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Foods, 14 (13), pp. 2235-2235.
Hafeez, Z., Beaubier, S., Aymes, A., Christophe, S., Akbar, S., Kapel, R., Miclo, L.
Lactic acid bacteria are well known for hydrolyzing milk proteins, but their application to
plant proteins remains limited. This study evaluated the ability of the cell-wall-anchored
PrtS protease from two Streptococcus thermophilus strains to hydrolyze rapeseed albumins
(RAs), aiming to generate bioactive peptides with potential food functionality. The specific
activity of PrtS was first determined using a chromogenic substrate. RAs were then
hydrolyzed using 10X- and 100X-concentrated cell pellets of each strain to assess the hydrolysis
kinetics and the enzymatic mechanism. The results showed concentration-dependent
hydrolysis, with protein conversion and the degree of hydrolysis increasing threefold at
100X for both strains. Despite the increased hydrolysis, the peptides produced had similar
average sizes, averaging at five amino acids, indicating a consistent “one-by-one” cleavage
mechanism. The in vitro testing of the RA hydrolysates produced with 100X PrtS from
S. thermophilus LMD-9 revealed dose-dependent antioxidant activity comparable to native
RAs. Importantly, unlike native RAs, these hydrolysates did not induce increased secretion
of the pro-inflammatory mediator IL-8 in inflamed HT-29 cells, suggesting a reduced proinflammatory
potential. These findings demonstrate that PrtS protease from S. thermophilus
can effectively hydrolyze rapeseed proteins to produce functional hydrolysates with improved
bioactivity profiles. Such hydrolysates have promising applications as functional
ingredients in plant-based food products, contributing both to health benefits and potential
food preservation through antioxidant activity.
Pratiques en nutrition, 21 (81), pp. 13-16.
Miclo, L.
Le curcuma est une épice qui entre traditionnellement dans la composition des currys, mais son utilisation s’est fortement diversifiée puisqu’il est aussi consommé sous forme de jus ou de compléments alimentaires. En effet, la curcumine a été amplement étudiée et a montré de nombreuses activités biologiques suggérant qu’elle pourrait jouer un rôle préventif ou curatif de pathologies très variées. Pourtant, son profil pharmacocinétique ne correspond pas au profil classique d’un médicament et pose question quant aux molécules porteuses des activités mises en évidence.
Turmeric is a spice traditionally used in curries, but its use has widely extended to others products such as juices but also food supplements. Indeed, curcumin has been extensively studied and displays many biological activities suggesting that it could be involved in the prevention or treatment of a large number of pathologies. However, its pharmacokinetic profile does not correspond to the classic profile of a drug and raise questions about the molecules that actually carry the described activities.
Pratiques en nutrition, 21 (81), pp. 17-21.
Miclo, L.
Le pain d’épices est un concentré d’épices exotiques – cannelle, badiane, clou de girofle, cardamome et noix de muscade –, qui ont pendant de nombreux siècles été rares et chères. Devenues aujourd’hui abordables pour le plus grand nombre, elles sont parées de nombreuses vertus pour la santé. Néanmoins, peu d’études cliniques sont disponibles pour étayer ces affirmations et certaines de ces épices contiennent des composés qui, consommés dans des quantités au-delà des recommandations, peuvent avoir des effets nocifs sur la santé.
Gingerbread is a concentrate of exotic spices – cinnamon, star anise, clove, cardamom and nutmeg –, which were rare and expensive for many centuries. Now affordable for most people, many health effects are attributed to them. However, few clinical studies are available to support these claims and some of these spices contain compounds that can have harmful health effects if consumed in amounts higher than recommended.
Pratiques en nutrition, 21 (81), pp. 29-33.
Rossary, A., Miclo, L.
La nutrition du patient diabétique renvoie souvent l’image d’une “chasse au sucre” ; or les nouvelles connaissances acquises doivent conduire à réévaluer cette idée. Les produits amylacés, par la richesse de leurs matrices, participent à la prévention du risque cardiovasculaire et dysmétabolique du patient diabétique. Par ailleurs, la chimie intime de l’amidon, mieux comprise aujourd’hui, éclaire l’intérêt d’une alimentation équilibrée, peu ou pas transformée. À la lumière de ces connaissances, les bénéfices que peuvent avoir certains aliments dits glucidiques dans la nutrition du patient diabétique seront mis en avant.
