scholarly journals A novel antimicrobial alternative of microbiota metabolic product deoxycholic acid controls chicken necrotic enteritis

2018 ◽  
Author(s):  
Hong Wang ◽  
Juan D. Latorre ◽  
Mohit Bansal ◽  
Bilal Al-Rubaye ◽  
Guillermo Tellez ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Broiler Chickens ◽  
Deoxycholic Acid ◽  
Immune Cell ◽  
Intestinal Inflammation ◽  
Cellular Level ◽  
Metabolic Product ◽  
Host Responses ◽  
Necrotic Enteritis ◽  
Mrna Accumulation

AbstractNecrotic enteritis (NE) caused by Clostridium perfringens infection has reemerged as a prevalent poultry disease worldwide due to reduced usage of prophylactic antibiotics. The lack of alternative antimicrobial strategies to control this disease is mainly due to limited insight into NE pathogenesis, microbiome relationships, and host responses. Here we reported that the metabolic byproduct of microbial metabolism of bile acids to deoxycholic acid (DCA), at as low as 50 μM, inhibited 82.8% of C. perfringens growth in Tryptic Soy Broth (P < 0.05). Sequential Eimeria maxima and C. perfringens challenge strongly induced NE, severe intestinal inflammation, and body weight (BW) loss in broiler chickens. These negative effects were diminished by 1.5 g/kg DCA diet. At the cellular level, DCA alleviated NE-associated ileal epithelial death and lamina propria immune cell apoptosis. Interestingly, DCA reduced C. perfringens invasion into villi without significantly altering the bacterial luminal colonization. Molecular analysis showed that DCA reduced inflammatory mediators of Infγ, Litaf (Tnfα), Il1β, and Mmp9 mRNA accumulation in ileal tissue. Mechanically, C. perfringens induced elevated expression of inflammatory cytokines of Infγ, Litaf, and Ptgs2 (COX-2 gene) in chicken splenocytes. Inhibiting the COX signaling by aspirin attenuated INFγ- or TNFa-induced inflammatory response in the splenocytes. Consistently, chickens fed 0.12 g/kg aspirin diet resisted against NE-induced BW loss, ileal inflammation, and villus apoptosis. In conclusion, microbial metabolic product DCA prevents NE-induced BW loss and ileal inflammation through curbing inflammatory response. These novel findings could serve as a stepping-stone for developing next generation antimicrobial alternatives against NE.

scholarly journals Microbial metabolite deoxycholic acid controlsClostridium perfringens-induced chicken necrotic enteritis through attenuating cyclooxygenase signaling

2018 ◽  
Author(s):  
Hong Wang ◽  
Juan D. Latorre ◽  
Mohit Bansal ◽  
Mussie Abraha ◽  
Bilal Al-Rubaye ◽  
...  
Keyword(s):  
Bile Acid ◽  
Inflammatory Response ◽  
Inflammatory Mediators ◽  
Cell Apoptosis ◽  
Deoxycholic Acid ◽  
Intestinal Inflammation ◽  
Metabolic Product ◽  
Intestinal Cell ◽  
Necrotic Enteritis ◽  
Secondary Bile Acid

