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Introduction
My research program is dedicated to the investigation of the role and therapeutic potential of the gut microbiota and its metabolites in the progression of non-gastrointestinal cancers and associated cachexia. Studying the crosstalk between gut microbes and the host in this context constitutes an innovative approach. Our long-term goal is the identification of new “druggable” targets and promising nutritional microbiota-targeted tools to tackle cancer cachexia.
Skills and Expertise
Current institution
Additional affiliations
July 2013 - June 2014
Publications
Publications (200)
The recent discovery of N-acyl taurines (NATs) as a class of endogenous bioactive lipids and the perspective of their possible pharmacological applications stimulated the development of mass spectrometry-based methods for their quantitative measurements in biological tissues and fluids. We report here for the first time a procedure validated both i...
Gut microbiota alterations are intimately linked to chronic constipation upon aging. We investigated the role of targeted changes in the gut microbiota composition in the relief of constipation symptoms after rhubarb extract (RE) supplementation in middle-aged volunteers. Subjects (95% women, average 58 years old) were randomized to three groups tr...
Purpose of Review
This review aims to summarize the recent findings about the contribution of the gut microbiome to muscle pathophysiology and discuss molecular pathways that may be involved in such process. Related findings in the context of cancer cachexia are outlined.
Recent Findings
Many bacterial metabolites have been reported to exert a ben...
Background
Current data suggest that dietary fibre (DF) interaction with the gut microbiota largely contributes to their physiological effects. The bacterial fermentation of DF leads to the production of metabolites, most of them are volatile. This study analyzed the breath volatile metabolites (BVM) profile in healthy individuals (n=15) prior and...
Background
Dietary interventions targeting the gut microbiota have been proposed as innovative strategies to improve obesity-associated metabolic disorders. Increasing physical activity (PA) is considered as a key behavioral change for improving health. We have tested the hypothesis that changing the PA status during a nutritional intervention base...
Activin A (ActA) is considered to play a major role in cancer-induced cachexia (CC). Indeed, circulating ActA levels are elevated and predict survival in patients with CC. However, the mechanisms by which ActA mediates CC development and in particular skeletal muscle (SM) atrophy in humans are not yet fully understood. In this work, we aimed to inv...
Objective: To investigate the abundance and the prevalence of Dysosmobacter welbionis J115T, a novel butyrate-producing bacterium isolated from the human gut both in the general population and in subjects with metabolic syndrome. To study the impact of this
bacterium on host metabolism using diet-induced obese and diabetic mice.
Design: We analysed...
Cachexia is a wasting syndrome characterized by devastating skeletal muscle atrophy that dramatically increases mortality in various diseases, most notably in cancer patients with a penetrance of up to 80%. Knowledge regarding the mechanism of cancer-induced cachexia remains very scarce, making cachexia an unmet medical need. In this study, we disc...
Introduction et but de l’étude
La cachexie cancéreuse cause une perte de masse et de force musculaire chez les patients, augmentant leur risque de mortalité. Cibler le microbiote intestinal pourrait être pertinent ici par son effet régulateur du métabolisme de l’hôte. Dans des modèles murins de leucémie, l’augmentation des Enterobacteriaceae dans l...
Résumé
Le traitement du diabète de type 2 (DT2) débute par la modification de l’alimentation et de l’activité physique, qui modulent tous deux, à des degrés différents, le microbiote. Si l’objectif glycémique n’est pas atteint, la metformine est introduite. Le traitement pourra ensuite être intensifié avec une bi-, voire une multi-thérapie. Les pre...
Bile acids are potent signaling molecules exerting diverse actions through bile acid-activated receptors. Among them, the Farnesoid X receptor (FXR) and the Takeda G protein-coupled receptor 5 (TGR5; GPBAR1), modulate the inflammation occurring in chronic/acute hepatitis, cholestasis, and inflammatory bowel disease. A role for other bile acid-respo...
Obesity is associated with an increased risk of several neurological and psychiatric diseases, but few studies report the contribution of biological features in the occurrence of mood disorders in obese patients. The aim of the study is to evaluate the potential links between serum metabolomics and gut microbiome, and mood disturbances in a cohort...
Alcohol use disorder (AUD) is a chronic relapsing disease associated with malnutrition, metabolic disturbances, and gut microbiota alterations that are correlated with the severity of psychological symptoms. This study aims at supplementing AUD patients with prebiotic fiber during alcohol withdrawal, in order to modulate the gut microbiota composit...
