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Mucosal healing progression after acute colitis in mice

World Journal of Gastroenterology 2019年第27期25卷 3572-3589页

作者： Sandra Vidal-Lletjós Mireille Andriamihaja Anne Blais Marta Grauso Patricia Lepage Anne-Marie Davila Claire Gaudichon Marion Leclerc Francois Blachier Annaig Lan UMR PNCA AgroParisTechINRAUniversite Paris-SaclayParis 75005France umr MICALIS INRAUniversite Paris-SaclayJouy-en-Josas 78350France

BACKGROUND Mucosal healing has become a therapeutic goal to achieve stable remission in patients with inflammatory bowel diseases. To achieve this objective, overlapping actions of complex cellular processes, such as migration, proliferation, and differentiation, are required. These events are longitudinally and tightly controlled by numerous factors including a wide range of distinct regulatory proteins. However, the sequence of events associated with colon mucosal repair after colitis and the evolution of the luminal content characteristics during this process have been little studied.AIM To document the evolution of colon mucosal characteristics during mucosal healing using a mouse model with chemically-induced colitis.METHODS C57 BL/6 male mice were given 3.5% dextran sodium sulfate(DSS) in drinking water for 5 d. They were euthanized 2(day 7), 5(day 10), 8(day 13), and 23(day28) d after DSS removal. The colonic luminal environment and epithelial repair processes during the inflammatory flare and colitis resolution were analyzed with reference to a non-DSS treated control group, euthanized at day 0. Epithelial repair events were assessed histo-morphologically in combination with functional permeability tests, expression of key inflammatory and repairing factors, and evaluation of colon mucosa-adherent microbiota composition by 16 S rRNA sequencing.RESULTS The maximal intensity of colitis was concomitant with maximal alterations of intestinal barrier function and histological damage associated with goblet cell depletion in colon mucosa. It was recorded 2 d after termination of the DSStreatment, followed by a progressive return to values similar to those of control mice. Although signs of colitis were severe(inflammatory cell infiltrate, crypt disarray, increased permeability) and associated with colonic luminal alterations(hyperosmolarity, dysbiosis, decrease in short-chain fatty acid content), epithelial healing processes were launched early during the inflammatory flare with increased gene expression of cert

关键词： Colon luminal environment Dextran sodium sulfate-induced colitis Dysbiosis Epithelial repair Acute colitis

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Fate of undigested proteins in the pig large intestine:What impact on the colon epithelium?

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Animal Nutrition 2022年第2期9卷 110-118页

作者： François Blachier Mireille Andriamihaja Xiang-Feng Kong UMR PNCA Nutrition Physiology and Alimentary BehaviorUniversite Paris-SaclayAgroParisTechINRAEParisFrance Key Laboratory of Agro-Ecological Processes in Subtropical Region Institute of Subtropical AgricultureChinese Academy of SciencesChangshaChina

Apart from its obvious agronomic interest in feeding billions of people worldwide,the porcine species represents an irreplaceable experimental model for intestinal physiologists and nutritionists.In this review,we give an overview on the fate of proteins that are not fully digested in the pig small intestine,and thus are transferred into the large intestine.In the large intestine,dietary and endogenous proteins are converted to peptides and amino acids(AA)by the action of bacterial proteases and peptidases.AA,which cannot,except in the neonatal period,be absorbed to any significant level by the colonocytes,are used by the intestinal microbes for protein synthesis and for the production of numerous metabolites.Of note,the production of the AA-derived metabolites greatly depends on the amount of undigested polysaccharides in the pig's diet.The effects of these AA-derived bacterial metabolites on the pig colonic epithelium have not yet been largely studied.However,the available data,performed on colonic mucosa,isolated colonic crypts and colonocytes,indicate that some of them,like ammonia,butyrate,acetate,hydrogen sulfide(H_(2)S),and p-cresol are active either directly or indirectly on energy metabolism in colonic epithelial cells.Further studies in that area will certainly gain from the utilization of the pig colonic organoid model,which allows for disposal of functional epithelial unities.Such studies will contribute to a better understanding of the potential causal links between diet-induced changes in the luminal concentrations of these AA-derived bacterial metabolites and effects on the colon epithelial barrier function and water/electrolyte absorption.

