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Papers by Muriel Thomas

Frontiers in Nutrition, Jan 4, 2023

HAL (Le Centre pour la Communication Scientifique Directe), 2021

International audienceThe population over 60 years could represent 35% of the French population i... more International audienceThe population over 60 years could represent 35% of the French population in 30 years and at least 30% of them suffer from sarcopenia and undernutrition. Various strategies exist to limit sarcopenia, but they can be unsuitable for frail people. Indeed, frail individuals present a decreased efficiency for food energy use associated with an alteration of their gut microbiota. In addition, as frail people are generally sitting (with a minimum exercise), they can be non-compliant to physical exercise advices. Other strategies to limit sarcopenia in this population should be developed and in particular novel nutritional recommendations/strategies. Probiotics are known to be able to modulate the composition of the microbiota and provide other health benefits. The aim of my thesis is then to investigate the potential of a probiotic strain to limit muscle mass loss in frail elderly population. Previous work from collaborators of the project have shown that when transferred to axenic mice, the microbiota from intestine-resected patient led to an increased release of GLP-1 and Ghrelin in rats, 2 peptides involved in appetite regulation of increased insulin sensitivity. We therefore postulated that specific microbes selected from these patients and further given to frail patients could modulate/alter gut peptides synthesis, increase insulin sensitivity and limit muscle mass loss. Selected bacterial strains isolated from an intestine-resected patient were screened in vitro for their ability to stimulate the secretion of gut peptides (GLP-1) in enterocytes and on Caenorhabditis elegans for their effect on worm longevity. The impact of probiotic microbes was assessed on protein-energy metabolism and insulin-sensitivity in old rats subjected to dietary restriction (to mimic frailty in humans). The results cannot be detailed in the present abstract since a patent deposit is pending concerning the strains and related health effects. We hope that the patent will be finalized for poster or oral presentation within the next months. The ultimate objective of my thesis will be to incorporate the most promising selected probiotic strain into a fermented food (soft cheese) in order to combine the beneficial effects on the metabolism of the strain with high protein intakes, this latter being also insufficiently supplied in frail elderly population

Clinical nutrition ESPEN, Dec 1, 2020

Keratinocyte (KC) apoptosis plays a critical role in regulating epidermal development and restrai... more Keratinocyte (KC) apoptosis plays a critical role in regulating epidermal development and restraining carcinogenesis. Apoptosis balances proliferation to maintain epidermal thickness, contributes to stratum corneum formation and may eliminate pre-malignant cells. Apart from the normal developmental program, KC apoptosis can be triggered by UV light and other stimuli. Dysfunctional apoptosis occurs in some skin diseases, such as psoriasis and skin cancer. Here we review the current state of knowledge of KC apoptosis, with particular focus on apoptotic signaling pathways and molecular mechanisms of apoptosis control, and discuss new insights into the complex role of apoptosis in skin carcinogenesis that are emerging from mouse models.

Nutrition clinique et métabolisme, Apr 1, 2020

Introduction et but de l’etude Le syndrome de grele court (SGC) resulte d’une resection etendue d... more Introduction et but de l’etude Le syndrome de grele court (SGC) resulte d’une resection etendue de l’intestin conduisant a une insuffisance intestinale chronique. Des adaptations spontanees (hyperphagie, dysbiose, adaptation morpho-fonctionnelle) sont observees chez les patients SGC. Nous avons valide un modele murin de SGC et montre la mise en place d’une adaptation intestinale avec hyperplasie colique puis jejunale et augmentation de l’expression et de la secretion de nombreuses hormones intestinales. Une forte augmentation de l’expression des neuropeptides orexigenes hypothalamiques (AgRP et NPY) a ete observee des 7 jours post-operatoires et precede l’apparition de l’hyperphagie. L’objectif de l’etude etait de caracteriser dans ce modele murin de SGC la composition du microbiote et de certains metabolites qu’il produit apres resection. Materiel et methodes Des rats Wistar ont subi une resection de 75 % d’intestin grele, de la valve ileo-caecale et une colectomie partielle (IR) ou une transsection intestinale (Sham). La perte de poids et la prise alimentaire ont ete mesurees pendant 28 jours. Les feces ont ete prelevees pour analyser leur composition en AGCC et lactate et en 6 groupes bacteriens par qPCR 16S. Les fragments intestinaux ont ete preleves pour analyses morphometriques ou pour analyser par RT-qPCR les ARNm codant les hormones intestinales, les transporteurs et recepteurs de nutriments ou AGCC. Les resultats sont exprimes en moyenne ±esm et analyses par des tests non parametriques Resultats et analyse statistique Cette etude confirme qu’apres une perte de poids importante la 1re semaine (−14 % vs +9 % pour les Shams p Conclusion Ces resultats montrent que notre modele murin de SGC reproduit la dysbiose observee chez les patients SGC : une presence importante de Lactobacilles associee a l’augmentation de lactate dans les feces. La forte diminution des AGCC dans les feces des rats IR ne permet pas pour le moment de determiner s’il y a des modifications de leur production ou de leur absorption, mais l’augmentation de l’expression du transporteur MCT1 suggere une adaptation du colon pouvant favoriser leur absorption. Nous recherchons chez les rats IR s’il existe des correlations entre ces modifications du microbiote et des AGCC et les autres parametres de l’adaptation.

