Malvyne Rolli-Derkinderen

Inserm U1235, Nantes · TENS

The growing incidence of human diseases involving inflammation and increased gut permeability makes the quest for protective functional foods more crucial than ever. Propionibacterium freudenreichii (Pf) is a beneficial bacterium used in the dairy and probiotic industries. Selected strains exert anti-inflammatory effects, and the present work addre...

Gut-brain axis and inflammation are two hot topics in Parkinson's disease. In this setting, the Leucine-rich repeat kinase 2 (LRRK2) gene, which encodes the eponym protein has attracted much attention. LRRK2 is not only the gene most commonly associated with Parkinson's disease but also a susceptibility gene for Crohn's disease, thereby suggesting...

Background and objective There is mounting evidence to suggest that the gut-brain axis is involved in the development of Parkinson’s disease (PD). In this regard, the enteroendocrine cells (EEC), which faces the gut lumen and are connected with both enteric neurons and glial cells have received growing attention. The recent observation showing that...

Inflammatory bowel diseases (IBD) constitute a growing concern in western countries. They coincide with gut microbiota dysbiosis, including a loss of immunomodulatory bacteria. Accordingly, probiotic products containing selected immunomodulatory bacterial strains mitigate IBD. Selected strains of Propionibacterium freudenreichii display promising m...

Although our understanding of the pathophysiology of inflammatory bowel disease (IBD) is increasing, the expanding body of knowledge does not simplify the equation but rather reveals diverse, interconnected, and complex mechanisms in IBD. In addition to immune overactivation, defects in intestinal epithelial barrier (IEB) functioning, dysbiosis, an...

The enteric nervous system (ENS) is a complex network of diverse molecularly defined classes of neurons embedded in the gastrointestinal wall and responsible for controlling the major functions of the gut. As in the central nervous system, the vast array of ENS neurons is interconnected by chemical synapses. Despite several studies reporting the ex...

The enteric nervous system (ENS) continues to dazzle scientists with its ability to integrate signals, from the outside as well as from the host, to accurately regulate digestive functions. Composed of neurons and enteric glial cells, the ENS interplays with numerous neighboring cells through the reception and/or the production of several types of...

There is mounting evidence to suggest that the gut-brain axis is involved in the development of Parkinson's disease (PD). In this regard, the enteroendocrine cells (EEC), which faces the gut lumen and are connected with both enteric neurons and glial cells have received growing attention. The recent observation showing that these cells express alph...

Background and aims Maternal diet plays a key role in preventing or contributing to the development of chronic diseases, such as obesity, allergy, and brain disorders. Supplementation of maternal diet with prebiotics has been shown to reduce the risk of food allergies and affect the intestinal permeability in offspring later in life. However, its r...

The gut microbiota plays a crucial role in the regulation of mucosal immunity and of the function of the intestinal barrier. Dysbiosis is accordingly associated with rupture of mucosal immune homeostasis, leading to inflammatory intestinal diseases. In this context, probiotic bacteria, including a new generation of intestinal probiotics, can mainta...

Leucine-rich repeat kinase 2 (LRRK2) gene, which is the gene most commonly associated with Parkinson's disease (PD), is also a susceptibility gene for Crohn's disease, thereby suggesting that LRRK2 may sit at the crossroads of gastrointestinal inflammation, Parkinson's and Crohn's disease. LRRK2 protein has been studied intensely in both CNS neuron...

Inflammatory bowel diseases (IBD), a heterogeneous group of inflammatory conditions that encompass both ulcerative colitis and Crohn's disease, represent a major public health concern. The etiology of IBD is not yet fully understood and no cure is available, with current treatments only showing long-term effectiveness in a minority of patients. A n...

Dysfunctions in the intestinal barrier, associated with an altered paracellular pathway, are commonly observed in inflammatory bowel disease (IBD). The AMP-activated protein kinase (AMPK), principally known as a cellular energy sensor, has also been shown to play a key role in the stabilization and assembly of tight junctions. Here, we aimed to inv...

Background and Aims Inflammatory bowel diseases (IBD) that encompass both ulcerative colitis and Crohn's disease are a major public health problem with an etiology that has not been fully elucidated. There is a need to improve disease outcomes and preventive measures by developing new effective and lasting treatments. While polyunsaturated fatty ac...