Nutrition of diabetic patients often offers a picture of a “sugar stalking” but, the new knowledge acquired must lead us to reevaluate this. Starchy products, through the richness of their matrices, contribute to the prevention of cardiovascular and dysmetabolic risks in diabetic patients. Furthermore, the intimate chemistry of starch, better understood today, highlights the benefits of a balanced diet, with little or no processed foods. With this in mind, we will focus on the benefits that so-called “carbohydrate” foods can have in the diet of diabetic patients.
Microbial Pathogenesis, 207 (6), pp. 107859-107859.
Siddique, A., Ali, R., Andleeb, S., Akbar, S., Hafeez, Z., Imran, M., Syoc, E.V., Yue, M., Ganda, E., Rahman, A.
Probiotics can provide an eco-friendly alternative solution to improve poultry production and disease resistance. Considering safer and more effective probiotic strains from cultured species, this study included three host-associated probiotics (HAPs): Limosilactobacillus reuteri PFS4, Enterococcus faecium PFS13, and PFS14, previously isolated from poultry gut. This study evaluated the effects of three HAPs blend and a commercial probiotic blend (ProtexinR) on broiler growth, intestinal morphology, serum immunoglobulins, and cecal microflora challenged with two fluoroquinolone-resistant Salmonella Typhimurium (ST) and Salmonella Enteritidis (SE). A total of 240-day-old broiler chicks were randomly assigned to six treatment groups (n = 40 in each group): negative control (NC), positive control (PC), HAPs control blend (IPRO-) without ST and SE challenge, HAPs blend with ST and SE challenge (IPRO+), Commercial probiotic (ProtexinR) blend with ST and SE challenge (CM+), Commercial probiotic (ProtexinR) control (CM-) blend without ST and SE challenge. Growth parameters, including body weight gain (BWG), average feed intake (AFI), and feed conversion ratio (FCR), along with microbial populations, were assessed weekly. Meanwhile, gut morphology, relative organ weight, and serum immunoglobulin levels were evaluated on days 7 and 28. The chicks infected with ST and SE were depressed, had high mortality (20 %), and reduced BWG. The growth performance parameters were significantly improved (p ≤ 0.005) in all groups administered probiotics, with the IPRO- group exhibiting the highest results. Similarly, light microscopy findings showed that all probiotic-fed groups significantly (p ≤ 0.005) improved their gut morphology compared to the positive control group. Both HAPs and commercial probiotic blend treatments increased serum IgA and IgG compared with the PC (p ≤ 0.001). IPRO+ treatment significantly (p ≤ 0.001) increased cecal populations of total Lactobacillus and total Enterococcus, while reducing cecal and liver populations of Salmonella. In conclusion, the use of HAPs showed better growth performance and enhanced MDR Salmonella control, suggesting that the poultry sector should prioritize the development and application of probiotics derived from host-specific strains rather than other sources.
Molecules, 29 (7), 1552.
Allouche, R., Hafeez, Z., Dary-Mourot, A., Genay, M., Miclo, L.
In addition to traditional use in fermented dairy products, S. thermophilus also exhibits anti-inflammatory properties both in live and heat-inactivated form. Recent studies have highlighted that some hydrolysates from surface proteins of S. thermophilus could be responsible partially for overall anti-inflammatory activity of this bacterium. It was hypothesized that anti-inflammatory activity could also be attributed to peptides resulting from the digestion of intracellular proteins of S. thermophilus. Therefore, total intracellular proteins (TIP) from two phenotypically different strains, LMD-9 and CNRZ-21N, were recovered by sonication followed by ammonium sulphate precipitation. The molecular masses of the TIP of both strains were very close to each other as observed by SDS-PAGE. The TIP were fractionated by size exclusion fast protein liquid chromatography to obtain a 3–10 kDa intracellular protein (IP) fraction, which was then hydrolysed with pancreatic enzyme preparation, Corolase PP. The hydrolysed IP fraction from each strain exhibited anti-inflammatory activity by modulating pro-inflammatory mediators, particularly IL-1β in LPS-stimulated THP-1 macrophages. However, a decrease in IL-8 secretion was only observed with hydrolysed IP fraction from CNRZ-21N, indicating that strain could be an important parameter in obtaining active hydrolysates. Results showed that peptides from the 3–10 kDa IP fraction of S. thermophilus could therefore be considered as postbiotics with potential beneficial effects on human health. Thus, it can be used as a promising bioactive ingredient for the development of functional foods to prevent low-grade inflammation.