Nutrition clinique et métabolisme, Nov 1, 2018

Cahiers de nutrition et de diététique, Dec 1, 2011

Nutrition clinique et métabolisme 25 (2011) S52-S153 / Cahiers de nutrition et de diététique 46 2... more Nutrition clinique et métabolisme 25 (2011) S52-S153 / Cahiers de nutrition et de diététique 46 2011(2011) S52-S153 de l'état nutritionnel et la réduction des besoins en NP, dans 24 cas de fistule entéro pariétale du grêle. Matériel et Méthodes.-Étude rétrospective de 24 patients (14H, 10F) traités par RC pour FEP. Les durées (j) sont exprimées en médiane ± interquartile ; l'albuminémie, le nutritional risk index (NRI) et les pertes digestives avant et pendant RC sont comparées par test de Student pour séries appariées (n = nombre de paires, moyennes ± écarts-type à comparer, p). Le seuil de NRI < 83,5 définit une dénutrition sévère. Résultats.-Le site des FEP était duodénal (3), jéjunal (19) ou iléal (2). Les orifices d'amont et d'aval étaient contigus (17) ou séparés (7). Le mécanisme en cause était cancéreux (5) mécanique (7), infectieux (11) ou traumatique (1). La RC a débuté 8 ± 13 j après l'admission et a été poursuivie pour 22/24 jusqu'à la sortie, pendant 74 ± 62 j.

Gastroenterology, May 1, 2012

Frontiers in Nutrition, Aug 10, 2022

Lacticaseibacillus casei CNCM I-5663 supplementation maintained muscle mass in a model of frail r... more Lacticaseibacillus casei CNCM I-5663 supplementation maintained muscle mass in a model of frail rodents.

Gastroenterology, May 1, 2012

HAL (Le Centre pour la Communication Scientifique Directe), Nov 10, 2021

Discipline: Expérimental/mécanismes cellulaires et moléculaires Présentation préférée: ORAL Intro... more Discipline: Expérimental/mécanismes cellulaires et moléculaires Présentation préférée: ORAL Introduction et but de l'étude: La sarcopénie, de par ses conséquences (chutes, dépendance) est une problématique majeure de santé publique. Les stratégies basées sur des supplémentations protéiques et/ou l'exercice peuvent partiellement limiter le développement de la sarcopénie mais selon l'état physio-pathologique du sénior (manque d'appétit, difficultés à faire de l'exercice), elles peuvent ne pas être optimales. Ainsi, des stratégies alternatives ou complémentaires doivent être développées et nous avons envisagé de cibler le microbiote via l'action de probiotiques. Il a été observé que des patients souffrant du syndrome de grêle court (SBS) se sont métaboliquement adaptés afin d'optimiser l'utilisation des nutriments. En particulier, ils présentent une forte augmentation des bactéries lactiques intestinales. Le transfert de ce microbiote à des rongeurs axéniques a montré le rôle partiellement causal de ce microbiote sur l'augmentation des niveaux plasmatique de GLP-1 et ghréline. Nous avons donc émis l'hypothèse que certaines souches bactériennes provenant de ces individus pourraient être intéressantes pour améliorer l'état sarcopénique des personnes âgées dénutries. Matériel et méthodes: A partir de fèces de patients SBS, une souche appartenant à Lactocaseibacillus casei (LC-5663) a été testée in vivo chez le rat âgé (18 mois ; n=25 par groupe) soumis à une restriction calorique modérée (75% Ad libitum) afin de mimer expérimentalement le développement d'une sarcopénie avec malnutrition (groupes R et R+5663). Ces deux groupes restreints sont comparés à un groupe témoin Ad libitum (AL). La composition corporelle (Echo-MRI), la masse musculaire et la sensibilité à l'insuline globale (OGTT, HOMA-IR) ont notamment été évaluées. Résultats et Analyse statistique: La restriction calorique a induit une diminution de la masse musculaire (-10% ; ANOVA, p<0,05, R vs AL) mais une prise quotidienne de LC-5663 pendant un mois (~10 9 UFC) a permis de contrecarrer cette fonte musculaire (+12% ; p<0,05, R+5663 vs R). Une amélioration de la sensibilité à l'insuline globale est observée dans le groupe R+5663 (-25% de l'indice HOMA-IR, groupe R+5663 avant et après 2 mois de traitement (p=0,056) et excursion glycémique diminuée à 30 min de l'OGTT pour R+5663 vs AL (p<0.01)). Cet effet insulino-sensibilisateur de LC-5663 pourrait être lié à une modulation de la production des acides gras à chaines courtes totaux (AGCC), qui tendent à diminuer avec la restriction (-16% ; p=0,08, R vs AL) mais maintenus avec la supplémentation en LC-5663 (NS, R+5663 vs AL). En parallèle, l'expression des récepteurs de ces acides gras GPR41 et 43 dans l'iléon diminue chez R vs AL (-48% et-42% respectivement, p<0,001) mais est partiellement maintenue chez les animaux R+5663 au niveau AL. Conclusion: Une stratégie impliquant le dialogue microbiote-intestin-muscle est une approche intéressante pour limiter la sarcopénie chez les personnes âgées. Bien qu'à confirmer, LC-5663 permettrait une amélioration de l'insulino-sensibilité globale par un mécanisme impliquant les AGCC et dont les impacts sur le maintien du muscle squelettique restent à étudier. Conflits d'intérêts: Aucun conflit à déclarer