AbstractClostridium perfringens-induced necrotic enteritis (NE) has reemerged as a prevalent chicken disease worldwide due to reduced usage of prophylactic antibiotics. The lack of antimicrobial alternative strategies to control NE is mainly due to limited insight into the disease pathogenesis. The aim of this study is to investigate the role of microbiota metabolic product secondary bile acid deoxycholic acid (DCA) on preventing NE.C. perfringensgrowth was inhibited by 82.8% in 50 μM DCA Tryptic Soy Broth. SequentialEimeria maximaandC. perfringenschallenges induced acute NE showed as severe intestinal inflammation and body weight (BW) loss in broiler chickens, while 1.5 g/kg DCA diet dramatically reduced the disease. At the cellular level, DCA alleviated NE-associated ileal epithelial death and reduced lamina propria cell apoptosis. Interestingly, DCA reducedC. perfringensinvasion into ileum without altering the bacterial ileal luminal colonization. Molecular analysis showed that DCA reduced inflammatory mediators ofInfγ,Litaf, andMmp9mRNA accumulation in ileal tissue. Mechanism studies revealed thatC. perfringensinduced elevated expression of inflammatory mediators ofInfγ,Litaf,Mmp9,andPtgs2(Cyclooxygenase- 2 (COX-2) gene) in chicken splenocytes. Blocking COX signaling by pharmacological inhibitor aspirin attenuated INFγ-induced inflammatory response in the splenocytes. Consistent with thein vitroassay, chickens fed 0.12 g/kg aspirin diet protected the birds against NE-induced ileal inflammation, intestinal cell apoptosis, and BW loss. In conclusion, microbial metabolic product DCA prevents NE-induced ileal inflammation and BW loss through attenuating inflammatory response. These novel findings offer new strategies againstC. perfringens-induced diseases.Significance StatementWidespread antimicrobial resistance has become a serious challenge to both agricultural and healthcare industries. Withdrawing antimicrobials without effective alternatives exacerbates chicken productivity loss at billions of dollars every year, caused by intestinal diseases, such as coccidiosis-andC. perfringens-induced necrotic enteritis. This study revealed that microbial metabolic product secondary bile acid DCA preventsC. perfringens-induced intestinal disease in chickens through modulating inflammatory COX signaling pathways. Therefore, microbiome and its downstream targets of host inflammatory responses could be used to control NE. These findings have opened new avenues for developing novel antimicrobial free alternatives to prevent or treatC. perfringens-induced diseases.

scholarly journals Microbial metabolite deoxycholic acid controls Clostridium perfringens-induced chicken necrotic enteritis through attenuating inflammatory cyclooxygenase signaling

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Hong Wang ◽  
Juan D. Latorre ◽  
Mohit Bansal ◽  
Mussie Abraha ◽  
Bilal Al-Rubaye ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Clostridium Perfringens ◽  
Inflammatory Mediators ◽  
Cell Apoptosis ◽  
Deoxycholic Acid ◽  
Intestinal Inflammation ◽  
Consumer Preferences ◽  
Intestinal Cell ◽  
Necrotic Enteritis ◽  
Secondary Bile Acid

Abstract Necrotic enteritis (NE) caused by Clostridium perfringens infection has reemerged as a prevalent poultry disease worldwide due to reduced usage of prophylactic antibiotics under consumer preferences and regulatory pressures. The lack of alternative antimicrobial strategies to control this disease is mainly due to limited insight into the relationship between NE pathogenesis, microbiome, and host responses. Here we showed that the microbial metabolic byproduct of secondary bile acid deoxycholic acid (DCA), at as low as 50 µM, inhibited 82.8% of C. perfringens growth in Tryptic Soy Broth (P < 0.05). Sequential Eimeria maxima and C. perfringens challenges significantly induced NE, severe intestinal inflammation, and body weight (BW) loss in broiler chickens. These negative effects were diminished (P < 0.05) by 1.5 g/kg DCA diet. At the cellular level, DCA alleviated NE-associated ileal epithelial death and significantly reduced lamina propria cell apoptosis. Interestingly, DCA reduced C. perfringens invasion into ileum (P < 0.05) without altering the bacterial ileal luminal colonization. Molecular analysis showed that DCA significantly reduced inflammatory mediators of Infγ, Litaf, Il1β, and Mmp9 mRNA accumulation in ileal tissue. Mechanism studies revealed that C. perfringens induced (P < 0.05) elevated expression of inflammatory mediators of Infγ, Litaf, and Ptgs2 (Cyclooxygenases-2 (COX-2) gene) in chicken splenocytes. Inhibiting the COX signaling by aspirin significantly attenuated INFγ-induced inflammatory response in the splenocytes. Consistent with the in vitro assay, chickens fed 0.12 g/kg aspirin diet protected the birds against NE-induced BW loss, ileal inflammation, and intestinal cell apoptosis. In conclusion, microbial metabolic product DCA prevents NE-induced BW loss and ileal inflammation through attenuating inflammatory response. These novel findings of microbiome protecting birds against NE provide new options on developing next generation antimicrobial alternatives against NE.