Bile acids exert diverse actions on host metabolism and immunity through bile acid-activated receptors, including Takeda G protein-coupled receptor 5 (TGR5). We have recently evidenced an alteration in bile acids in cancer cachexia, an inflammatory and metabolic syndrome contributing to cancer death. This current study aims to further explore the l...
Abstract Background Type 2 diabetes mellitus (T2DM) is a strong risk factor for liver fibrosis in non-alcoholic fatty liver disease (NAFLD). It remains uncertain why T2DM increases the risk of liver fibrosis. It has been suggested that growth differentiation factor-15 (GDF-15) concentrations increase the risk of liver fibrosis. We aimed to investig...
Background & Aims
Through FXR and TGR5 signaling, bile acids (BA) modulate lipid and glucose metabolism, inflammation and fibrosis. Hence, BA brought back to the liver after enteric secretion, modification and reabsorption may contribute to nonalcoholic steatohepatitis (NASH) pathogenesis. Here, we characterized the enterohepatic profile and signal...
Purpose
Inulin-type fructans (ITF) are prebiotic dietary fibre (DF) that may confer beneficial health effects, by interacting with the gut microbiota. We have tested the hypothesis that a dietary intervention promoting inulin intake versus placebo influences fecal microbial-derived metabolites and markers related to gut integrity and inflammation i...
Background & Aims
Retrospective cross-sectional studies linked sarcopenia and myosteatosis with metabolic dysfunction-associated fatty liver disease (MAFLD). Here, we wanted to clarify the dynamic relationship between sarcopenia, myosteatosis and MAFLD.
Methods
A cohort of 48 obese patients was randomized for a dietary intervention consisting of 16...
Berberine and curcumin, used as food additives or food supplements, possess interesting anti-inflammatory and antioxidant properties. We tested the potential protective effect of both phytochemicals in genetically obese mice and we determined whether these effects can be related to the modulation of gut functions and microbiota. Ob/ob mice were fed...
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Background
The gut microbiota plays a role in the occurrence of nonalcoholic fatty liver disease (NAFLD), notably through the production of bioactive metabolites. Indole, a bacterial metabolite of tryptophan, has been proposed as a pivotal metabolite modulating inflammation, metabolism, and behavior.
Objectives
The aim of our study was to mimic an...
Background & Aims
Chronic alcohol consumption can cause malnutrition that may contribute to alcohol-induced organ injury and psychological disorders. We evaluated the link between nutrient intake, especially dietary fibers and different parameters reflecting mental health and well being, namely anxiety, depression, alcohol craving, sociability, fat...
Background:
Cancer cachexia is a multifactorial syndrome characterized by multiple metabolic dysfunctions. Besides the muscle, other organs such as the liver and the gut microbiota may also contribute to this syndrome. Indeed, the gut microbiota, an important regulator of the host metabolism, is altered in the C26 preclinical model of cancer cache...
Several studies suggest that microbial alterations (dysbiosis) are intimately linked to chronic inflammation occurring upon aging. The aim of this study was to investigate the potential interest of a synbiotic approach (co-administration of a probiotic bacteria and a prebiotic dietary fibre) to improve gastrointestinal wellness and inflammatory mar...
Background and aims
Metabolic and behavioral diseases, which are often related to obesity, have been associated to alterations of the gut microbiota considered as an interesting therapeutic target. We have analyzed in a cohort of obese patients treated with prebiotic inulin versus placebo the potential link between gut microbiota changes occurring...
Obesity could lead to metabolic dysfunction-associated fatty liver disease (MAFLD), which severity could be linked to muscle and gut microbiota disturbances. Our prospective study enrolled 52 obese patients whose MAFLD severity was estimated by transient elastography. Patients with severe steatosis (n = 36) had higher ALAT values, fasting blood glu...
The fermentation of dietary fibre (DF) leads to the production of bioactive metabolites, the most volatile ones being excreted in the breath. The aim of this study was to analyze the profile of exhaled breath volatile metabolites (BVM) and gastrointestinal symptoms in healthy volunteers after a single ingestion of maltodextrin (placebo) versus chit...
Background:
Cancer cachexia is a debilitating metabolic syndrome contributing to cancer death. Organs other than the muscle may contribute to the pathogenesis of cancer cachexia. This work explores new mechanisms underlying hepatic alterations in cancer cachexia.
Methods:
We used transcriptomics to reveal the hepatic gene expression profile in t...
Rationale: Obesity could lead to several metabolic alterations, including non-alcoholic fatty liver disease (NAFLD), muscle dysfunctions and gut dysbiosis. Here, we propose to evaluate the gut microbiota composition depending on the degree of NAFLD severity. Methods: Obese patients recruited prospectively at St-Luc Hospital (FOOD4GUT project, Belgi...