HAL (Le Centre pour la Communication Scientifique Directe), Jun 4, 2015

Impact of intestinal dysbiosis on mouse models of colonic hypersensitivity. NeuroGASTRO 201

Frontiers in Cellular and Infection Microbiology

Extensive intestinal resection leads to Short Bowel Syndrome (SBS), the main cause of chronic int... more Extensive intestinal resection leads to Short Bowel Syndrome (SBS), the main cause of chronic intestinal failure. Colon preservation is crucial for spontaneous adaptation, to improve absorption and reduce parenteral nutrition dependence. Fecal microbiota transplantation (FMT), a promising approach in pathologies with dysbiosis as the one observed in SBS patients, was assessed in SBS rats with jejuno‐colonic anastomosis. The evolution of weight and food intake, the lenght of intestinal villi and crypts and the composition of fecal microbiota of Sham and SBS rats, transplanted or not with high fat diet rat microbiota, were analyzed. All SBS rats lost weight, increased their food intake and exhibited jejunal and colonic hyperplasia. Microbiota composition of SBS rats, transplanted or not, was largely enriched with Lactobacillaceae, and α‐ and β‐diversity were significantly different from Sham. The FMT altered microbiota composition and α‐ and β‐diversity in Sham but not SBS rats. FMT f...

Gut Microbes, 2020

Induction chemotherapy (7 + 3 regimen) remains the gold standard for patients with acute myeloid ... more Induction chemotherapy (7 + 3 regimen) remains the gold standard for patients with acute myeloid leukemia (AML) but is responsible for gut damage leading to several complications such as bloodstream infection (BSI). We aimed to investigate the impact of induction chemotherapy on the intestinal barrier of patients with AML and in wild-type mice. Next, we assessed the potential benefit of strengthening the mucosal barrier in transgenic mice releasing a recombinant protein able to reinforce the mucus layer (Tg222). In patients, we observed a decrease of plasma citrulline, which is a marker of the functional enterocyte mass, of short-chain fatty acids and of fecal bacterial load, except for Escherichia coli and Enterococcus spp., which became dominant. Both the α and βdiversities of fecal microbiota decreased. In wild-type mice, citrulline levels decreased under chemotherapy along with an increase of E. coli and Enterococcus spp load associated with concomitant histologic impairment. By comparison with wild-type mice, Tg222 mice, 3 days after completing chemotherapy, had higher citrulline levels, a faster healing epithelium, and preserved α-diversity of their intestinal microbiota. This was associated with reduced bacterial translocations. Our results highlight the intestinal damage and the dysbiosis induced by the 7 + 3 regimen. As a proof of concept, our transgenic model suggests that strengthening the intestinal barrier is a promising approach to limit BSI and improve AML patients' outcome.

Gut Microbes, 2020

Fecal microbiota transplantation is now recommended for treating recurrent forms of Clostridioide... more Fecal microbiota transplantation is now recommended for treating recurrent forms of Clostridioides difficile infection. Recent studies have reported protocols using capsules of either frozen or freeze-dried stool allowing oral administration in in-and outpatient settings. However, a central question remains the viability, engraftment, and efficacy of the microbiome over time during storage life. This study shows that both the freeze-drying and freezing procedures for fecal samples allowed preserving viability, short-chain fatty acids concentration, and anti-Clostridioides difficile properties of microbiota without significant alteration after storage for 12 months. Fecal transplantation with freeze-dried microbiota allowed engraftment of microbiota leading to clearance of Clostridioides difficile infection in a preclinical murine model with a survival rate of 70% versus 53-60% in mice treated with frozen inocula, and 20% in the untreated group. Moreover, the freeze-dried powder can be used to fill oral hard capsules using a very low amount (0.5%) of glidant excipient, allowing oral formulation. Altogether, this study showed that freeze-dried inocula can be used for the treatment of Clostridioides difficile infection with long-lasting stability of the fecal microbiota. This formulation facilitates biobanking and allows the use of hard capsules, an essential step to simplify patient access to treatment.