American Journal of Medical Genetics, 194 (9), e63.
Blanc, A., Bonnet, C., Wandzel, M., Roth, V., Duffourd, Y., Safraou, H., Leheup, B., Muller, F., Colne, J.D., Feillet, F., Schmitt, E., Castro, M., Savatt, J., Burcheri, A., Nemos, C., Philippe, C., Lambert, L.
The autosomal dominant Okur–Chung neurodevelopmental syndrome (OCNDS: OMIM #617062) is a rare neurodevelopmental disorder first described in 2016. Features include developmental delay (DD), intellectual disability (ID), behavioral problems, hypotonia, language deficits, congenital heart abnormalities, and non-specific dysmorphic facial features. OCNDS is caused by heterozygous pathogenic variants in CSNK2A1 (OMIM *115440; NM_177559.3). To date, 160 patients have been diagnosed worldwide. The number will likely increase due to the growing use of exome sequencing (ES) and genome sequencing (GS). Here, we describe a novel OCNDS patient carrying a CSNK2A1 variant (NM_177559.3:c.140G>A; NP_808227.1:p.Arg47Gln). Phenotypically, he presented with DD, ID, generalized hypotonia, speech delay, short stature, microcephaly, and dysmorphic features such as low-set ears, hypertelorism, thin upper lip, and a round face. The patient showed several signs not yet described that may extend the phenotypic spectrum of OCNDS. These include prenatal bilateral clubfeet, exotropia, and peg lateral incisors. However, unlike the majority of descriptions, he did not present sleep disturbance, seizures or gait difficulties. A literature review shows phenotypic heterogeneity for OCNDS, whether these patients have the same variant or not. This case report is an opportunity to refine the phenotype of this syndrome and raise the question of the genotype–phenotype correlation.
Journal of Drug Delivery Science and Technology, 95 (5), pp. 105585-105585.
Mirza, R., Khan, A.U., Shah, K.U., Ullah, N., Nawaz, A., Ghani, S.F., Javed, A., Shah, S.U., Alasmari, A.F., Alharbi, M., Alasmari, F., Hafeez, Z.
In the present study, cefepime loaded transfersomes based in situ gel (CFP-TSFG) were developed for brain targeting via intranasal delivery. Cefepime loaded transfersomes (CFP-TSFs) prepared by thin film hydration method. Box–Behnken design was applied for optimization by analyzing the effect of independent variables i.e., phospholipon 90G, tween-80, and cefepime on particle size (PS), polydispersity index (PDI), zeta potential (ZP), and entrapment efficiency (EE%). The optimized CFP-TSFs formulation was found to be spherical shaped with PS 111.1±0.6nm, PDI 0.28±0.05, ZP -27±0.9mV, EE 84±0.3%, and deformability index 73±0.3. Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction technique (XRD), were performed to analyze the chemical interactions and crystallinity of excipients and formulation respectively. CFP-TSFs were effectively loaded in optimized thermosensitive in situ gel. CFP-TSFG was evaluated for its physicochemical properties, in vitro, antimicrobial, ex vivo, and in vivo studies. In vitro studies showed sustained behavior of CFP-TSFG. Ex vivo permeation studies of CFP-TSFG showed 34-fold increased permeation compared to conventional gel. In vivo studies demonstrating improved targeting efficiency of developed CFP-TSFG via the intranasal route. The biocompatibility of the CFP-TSFG was evaluated and confirmed by toxicity studies. In conclusion, the optimized CFP-TSFG system could be a potential formulation for brain targeting via intranasal delivery.