scholarly journals Microbiota attenuates chicken transmission-exacerbated campylobacteriosis in Il10−/− mice

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ying Fu ◽  
Ayidh Almansour ◽  
Mohit Bansal ◽  
Tahrir Alenezi ◽  
Bilal Alrubaye ◽  
...  
Keyword(s):  
Campylobacter Jejuni ◽  
Intestinal Inflammation ◽  
Foodborne Pathogen ◽  
Neutrophil Infiltration ◽  
Cellular Level ◽  
Colon Tissue ◽  
Mrna Accumulation ◽  
Inflammatory Gene Expression ◽  
Specific Pathogen ◽  
Human Campylobacteriosis

AbstractCampylobacter jejuni is a prevalent foodborne pathogen mainly transmitting through poultry. It remains unknown how chicken-transmitted C. jejuni and microbiota impact on human campylobacteriosis. Campylobacter jejuni AR101 (Cj-P0) was introduced to chickens and isolated as passage 1 (Cj-P1). Campylobacter jejuni Cj-P1-DCA-Anaero was isolated from Cj-P0-infected birds transplanted with DCA-modulated anaerobic microbiota. Specific pathogen free Il10−/− mice were gavaged with antibiotic clindamycin and then infected with Cj-P0, Cj-P1, or Cj-P1-DCA-Anaero, respectively. After 8 days post infection, Il10−/− mice infected with Cj-P1 demonstrated severe morbidity and bloody diarrhea and the experiment had to be terminated. Cj-P1 induced more severe histopathology compared to Cj-P0, suggesting that chicken transmission increased C. jejuni virulence. Importantly, mice infected with Cj-P1-DCA-Anaero showed attenuation of intestinal inflammation compared to Cj-P1. At the cellular level, Cj-P1 induced more C. jejuni invasion and neutrophil infiltration into the Il10−/− mouse colon tissue compared to Cj-P0, which was attenuated with Cj-P1-DCA-Anaero. At the molecular level, Cj-P1 induced elevated inflammatory mediator mRNA accumulation of Il17a, Il1β, and Cxcl1 in the colon compared to Cj-P0, while Cj-P1-DCA-Anaero showed reduction of the inflammatory gene expression. In conclusion, our data suggest that DCA-modulated anaerobes attenuate chicken-transmitted campylobacteriosis in mice and it is important to control the elevation of C. jejuni virulence during chicken transmission process.

scholarly journals Jagged1-mediated myeloid Notch1 signaling activates HSF1/Snail and controls NLRP3 inflammasome activation in liver inflammatory injury

2019 ◽  
Vol 17 (12) ◽  
pp. 1245-1256 ◽  
Author(s):  
Yuting Jin ◽  
Changyong Li ◽  
Dongwei Xu ◽  
Jianjun Zhu ◽  
Song Wei ◽  
...  
Keyword(s):  
Liver Injury ◽  
Inflammatory Response ◽  
Immune Cell ◽  
Ischemia Reperfusion ◽  
Inflammasome Activation ◽  
Inflammatory Injury ◽  
Notch1 Signaling ◽  
Caspase 1 ◽  
Hepatocellular Damage ◽  
Hepatocellular Apoptosis