The Journal of Nutrition, 2002

Of the oil-soluble organosulfur compounds derived from garlic, diallyl disulfide (DADS) is one of... more Of the oil-soluble organosulfur compounds derived from garlic, diallyl disulfide (DADS) is one of the most abundant. We examined the effect of DADS on gene expression in rat liver. By suppressive subtractive hybridization, we identified the heavy (H)-ferritin gene as a DADSstimulated gene in the rat liver epithelial (REL) cells. DADS stimulation of Hand L (light)-ferritin mRNA was analyzed in REL cells and in rat liver. Incubation of the REL cells in 10 mol/L DADS for 4 h increased H-ferritin 1.9 ؎ 0.2-fold, n ‫؍‬ 3) and light(L)-ferritin mRNA 1.5 ؎ 0.2-fold, n ‫؍‬ 3). Stimulation did not occur in the presence of an inhibitor of transcription, actinomycin D. Stimulation of ferritin at the RNA and protein levels was also found in rats administered a DADS-enriched oil solution intragastrically. There was a 3 ؎ 1.1-fold increase in Hand 3 ؎ 0.14-fold increase for L-ferritin mRNA 24 h after the end of the infusion in the presence of DADS, (n ‫؍‬ 3). The expression of the transferrin receptor, an iron transporter, was also enhanced by DADS in rat liver. In conclusion, our data suggest that DADS could modify iron homeostasis through the modulation of ferritin and transferrin receptor gene expression.

Frontiers in physiology, 2017

Short bowel syndrome (SBS) is characterized by severe intestinal malabsorption following restrict... more Short bowel syndrome (SBS) is characterized by severe intestinal malabsorption following restrictive surgery. The objective of this study was to determine the functional contribution of SBS-microbiota after resection. It is well-known that SBS-microbiota displayed specific features with a prevalence of Lactobacillus, a low amount of some anaerobic microbes (Clostridium leptum) and an accumulation of fecal lactate in some patients. Patients with jejuno-colonic anastomosis were stratified according to the presence of lactate in their feces and, we observe that the lactate-producing bacteria were predominant in the sub-group of patients accumulating fecal lactate. One case of D-encephalopathy crisis occurred when the D-lactate isoform accumulated in the feces and plasma bicarbonate levels decreased. The fecal sample at the time of the encephalopathy was transferred to germ free rats (SBS-H rats). The SBS-H microbiota conserved some characteristics of the SBS donnor, predominated by lac...

Gastroenterology, 2012

The lactic acid bacterium Streptococcus thermophilus is the archetype of lactose-adapted bacteria... more The lactic acid bacterium Streptococcus thermophilus is the archetype of lactose-adapted bacteria and so far, its sugar metabolism has been mainly investigated In Vitro. S. thermophilus, consumed by Humans for centuries, is widely and traditionally used in food industry for yogurt-and cheese-making but few data are available about its behaviour in the gastrointestinal tract (GIT). In this context, we studied the crosstalk between S. thermophilus and GIT in gnotobiotic rats. Recently, we showed that S. thermophilus was able i) to adapt its global metabolism to the gut environment toward carbohydrate metabolism and ii) to induce a host response (Rul et al., J Biol Chem., 2011). We thus proposed that lactate, resulting from the adaptive metabolic activity of S. thermophilus, may serve as a biological signal to communicate and modulate colonic host epithelium. Moreover, we have shown that the presence of lactose acts as a prebiotic by enhancing S. thermophilus level and kinetic of implantation, and fermentative activity in the GIT (Thomas et al., Plos One, 2011). In a context where probiotics are claimed to have a protective action toward GIT, our aim was to evaluate the ability of S. thermophilus in enhancing mucosal protection through the goblet cells production. Each germ-free (GF) rat was inoculated orally with 5x10 9 S. thermophilus and was euthanized 30 days later. Goblet cells on colon sections were stained with Alcian blue or periodic acid-Schiff and Mucin 2 (MUC2) immunohistochemistry was performed. Krüppel Like Factor 4 (KLF4) protein, a goblet cells differentiation marker, was quantified by Western blot. We showed that S. thermophilus significantly increased the percentage of goblet cells per crypt compared to GF rats (41% and 29%, respectively) and the amount of KLF4 protein (2.2 ±0.5-fold). Quantification of goblet cells markers mRNA is currently in progress. Our hypothesis was that lactate produced at high level (from 15 to 50 mM) by S. thermophilus in GIT might be involved in the induction of goblet cells. To test this hypothesis, confluent HT29-MTX cells (a cell line producing mucus) were incubated with 20 or 50 mM lactate for 17 hours and we observed that lactate significantly increased the amount of KLF4 protein In Vitro (2.3 ±0.3-fold). To conclude, we proposed that lactate produced by S. thermophilus in the GIT of mono-associated rats may act as a bacterial signal to trigger goblet cells differentiation pathway suggesting a novel protective function of this probiotic bacterium.

Microbial Cell Factories, 2015

This paper concerns the procedure and the scientific approach to obtain market authorization for ... more This paper concerns the procedure and the scientific approach to obtain market authorization for a microorganism to be recognized as a novel food with a health claim. Microorganisms that have not been traditionally used during food production in Europe prior to 1997 are considered as novel foods, which should undergo an in-depth characterization and safety assessment before being authorized on the European market. If a novel food bacterium is claimed to provide a beneficial effect on health, these claims must also be investigated before they can be authorized. Some requirements to obtain novel food certification are shared with those required to obtain a health claim. Although regulation exists that deals with these issues for foods in general, bacteria in food raise a specific set of questions that are only minimally addressed in official documentation. We propose a framework and suggest a list of criteria that should be assessed to obtain marketing authorization and health claim for a bacterium in accordance with European health policy.