The enteric nervous system plays a critical role in the regulation of gastrointestinal tract functions and is often referred to as the ‘second brain’ because it shares many features with the central nervous system. These similarities include among others a large panel of neurotransmitters, a large population of glial cells and a susceptibility to n...

Objective The intestinal epithelial barrier (IEB) restricts the passage from the lumen through the paracellular space of potentially harmful substances and microbes, and rupture of its integrity is associated with a variety of gastrointestinal disorders and extra-digestive diseases. Increased IEB permeability has been linked to disruption of metabo...

While the pathogenesis of Parkinson’s disease is not fully understood, there is increasing evidence that inflammatory responses in the brain are implicated in both disease initiation and progression. The inflammatory process in Parkinson’s disease is, however, not limited to the brain but also involves the gastrointestinal tract. High amounts of cy...

A sizeable body of evidence has recently emerged to suggest that gastrointestinal (GI) inflammation might be involved in the development of Parkinson's disease (PD). There is now strong epidemiological and genetical evidence linking PD to inflammatory bowel diseases and we recently demonstrated that the neuronal protein alpha-synuclein, which is cr...

A sizeable body of evidence has recently emerged to suggest that gastrointestinal inflammation might be involved in the development of Parkinson's disease. There is now strong epidemiological and genetical evidence linking Parkinson's disease to inflammatory bowel diseases and we recently demonstrated that the neuronal protein alpha-synuclein, whic...

Oligosaccharides (OS) are commonly added to infant formulas, however, their physiological impact, particularly on adult health programming, is poorly described. In adult animals, OS modify microbiota and stimulate colonic fermentation and enteroendocrine cell (EEC) activity. Since neonatal changes in microbiota and/or EEC density could be long-last...

Oligosaccharides (OS) are commonly added to infant formulae but their physiological impacts, particularly those potentially involved in adult health programming, are poorly described. In adult animals, OS modify microbiota and stimulate colonic fermentation and enteroendocrine cells (EEC) activity. Since neonatal changes in microbiota and/or EEC de...

Background Half of Crohn’s disease (CD) patients require surgery within 20 years of diagnosis, and post-operative recurrence (POR) is frequent. Among the risk factors of POR, the presence of myenteric plexitis (≥ one immune cell in contact with myenteric ganglia) at the proximal resection margin has been incorporated in the European guidelines. How...

The protein alpha‐synuclein whose expression is strongly implicated in Parkinson's disease (PD) is not only expressed in the central nervous system (CNS) but also in the enteric nervous system (ENS). The growing body of evidence suggesting that gastrointestinal inflammation is involved in the development of PD led us to investigate the effects of i...

Tau is normally a highly soluble phosphoprotein found predominantly in neurons. Six different isoforms of tau are expressed in the adult human CNS. Under pathological conditions, phosphorylated tau aggregates are a defining feature of neurodegenerative disorders called tauopathies. Recent findings have suggested a potential role of the gut-brain ax...

Gone are the days when enteric glial cells (EGC) were considered merely as satellites of enteric neurons. Like their brain counterpart astrocytes, EGC express an impressive number of receptors for neurotransmitters and intercellular messengers, thereby contributing to neuroprotection and to the regulation of neuronal activity. EGC also produce diff...

Background: Postoperative ileus (POI) is observed in 20-30% of patients undergoing colorectal cancer surgery, despite enhanced recovery programs (ERPs). Cyclooxygenase (COX)-2 is identified as a key enzyme in POI, but other arachidonic acid pathway enzymes have received little attention despite their potential as selective targets to prevent POI....

But La réhabilitation améliorée (RA) diminue la durée de reprise du transit mais 20–30 % des patients continuent à présenter un iléus. Le but de ce travail était de comparer l’expression des enzymes du métabolisme de l’acide arachidonique (AA) (i) entre les patients ayant une résection colorectale et suivant ou ne suivant pas un protocole de RA, (i...

Background: Neuroplastic changes in the enteric nervous system (ENS) observed during IBD might participate in physiopathological processes. Vasoactive intestinal polypeptide has been shown to be involved in intestinal inflammation and barrier functions. We aimed to investigate the modulation of VIP expression in colonic biopsies of IBD patient, th...