Background
Undernutrition predisposes children to a greater incidence and duration of diarrhea. No review and meta-analysis have yet been conducted to assess effectiveness of probiotics and synbiotics in malnourished children.
Aims
To assess the effectiveness of probiotics and synbiotics on diarrhea in undernourished children.
Methods
Randomized,...
Cachexia is a complication of dismal prognosis, which often represents the last step of several chronic diseases. For this reason, the comprehension of the molecular drivers of such a condition is crucial for the development of management approaches. Importantly, cachexia is a syndrome affecting various organs, which often results in systemic compl...
Dietary fibers are considered beneficial nutrients for health. Current data suggest that their interaction with the gut microbiota largely contributes to their physiological effects. In this context, chitin-glucan (CG) improves metabolic disorders associated with obesity in mice, but its effect on gut microbiota has never been evaluated in humans....
Loss of skeletal muscle mass in cancer cachexia is recognized as a predictor of mortality. This study aimed to characterize the changes in the muscle secretome associated with cancer cachexia to gain a better understanding of the mechanisms involved and to identify secreted proteins which may reflect this wasting process. The changes in the muscle...
Patients with alcohol use disorder (AUD) present with important emotional, cognitive, and social impairments. The gut microbiota has been recently shown to regulate brain functions and behavior but convincing evidence of its role in AUD is lacking. Here, we show that gut dysbiosis is associated with metabolic alterations that affect behavioral (dep...
Background & aims
Binge eating disorder (BED) is a frequent eating disorder associated with obesity and co-morbidities including psychiatric pathologies, which represent a big health burden on the society.
The biological processes related to BED remain unknown. Based on psychological testing, anthropometry, clinical biology, gut microbiota analysis...
Mol. Nutr. Food Res. 2020, 64, 2000162
DOI: 10.1002/mnfr.202000162
Utilizing germ‐free mice colonized with complex gut microbiomes devoid of Akkermansia muciniphila, Segura Munoz and colleagues found that feeding transgenic soybean oil enriched in n‐3 PUFA reduced fat deposition, improved glucose metabolism, and increased tissue n‐3 PUFAs independe...
Background: The fermentation of dietary fibers (DF) leads to the production of bioactive metabolites, the most volatile ones being excreted in the breath. The aim of this study was to analyze the profile of exhaled breath volatile metabolites (BVM) and gastro-intestinal symptoms in healthy volunteers after a single ingestion of maltodextrin (placeb...
Abstract
Introduction
In kidney transplantation, tacrolimus (TAC) is at the cornerstone of current immunosuppressive strategies. Though because of its narrow therapeutic index, it is critical to ensure that TAC levels are maintained within this sharp window through reactive adjustments. This would allow maximizing efficiency while limiting drug-as...
Introduction
In kidney transplantation, tacrolimus (TAC) is at the cornerstone of current immunosuppressive strategies. Though because of its narrow therapeutic index, it is critical to ensure that TAC levels are maintained within this sharp window through reactive adjustments. This would allow maximizing efficiency while limiting drug-associated t...
Scope
Previous studies have suggested that diets rich in omega‐3 and low in omega‐6 long‐chain polyunsaturated fatty acids (PUFAs) can limit the development of metabolic syndrome (MetS). Transgenic soybeans yielding oils enriched for omega‐3 PUFAs represent a new and readily‐available option for incorporating omega‐3 PUFAs into diets to provide hea...
AU-rich element (ARE)-mediated mRNA decay represents a key mechanism to avoid excessive production of inflammatory cytokines. Tristetraprolin (TTP, encoded by Zfp36) is a major ARE-binding protein, since Zfp36−/− mice develop a complex multiorgan inflammatory syndrome that shares many features with spondyloarthritis. The role of TTP in intestinal h...
Background
The gut microbiota is altered in obesity and is strongly influenced by nutrients and xenobiotics. We have tested the impact of native inulin as prebiotic present in vegetables and added as a supplement on gut microbiota-related outcomes in obese patients. Metformin treatment was analyzed as a potential modulator of the response.
Methods...
Introduction et but de l’étude
L’Anorexie mentale est une maladie complexe impliquant des facteurs biologiques, psychologiques et environnementaux. Le microbiote intestinal a récemment été proposé comme étant l’un de ces facteurs et pourrait jouer un rôle dans l’apparition ou la chronicité de l’Anorexie mentale. Afin de mieux comprendre le rôle pot...