Probiotics and Antimicrobial Proteins, 15 (2), pp. 387-399.
Hadef, S., Idoui, T., Sifour, M., Genay, M., Dary-Mourot, A.
Twenty-five lactic acid bacterial (LAB) strains have been isolated from traditional goat butter and three types of cheese (dry Klila, frech Klila, and Bouhezza) and evaluated for technological abilities, probiotic properties, and potentials as starter cultures. The twenty-five LAB strains comprised eight strains belonging to Lactobacillus, four strains belonging to Lactococcus, eleven strains belonging to Enterococcus, and two strains belonging to Leuconostoc. A non-hierarchical cluster analysis was performed in order to select the performing strains. After carrying out the preliminary phenotypic characterizations and the probiotic potential, three strains designated as BM10, B15, and C30 belonging to the genus Lactobacillus and Enterococcus with good tolerance to acidity were selected. The strains showed a significant resistance to 0.5% bile salts and 0.4% phenol. Hemolytic activity was not detected; in addition, good hydrophobicity and autoaggregation was obtained. A significant antimicrobial activity was exhibited by all selected strains against Listeria innocua. Genotypic identification by 16S rRNA allowed the identification of B15, BM10, and C30 as Lactobacillus plantarum, Lactobacillus casei, and Enterococcus durans, respectively. The results of the current study suggest that the strains isolated from Algerian fermented dairy products have high potential as probiotic starter cultures in the goat butter and cheese industry.
Pratiques en nutrition, 19 (73), pp. 36-40.
Miclo, L.
Les consommateurs qui recherchent des produits peu transformés d’origine végétale incluent de nouvelles graines dans leur alimentation. Parfois qualifiées de superaliments, elles sont parées de vertus pour la santé. Si des activités biologiques ont pu être établies dans des modèles, leur transposition à l’échelle de l’individu nécessiterait des études cliniques plus nombreuses. Certaines de ces graines contiennent des substances pouvant exercer un impact sur la biodisponibilité de nutriments ou la sécurité alimentaire.
Consumers by seeking less-processed products of plant origin, are including new seeds in their diet. Sometimes called superfoods, many health effects are attributed to them. While some biological activities was established in models, their transposition to humans would require more clinical studies. Some of these seeds contain substances that can impact the bioavailability of nutrients or food security.
Pratiques en nutrition, 19 (75), pp. 41-44.
Miclo, L.
Les messages émis par les autorités de santé concernant une consommation excessive de sucre ont été intégrés par les consommateurs qui se tournent vers des sources alternatives au sucre de canne ou de betterave, tout en recherchant une certaine naturalité du produit. Ces alternatives peuvent être des sources de fructose, glucide susceptible d’avoir un impact sur le risque de survenue de certaines pathologies. La préparation de la majorité d’entre eux repose, tout comme le sucre raffiné, sur une série de procédés technologiques.
Consumers have heeded the messages issued by health authorities regarding excessive sugar consumption, but they are nevertheless looking for cane or beet sugar substitutes with the desire to find a natural product. These substitutes can be sources of fructose from beet or cane, a carbohydrate that can have an impact on the risk of developing certain pathologies. In addition, the majority of these substitutes undergo, like refined sugar, technological processes for their preparation.
Pratiques en Nutrition, 19 (76), pp. 8-11.
Miclo, L.
Dans les pays occidentaux, la consommation d’algues est à la hausse, notamment chez les personnes qui suivent un régime végétarien. Les macroalgues sont une source de macronutriments et de micronutriments variés dont la concentration et la biodisponibilité dépendent néanmoins des espèces considérées. La forte capacité de bioaccumulation des macroalgues peut augmenter la concentration de certains nutriments et composés toxiques, ce qui implique de fixer les quantités qu’il est possible d’ingérer sans risque.
