species present at a sub-dominant level in the human gut microbiota. This commensal turns into an opportunistic pathogen under specific conditions involving dysbiosis and host immune deficiency. E. faecalis is also the only intestinal pathobiont identified to date as contributing to liver damage in alcoholic liv...

Background: The microbiota interacts with the brain through the gut-brain axis, and a distinct dysbiosis may lead to major depressive episodes. Bacteria can pass through the gut barrier and be found in the blood. Using a multiomic approach, we investigated whether a distinct blood microbiome and metabolome was associated with major depressive epis...

Background & Aims Bile-acid metabolism and the intestinal microbiota are impaired in alcoholic liver disease. Activation of the bile-acid receptor TGR5 both controls biliary homeostasis and inflammatory processes. We examined the role of TGR5 in alcohol-induced liver injury in mice. Methods We used TGR5-deficient (TGR5-KO) and wildtype (WT) female...

Studies support the beneficial effects of glucocorticoids (GCs) during septic shock, steering research towards the potential role of GC‐induced proteins in controlling excessive inflammatory responses. GILZ is a glucocorticoid‐induced protein involved in the anti‐inflammatory effects of GCs. We investigated whether the overexpression of GILZ specif...

Résumé La stéatopathie métabolique ou NAFLD regroupe un spectre de lésions du foie qui vont apparaître chez des individus en surpoids ou obèses présentant un syndrome métabolique. Cependant, tous ces individus ne développent pas les stades sévères de NAFLD ce qui a mené à l’identification de cofacteurs aggravants ou inversement protecteurs dont le...

Introduction et but de l’étude La stéatohépatite non-alcoolique (NASH) est une maladie chronique du foie dont la prévalence est en constante augmentation, en corrélation avec l’épidémie d’obésité mondiale. Si des composantes génétiques et environnementales sont liées au développement de cette pathologie, il a été démontré que le microbiote intestin...

Purpose Trans-acting splicing factors (SF) shape the eukaryotic transcriptome by regulating alternative splicing (AS). This process is recurrently modulated in liver cancer suggesting its direct contribution to the course of liver disease. The aim of our study was to investigate the relationship between the regulation of SFs expression and liver da...

Background Intestinal microbiota plays an important role in bile acid homeostasis. Aim To study the structure of the intestinal microbiota and its function in bile acid homeostasis in alcoholic patients based on the severity of alcoholic liver disease. Methods In this prospective study, we included four groups of active alcoholic patients (N = 10...

Human microbiota-associated (HMA) mice are an important model to study the relationship between liver diseases and intestinal microbiota. We describe a new method to humanize conventional mice based on bowel cleansing with polyethylene glycol followed by fecal microbiota transplantation (FMT) from a human donor. Four successive bowel cleansings wer...

Excessive alcohol consumption leads to severe alcoholic hepatitis (sAH) or chronic alcoholic pancreatitis (CAP) only in a subset of patients. We aimed to characterize the intestinal microbiota profiles of alcoholic patients according to the presence and nature of the complications observed: sAH or CAP. Eighty two alcoholic patients were included ac...

Alcoholic liver disease (ALD) is a major cause of morbidity and mortality worldwide. Only 20% of heavy alcohol consumers develop alcoholic liver cirrhosis. The intestinal microbiota (IM) has been recently identified as a key player in the severity of liver injury in ALD. Common features of ALD include a decrease of gut epithelial tight junction pro...

Microbiota, Liver Diseases, and Alcohol, Page 1 of 2 Abstract Being overweight and obesity are the leading causes of liver disease in Western countries. Liver damage induced by being overweight can range from steatosis, harmless in its simple form, to steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Alcohol consumption is an ad...

Objective: Alcoholic liver disease (ALD) is a global health problem with limited therapeutic options. Intestinal barrier integrity and the microbiota modulate susceptibility to ALD. Akkermansia muciniphila, a Gram-negative intestinal commensal, promotes barrier function partly by enhancing mucus production. The aim of this study was to investigate...

TGF-β1 is a master cytokine in many biological processes including tissue homeostasis, epithelial to mesenchymal transition and wound repair. Here we report that the four and a half LIM-only protein 2 (FHL2) is a critical regulator of TGF-β1 expression. Devoid of DNA-binding domain, FHL2 is a transcriptional co-factor that plays the role of co-acti...