关键词： Gut microbiota Amino acids Bacterial metabolites Pig Large intestine

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Intrauterine growth retardation affects liver bile acid metabolism in growing pigs:effects associated with the changes of colonic bile acid derivatives

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Journal of Animal Science and Biotechnology 2023年第2期14卷 711-728页

作者： Yang Liu MdAbul Kalam Azad Wanghong Zhang Liang Xiong Francois Blachier Zugong Yu Xiangfeng Kong Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process Key Laboratory of Agro‑Ecological Processes in Subtropical RegionInstitute of Subtropical AgricultureChinese Academy of SciencesChangsha 410125HunanChina College of Veterinary Medicine Nanjing Agricultural UniversityNanjing 210095JiangsuChina UMR PNCA Universite Paris-SaclayINRAE75005 AgroParisTechParisFrance.

Background:Intrauterine growth retardation(IUGR)is associated with severely impaired nutrient metabolism and intestinal development of pigs.Our previous study found that IUGR altered intestinal microbiota and metabolites in the colon.However,the consequences of IUGR on bile acid metabolism in pigs remained unclear.The present study aimed to investigate the bile acid metabolism in the liver and the profile of bile acid derivatives in the colon of grow-ing pigs with IUGR using bile acid targeted metabolomics.Furthermore,we determined correlations between colonic microbiota composition and metabolites of IUGR and normal birth weight(NBW)pigs at different growth stages that were 7,21,and 28-day-old,and the average body weight(BW)of 25,50,and 100 kg of the NBW pigs.Results:The results showed that the plasma total bile acid concentration was higher(P<0.05)at the 25 kg BW stage and tended to increase(P=0.08)at 28-day-old in IUGR pigs.The hepatic gene expressions related to bile acid synthe-sis(CYP7A1,CYP27A1,and NTCP)were up-regulated(P<0.05),and the genes related to glucose and lipid metabolism(ATGL,HSL,and PC)were down-regulated(P<0.05)at the 25 kg BW stage in IUGR pigs when compared with the NBW group.Targeted metabolomics analysis showed that 29 bile acids and related compounds were detected in the colon of pigs.The colonic concentrations of dehydrolithocholic acid and apocholic acid were increased(P<0.05),while isodeoxycholic acid and 6,7-diketolithocholic acid were decreased(P<0.05)in IUGR pigs,when compared with the NBW pigs at the 25 kg BW stage.Moreover,Spearman’s correlation analysis revealed that colonic Unclassified_[Mogi-bacteriaceae],Lachnospira,and Slackia abundances were negatively correlated(P<0.05)with dehydrolithocholic acid,as well as the Unclassified_Clostridiaceae abundance with 6,7-diketolithocholic acid at the 25 kg BW stage.Conclusions:These findings suggest that IUGR could affect bile acid and glucolipid metabolism in growing pigs,especially at the 25 kg BW stage,these effects being paralleled

关键词： Bile acid metabolism Glucolipid metabolism Intestinal microbiota Intrauterine growth retardation Pigs

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Orexins:A promising target to digestive cancers,inflammation,obesity and metabolism dysfunctions

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World Journal of Gastroenterology 2021年第44期27卷 7582-7596页

作者： Alain Couvineau Thierry Voisin Pascal Nicole Valerie Gratio Anne Blais INSERM umr1149/Inflammation Research Center Team“From inflammation to cancer in digestive diseases”labeled by“la Ligue Nationale contre le Cancer”University of ParisDHU UNITYParis 75018France UMR PNCA AgroParisTechINRAUniversitéParis-SaclayParis 75005France

Hypothalamic neuropeptides named hypocretin/orexins which were identified in 1998 regulate critical functions such as wakefulness in the central nervous system.These past 20 years had revealed that orexins/receptors system was also present in the peripheral nervous system where they participated to the regulation of multiple functions including blood pressure regulation,intestinal motility,hormone secretion,lipolyze and reproduction functions.Associated to these peripheral functions,it was found that orexins and their receptors were involved in various diseases such as acute/chronic inflammation,metabolic syndrome and cancers.The present review suggests that orexins or the orexin neural circuitry represent potential therapeutic targets for the treatment of multiple pathologies related to inflammation including intestinal bowel disease,multiple sclerosis and septic shock,obesity and digestive cancers.

