scholarly journals P082 Assessment of anti-inflammatory effect of high acetate administration in UC patient-derived epithelial monolayer cultures

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S182-S183
Author(s):  
S Deleu ◽  
K Arnauts ◽  
K Machiels ◽  
G R B Huys ◽  
J Thevelein ◽  
...  

Abstract Background Human organoid-based intestinal monolayer cultures provide an interesting tool to preclinically assess new therapeutic properties in inflammatory bowel disease (IBD). Recently, short-chain fatty acids (SCFA) such as acetate and butyrate have gained interest for their potential beneficial effects in IBD therapy. Most studies have focused on butyrate, given its beneficial effects on gut microbiome composition, intestinal barrier function and the immune system1. Effects of acetate are less well known, despite its lower toxicity to epithelial cells and its potential to support growth of butyrate-producing bacteria by metabolic cross-feeding2. In fact, a recent report suggested that the probiotic potential of Saccharomyces cerevisiae var. boulardii might be related to its high acetic acid production3. We here studied the effect of acetate on organoid-derived epithelial monolayer cultures from ulcerative colitis (UC) patients. Methods Colonic biopsies were obtained from non-inflamed regions in 3 patients with UC. Crypts were isolated, cultured and expanded as 3D-organoids. These organoids were then dissociated and transferred to transwell inserts as monolayer cultures. Upon confluency of the monolayer, evaluated by Transepithelial electrical resistance (TEER), cells were basolaterally stimulated with control medium (CTRL) or an inflammatory mix (INFL) containing 100 ng/ml TNF-α, 20 ng/ml IL-1β and 1 µg/ml Flagellin (Fig. 1). After 24h, cells were apically stimulated with control medium or high acetate (HA) (100mM). TEER was measured at 0, 24 and 48h stimulation. After 48h, cells were subjected to RNA extraction followed by reverse transcriptase qPCR targeting a selection of key diagnostic marker genes. The apical and basolateral media were collected for cytokine determination by Mesoscale (Proinflammatory panel 1). Data were analyzed using GraphPad Prism 9 (D’Agostino & Pearson test for normality followed by a Friedman test). Results A protective effect (Fig. 2) of high acetate administration on TEER values (HA vs INFL: p=0˒017) was observed, together with a trend towards decrease in IL8 (p=0˒11), TNFA (INFL vs INFL+HA: p=0˒68) and CLDN2 (CTRL vs HA: p=0˒03). Moreover, this was confirmed by a decrease of most proinflammatory cytokines (Fig. 3) in the apical and basolateral media upon HA stimulation e.g., IFN-γ (INFL vs INFL+HA: p=0˒25) and IL 10 (CTRL vs HA: p=0˒11). Conclusion In this patient-derived human epithelial cell culture model, a protective effect of high acetate administration on TEER-values, gene expression and cytokine production was observed. Ongoing experiments are expanding the number of patients to 10. References

Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1284 ◽  
Author(s):  
Yuanyifei Wang ◽  
Yan Zou ◽  
Jin Wang ◽  
Hui Ma ◽  
Bowei Zhang ◽  
...  

As the richest component in human milk oligosaccharides (HMOs), 2’-fucosyllactose (2’-FL) can reduce the colonization of harmful microbiota in vivo, thus lowering the risk of infection; however, the mechanism for this is still unclear. In this study, a model of Escherichia coli O157 infection in healthy adult mice was established to explore the effect of 2’-FL intervention on E. coli O157 colonization and its protective effects on mice. The results showed that 2’-FL intake reduced E. coli O157 colonization in mice intestine by more than 90% (p < 0.001), and it also reduced intestinal inflammation, increased the content of fecal short-chain fatty acids, and enhanced intestinal barrier function. These beneficial effects were attributed to the increased expression of mucins such as MUC2 (increased by more than 20%, p < 0.001), and inhibition of E. coli O157 cell adhesion (about 30% reduction, p < 0.001), and were associated with the modulation of gut microbiota composition. 2’-FL significantly increased the abundance of Akkermansia, a potential probiotic, which may represent the fundamental means by which 2’-FL enhances the expression of mucin and reduces the colonization of harmful bacteria. The current study may support the use of 2’-FL in the prevention of foodborne pathogen infections in human.