Frontiers in Nutrition, Jan 4, 2023

HAL (Le Centre pour la Communication Scientifique Directe), 2021

International audienceThe population over 60 years could represent 35% of the French population i... more International audienceThe population over 60 years could represent 35% of the French population in 30 years and at least 30% of them suffer from sarcopenia and undernutrition. Various strategies exist to limit sarcopenia, but they can be unsuitable for frail people. Indeed, frail individuals present a decreased efficiency for food energy use associated with an alteration of their gut microbiota. In addition, as frail people are generally sitting (with a minimum exercise), they can be non-compliant to physical exercise advices. Other strategies to limit sarcopenia in this population should be developed and in particular novel nutritional recommendations/strategies. Probiotics are known to be able to modulate the composition of the microbiota and provide other health benefits. The aim of my thesis is then to investigate the potential of a probiotic strain to limit muscle mass loss in frail elderly population. Previous work from collaborators of the project have shown that when transferred to axenic mice, the microbiota from intestine-resected patient led to an increased release of GLP-1 and Ghrelin in rats, 2 peptides involved in appetite regulation of increased insulin sensitivity. We therefore postulated that specific microbes selected from these patients and further given to frail patients could modulate/alter gut peptides synthesis, increase insulin sensitivity and limit muscle mass loss. Selected bacterial strains isolated from an intestine-resected patient were screened in vitro for their ability to stimulate the secretion of gut peptides (GLP-1) in enterocytes and on Caenorhabditis elegans for their effect on worm longevity. The impact of probiotic microbes was assessed on protein-energy metabolism and insulin-sensitivity in old rats subjected to dietary restriction (to mimic frailty in humans). The results cannot be detailed in the present abstract since a patent deposit is pending concerning the strains and related health effects. We hope that the patent will be finalized for poster or oral presentation within the next months. The ultimate objective of my thesis will be to incorporate the most promising selected probiotic strain into a fermented food (soft cheese) in order to combine the beneficial effects on the metabolism of the strain with high protein intakes, this latter being also insufficiently supplied in frail elderly population

Clinical nutrition ESPEN, Dec 1, 2020

Keratinocyte (KC) apoptosis plays a critical role in regulating epidermal development and restrai... more Keratinocyte (KC) apoptosis plays a critical role in regulating epidermal development and restraining carcinogenesis. Apoptosis balances proliferation to maintain epidermal thickness, contributes to stratum corneum formation and may eliminate pre-malignant cells. Apart from the normal developmental program, KC apoptosis can be triggered by UV light and other stimuli. Dysfunctional apoptosis occurs in some skin diseases, such as psoriasis and skin cancer. Here we review the current state of knowledge of KC apoptosis, with particular focus on apoptotic signaling pathways and molecular mechanisms of apoptosis control, and discuss new insights into the complex role of apoptosis in skin carcinogenesis that are emerging from mouse models.

Nutrition clinique et métabolisme, Apr 1, 2020

Introduction et but de l’etude Le syndrome de grele court (SGC) resulte d’une resection etendue d... more Introduction et but de l’etude Le syndrome de grele court (SGC) resulte d’une resection etendue de l’intestin conduisant a une insuffisance intestinale chronique. Des adaptations spontanees (hyperphagie, dysbiose, adaptation morpho-fonctionnelle) sont observees chez les patients SGC. Nous avons valide un modele murin de SGC et montre la mise en place d’une adaptation intestinale avec hyperplasie colique puis jejunale et augmentation de l’expression et de la secretion de nombreuses hormones intestinales. Une forte augmentation de l’expression des neuropeptides orexigenes hypothalamiques (AgRP et NPY) a ete observee des 7 jours post-operatoires et precede l’apparition de l’hyperphagie. L’objectif de l’etude etait de caracteriser dans ce modele murin de SGC la composition du microbiote et de certains metabolites qu’il produit apres resection. Materiel et methodes Des rats Wistar ont subi une resection de 75 % d’intestin grele, de la valve ileo-caecale et une colectomie partielle (IR) ou une transsection intestinale (Sham). La perte de poids et la prise alimentaire ont ete mesurees pendant 28 jours. Les feces ont ete prelevees pour analyser leur composition en AGCC et lactate et en 6 groupes bacteriens par qPCR 16S. Les fragments intestinaux ont ete preleves pour analyses morphometriques ou pour analyser par RT-qPCR les ARNm codant les hormones intestinales, les transporteurs et recepteurs de nutriments ou AGCC. Les resultats sont exprimes en moyenne ±esm et analyses par des tests non parametriques Resultats et analyse statistique Cette etude confirme qu’apres une perte de poids importante la 1re semaine (−14 % vs +9 % pour les Shams p Conclusion Ces resultats montrent que notre modele murin de SGC reproduit la dysbiose observee chez les patients SGC : une presence importante de Lactobacilles associee a l’augmentation de lactate dans les feces. La forte diminution des AGCC dans les feces des rats IR ne permet pas pour le moment de determiner s’il y a des modifications de leur production ou de leur absorption, mais l’augmentation de l’expression du transporteur MCT1 suggere une adaptation du colon pouvant favoriser leur absorption. Nous recherchons chez les rats IR s’il existe des correlations entre ces modifications du microbiote et des AGCC et les autres parametres de l’adaptation.