In Western countries, seaweed consumption is on the rise, especially among people following a vegetarian diet. Macroalgae are a source of numerous macronutrients and micronutrients, the concentration and bioavailability of which depend on the species considered. The high bioaccumulation capacity of macroalgae can increase the concentration of certain nutrients and toxic compounds leading to determine the quantities that can be consumed without any risk.
Nutrients, 14 (22), pp. 4777.
Allouche, R., Genay, M., Dary-Mourot, A., Hafeez, Z., Miclo, L.
Streptococcus thermophilus, a food grade bacterium, is extensively used in the manufacture of fermented products such as yogurt and cheeses. It has been shown that S. thermophilus strains exhibited varying anti-inflammatory activities in vitro. Our previous study displayed that this activity could be partially due to peptide(s) generated by trypsin hydrolysis of the surface proteins of S. thermophilus LMD-9. Surface protease PrtS could be the source of these peptides during gastrointestinal digestion. Therefore, peptide hydrolysates were obtained by shaving two phenotypically distinct strains of S. thermophilus (LMD-9 PrtS+ and CNRZ-21N PrtS−) with pepsin, a gastric protease, followed or not by trypsinolysis. The peptide hydrolysates of both strains exhibited anti-inflammatory action through the modulation of pro-inflammatory mediators in LPS-stimulated THP-1 macrophages (COX-2, Pro-IL-1β, IL-1β, and IL-8) and LPS-stimulated HT-29 cells (IL-8). Therefore, peptides released from either PrtS+ or PrtS− strains in the gastrointestinal tract during digestion of a product containing this bacterium may display anti-inflammatory effects and reduce the risk of inflammation-related chronic diseases.
Foods, 11 (8), pp. 1157.
Allouche, R., Hafeez, Z., Papier, F., Dary-Mourot, A., Genay, M., Miclo, L.
Nutrients, 14 (11), pp. 2212.
Benoit, S., Chaumontet, C., Violle, N., Boulier, A., Hafeez, Z., Cakir-Kiefer, C., Tomé, D., Schwarz, J., Miclo, L.
Frontiers in Nutrition, 9, doi:10.3389/fnut.2022.888179.
Gagnaire, V., Lecomte, X., Richoux, R., Genay, M., Jardin, J., Briard-Bion, V., Kerjean, J.-R., Thierry, A.
Pratiques en nutrition, 18 (71), pp. 40-44.
Miclo, L.
Les polyols sont des édulcorants de masse incorporés dans des produits alimentaires en substitution des sucres. Ils possèdent un pouvoir sucrant et une valeur énergétique inférieurs à ceux du saccharose mais leurs propriétés laxatives limitent leur emploi, bien que celles-ci dépendent largement du polyol considéré. Ce sont des fermentable oligo-, di-, monosaccharides and polyols, dont l’utilisation doit être surveillée chez les personnes sensibles, bien qu’ils aient des effets prébiotiques importants pour le microbiote intestinal.
Polyols are bulk sweeteners used in food products as a substitute for sugars. They have a sweetness and a caloric value lower than those of sucrose, but their laxative effects limit their use although these largely depend on the polyol in question. Being a part of Fermentable Oligo-, Di-, Monosaccharides and Polyols, their use should bear continued scrutiny in sensitive people, knowing that they have major prebiotic effects for the gut microbiota.
Toxics, 10 (4), pp. 180.
Morel, C., Christophe, A., Maguin Gaté, K., Paoli, J., Turner, J.D., Schroeder, H., Grova, N.
Environmental Chemistry Letters, Jan 23, pp. 1-6.
Morel, C., Schroeder, H., Emond, C., Turner, J.D., Lichtfouse, E., Grova, N.
Dying immediately in fames or from poisoning in the long run is the cornelian dilemma induced by the use of brominated fame-retardants. Indeed, these compounds have been intensively used to slow down fres in houses and buildings, thus increasing escape time from about 2 min to 20 min. They were initially thought to be safe, notably because their adhesive properties make them unlikely to reach human tissues. However, recent research has disclosed that brominated fame-retardants are developmental neurotoxicants that trigger neurodevelopmental defcits in young children (Gray and Billock 2017) (Fig. 1). Since infants and young children have been exposed to brominated fame-retardants since the early 1970s, we are now observing the long-term developmental impact of this 50-year-old ticking time bomb. Here we discuss the occurrence of brominated fame-retardants, exposure at home, neurodevelopmental diseases and alternative fame retardants.