AbstractNotch signaling plays important roles in the regulation of immune cell functioning during the inflammatory response. Activation of the innate immune signaling receptor NLRP3 promotes inflammation in injured tissue. However, it remains unknown whether Jagged1 (JAG1)-mediated myeloid Notch1 signaling regulates NLRP3 function in acute liver injury. Here, we report that myeloid Notch1 signaling regulates the NLRP3-driven inflammatory response in ischemia/reperfusion (IR)-induced liver injury. In a mouse model of liver IR injury, Notch1-proficient (Notch1FL/FL) mice receiving recombinant JAG1 showed a reduction in IR-induced liver injury and increased Notch intracellular domain (NICD) and heat shock transcription factor 1 (HSF1) expression, whereas myeloid-specific Notch1 knockout (Notch1M-KO) aggravated hepatocellular damage even with concomitant JAG1 treatment. Compared to JAG1-treated Notch1FL/FL controls, Notch1M-KO mice showed diminished HSF1 and Snail activity but augmented NLRP3/caspase-1 activity in ischemic liver. The disruption of HSF1 reduced Snail activation and enhanced NLRP3 activation, while the adoptive transfer of HSF1-expressing macrophages to Notch1M-KO mice augmented Snail activation and mitigated IR-triggered liver inflammation. Moreover, the knockdown of Snail in JAG1-treated Notch1FL/FL livers worsened hepatocellular functioning, reduced TRX1 expression and increased TXNIP/NLRP3 expression. Ablation of myeloid Notch1 or Snail increased ASK1 activation and hepatocellular apoptosis, whereas the activation of Snail increased TRX1 expression and reduced TXNIP, NLRP3/caspase-1, and ROS production. Our findings demonstrated that JAG1-mediated myeloid Notch1 signaling promotes HSF1 and Snail activation, which in turn inhibits NLRP3 function and hepatocellular apoptosis leading to the alleviation of IR-induced liver injury. Hence, the Notch1/HSF1/Snail signaling axis represents a novel regulator of and a potential therapeutic target for liver inflammatory injury.

scholarly journals Supplementing Garlic Nanohydrogel Optimized Growth, Gastrointestinal Integrity and Economics and Ameliorated Necrotic Enteritis in Broiler Chickens Using a Clostridium perfringens Challenge Model

Animals ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 2027
Author(s):  
Doaa Ibrahim ◽  
Tamer Ahmed Ismail ◽  
Eman Khalifa ◽  
Shaimaa A. Abd El-Kader ◽  
Dalia Ibrahim Mohamed ◽  
...  
Keyword(s):  
Growth Performance ◽  
Clostridium Perfringens ◽  
Broiler Chickens ◽  
Body Weight Gain ◽  
Economic Benefits ◽  
Production Costs ◽  
Broiler Chicks ◽  
Necrotic Enteritis ◽  
Feed Conversion ◽  
Intestinal Lesion

Necrotic enteritis (NE) caused by Clostridium perfringens (C. perfringens) results in impaired bird growth performance and increased production costs. Nanotechnology application in the poultry industry to control NE outbreaks is still not completely clarified. Therefore, the efficacy of dietary garlic nano-hydrogel (G-NHG) on broilers growth performance, intestinal integrity, economic returns and its potency to alleviate C. perfringens levels using NE challenge model were addressed. A total of 1200 male broiler chicks (Ross 308) were assigned into six groups; four supplemented with 100, 200, 300 or 400 mg of G-NHG/kg diet and co-challenged with C. perfringens at 21, 22 and 23 d of age and two control groups fed basal diet with or without C. perfringens challenge. Over the total growing period, the 400 mg/kg G-NHG group had the most improved body weight gain and feed conversion efficiency regardless of challenge. Parallel with these results, the mRNA expression of genes encoding digestive enzymes (alpha 2A amylase (AMY2A), pancreatic lipase (PNLIP) and cholecystokinin (CCK)) and intestinal barriers (junctional adhesion molecule-2 (JAM-2), occludin and mucin-2 (Muc-2)) were increased in groups fed G-NHG at higher levels to be nearly similar to those in the unchallenged group. At 14 d post challenge, real-time PCR results revealed that inclusion of G-NHG led to a dose-dependently decrease in the C. perfringens population, thereby decreasing the birds’ intestinal lesion score and mortality rates. Using 400 mg/kg of G-NHG remarkably ameliorated the adverse effects of NE caused by C. perfringens challenge, which contributed to better growth performance of challenged birds with rational economic benefits.