2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii312-iii312
Author(s):  
Donald C Macarthur ◽  
Conor Mallucci ◽  
Ian Kamaly-Asl ◽  
John Goodden ◽  
Lisa C D Storer ◽  
...  

Abstract Paediatric Ependymoma is the second most common malignant brain tumour of childhood with approximately 50% of cases recurring. It has been described as a “surgical” disease since patients who have undergone a gross total surgical resection (GTR) have a better prognosis than those who have a subtotal resection (STR). Analysis of the UKCCSG/SIOP 1992 04 clinical trial has shown that only 49% of cases had a GTR, with 5-year survival rates for STR of 22–47% and GTR of 67–80%. As part of the SIOP II Ependymoma trial the UK established a panel of experts in the treatment of Ependymoma from Neuro-oncology, Neuro-radiology and Neuro-surgery. Meeting weekly, cases are discussed to provide a consensus on radiological review, ensuring central pathological review, trial stratification and whether further surgery should be advocated on any particular case. Evaluation of the first 68 UK patients has shown a GTR in 47/68 (69%) of patients and STR in 21/68 (31%) of patients. Following discussion at EMAG it was felt that 9/21 (43%) STR patients could be offered early second look surgery. Following this 2nd look surgery the number of cases with a GTR increased to 56/68 (82%). There has been a clear increase in the number of patients for whom a GTR has been achieved following discussion at EMAG and prior to them moving forwards with their oncological treatment. This can only have beneficial effects in decreasing their risk of tumour recurrence or CSF dissemination and also in reducing the target volume for radiotherapy.


Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 677
Author(s):  
Cristina Serra-Castelló ◽  
Ilario Ferrocino ◽  
Anna Jofré ◽  
Luca Cocolin ◽  
Sara Bover-Cid ◽  
...  

Formulations with lactate as an antimicrobial and high-pressure processing (HPP) as a lethal treatment are combined strategies used to control L. monocytogenes in cooked meat products. Previous studies have shown that when HPP is applied in products with lactate, the inactivation of L. monocytogenes is lower than that without lactate. The purpose of the present work was to identify the molecular mechanisms underlying the piezo-protection effect of lactate. Two L. monocytogenes strains (CTC1034 and EGDe) were independently inoculated in a cooked ham model medium without and with 2.8% potassium lactate. Samples were pressurized at 400 MPa for 10 min at 10 °C. Samples were subjected to RNA extraction, and a shotgun transcriptome sequencing was performed. The short exposure of L. monocytogenes cells to lactate through its inoculation in a cooked ham model with lactate 1h before HPP promoted a shift in the pathogen’s central metabolism, favoring the metabolism of propanediol and ethanolamine together with the synthesis of the B12 cofactor. Moreover, the results suggest an activated methyl cycle that would promote modifications in membrane properties resulting in an enhanced resistance of the pathogen to HPP. This study provides insights on the mechanisms developed by L. monocytogenes in response to lactate and/or HPP and sheds light on the understanding of the piezo-protective effect of lactate.


Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 1016
Author(s):  
María Jesús Rodríguez-Sojo ◽  
Antonio Jesús Ruiz-Malagón ◽  
María Elena Rodríguez-Cabezas ◽  
Julio Gálvez ◽  
Alba Rodríguez-Nogales

Probiotics microorganisms exert their health-associated activities through some of the following general actions: competitive exclusion, enhancement of intestinal barrier function, production of bacteriocins, improvement of altered microbiota, and modulation of the immune response. Among them, Limosilactobacillus fermentum CECT5716 has become one of the most promising probiotics and it has been described to possess potential beneficial effects on inflammatory processes and immunological alterations. Different studies, preclinical and clinical trials, have evidenced its anti-inflammatory and immunomodulatory properties and elucidated the precise mechanisms of action involved in its beneficial effects. Therefore, the aim of this review is to provide an updated overview of the effect on host health, mechanisms, and future therapeutic approaches.