Nutrition clinique et métabolisme, Nov 1, 2018

Cahiers de nutrition et de diététique, Dec 1, 2011

Nutrition clinique et métabolisme 25 (2011) S52-S153 / Cahiers de nutrition et de diététique 46 2... more Nutrition clinique et métabolisme 25 (2011) S52-S153 / Cahiers de nutrition et de diététique 46 2011(2011) S52-S153 de l'état nutritionnel et la réduction des besoins en NP, dans 24 cas de fistule entéro pariétale du grêle. Matériel et Méthodes.-Étude rétrospective de 24 patients (14H, 10F) traités par RC pour FEP. Les durées (j) sont exprimées en médiane ± interquartile ; l'albuminémie, le nutritional risk index (NRI) et les pertes digestives avant et pendant RC sont comparées par test de Student pour séries appariées (n = nombre de paires, moyennes ± écarts-type à comparer, p). Le seuil de NRI < 83,5 définit une dénutrition sévère. Résultats.-Le site des FEP était duodénal (3), jéjunal (19) ou iléal (2). Les orifices d'amont et d'aval étaient contigus (17) ou séparés (7). Le mécanisme en cause était cancéreux (5) mécanique (7), infectieux (11) ou traumatique (1). La RC a débuté 8 ± 13 j après l'admission et a été poursuivie pour 22/24 jusqu'à la sortie, pendant 74 ± 62 j.

Gastroenterology, May 1, 2012

Frontiers in Nutrition, Aug 10, 2022

Lacticaseibacillus casei CNCM I-5663 supplementation maintained muscle mass in a model of frail r... more Lacticaseibacillus casei CNCM I-5663 supplementation maintained muscle mass in a model of frail rodents.

Gastroenterology, May 1, 2012

HAL (Le Centre pour la Communication Scientifique Directe), Nov 10, 2021

Discipline: Expérimental/mécanismes cellulaires et moléculaires Présentation préférée: ORAL Intro... more Discipline: Expérimental/mécanismes cellulaires et moléculaires Présentation préférée: ORAL Introduction et but de l'étude: La sarcopénie, de par ses conséquences (chutes, dépendance) est une problématique majeure de santé publique. Les stratégies basées sur des supplémentations protéiques et/ou l'exercice peuvent partiellement limiter le développement de la sarcopénie mais selon l'état physio-pathologique du sénior (manque d'appétit, difficultés à faire de l'exercice), elles peuvent ne pas être optimales. Ainsi, des stratégies alternatives ou complémentaires doivent être développées et nous avons envisagé de cibler le microbiote via l'action de probiotiques. Il a été observé que des patients souffrant du syndrome de grêle court (SBS) se sont métaboliquement adaptés afin d'optimiser l'utilisation des nutriments. En particulier, ils présentent une forte augmentation des bactéries lactiques intestinales. Le transfert de ce microbiote à des rongeurs axéniques a montré le rôle partiellement causal de ce microbiote sur l'augmentation des niveaux plasmatique de GLP-1 et ghréline. Nous avons donc émis l'hypothèse que certaines souches bactériennes provenant de ces individus pourraient être intéressantes pour améliorer l'état sarcopénique des personnes âgées dénutries. Matériel et méthodes: A partir de fèces de patients SBS, une souche appartenant à Lactocaseibacillus casei (LC-5663) a été testée in vivo chez le rat âgé (18 mois ; n=25 par groupe) soumis à une restriction calorique modérée (75% Ad libitum) afin de mimer expérimentalement le développement d'une sarcopénie avec malnutrition (groupes R et R+5663). Ces deux groupes restreints sont comparés à un groupe témoin Ad libitum (AL). La composition corporelle (Echo-MRI), la masse musculaire et la sensibilité à l'insuline globale (OGTT, HOMA-IR) ont notamment été évaluées. Résultats et Analyse statistique: La restriction calorique a induit une diminution de la masse musculaire (-10% ; ANOVA, p<0,05, R vs AL) mais une prise quotidienne de LC-5663 pendant un mois (~10 9 UFC) a permis de contrecarrer cette fonte musculaire (+12% ; p<0,05, R+5663 vs R). Une amélioration de la sensibilité à l'insuline globale est observée dans le groupe R+5663 (-25% de l'indice HOMA-IR, groupe R+5663 avant et après 2 mois de traitement (p=0,056) et excursion glycémique diminuée à 30 min de l'OGTT pour R+5663 vs AL (p<0.01)). Cet effet insulino-sensibilisateur de LC-5663 pourrait être lié à une modulation de la production des acides gras à chaines courtes totaux (AGCC), qui tendent à diminuer avec la restriction (-16% ; p=0,08, R vs AL) mais maintenus avec la supplémentation en LC-5663 (NS, R+5663 vs AL). En parallèle, l'expression des récepteurs de ces acides gras GPR41 et 43 dans l'iléon diminue chez R vs AL (-48% et-42% respectivement, p<0,001) mais est partiellement maintenue chez les animaux R+5663 au niveau AL. Conclusion: Une stratégie impliquant le dialogue microbiote-intestin-muscle est une approche intéressante pour limiter la sarcopénie chez les personnes âgées. Bien qu'à confirmer, LC-5663 permettrait une amélioration de l'insulino-sensibilité globale par un mécanisme impliquant les AGCC et dont les impacts sur le maintien du muscle squelettique restent à étudier. Conflits d'intérêts: Aucun conflit à déclarer