Lewy bodies and neurites, the pathological hallmarks found in the brain of Parkinson’s disease (PD) patients, are primarily composed of aggregated and hyperphosphorylated alpha-synuclein. The observation that alpha-synuclein inclusions are also found in the gut of the vast majority of parkinsonian patients has led to an increasing number of studies...

Enseignement et formation de troisième cycle

In healthy gut enteric glial cells (EGC) are essential to intestinal epithelial barrier (IEB) functions. In Crohn’s Disease (CD), both EGC phenotype and IEB functions are altered, but putative involvement of EGC in CD pathogenesis remains unknown and study of human EGC are lacking. EGC isolated from CD and control patients showed similar expression...

Introduction Le développement de nouvelles stratégies thérapeutiques pour prévenir et traiter l'obésité se situe au cœur d'une problématique de santé publique, largement relayée par les médias au sein de notre société. La fonction barrière de l'intestin est altérée au cours de l'obésité et pourrait favoriser le développement de l'endotoxémie de fai...

Background and objectives The IL-36 family of cytokines comprises three agonists: IL-36α, IL-36β and IL-36γ, an antagonist: IL-36Ra, and IL-38: another potential IL-36 inhibitor. IL-36 agonists are highly expressed in skin and are involved in the pathogenesis of psoriasis, while antagonists limit uncontrolled inflammation. The expression and role o...

IL-36α, IL-36β and IL-36γ are highly expressed in skin and are involved in the pathogenesis of psoriasis, while the antagonist IL-36Ra or IL-38, another potential IL-36 inhibitor, limit uncontrolled inflammation. The expression and role of IL-36 cytokines in rheumatoid arthritis (RA) and Crohn's disease (CD) is currently debated. Here, we observed...

Background & aims: Enteric glial cells (EGCs) produce soluble mediators that regulate homeostasis and permeability of the intestinal epithelial barrier (IEB). We investigated the profile of polyunsaturated fatty acid (PUFA) metabolites produced by EGCs from rats and from patients with Crohn's disease (CD), compared with controls, along with the ab...

Recent works provide evidence of the importance of the prostaglandin D2 (PGD2) metabolic pathway in inflammatory bowel diseases. We investigated the expression of PGD2 metabolic pathway actors in Crohn's disease (CD) and the ability of the enteric nervous system (ENS) to produce PGD2 in inflammatory conditions. Expression of key actors involved in...

Background Evidence continues to mount concerning the importance of the enteric nervous system (ENS) in controlling numerous intestinal functions in addition to motility and epithelial functions. Nevertheless, little is known concerning the direct participation of the ENS in the inflammatory response of the gut during infectious or inflammatory ins...

Since their discovery at the end of the 19(th)century, enteric glial cells (EGC), the major cellular component of the enteric nervous system, have long been considered as mere supportive cells for neurons. However, recent evidence has challenged this view and highlighted their central role in the regulation of gut homeostasis, as well as their impl...

OBJECTIVE: Accumulating data demonstrate that under physiological conditions, enteric glial cells (EGC) positively regulate the intestinal epithelial barrier (IEB). EGC are necessary for IEB homeostasis, increase IEB healing and decrease IEB permeability, identifying EGC as a source for soluble factors able to reinforce the IEB. The most recently d...

OBJECTIVE: Enteric glia, the major constituent of the enteric nervous system, plays a key role in the control of intestinal epithelial barrier (IEB) functions. Under physiological conditions, enteric glial cells (EGC) inhibit intestinal epithelial cells (IEC) proliferation, enhance IEB repair and increase its resistance to pathogens. All these mech...

Background: In inflammatory bowel disease (IBD) patients, enteric glial cells (EGC) present some differences in the expression level of glial markers. Whether these changes are determined by the pathological environment or represent a constitutive feature of pathological EGC is unknown. The purpose of our study is (i) to determine if, ex vivo, huma...

Background Increasing evidence implicates overactivation of RhoA as a critical component of the pathogenesis of hypertension. Although a substantial body of work has established that Rac1 functions antagonize RhoA in a broad range of physiological processes, the role of Rac1 in the regulation of vascular tone and blood pressure is not fully elucida...