scholarly journals Pretreatment with probiotics ameliorate gut health and necrotic enteritis in broiler chickens, a substitute to antibiotics

AMB Express ◽  
2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Danish Sharafat Rajput ◽  
Dong Zeng ◽  
Abdul Khalique ◽  
Samia Sharafat Rajput ◽  
Hesong Wang ◽  
...  
Keyword(s):  
Broiler Chickens ◽  
Production Systems ◽  
Economic Losses ◽  
Necrotic Enteritis ◽  
Poultry Production ◽  
Gut Health ◽  
Growth Promoters ◽  
Broiler Performance ◽  
Antibiotic Growth Promoters ◽  
Microbial Strains

AbstractNecrotic enteritis (NE) is being considered as one of the most important intestinal diseases in the recent poultry production systems, which causes huge economic losses globally. NE is caused by Clostridium perfringens, a pathogenic bacterium, and normal resident of the intestinal microflora of healthy broiler chickens. Gastrointestinal tract (GIT) of broiler chicken is considered as the most integral part of pathogen’s entrance, their production and disease prevention. Interaction between C. perfringens and other pathogens such as Escherichia coli and Salmonella present in the small intestine may contribute to the development of NE in broiler chickens. The antibiotic therapy was used to treat the NE; however European Union has imposed a strict ban due to the negative implications of drug resistance. Moreover, antibiotic growth promoters cause adverse effects on human health as results of withdrawal of antibiotic residues in the chicken meat. After restriction on use of antibiotics, numerous studies have been carried out to investigate the alternatives to antibiotics for controlling NE. Thus, possible alternatives to prevent NE are bio-therapeutic agents (Probiotics), prebiotics, organic acids and essential oils which help in nutrients digestion, immunity enhancement and overall broiler performance. Recently, probiotics are extensively used alternatives to antibiotics for improving host health status and making them efficient in production. The aim of review is to describe a replacement to antibiotics by using different microbial strains as probiotics such as bacteria and yeasts etc. having bacteriostatic properties which inhibit growth of pathogens and neutralize the toxins by different modes of action.

scholarly journals Dietary sophorolipid accelerates growth by modulation of gut microbiota population and intestinal environments in broiler chickens

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Min-Jin Kwak ◽  
Min-Young Park ◽  
Yong-Soon Choi ◽  
Junghwan Cho ◽  
Duleepa Pathiraja ◽  
...  
Keyword(s):  
Body Weight ◽  
Barrier Function ◽  
Broiler Chickens ◽  
Pathogenic Bacteria ◽  
Inflammatory Cytokine ◽  
Intestinal Inflammation ◽  
Defense System ◽  
Villus Height ◽  
Treatment Groups ◽  
Gut Barrier Function

Abstract Background Gut is a crucial organ for the host’s defense system due to its filtering action of the intestinal membrane from hazardous foreign substances. One strategy to strengthen the gut epithelial barrier function is to upregulate beneficial microflora populations and their metabolites. Sophorolipid (SPL), which is a glycolipid bio-surfactant, could increase beneficial microflora and decrease pathogenic bacteria in the gastrointestinal tract. Therefore, herein, we conducted an experiment with broiler chickens to investigate the fortifying effects of SPL on the host’s gut defense system by modulating the microbiota population. Methods A total of 540 1-day-old chicks (Ross 308) were used, and they were immediately allotted into three treatment groups (6 replications with 30 chicks/pen) according to their initial body weight. The dietary treatments consisted of CON (basal diet), BAM (10 mg/kg bambermycin), and SPL (10 mg/kg SPL). During the experiment, birds freely accessed feed and water, and body weight and feed intake were measured at the end of each phase. On d 35, birds (one bird/pen) were sacrificed to collect jejunum and cecum samples. Results Dietary SPL and BAM supplementation significantly accelerated birds’ growth and also significantly improved feed efficiency compared to CON. Intestinal microbial community was significantly separated by dietary SPL supplementation from that of CON, and dietary SPL supplementation significantly increased Lactobacillus spp. and Akkermansia muciniphila. Moreover, birds fed with dietary SPL also showed the highest concentration of cecal butyrate among all treatment groups. Gut morphological analysis showed that dietary SPL significantly increased villus height, ratio of villus height to crypt depth, goblet cell numbers, and the gene expression levels of claudin-1 and mucin 2. Additionally, dietary SPL significantly decreased the mRNA expression level of pro-inflammatory cytokine, interleukin-6, and increased that of anti-inflammatory cytokine, interleukin-10, compared to other treatments. Conclusions Dietary SPL increases the beneficial bacterial population and butyrate concentration, which leads to a strengthened gut barrier function. In addition, the intestinal inflammation was also downregulated by dietary SPL supplementation.