Objective
The gut microbiota has been proposed as an interesting therapeutic target for metabolic disorders. Inulin as a prebiotic has been shown to lessen obesity and related diseases. The aim of the current study was to investigate whether preintervention gut microbiota characteristics determine the physiological response to inulin.
Design
The s...
The gut microbiota participates in the control of energy homeostasis partly through fermentation of dietary fibers hence producing short-chain fatty acids (SCFAs), which in turn promote the secretion of the incretin Glucagon-Like Peptide-1 (GLP-1) by binding to the SCFA receptors FFAR2 and FFAR3 on enteroendocrine L-cells. We have previously shown...
Background & aims:
Dysbiosis of the intestinal microbiota has been associated with nonalcoholic fatty liver disease (NAFLD). We investigated whether administration of a synbiotic combination of probiotic and prebiotic agents affected liver fat content, biomarkers of liver fibrosis, and the composition of the fecal microbiome in patients with NAFLD...
Objectives:We describe the methodology of a trial designed to highlight the interest of vegetables rich in ITF-prebiotics in obese adults. DESIGN:150 obese subjects (BMI> 30 kg.m-2; 18–65 years) recruited in three different university hospitals in Belgium will be selected with at least one of the following criteria: (pre-)diabetes, hypertension, dy...
Knowing how dietary fibre nourishes gut microorganisms might suggest ways to boost health-promoting bacteria. A method developed to pinpoint bacteria that consume particular types of dietary fibre could advance such efforts. Method pinpoints bacteria that consume particular types of dietary fibre.
The vascular dysfunction is the primary event in the occurrence of cardio-vascular risk, and no treatment exists until now. We tested for the first time the hypothesis that chitin-glucan (CG) - an insoluble fibre with prebiotic properties- and polyphenol-rich pomegranate peel extract (PPE) can improve endothelial and inflammatory disorders in a mou...
Scope:
Cereals are important sources of carbohydrates, but also contain nutrients that could impact adiposity. We analyzed the contribution of gluten on obesity and the effects of prebiotics -arabinoxylo-oligosaccharides (AXOS) and fructo-oligosaccharides (FOS)- that can be extracted from gluten-containing cereals.
Methods and results:
Mice were...
Cachexia occurs in many chronic diseases and is associated with increased morbidity and mortality. It is treated by nutritional support but often with limited effectiveness, leading to the search of other therapeutic strategies. The modulation of gut microbiota, whether through pro-, pre-, syn- or antibiotics or fecal transplantation, is attracting...
Obesity has been recognized by the World Health Organization as a global epidemic. The gut microbiota is considered as a factor involved in the regulation of numerous metabolic pathways by impacting several functions of the host. It has been suggested that probiotics can modulate host gene expression and metabolism, and thereby positively influence...
The prevalence of osteoarthritis (OA) increases not only because of longer life expectancy but also because of the modern lifestyle, in particular physical inactivity and diets low in fiber and rich in sugar and saturated fats, which promote chronic low-grade inflammation and obesity. Adverse alterations of the gut microbiota (GMB) composition, cal...
Background:
Inulin-type fructans (ITFs) are a type of fermentable dietary fiber that can confer beneficial health effects through changes in the gut microbiota. However, their effect on gut sensitivity and nutritional behavior is a matter of debate.
Objective:
We evaluated the impact of consuming ITF-rich vegetables daily on gut microbiota, gast...
Orosensory perception of sweet stimulus is blunted in diet-induced obese (DIO) rodents.
Although this alteration might contribute to unhealthy food choices, its origin remains to be
understood. Cumulative evidence indicates that prebiotic manipulations of the gut microbiota
are associated with changes in food intake by modulating hedonic and motiva...
Discipline
Expérimental/mécanismes cellulaires et moléculaires.
Introduction et but de l’étude
Il a été précédemment démontré qu’une supplémentation avec des prébiotiques, de type inuline, pouvait améliorer les désordres métaboliques associés à l’obésité chez certains patients. En utilisant un modèle de souris « humanisées » grâce à un transfert d...
Discipline
Éxpérimental/mécanismes cellulaires et moléculaires.
Introduction et but de l’étude
L’obésité est associée à des altérations du microbiote et de la barrière intestinale et à l’établissement d’une inflammation à bas bruit. Dans ce contexte, les lipides polaires laitiers (LP) ont montré des effets bénéfiques sur le métabolisme lipidique c...
Mol. Nutr. Food Res. 2019, 63, 1801078
DOI: 10.1002/mnfr.201801078
Polar lipids of the milk fat globule membrane are an emerging functional ingredient. In article number 1801078, Marie‐Caroline Michalski and co‐workers show in mice that when added to a high‐fat diet, 1.6% of milk polar lipids reduces body weight gain, modulates the abundance of bac...