Author(s):  
Zachary T Traughber ◽  
Fei He ◽  
Jolene M Hoke ◽  
Gary M Davenport ◽  
Maria R C de Godoy

Abstract Ancient grains are becoming an increasingly abundant carbohydrate source in the pet food market as a result of their popularity and novelty in the human market. Thus, it is imperative to evaluate the characteristics of these ingredients in vivo. Ten adult intact female beagles were used in a replicated 5x5 Latin square design. Five dietary treatments were evaluated containing either: rice (CON), amaranth (AM), white proso millet (WPM), quinoa (QU), or oat groats (OG). All diets were formulated to include 40% of the test grain and to be isonitrogenous, isocaloric, and nutritionally complete and balanced for adult dogs at maintenance. The objectives were (1) to evaluate the effects of the novel carbohydrate sources on total apparent total tract digestibility (ATTD), fecal microbiota, and fermentative end-product concentrations and (2) to evaluate the effects of novel carbohydrate sources on the post-prandial glycemic and insulinemic responses in healthy adult dogs. All diets were well-accepted by the dogs and fecal scores remained within ideal range for all treatments. In terms of ATTD, all diets were well-digested by the dogs; WPM had the highest digestibility of dry and organic matter in contrast with dogs fed the other treatments (P &lt; 0.05). Additionally, ATTD of total dietary fiber was highest for WPM (72.6%) in contrast with QU (63.5%) and CON (50.8%) but did not differ from AM (65.7%) and OG (66.6%). Dogs fed AM or OG had greater (P &lt; 0.05) fecal concentrations of total short-chain fatty acids, as well as propionate and butyrate concentrations, than CON. Ancient grain inclusion appears to beneficially shift fecal microbial populations, with increases in relative abundances of butyrogenic bacteria (i.e., members of the Lachnospiraceae family) observed for OG and reductions in Fusobacteriaceae for both AM and OG when compared with CON. Post-prandial glycemic and insulinemic responses did not differ among treatments. Together, these data suggest that ancient grains can be included up to 40% of the diet while eliciting beneficial effects on overall host health without detrimentally affecting nutrient digestibility.


Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 682
Author(s):  
Serena Coppola ◽  
Carmen Avagliano ◽  
Antonio Calignano ◽  
Roberto Berni Canani

Worldwide obesity is a public health concern that has reached pandemic levels. Obesity is the major predisposing factor to comorbidities, including type 2 diabetes, cardiovascular diseases, dyslipidemia, and non-alcoholic fatty liver disease. The common forms of obesity are multifactorial and derive from a complex interplay of environmental changes and the individual genetic predisposition. Increasing evidence suggest a pivotal role played by alterations of gut microbiota (GM) that could represent the causative link between environmental factors and onset of obesity. The beneficial effects of GM are mainly mediated by the secretion of various metabolites. Short-chain fatty acids (SCFAs) acetate, propionate and butyrate are small organic metabolites produced by fermentation of dietary fibers and resistant starch with vast beneficial effects in energy metabolism, intestinal homeostasis and immune responses regulation. An aberrant production of SCFAs has emerged in obesity and metabolic diseases. Among SCFAs, butyrate emerged because it might have a potential in alleviating obesity and related comorbidities. Here we reviewed the preclinical and clinical data that contribute to explain the role of butyrate in this context, highlighting its crucial contribute in the diet-GM-host health axis.


2020 ◽  
Vol 11 (12) ◽  
pp. 10839-10851
Author(s):  
Zhi-jie Ma ◽  
Huan-jun Wang ◽  
Xiao-jing Ma ◽  
Yue Li ◽  
Hong-jun Yang ◽  
...  

Ginger extract showed beneficial effects on rats with antibiotic-associated diarrhea, and the underlying mechanism might be associated with the recovery of gut microbiota and intestinal barrier function.


Author(s):  
Xiaoling Qi ◽  
Li Zhang ◽  
Jing Xu ◽  
Zheying Tao ◽  
Xiaoli Wang ◽  
...  