关键词： Orexin Neuropeptide G-protein coupled receptor superfamily Inflammation Metabolic syndrome Cancer

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Dietary bile acid supplementation in weaned piglets with intrauterine growth retardation improves colonic microbiota,metabolic activity,and epithelial function

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Journal of Animal Science and Biotechnology 2023年第6期14卷 2578-2595页

作者： Yang Liu MdAbul Kalam Azad Sujuan Ding Qian Zhu Francois Blachier Zugong Yu Haijun Gao Xiangfeng Kong Key Laboratory of Agro‑Ecological Process in Subtropical Region Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic ProcessInstitute of Subtropical AgricultureChinese Academy of SciencesChangsha 410125HunanChina. College of Veterinary Medicine Nanjing Agricultural UniversityNanjingJiangsu 210095China. Universite Paris-SaclayAgroParisTech INRAEUMR PNCA75005ParisFrance. College of Medicine Howard UniversityWashingtonDC 20059USA.

Background Intrauterine growth retardation(IUGR)is one of the major constraints in animal production.Our previ-ous study showed that piglets with IUGR are associated with abnormal bile acid(BA)metabolism.This study explored whether dietary BA supplementation could improve growth performance and colonic development,function,micro-biota,and metabolites in the normal birth weight(NBW)and IUGR piglets.A total of 48 weaned piglets(24 IUGR and 24 NBW)were allocated to four groups(12 piglets per group):(i)NBW group,(ii)NBW+BA group,(iii)IUGR group,and(iv)IUGR+BA group.Samples were collected after 28 days of feeding.Results The results showed that dietary BA supplementation increased the length and weight of the colon and colon weight to body weight ratio,while decreased the plasma diamine oxidase(DAO)concentration in the NBW pig-lets(P<0.05).Dietary BA supplementation to IUGR piglets decreased(P<0.05)the plasma concentrations of D-lactate and endotoxin and colonic DAO and endotoxin,suggesting a beneficial effect on epithelial integrity.Moreover,dietary BA supplementation to NBW and IUGR piglets increased Firmicutes abundance and decreased Bacteroidetes abundance(P<0.05),whereas Lactobacillus was the dominant genus in the colon.Metabolome analysis revealed 65 and 51 differential metabolites in the colon of piglets fed a diet with/without BA,respectively,which was associated with the colonic function of IUGR piglets.Furthermore,dietary BA supplementation to IUGR piglets upregulated the expressions of CAT,GPX,SOD,Nrf1,IL-2,and IFN-γin colonic mucosa(P<0.05).Conclusions Collectively,dietary BA supplementation could improve the colonic function of IUGR piglets,which was associated with increasing proportions of potentially beneficial bacteria and metabolites.Furthermore,BA shows a promising application prospect in improving the intestinal ecosystem and health of animals.

关键词： Bile acid Intrauterine growth retardation Metabolite Microbiota Piglet

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Intrauterine growth restriction alters growth performance, plasma hormones,and small intestinal microbial communities in growing-finishing pigs

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Journal of Animal Science and Biotechnology 2021年第1期12卷 340-357页

作者： Liang Xiong Jinming You Wanghong Zhang Qian Zhu Francois Blachier Yulong Yin Xiangfeng Kong CAS Key Laboratory of Agro-ecological Processes in Subtropical Regions Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic ProcessNational Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry ProductionInstitute of Subtropical AgricultureChinese Academy of SciencesChangsha 410125HunanChina Key Laboratory of Animal Nutrition in Jiangxi Province College of Animal Science and TechnologyJiangxi Agricultural UniversityNanchang 440000JiangxiChina UniversitéParis-Saclay AgroParisTechINRAEUMR PNCA75005 ParisFrance.