Nutrients, 14 (24), pp. 5338.
Pinchaud, K., Hafeez, Z., Auger, S., Chatel, J.-M., Chadi, S., Langella, P., Paoli, J., Dary-Mourot, A., Maguin-Gaté, K., Olivier, J.-L.
Although arachidonic acid (ARA) is the precursor of the majority of eicosanoids, its influence as a food component on health is not well known. Therefore, we investigated its impact on the gut microbiota and gut–brain axis. Groups of male BALB/c mice were fed either a standard diet containing 5% lipids (Std-ARA) or 15%-lipid diets without ARA (HL-ARA) or with 1% ARA (HL + ARA) for 9 weeks. Fatty acid profiles of all three diets were the same. The HL-ARA diet favored the growth of Bifidobacterium pseudolongum contrary to the HL + ARA diet that favored the pro-inflammatory Escherichia–Shigella genus in fecal microbiota. Dietary ARA intake induced 4- and 15-fold colic overexpression of the pro-inflammatory markers IL-1β and CD40, respectively, without affecting those of TNFα and adiponectin. In the brain, dietary ARA intake led to moderate overexpression of GFAP in the hippocampus and cortex. Both the hyperlipidic diets reduced IL-6 and IL-12 in the brain. For the first time, it was shown that dietary ARA altered the gut microbiota, led to low-grade colic inflammation, and induced astrogliosis in the brain. Further work is necessary to determine the involved mechanisms.
BMC Genomics, 23, pp. 210.
Roux, É., Nicolas, A., Valence, F., Siekaniec, G., Chuat, V., Nicolas, J., Le Loir, Y., Guédon, E.
Microorganisms, 9 (11), pp. 2380.
Awussi, A. A., Roux, É., Humeau, C., Hafeez, Z., Maigret, B., Chang, O.K., Lecomte, X., Humbert, G., Miclo, L., Genay, M., Perrin, C., Dary-Mourot, A.
Growth of the lactic acid bacterium Streptococcus thermophilus in milk depends on its capacity to hydrolyze proteins of this medium through its surface proteolytic activity. Thus, strains exhibiting the cell envelope proteinase (CEP) PrtS are able to grow in milk at high cellular density. Due to its LPNTG motif, which is possibly the substrate of the sortase A (SrtA), PrtS is anchored to the cell wall in most S. thermophilus strains. Conversely, a soluble extracellular PrtS activity has been reported in the strain 4F44. It corresponds, in fact, to a certain proportion of PrtS that is not anchored to the cell wall but rather is released in the growth medium. The main difference between PrtS of strain 4F44 (PrtS4F44) and other PrtS concerns the absence of a 32-residue imperfect duplication in the prodomain of the CEP, postulated as being required for the maturation and correct subsequent anchoring of PrtS. In fact, both mature (without the prodomain at the N-terminal extremity) and immature (with the prodomain) forms are found in the soluble PrtS4F44 form along with an intact LPNTG at their C-terminal extremity. Investigations we present in this work show that (i) the imperfect duplication is not implied in PrtS maturation; (ii) the maturase PrtM is irrelevant in PrtS maturation which is probably automaturated; and (iii) SrtA allows for the PrtS anchoring in S. thermophilus but the SrtA of strain 4F44 (SrtA4F44) displays an altered activity.
Archives of Toxicology, 95 (9), pp. 3085-3099.
Bernal Melendez, E., Callebert, J., Bouillaud-Kremarik, P., Persuy, M.-A., Olivier, B., Badonnel, K., Chavatte-Palmer, P., Baly, C., Schroeder, H.