Enteric glial cells (EGCs) are in many respects similar to astrocytes of the central nervous system and express similar proteins including glial fibrillary acidic protein (GFAP). Changes in GFAP expression and/or phosphorylation have been reported during brain damage or central nervous system degeneration. As in Parkinson's disease (PD) the enteric...

A dysregulated response of CD4(+) T cells against the microbiota contributes to the development of inflammatory bowel diseases (IBD). Effector CD4(+) T cells, generated in response to microbe-derived antigens, can reduce somatic inflammatory pain, through the local release of opioids. We investigated whether colitogenic CD4(+) T cells that accumula...

Enteric glial cells (EGC) are major regulators of neuronal and intestinal epithelial cell (IEC) functions. Simple isolation methods of EGC, especially human tissues, remain scarce and limit their study. We present herein a method to isolate EGC and we characterize EGC phenotype and their functional impact on IEC. Longitudinal muscle and myenteric p...

The monolayer of columnar epithelial cells lining the gastrointestinal tract-the intestinal epithelial barrier (IEB)-is the largest exchange surface between the body and the external environment. The permeability of the IEB has a central role in the regulation of fluid and nutrient intake as well as in the control of the passage of pathogens. The f...

Objectives Enteric glial cells (EGC), the major constituents of the enteric nervous system, have been identified as key regulators of intestinal epithelial barrier (IEB) homeostasis. Under physiological condition, EGC-derived soluble factors enhance IEB healing,reduce its permeability, and increase its resistance to pathogen aggression. These barri...

Estradiol (E2) mediates numerous beneficial effects assigned to estrogens, but whereas mechanisms have been described at the endothelial level, direct effects on vascular smooth muscle cells (VSMC) are poorly documented. As evidence accumulates regarding the role of RhoA in vascular pathophysiology and the benefit of RhoA-Rho associated protein kin...

The intestinal epithelial barrier (IEB) plays a key role in the maintenance of gut homeostasis and the development of the immune systemin newborns. The enteric nervous system(ENS), a key regulator of gastrointestinal functions, has been shown to be modulated by nutritional factors. However, it remains currently unknown whether maternal diet, in par...

Enteric glial cells (EGCs) are important regulators of intestinal epithelial barrier (IEB) functions. EGC-derived S-nitrosoglutathione (GSNO) has been shown to regulate IEB permeability. Whether EGCs and GSNO protect the IEB during infectious insult by pathogens such as Shigella flexneri is not known. S flexneri effects were characterised using in...

Although overactivation of RhoA is recognized as a common component of vascular disorders, the molecular mechanisms regulating RhoA activity in vascular smooth muscle cells (VSMC) are still unclear. We have previously shown that in VSMC, RhoA is phosphorylated on Ser188 by nitric oxide (NO)-stimulated cGMP-dependent kinase (PKG), which leads to Rho...

Hypertension is one of the most frequent pathologies in the industrialized world. Although recognized to be dependent on a combination of genetic and environmental factors, its molecular basis remains elusive. Increased activity of the monomeric G protein RhoA in arteries is a common feature of hypertension. However, how RhoA is activated and wheth...

Pulmonary arterial hypertension (PAH) is associated with increased contraction and proliferation of pulmonary vascular smooth muscle cells. The anti-diabetic drug metformin has been shown to have relaxant and anti-proliferation properties. We thus examined the effect of metformin in PAH. Metformin effects were analysed in hypoxia- and monocrotaline...

Angiotensin II (ANG II) is a major regulator of blood pressure that essentially acts through activation of ANG II type 1 receptor (AT1R) of vascular smooth muscle cells (VSMC). AT1R activates numerous intracellular signaling pathways, including the small G protein RhoA known to control several VSMC functions. Nevertheless, the mechanisms leading to...

Hypoxia and inflammation play a major role in the revascularization following ischemia. Sildenafil inhibits phosphodiesterase-5, increases intracellular cGMP content and thus induces vasodilation. Sildenafil also induces neovascularization following ischemia but through a pathway remaining incompletely understood. Thus, we investigated the conseque...