Background: The interaction of the gut microbiota with key metabolic and physiological processes may be associated with poor growth outcomes in animals born with intrauterine growth restriction(IUGR).Results: Growth performance, plasma hormone concentrations, and intestinal microbiota composition were analyzed in IUGR pigs and in normal birth weight(NBW) pigs when the NBW pigs reached 25, 50, and 100 kg of body weight(BW). Compared to NBW pigs, IUGR pigs had lower initial, weaned, and final BW, and lower average daily gain and average daily feed intake in all the considered time points. In the 25 kg BW group, IUGR pigs had higher concentrations of plasma ghrelin and pancreatic polypeptide(PP), but lower insulin concentration than NBW pigs, while the situation was reversed in the 50 kg BW group. As compared to NBW pigs, IUGR pigs had higher microbial alpha diversity in the jejunum and ileum;in the 50 and 100 kg BW groups, IUGR pigs had higher Firmicutes abundance but lower Proteobacteria abundance in the jejunum, and lower Lactobacillus abundance in the jejunum and ileum;in the 25 kg BW group, IUGR pigs showed higher unclassified Ruminococcaceae abundance in the ileum;and in 25 and 50 kg BW groups, IUGR pigs showed lower Ochrobactrum abundance in the jejunum.Spearman's correlation revealed that Lactobacillus was negatively correlated with growth performance, while unclassified Ruminococcaceae was positively correlated. Predictive metagenomic analysis detected significantly different expression of genes in the intestinal microbiota between IUGR and NBW pigs, suggesting different metabolic capabilities between the two groups.Conclusions: Growing-finishing IUGR pigs showed lower growth performance, higher microbial alpha diversity, and differences in plasma hormone concentrations compared to NBW pigs. Alterations in the abundance of Firmicutes,Proteobacteria, Ruminococcaceae, Lactobacillus, and Ochrobactrum in the small intestine may be associated with IUGR, and may therefore serve as a future target for gut microbio

关键词： Growing-finishing pigs Growth performance Intrauterine growth restriction Microbial community Small intestine

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Functional trait composition of carabid beetle communities predicts prey suppression through both mass ratio and niche complementarity mechanisms

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Insect Science 2024年第2期31卷 562-574页

作者： Abdelhak Rouabah Francoise Lasserre-Joulin Sylvain Plantureux Simon Taugourdeau Bernard Amiaud Universite de Loraine INRAELAENancyF-54000France umr SELMET CIRADINRAEInstitut AgroUniversite de MontpellierMontpellier34000France CIRAD UMR SELMET-PPZSDakarSéenegal umr Siva Universitéde LorraineAgroParisTechINRAEVandoeuvreLes Nancy54506France

Several components of predator functional diversity have been hypothesized to influence prey suppression through either niche complementarity or mass ratio effects.Nevertheless,most studies have used a functional group approach when assessing the role of these predators in ecosystem functioning.By adopting a trait-based approach,we evaluated the relative contributions of carabid diversity components in predicting prey suppression.Our results highlight the importance of both taxonomic and functional diversity components of carabids as key drivers of prey suppression.Prey suppression was best predicted by carabid densities,with the dominance of Poecilus cupreus potentially driving the positive effect of community total abundance through the mass ratio effect.Prey suppression increased with increasing the density of large carabids.In addition,carabid eye diameter and antennal length were key functional traits for predicting prey suppression.Furthermore,prey suppression increased with increasing carabid functional richness following the niche complementarity effect.In contrast to functional richness,functional evenness and functional divergence of carabid communities were weakly correlated with prey suppression.By identifying which diversity components of carabid communities contribute the most to increase prey suppression,our results can guide efforts aiming to predict the relationship between diversity of these predators and ecosystem functioning.

关键词： abundance distribution biological control body size ecosystem function functional richness predator-prey interactions

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First Report of a Successful Development of Yam Hybrids(Dioscorea alata L.)from Lyophilized and Long-Term Stored Pollens

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国际实验植物学杂志(英文) 2023年第10期92卷 2861-2874页

作者： Erick Malédon Elie Nudol Christophe Perrot Marie-Claire Gravillon Ronan Rivallan Denis Cornet Hâna Chair Komivi Dossa CIRAD UMR AGAP InstitutPetit BourgGuadeloupe97170France umr AGAP Institut Univ MontpellierCIRADINRAEInstitut AgroMontpellierF-34398France CIRAD UMR AGAP InstitutMontpellierF-34398France