Background & AimsAlcoholic liver disease (ALD) is a leading cause of liver failure and mortality. In humans, severe alcoholic hepatitis is associated with key changes to intestinal microbiota (IM), which influences individual sensitivity to develop advanced ALD. We used the different susceptibility to ALD observed in two distinct animal facilities...

Recent advances in the intestinal microbiota (IM) knowledge provide emerging evidence that dysbiosis plays a role in several diseases in hepato-gastroenterology. The inequality regarding the risk of hepatocellular carcinoma (HCC) in cirrhotic patients encourages the identification new risk factors. Dysbiosis may play a role in several signaling pat...

The increase consumption of fructose in diet is associated with liver inflammation. As a specific fructan substrate, fructose may modify the gut microbiota which is involved in obesity-induced liver disease. Here, we aimed to assess whether fructose-induced liver damage was associated with a specific dysbiosis, especially in mice fed a high fat die...

Objective: There is substantial inter-individual diversity in the susceptibility of alcoholics to liver injury. Alterations of intestinal microbiota (IM) have been reported in alcoholic liver disease (ALD), but the extent to which they are merely a consequence or a cause is unknown. We aimed to demonstrate that a specific dysbiosis contributes to...

Background & aim: Kupffer cells (KC) play a key role in the onset of inflammation in non-alcoholic steatohepatitis (NASH). The glucocorticoid receptor (GR) induces glucocorticoid-induced leucine zipper (GILZ) expression in monocytes/macrophages and is involved in several inflammatory processes. We hypothesized that the GR-GILZ axis in KC may contr...

The four and a half LIM-only protein 2 (FHL2) is a multifunctional protein involved in many biological and physiopathological processes. We previously showed that enhanced expression of FHL2 in hepatocytes increases both cell proliferation and apoptosis, and promotes liver tumorigenesis associated with activation of the Wnt/β-catenin signaling (Nou...

Homing of inflammatory cells to the liver is key in the progression of non-alcoholic steatohepatitis (NASH). An abnormal response of CD4+ T cells from obese mice to the chemotactic effect of CXCL12 has been reported but the mechanism involved in this process and relevance in patients are unknown. We aimed to explore the mechanism involved in the ab...

Background & aimsPatients with alcoholic liver disease (ALD) display inflammation of the subcutaneous adipose tissue (SAT) which correlates with liver lesions. We examined macrophage markers and polarization in the SAT of alcoholic patients and adipokine expression according to liver inflammation; we studied the consequences of alcohol withdrawal.P...

Four-and-a-half LIM-only protein 2 (FHL2) is an important mediator in many signaling pathways. In this study, we analyzed the functions of FHL2 in nuclear factor κB (NF-κB) signaling in the liver. We show that FHL2 enhanced tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) activity in transcriptional activation of NF-κB targets by st...

Objective: Non-alcoholic fatty liver disease (NAFLD) is prevalent among obese people and is considered the hepatic manifestation of metabolic syndrome. However, not all obese individuals develop NAFLD. Our objective was to demonstrate the role of the gut microbiota in NAFLD development using transplantation experiments in mice. Design: Two donor...

Non-alcoholic steatohepatitis (NASH) is characterized by steatosis associated with liver inflammation. Steatosis causes recruitment of lymphocytes into the liver and this is worsened by lipopolysaccharides (LPS). As macrophages may be involved in the lymphocyte homing, we studied the role of lipids in determining the phenotype of Kupffer cells (KCs...

Non-alcoholic fatty liver disease (NAFLD) is the liver manifestation of the metabolic syndrome and one of the most common liver diseases in developed countries. NAFLD refers to a wide range of liver damage, ranging from pure steatosis to a more severe pathology, namely steatohepatitis (NASH) characterized, in addition to steatosis, by inflammation...

Quantification of gene expression using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) requires normalization to an endogenous reference gene termed housekeeping gene (HKG). Many of the commonly used HKGs are regulated and vary under experimental conditions and disease stages. Alcoholic liver disease (ALD) is associated with...

ntroduction Obesity predisposes people to several severe pathologies, including NAFLD (Non Alcoholic Fatty Liver Disease). NAFLD consists in variable stages of severity, from lipid accumulation in the liver (steatosis) to steatohepatitis and cirrhosis. Such pathologies are characterized by liver inflammation and metabolic disorders like insulino-re...

Nonalcoholic fatty liver disease (NAFLD) is the liver manifestation of the metabolic syndrome and one of the most common liver diseases in developed countries. NAFLD refers to a wide range of liver damage, ranging from pure steatosis to a more severe pathology namely steatohepatitis (NASH) characterized, in addition to steatosis, by inflammation an...