HAL (Le Centre pour la Communication Scientifique Directe), Jun 4, 2015

Impact of intestinal dysbiosis on mouse models of colonic hypersensitivity. NeuroGASTRO 201

Frontiers in Cellular and Infection Microbiology

Extensive intestinal resection leads to Short Bowel Syndrome (SBS), the main cause of chronic int... more Extensive intestinal resection leads to Short Bowel Syndrome (SBS), the main cause of chronic intestinal failure. Colon preservation is crucial for spontaneous adaptation, to improve absorption and reduce parenteral nutrition dependence. Fecal microbiota transplantation (FMT), a promising approach in pathologies with dysbiosis as the one observed in SBS patients, was assessed in SBS rats with jejuno‐colonic anastomosis. The evolution of weight and food intake, the lenght of intestinal villi and crypts and the composition of fecal microbiota of Sham and SBS rats, transplanted or not with high fat diet rat microbiota, were analyzed. All SBS rats lost weight, increased their food intake and exhibited jejunal and colonic hyperplasia. Microbiota composition of SBS rats, transplanted or not, was largely enriched with Lactobacillaceae, and α‐ and β‐diversity were significantly different from Sham. The FMT altered microbiota composition and α‐ and β‐diversity in Sham but not SBS rats. FMT f...

Gut Microbes, 2020

Induction chemotherapy (7 + 3 regimen) remains the gold standard for patients with acute myeloid ... more Induction chemotherapy (7 + 3 regimen) remains the gold standard for patients with acute myeloid leukemia (AML) but is responsible for gut damage leading to several complications such as bloodstream infection (BSI). We aimed to investigate the impact of induction chemotherapy on the intestinal barrier of patients with AML and in wild-type mice. Next, we assessed the potential benefit of strengthening the mucosal barrier in transgenic mice releasing a recombinant protein able to reinforce the mucus layer (Tg222). In patients, we observed a decrease of plasma citrulline, which is a marker of the functional enterocyte mass, of short-chain fatty acids and of fecal bacterial load, except for Escherichia coli and Enterococcus spp., which became dominant. Both the α and βdiversities of fecal microbiota decreased. In wild-type mice, citrulline levels decreased under chemotherapy along with an increase of E. coli and Enterococcus spp load associated with concomitant histologic impairment. By comparison with wild-type mice, Tg222 mice, 3 days after completing chemotherapy, had higher citrulline levels, a faster healing epithelium, and preserved α-diversity of their intestinal microbiota. This was associated with reduced bacterial translocations. Our results highlight the intestinal damage and the dysbiosis induced by the 7 + 3 regimen. As a proof of concept, our transgenic model suggests that strengthening the intestinal barrier is a promising approach to limit BSI and improve AML patients' outcome.

Gut Microbes, 2020

Fecal microbiota transplantation is now recommended for treating recurrent forms of Clostridioide... more Fecal microbiota transplantation is now recommended for treating recurrent forms of Clostridioides difficile infection. Recent studies have reported protocols using capsules of either frozen or freeze-dried stool allowing oral administration in in-and outpatient settings. However, a central question remains the viability, engraftment, and efficacy of the microbiome over time during storage life. This study shows that both the freeze-drying and freezing procedures for fecal samples allowed preserving viability, short-chain fatty acids concentration, and anti-Clostridioides difficile properties of microbiota without significant alteration after storage for 12 months. Fecal transplantation with freeze-dried microbiota allowed engraftment of microbiota leading to clearance of Clostridioides difficile infection in a preclinical murine model with a survival rate of 70% versus 53-60% in mice treated with frozen inocula, and 20% in the untreated group. Moreover, the freeze-dried powder can be used to fill oral hard capsules using a very low amount (0.5%) of glidant excipient, allowing oral formulation. Altogether, this study showed that freeze-dried inocula can be used for the treatment of Clostridioides difficile infection with long-lasting stability of the fecal microbiota. This formulation facilitates biobanking and allows the use of hard capsules, an essential step to simplify patient access to treatment.