scholarly journals Membrane-Associated Proteins of a Lipopolysaccharide-Deficient Mutant of Neisseria meningitidis Activate the Inflammatory Response through Toll-Like Receptor 2

2001 ◽  
Vol 69 (4) ◽  
pp. 2230-2236 ◽  
Author(s):  
Robin R. Ingalls ◽  
Egil Lien ◽  
Douglas T. Golenbock
Keyword(s):  
Cell Wall ◽  
Inflammatory Response ◽  
Neisseria Meningitidis ◽  
Parental Strain ◽  
Host Responses ◽  
Deficient Mutant ◽  
Toll Like Receptor ◽  
Gram Negative ◽  
Negative Cell ◽  
Toll Like Receptor 2

ABSTRACT The recent isolation of a lipopolysaccharide (LPS)-deficient mutant of Neisseria meningitidis has allowed us to explore the roles of other gram-negative cell wall components in the host response to infection. The experiments in this study were designed to examine the ability of this mutant strain to activate cells. Although it was clearly less potent than the parental strain, we found the LPS-deficient mutant to be a capable inducer of the inflammatory response in monocytic cells, inducing a response similar to that seen with Staphylococcus aureus. Cellular activation by the LPS mutant was related to expression of CD14, a high-affinity receptor for LPS and other microbial products, as well as Toll-like receptor 2, a member of the Toll family of receptors recently implicated in host responses to gram-positive bacteria. In contrast to the parental strain, the synthetic LPS antagonist E5564 did not inhibit the LPS-deficient mutant. We conclude that even in the absence of LPS, the gram-negative cell wall remains a potent inflammatory stimulant, utilizing signaling pathways independent of those involved in LPS signaling.

scholarly journals Influence of Glutamine on Intestinal Inflammatory Response, Mucosa Structure Alterations and Apoptosis following Traumatic Brain Injury in Rats

2007 ◽  
Vol 35 (5) ◽  
pp. 644-656 ◽  
Author(s):  
D Feng ◽  
W Xu ◽  
G Chen ◽  
C Hang ◽  
H Gao ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Inflammatory Response ◽  
Intestinal Inflammation ◽  
Glutamine Supplementation ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Tissue Samples ◽  
Weight Drop ◽  
Factor Α

Traumatic brain injury (TBI) can induce a persistent inflammatory response, histopathological changes and apoptosis in the intestine. Glutamine has been shown to reduce bacterial translocation and maintain intestine mucosal integrity, but its effects on the inflammatory response, structural alterations and apoptosis in intestinal mucosa following TBI have not been previously investigated. Using the weight-drop method, a right parietal cortical contusion was induced in rats and, for the next 5 days, they were fed either chow alone or chow mixed with glutamine. Intestinal tissue samples were then removed for analysis. Following TBI, glutamine supplementation was found to: decrease intestinal concentrations of interleukin (IL) −1β, tumour necrosis factor-α (TNF-α) and IL-6; downregulate intercellular adhesion molecule-1 (ICAM-1) expression; attenuate TBI-induced damage to the intestine structure; and reduce apoptosis. These results suggest that post-TBI glutamine administration could suppress intestinal inflammation, protect intestinal mucosal structure and reduce mucosal apoptosis.

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