Performing Department
(N/A)
Non Technical Summary
Necrotic enteritis (NE), caused by Clostridium perfringens, ranks among the most financially devastating diseases in poultry. Unfortunately, there are currently no effective preventive or therapeutic measures available. The intestinal bacteria plays a critical role in maintaining animal health and productivity by resisting the colonization and infection of invading pathogens. In a recent screening of a library of chicken intestinal bacteria, we identified several bacteria with a strong ability to inhibit C. perfringens, while also enhancing innate immunity through the induction of host defense peptide (HDP) synthesis. Notably, oral administration of a selected commensal bacterium markedly improved animal survival and alleviated intestinal lesions in a chicken model of NE. These findings provide a timely opportunity to explore the potential of commensal bacteria in resisting NE. In this project, we will screen additional commensal bacteria for their ability to inhibit C. perfringens growth andinduce HDP synthesis. Lead bacterial candidates will be further evaluated for their protective efficacy in NE-infectedchickens. Moreover, we will study the mechanism of action of the most effective bacterium. Upon completion, we expect to identify several commensal bacteria that are highly effective in mitigating NE and further reveal their major mechanism of action. The outcome will facilitate the development of an innovative antibiotic-free approach to combat NE and potentially other enteric diseases in poultry.
Animal Health Component
100%
Research Effort Categories
Basic
80%
Applied
(N/A)
Developmental
20%
Goals / Objectives
Necrotic enteritis (NE) is a major poultry disease caused by Clostridiumperfringenswith no effective mitigation strategies. The overall goal of this project is to identify commensal bacteria that are highly effective in suppressing intestinal colonization of C. perfringens and further elucidate their mechanisms of action. We hypothesize that commensal bacteria resistant to C. perfringens colonization confer protection against NE. To test this hypothesis, we will pursue three specific objectives: 1) screening for commensal bacteria showing strong colonization resistance to C. perfringens, 2) determiningthe efficacy of selected bacteria in alleviating NE, and 3) revealing the mechanisms by which the most effective bacterium resists NE. We expect to identify several commensal bacteria that provide robust colonization resistance to NE. The outcomes will pave the way for developing a novel microbiome-based approach to mitigate NE and potentially other enteric diseases in poultry.
Project Methods
The long-term goal of our research is to develop innovative antibiotic-free approaches to combat necrotic enteritis (NE) and other significant enteric diseases. The overall goal of this project is to identify bacteria that are highly effective in resisting intestinal colonization of Clostridium perfringens and further elucidate their mechanisms of action. We hypothesize that commensal bacteria capable of resisting C. perfringens colonization confer protection against NE. To test our hypothesis, we will pursue three specific objectives: 1) Screen for commensal bacteria that exhibit strong colonization resistance to C. perfringens. We will screen a large collection of chicken intestinal bacteria for their ability to inhibit C. perfringens growth and also induce host defense peptide (HDP) synthesis in a cell-based high-throughput screening assay. A minimum of six bacteria that demonstrate strong suppression of C. perfringens growth and/or enhancement of HDP synthesis will be selected for further evaluation to assess their efficacy in resisting the intestinal colonization of C. perfringens in a chicken model of NE. 2) Determine the efficacy of selected commensal bacteria in alleviating necrotic enteritis. We will individually inoculate six selected bacteriainto chickens to evaluate their efficacy in mitigating NE. Animal survival, weight gain, intestinal lesion, and the C. perfringens titer will be compared. The bacterium that proves most effective in improving animal survival and reducing disease severity will be selected for further investigation into its mechanism of action. 3) Elucidate the mechanisms by which the most effective bacterium resists necrotic enteritis. We will assess its impact on the development of the intestinal microbiome, mucosal immunity, and barrier function in healthy and NE-infectedchickens. A comprehensive understanding of the bacterium's colonization resistance mechanism will be achieved through a multi-omics approach that integrates the microbiome composition, metatranscriptome and metabolome with single-cell sequencing-based host transcriptome. Upon completion, we expect to identify several highly effective commensal bacteria that offer robust colonization resistance against NE. The outcome will pave the way for developing a novel microbiome-based, antibiotic-free approach to mitigate NE and potentially other enteric diseases. Given the increasing concern over antibiotic-resistant pathogens and the use of in-feed antibiotics, this research will contribute to ensuring animal health, production efficiency, and food safety, while reducing the risk of antimicrobial resistance.