Various biological constraints including erratic and asynchronous flowering between male and female plants hinder successful hybrid development and genetic gains in greater yam breeding programs.Therefore,pollen storage has gained much attention to facilitate artificial pollinations and increase the genetic gains.This 4-year study aimed at developing a practical long-term pollen storage technique for the successful development of yam hybrids.Fresh pollens were collected from two Dioscorea alata males,then lyophilized(two lyophilization treatments were applied),followed by storage at room temperature(24℃–25℃)for 12 months.Moreover,the lyophilized and stored pollens were tested for viability by crossing with four female varieties.Our results showed that lyophilization is effective for achieving viable pollens after 12 months of storage.Treatment 1(48 h drying)showed higher pollen germination and fertility rates than Treatment 2(72 h drying).Although we observed a reduction in viability of lyophilized pollens after 12 months of storage,we generated hybrid seedlings with success rates from 12%to 21%compared to 21%–31%when using fresh pollens.Paternity testing based on molecular genotyping confirmed the hybrid status of the obtained seedlings,which grew well in a greenhouse.Lyophilization is a practical approach for a long-term storage of greater yam pollen samples.This protocol will positively impact yam breeding programs particularly in developing countries.

关键词： Yam freeze-drying pollen conservation genetic gain

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Punch‑excised explants of bovine mammary gland to model early immune response to infection

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Journal of Animal Science and Biotechnology 2023年第6期14卷 2649-2662页

作者： Pablo Gomes Noleto Florence B.Gilbert Christelle Rossignol Patricia Cunha Pierre Germon Pascal Rainard Rodrigo Prado Martins ISP INRAEUniversitéde ToursUMR1282NouzillyFrance

Background Mammary gland(MG)infections(mastitis)are frequent diseases of dairy cows that affect milk quality,animal welfare and farming profitability.These infections are commonly associated with the bacteria Escherichia coli and Staphylococcus aureus.Different in vitro models have been used to investigate the early response of the MG to bacteria,but the role of the teat in mastitis pathogenesis has received less attention.In this study,we used punch-excised teat tissue as an ex vivo model to study the immune mechanisms that arise early during infection when bacteria have entered the MG.Results Cytotoxicity and microscopic analyses showed that bovine teat sinus explants have their morphology and viability preserved after 24 h of culture and respond to ex vivo stimulation with TLR-agonists and bacteria.LPS and E.coli trigger stronger inflammatory response in teat when compared to LTA and S.aureus,leading to a higher produc-tion of IL-6 and IL-8,as well as to an up-regulation of proinflammatory genes.We also demonstrated that our ex vivo model can be applied to frozen-stored explants.Conclusions In compliance with the 3Rs principle(replacement,reduction and refinement)in animal experimenta-tion,ex vivo explant analyses proved to be a simple and affordable approach to study MG immune response to infec-tion.This model,which better reproduces organ complexity than epithelial cell cultures or tissue slices,lends itself particularly well to studying the early phases of the MG immune response to infection.

关键词： Bovine teat Escherichia coli Explant Mastitis Staphylococcus aureus 3Rs

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Clarifying predictions for COVID-19 from testing data: The example of New York State

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Infectious Disease Modelling 2021年第1期6卷 273-283页

作者： Quentin Griette Pierre Magal Univ.Bordeaux IMBUMR 5251F-33400TalenceFrance CNRS IMBUMR 5251F-33400TalenceFrance

With the spread of COVID-19 across the world,a large amount of data on reported cases has become available.We are studying here a potential bias induced by the daily number of tests which may be insufficient or vary over time.Indeed,tests are hard to produce at the early stage of the epidemic and can therefore be a limiting factor in the detection of cases.Such a limitation may have a strong impact on the reported cases data.Indeed,some cases may be missing from the official count because the number of tests was not sufficient on a given day.In this work,we propose a new differential equation epidemic model which uses the daily number of tests as an input.We obtain a good agreement between the model simulations and the reported cases data coming from the state of New York.We also explore the relationship between the dynamic of the number of tests and the dynamics of the cases.We obtain a good match between the data and the outcome of the model.Finally,by multiplying the number of tests by 2,5,10,and 100 we explore the consequences for the number of reported cases.

关键词： Corona virus Testing data Reported and unreported cases Isolation Quarantine Public closings Epidemic mathematical model

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