The Journal of Nutrition, 2002

Of the oil-soluble organosulfur compounds derived from garlic, diallyl disulfide (DADS) is one of... more Of the oil-soluble organosulfur compounds derived from garlic, diallyl disulfide (DADS) is one of the most abundant. We examined the effect of DADS on gene expression in rat liver. By suppressive subtractive hybridization, we identified the heavy (H)-ferritin gene as a DADSstimulated gene in the rat liver epithelial (REL) cells. DADS stimulation of Hand L (light)-ferritin mRNA was analyzed in REL cells and in rat liver. Incubation of the REL cells in 10 mol/L DADS for 4 h increased H-ferritin 1.9 ؎ 0.2-fold, n ‫؍‬ 3) and light(L)-ferritin mRNA 1.5 ؎ 0.2-fold, n ‫؍‬ 3). Stimulation did not occur in the presence of an inhibitor of transcription, actinomycin D. Stimulation of ferritin at the RNA and protein levels was also found in rats administered a DADS-enriched oil solution intragastrically. There was a 3 ؎ 1.1-fold increase in Hand 3 ؎ 0.14-fold increase for L-ferritin mRNA 24 h after the end of the infusion in the presence of DADS, (n ‫؍‬ 3). The expression of the transferrin receptor, an iron transporter, was also enhanced by DADS in rat liver. In conclusion, our data suggest that DADS could modify iron homeostasis through the modulation of ferritin and transferrin receptor gene expression.

Frontiers in physiology, 2017

Short bowel syndrome (SBS) is characterized by severe intestinal malabsorption following restrict... more Short bowel syndrome (SBS) is characterized by severe intestinal malabsorption following restrictive surgery. The objective of this study was to determine the functional contribution of SBS-microbiota after resection. It is well-known that SBS-microbiota displayed specific features with a prevalence of Lactobacillus, a low amount of some anaerobic microbes (Clostridium leptum) and an accumulation of fecal lactate in some patients. Patients with jejuno-colonic anastomosis were stratified according to the presence of lactate in their feces and, we observe that the lactate-producing bacteria were predominant in the sub-group of patients accumulating fecal lactate. One case of D-encephalopathy crisis occurred when the D-lactate isoform accumulated in the feces and plasma bicarbonate levels decreased. The fecal sample at the time of the encephalopathy was transferred to germ free rats (SBS-H rats). The SBS-H microbiota conserved some characteristics of the SBS donnor, predominated by lac...

Gastroenterology, 2012

The lactic acid bacterium Streptococcus thermophilus is the archetype of lactose-adapted bacteria... more The lactic acid bacterium Streptococcus thermophilus is the archetype of lactose-adapted bacteria and so far, its sugar metabolism has been mainly investigated In Vitro. S. thermophilus, consumed by Humans for centuries, is widely and traditionally used in food industry for yogurt-and cheese-making but few data are available about its behaviour in the gastrointestinal tract (GIT). In this context, we studied the crosstalk between S. thermophilus and GIT in gnotobiotic rats. Recently, we showed that S. thermophilus was able i) to adapt its global metabolism to the gut environment toward carbohydrate metabolism and ii) to induce a host response (Rul et al., J Biol Chem., 2011). We thus proposed that lactate, resulting from the adaptive metabolic activity of S. thermophilus, may serve as a biological signal to communicate and modulate colonic host epithelium. Moreover, we have shown that the presence of lactose acts as a prebiotic by enhancing S. thermophilus level and kinetic of implantation, and fermentative activity in the GIT (Thomas et al., Plos One, 2011). In a context where probiotics are claimed to have a protective action toward GIT, our aim was to evaluate the ability of S. thermophilus in enhancing mucosal protection through the goblet cells production. Each germ-free (GF) rat was inoculated orally with 5x10 9 S. thermophilus and was euthanized 30 days later. Goblet cells on colon sections were stained with Alcian blue or periodic acid-Schiff and Mucin 2 (MUC2) immunohistochemistry was performed. Krüppel Like Factor 4 (KLF4) protein, a goblet cells differentiation marker, was quantified by Western blot. We showed that S. thermophilus significantly increased the percentage of goblet cells per crypt compared to GF rats (41% and 29%, respectively) and the amount of KLF4 protein (2.2 ±0.5-fold). Quantification of goblet cells markers mRNA is currently in progress. Our hypothesis was that lactate produced at high level (from 15 to 50 mM) by S. thermophilus in GIT might be involved in the induction of goblet cells. To test this hypothesis, confluent HT29-MTX cells (a cell line producing mucus) were incubated with 20 or 50 mM lactate for 17 hours and we observed that lactate significantly increased the amount of KLF4 protein In Vitro (2.3 ±0.3-fold). To conclude, we proposed that lactate produced by S. thermophilus in the GIT of mono-associated rats may act as a bacterial signal to trigger goblet cells differentiation pathway suggesting a novel protective function of this probiotic bacterium.

Microbial Cell Factories, 2015

This paper concerns the procedure and the scientific approach to obtain market authorization for ... more This paper concerns the procedure and the scientific approach to obtain market authorization for a microorganism to be recognized as a novel food with a health claim. Microorganisms that have not been traditionally used during food production in Europe prior to 1997 are considered as novel foods, which should undergo an in-depth characterization and safety assessment before being authorized on the European market. If a novel food bacterium is claimed to provide a beneficial effect on health, these claims must also be investigated before they can be authorized. Some requirements to obtain novel food certification are shared with those required to obtain a health claim. Although regulation exists that deals with these issues for foods in general, bacteria in food raise a specific set of questions that are only minimally addressed in official documentation. We propose a framework and suggest a list of criteria that should be assessed to obtain marketing authorization and health claim for a bacterium in accordance with European health policy.