Nonalcoholic fatty liver disease (NAFLD) is the liver manifestation of the metabolic syndrome and one of the most common liver diseases in developed countries. NAFLD refers to a wide range of liver damage, ranging from pure steatosis to a more severe pathology namely steatohepatitis (NASH) characterized, in addition to steatosis, by inflammation an...

Adipose tissue is an important source of cytokines. Excess weight is an independent risk factor for steatosis, acute alcoholic hepatitis (AAH), and cirrhosis in patients with alcoholic liver disease (ALD). In this study, we investigated the role of adipose tissue in human ALD. Fifty patients with ALD underwent liver and abdominal subcutaneous adipo...

Background & Aims: Hepatic lipid retention (steatosis) predisposes hepatitis. We investigated the mechanisms of lymphocyte homing to fatty liver and the role of lipopolysaccharide (LPS) in the onset of inflammation in ob/ob mice. Methods: We decreased intestinal bacterial compounds by oral antibiotic treatment to test the role of endogenous LPS in...

Unlabelled: Glucocorticoid-induced leucine zipper (GILZ), a recently identified protein induced by glucocorticoids (GCs), inhibits the nuclear factor kappaB pathway and the activation of monocytes/macrophages by lipopolysaccharides (LPS). This study aimed to elucidate the contribution of GILZ to the pathogenesis of alcoholic hepatitis (AH): we (1)...

In contrast to trunk fat mass (TFM), which is associated with cardiovascular risk markers, leg fat mass (LFM) displays independent protective effects against atherosclerosis. Little is known about the respective influence of central and peripheral adiposity on liver enzyme levels. Aims: To assess the respective influence of TFM and LFM on alanine a...

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in Western countries. It encompasses a wide spectrum of liver lesions, from pure steatosis to end-stage liver disease with cirrhosis and hepatocellular carcinoma. Nonalcoholic steatohepatitis corresponds only to one stage of NAFLD. As NAFLD can be considered a liver manifesta...

The mitochondrion is a major organelle contributing to energy metabolism but also a main site of ROS (reactive oxygen species) production. LPS (lipopolysaccharide)-induced ROS signalling is a critical event in macrophage activation. In the present paper we report that part of LPS-mediated ROS signalling comes from mitochondria inside a signal ampli...

This study focused on the stability of UCP2 (uncoupling protein 2), a mitochondrial carrier located in the inner membrane of mitochondrion. UCP2 is very unstable, with a half-life close to 30min, compared to 30h for its homologue UCP1, a difference that may highlight different physiological functions. Heat production by UCP1 in brown adipocytes is...

A large number of studies have established the mitochondrial uncoupling protein UCP1 as a specific marker of brown adipocytes, where it controls energy dissipation of fatty acid oxidation as heat in response to physiological requirements. Following the recent report of the detection of UCP1 in thymocytes of rats and mice, we reinvestigated its pres...

The uncoupling protein 2 (UCP2) is located in the inner mitochondrial membrane and downregulates the production of reactive oxygen species (ROS). Recent data suggested a role for UCP2 in the immune response. We analyzed further this hypothesis during acute Listeria monocytogenes infection in mice. Death of infected Ucp2(-/-) mice was delayed in com...

Mitochondrial respiration is the main source of energy in aerobic animal cells and is adapted to the energy demand by respiratory coupling. Uncoupling proteins (UCPs) perturb respiratory coupling by inducing a proton leak through the mitochondrial inner membrane. Although this could lead to deleterious energy waste, it may prevent the production of...

Uncoupling proteins (UCPs) are mitochondrial transporters present in the inner membrane of mitochondria. They are found in all mammals and in plants. They belong to the family of anion mitochondrial carriers including adenine nucleotide transporters. The term "uncoupling protein" was originally used for UCP1, which is uniquely present in mitochondr...

Uncoupling proteins (UCPs) are transporters of the inner mitochondrial membrane. Whereas UCP1 is uniquely present in brown adipose tissue where it uncouples respiration from ATP synthesis and activates respiration and heat production, UCP2 is present in numerous tissues, and its exact function remains to be clarified. Two sets of data provided the...

The mitochondrial uncoupling protein 2 (UCP2) is expressed in spleen, lung, intestine, white adipose tissue, and immune cells. Bone marrow transplantation in mice was used to assess the contribution of immune cells to the expression of UCP2 in basal condition and during inflammation. Immune cells accounted for the total amount of UCP2 expression in...