This review presents mechanistic studies performed in vitro and in animal models, as well as data obtained in patients that contribute to a better understanding of the impact of nutrients interacting with the gut microbiota on metabolic and behavioural alterations linked to obesity. The gut microbiota composition and function are altered in several...
Scope
: Enhanced adiposity and metabolic inflammation are major features of obesity associated with altered gut microbiota and intestinal barrier. We investigated in mice fed a mixed high‐fat (HF) diet how these metabolic outcomes could be impacted by milk polar lipids (MPL), naturally containing 25% of sphingomyelin.
Methods and results
: Male C5...
Although UHT heat treatment is being optimized to improve the stability and functional properties of dairy products, its metabolic effects remain scarcely known. As such, we studied the effect of the type of UHT process on lipid metabolism, intestinal barrier, and inflammation in mice. Nine-week-old male C57Bl/6J mice were fed a diet composed of no...
Escherichia coli is a facultative anaerobic symbiont found widely among mammalian gastrointestinal tracts. Several human studies have reported increased commensal E. coli abundance in the intestine during inflammation; however, host immunological responses toward commensal E. coli during inflammation are not well-defined. Here, we show that coloniz...
Figure S1 Cachexia, LPS‐induced sepsis and STZ‐induced diabetes are associated with muscle atrophy. Gastrocnemius weight of cachectic vs CTR mice (A, n = 8/group), LPS vs CTR mice (B, n = 6/group), and STZ or STZ + INS vs CTR rats (C, n = 6/group). Results are means ± SE. Statistical analysis was performed using unpaired t‐test or 1‐way ANOVA and T...
Cancer cachexia is a complex multi-organ syndrome characterized by body weight loss, weakness, muscle atrophy and fat depletion. With a prevalence of 1 million people in Europe and only limited therapeutic options, there is a high medical need for new approaches to treat cachexia. Our latest results highlighted microbial dysbiosis, characterized by...
Aims/hypothesis:
Dipeptidyl peptidase 4 (DPP-4) inhibitors are agents designed to increase the half-life of incretins. Although they are administered orally, little is known about their effects on the gut microbiota and functions, despite the fact that some bacteria present in the gut microbiota exhibit DPP-4-like activity. Our objective was to st...
Purpose of review:
Recent studies have highlighted the importance of developing a multimodal therapeutic strategy for cancer cachectic patients. Considering the central role of metabolism and anorexia in this disease, optimized nutritional advice should be an integral part of this strategy. Current recommendations mainly focus on meeting caloric r...
Background
Glucocorticoids (GC) play a major role in muscle atrophy. As skeletal muscle is a secretory organ, characterization of the muscle secretome elicited by muscle atrophy should allow to better understand the cellular mechanisms and to identify circulating biomarkers of this condition. Our project aimed to identify the changes in the muscle...
An integrative multiomics approach in nondiabetic obese women identifies phenylacetate as a microbial metabolite contributing to the accumulation of lipids in the liver and hence to nonalcoholic steatohepatitis.
The gut microbiota regulates key hepatic functions, notably through the production of bacterial metabolites that are transported via the portal circulation. We evaluated the effects of metabolites produced by the gut microbiota from aromatic amino acids (phenylacetate, benzoate, p-cresol, and indole) on liver inflammation induced by bacterial endot...
Background:
Non-alcoholic fatty liver disease (NAFLD) represents a spectrum of fat-related conditions ranging from simple fatty liver, to non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis. There is growing evidence that NAFLD is a multisystem disease, affecting several extra-hepatic organs and regulatory pathways. Furthermore, since the...
Postprandial hyperlipidemia is an important risk factor for cardiovascular diseases in the context of obesity. Inulin is a non-digestible carbohydrate, known for its beneficial properties in metabolic disorders. We investigated the impact of inulin on postprandial hypertriglyceridemia and on lipid metabolism in a mouse model of diet-induced obesity...
Intestinal disorders often occur in cancer patients, in association with body weight loss, and this alteration is commonly attributed to the chemotherapy. Here, using a mouse model of cancer cachexia induced by ectopic transplantation of C26 cancer cells, we discovered a profound alteration in the gut functions (gut permeability, epithelial turnove...
Background:
Non-digestible carbohydrates present in cereals such as fructans and arabinoxylans represent promising prebiotic nutrients to prevent the development of obesity and related metabolic disorders.
Objective and design:
The aim of this study was to determine the corrective effects of wheat bran-derived arabinoxylan oligosaccharides in ob...