BackgroundWe previously found that microbial disruption in Pseudomonas aeruginosa ventilator-associated pneumonia (PA-VAP) patients are long-lasting. Long-term microbial dysbiosis may lead to changes in metabolites. Short-chain fatty acids (SCFAs) are microbial fermentation products and show beneficial effects in patients with pneumonia. In this study, we aimed to explore the association between circulating SCFA levels and clinical outcomes in patients with PA-VAP.MethodsIn this study, we analyzed SCFAs in the serum of 49 patients with PA-VAP by gas chromatography-mass spectrometry analysis. Twenty of these patients died, and 29 survived. The correlation between serum SCFAs and patient survival and immune parameters was analyzed.ResultsWe developed a partial least squares discriminant analysis (PLS-DA) model to examine differential SCFAs in 49 patients with PA-VAP. Among the seven SCFAs, only acetic acid was increased in non-survivors (P = 0.031, VIP &gt; 1). Furthermore, high levels of acetic acid (&gt;1.96ug/ml) showed increased 90-day mortality compared to low levels of acetic acid (&lt;1.96ug/ml) in Kaplan-Meier survival analyses (P = 0.027). Increased acetic acid also correlated with reduced circulating lymphocyte and monocyte counts.ConclusionOur study showed that increased circulating acetic acid is associated with 90-day mortality in PA-VAP patients. The decrease in lymphocytes and monocytes might be affected by acetic acid and involved in the poor prognosis.


2021 ◽  
Author(s):  
Shuai Liu ◽  
Yunxia Xiong ◽  
Jingping Chen ◽  
Hao Xiao ◽  
Qiwen Wu ◽  
...  

Abstract BACKGROUND: The beneficial function of fermented feed in livestock industry has been widely investigated. However, little is known about the effects of fermented feed on different weaned-day piglets. This study aimed to investigate the effects of fermented diet on the growth performance, intestinal function and microbiota of piglets weaned at age of 21 days and 28 days.RESULTS: The results found that weaning on d 21 significantly increased (P < 0.05) ADG, and ADFI (calculated based on wet weight and dry matter), while reduced (P < 0.05) F: G, the activities of trypsin and lipase of jejunum and villus height of ileum, compared with 28-d weaning. The protein levels of Occludin, Claudin-1, ZO-1 of ileum in the groups weaning on d 21 were less (P < 0.05) than the groups weaning on d 28. Moreover, dietary supplementation with fermented diet upregulated (P < 0.05) Occludin, Claudin-1, ZO-1 proteins of ileum, compared with the groups treated with control diet both weaning on d 21 and d 28. In addition, dietary supplementation with fermented diet decreased (P < 0.05) the relative abundance of Clostridia (class) and increased (P < 0.05) Bacteroidia (class) level of cecal microbiota, compared with the groups treated with control diet both weaning on d 21 and d 28. However, supplementation with fermented diet did not affect the concentrations of short-chain fatty acids in the cecum (P > 0.05).CONCLUSION: Therefore, our data suggest that feed digestibility is improved in piglets weaned at 21 days, but intestinal barrier function is weaker than in piglets weaned at 28 days. However, compared with feeding control diet, supplementation with fermented diet both improved feed conversion and intestinal barrier function of weaned piglets by modulating intestinal microbiota.


2017 ◽  
Vol 17 (3) ◽  
pp. 627-644 ◽  
Author(s):  
Marianna Flis ◽  
Wiesław Sobotka ◽  
Zofia Antoszkiewicz

Abstract The present review summarizes the results of 37 experiments in which different types and levels (from 0.5 to 29.7%) of fibrous supplements were used in the formulation of diets for weaned piglets. Diets were supplemented with different sources of insoluble dietary fiber (iDF), soluble dietary fiber (sDF), or mixed DF sources. Most of the applied DF sources decreased the ileal and fecal organic matter digestibility, and they often lowered crude protein digestibility. A moderate addition (1.5-8%) of iDF sources increased average daily feed intake (ADFI) and, frequently, average daily gains (ADG). Sources of sDF as well as high inclusion levels of fiber-rich feeds tended to decrease ADFI and ADG. Improved fecal consistency, decreased diarrhea incidence and antibiotic interventions were confirmed in piglets fed diets with added lignocellulose, cooked or raw oat hulls and wheat bran. The dietary inclusion of iDF rather than sDF sources improved gastrointestinal tract (GIT) development, enzyme activity and gut morphology. An increase in the counts of beneficial gut microbiota and the concentrations of short-chain fatty acids was stimulated by diets with addition iDF or sDF sources. Such diets also slowed down proteolytic fermentation which negatively affects the colonic mucosa. Some research findings indicate that iDF sources improve intestinal barrier function. The analyzed experimental data suggest that the addition of 1.5-2% of a lignocellulose preparation, 2% of oat hulls, 4-8% of coarse wheat bran to diets for weaned piglets may be recommended to promote GIT development and health, and to improve growth performance.


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