Limited studies in humans and in animal models have investigated the neurotoxic risks related to a gestational exposure to diesel exhaust particles (DEP) on the embryonic brain, especially those regarding monoaminergic systems linked to neurocognitive disorders. We previously showed that exposure to DEP alters monoaminergic neurotransmission in fetal olfactory bulbs and modifies tissue morphology along with behavioral consequences at birth in a rabbit model. Given the anatomical and functional connections between olfactory and central brain structures, we further characterized their impacts in brain regions associated with monoaminergic neurotransmission. At gestational day 28 (GD28), fetal rabbit brains were collected from dams exposed by nose-only to either a clean air or filtered DEP for 2 h/day, 5 days/week, from GD3 to GD27. HPLC dosage and histochemical analyses of the main monoaminergic systems, i.e., dopamine (DA), noradrenaline (NA), and serotonin (5-HT) and their metabolites were conducted in microdissected fetal brain regions. DEP exposure increased the level of DA and decreased the dopaminergic metabolites ratios in the prefrontal cortex (PFC), together with sex-specific alterations in the hippocampus (Hp). In addition, HVA level was increased in the temporal cortex (TCx). Serotonin and 5-HIAA levels were decreased in the fetal Hp. However, DEP exposure did not significantly modify NA levels, tyrosine hydroxylase, tryptophan hydroxylase or AChE enzymatic activity in fetal brain. Exposure to DEP during fetal life results in dopaminergic and serotonergic changes in critical brain regions that might lead to detrimental potential short-term neural disturbances as precursors of long-term neurocognitive consequences.
Frontiers in Genetics Epigenomics and Epigenetics, 657171 (1), pp. 1-13.
Fernandes, S.B., Grova, N., Roth, S., Duca, R.D., Godderis, L., Guebels, P., Mérieux, S., Lumley, A.I., Bouillaud-Kremarik, P., Ernens, I., Devaux, Y., Schroeder, H., Turner, J.D.
DNA methylation is one of the most important epigenetic modifications and is closely related with several biological processes such as regulation of gene transcription and the development of non-malignant diseases. The prevailing dogma states that DNA methylation in eukaryotes occurs essentially through 5-methylcytosine but recently adenine methylation was also found to be present in eukaryotes. In mouse embryonic stem cells, 6-methyladenine was associated with the repression and silencing of genes, particularly in the X-chromosome, known to play an important role in cell fate determination. Here, we have demonstrated that 6mA is a ubiquitous eukaryotic epigenetic modification that is put in place during epigenetically sensitive periods such as embryogenesis and foetal development. In somatic cells there are clear tissue specificity in 6mA levels, with the highest 6mA levels being observed in the brain. In zebrafish, during the first 120h of embryo development, from a single pluripotent cell to an almost fully formed individual, 6mA levels steadily increase. An identical pattern was observed over embryonic days 7-21 in the mouse. Furthermore, exposure to a neurotoxic environmental pollutant during the same early life period may led to a decrease in the levels of this modification in female rats. The identification of the periods during which 6mA epigenetic marks are put in place increases our understanding of this mammalian epigenetic modification, and raises the possibility that it may be associated with developmental processes.
Food & Function, 12, pp. 1415-1431.
Hafeez, Z., Benoit, S., Cakir-Kiefer, C., Dary, A., Miclo, L.
About one in three people are affected by anxiety disorders during their lifetime. Anxiety episodes can be brief due to a stressful event, but anxiety disorders can last at least 6 months. A wide variety of therapeutic drugs is available for the treatment of anxiety disorders, but due to the associated side effects of these anxiolytics, it is interesting to find alternatives. Some food protein hydrolysates or active peptide fragments present in such hydrolysates provide a natural and promising mean for preventing certain forms of anxiety. To date, only a few numbers of hydrolysates or peptides from food proteins with anxiolytic-like activity have been characterized. Most of these hydrolysates or peptides have displayed potent anxiolytic profiles in animal or clinical studies. The results suggest that these molecules may exert their effects at different levels. This paper reviews data of the structure/activity relationship of anxiolytic peptides, their physiological effects displayed in in vitro and in vivo assays, bioavailability, and safety profiles.
Toxics, 9 (50), pp. 1-18.
Saber Cherif, L., Cao-Lei, L., Farinelle, S., Muller, C.P., Turner, J.T., Schroeder, H., Grova, N.
The potent neurotoxicity of benzo[a]pyrene (B[a]P) has been suggested to be a susceptibility factor accelerating the onset of brain tumours and the emergence of neurobehavioural disturbances. B[a]P has been shown to be neurotoxic, acting directly on both the central and peripheral nervous systems, as well as indirectly via peripheral organs like liver and gut. By using a realistic B[a]P exposure scenario (0.02–200 mg/kg/day, 10 days) in mice, we elucidated brain-specific B[a]P metabolism and at identified hydroxylated B[a]P metabolites in serum which could be used as markers of cognitive impairment. Repeated oral administration of B[a]P led to, at the doses of 20 and 200 mg/kg/day, significant overexpression of Cyp1a1/Cyp1b1 in 2 out of the 3 brain regions considered, thereby suggesting the ability of the brain to metabolize B[a]P itself. At the same doses, mice exhibited a reduction in anxiety in both the elevated plus maze and the hole board apparatus. Concomitantly, B[a]P triggered dose-dependent changes in Nmda subunit expression (Nr1 and Nr2a/Nr2b) in areas involved in cognition. We detected 9-OH-B[a]P and 7,8-diol-B[a]P in serum at the level for which cognitive impairment was observed. We suggest that these metabolites may, in the future be exploited as potent biomarkers of B[a]P-induced cognitive impairments.
Microbial Genomics, 7 (11), 000654.
Siekaniec, G., Roux, É., Lemane, T., Guédon, É., Nicolas, J.
This study aimed to provide efficient recognition of bacterial strains on personal computers from MinION (Nanopore) long read data. Thanks to the fall in sequencing costs, the identification of bacteria can now proceed by whole genome sequencing. MinION is a fast, but highly error-prone sequencing device and it is a challenge to successfully identify the strain content of unknown simple or complex microbial samples. It is heavily constrained by memory management and fast access to the read and genome fragments. Our strategy involves three steps: indexing of known genomic sequences for a given or several bacterial species; a request process to assign a read to a strain by matching it to the closest reference genomes; and a final step looking for a minimum set of strains that best explains the observed reads. We have applied our method, called ORI, on 77 strains of Streptococcus thermophilus. We worked on several genomic distances and obtained a detailed classification of the strains, together with a criterion that allows merging of what we termed ‘sibling’ strains, only separated by a few mutations. Overall, isolated strains can be safely recognized from MinION data. For mixtures of several non-sibling strains, results depend on strain abundance.
Microorganisms, 9 (6), pp. 1113-1113.
Uriot, O., Kebouchi, M., Lorson-Dalibard, É., Galia, W., Denis, S., Chalançon, S., Hafeez, Z., Roux, É., Genay, M., Blanquet-Diot, S., Dary-Mourot, A.
Despite promising health effects, the probiotic status of Streptococcus thermophilus, a lactic
acid bacterium widely used in dairy industry, requires further documentation of its physiological
status during human gastrointestinal passage. This study aimed to apply recombinant-based in vivo
technology (R-IVET) to identify genes triggered in a S. thermophilus LMD-9 reference strain under
simulated digestive conditions. First, the R-IVET chromosomal cassette and plasmid genomic library
were designed to positively select activated genes. Second, recombinant clones were introduced
into complementary models mimicking the human gut, the Netherlands Organization for Applied
Scientific Research (TNO) gastrointestinal model imitating the human stomach and small intestine,
the Caco-2 TC7 cell line as a model of intestinal epithelium, and anaerobic batch cultures of human
feces as a colon model. All inserts of activated clones displayed a promoter activity that differed
from one digestive condition to another. Our results also showed that S. thermophilus adapted its
metabolism to stressful conditions found in the gastric and colonic competitive environment and
modified its surface proteins during adhesion to Caco-2 TC7 cells. Activated genes were investigated
in a collection of S. thermophilus strains showing various resistance levels to gastrointestinal stresses,
a first stage in the identification of gut resistance markers and a key step in probiotic selection.