Necrotic enteritis challenge regulates peroxisome proliferator-1 activated receptors signaling and β-oxidation pathways in broiler chickens

Abstract

Necrotic enteritis (NE) is an important enteric disease in poultry and has become a major concern in poultry production in the post-antibiotic era. The infection with NE can damage the intestinal mucosa of the birds leading to impaired health and, thus, productivity. To gain a better understanding of how NE impacts the gut function of infected broilers, global mRNA sequencing (RNA-seq) was performed in the jejunum tissue of NE challenged and non-challenged broilers to identify the pathways and genes affected by this disease. Briefly, to induce NE, birds in the challenge group were inoculated with 1 mL of Eimeria species on day 9 followed by 1 mL of approximately 10 8 CFU/mL of a NetB producing Clostridium perfringens on days 14 and 15. On day 16, 2 birds in each treatment were randomly selected and euthanized and the whole intestinal tract was evaluated for lesion scores. Duodenum tissue samples from one of the euthanized birds of each replicate ( n = 4) was used for histology, and the jejunum tissue for RNA extraction. RNA-seq analysis was performed with an Illumina RNA HiSeq 2000 sequencer. The differentially expressed genes (DEG) were identified and functional analysis was performed in DAVID to find protein–protein interactions (PPI). At a false discovery rate threshold <0.05, a total of 377 DEG (207 upregulated and 170 downregulated) DEG were identified. Pathway enrichment analysis revealed that DEG were considerably enriched in peroxisome proliferator-activated receptors (PPAR) signaling ( P < 0.01) and β-oxidation pathways ( P < 0.05). The DEG were mostly related to fatty acid metabolism and degradation (cluster of differentiation 36 [ CD36 ], acyl-CoA synthetase bubblegum family member-1 [ ACSBG1 ] , fatty acid-binding protein-1 and -2 [ FABP1 ] and [ FABP2 ]; and acyl-coenzyme A synthetase-1 [ ACSL1 ]), bile acid production and transportation (acyl-CoA oxidase-2 [ ACOX2 ], apical sodium–bile acid transporter [ ASBT ]) and essential genes in the immune system (interferon-, [ IFN-γ ], LCK proto-oncogene, Src family tyrosine kinase [ LCK ], zeta chain of T cell receptor associated protein kinase 70 kDa [ ZAP70 ], and aconitate decarboxylase 1 [ ACOD1 ]). Our data revealed that pathways related to fatty acid digestion were significantly compromised which thereby could have affected metabolic and immune responses in NE infected birds.

A blend of microencapsulated organic acids and botanicals reduces necrotic enteritis via specific signaling pathways in broilers

“…The kinome arrays can also be used to dissect signaling pathways and identify biomarkers associated with animal diseases such as bovine viral diarrhea virus ( Van Wyk et al, 2016 ) and Johne's disease in cattle ( Arsenault et al, 2012 ) and Salmonella in chickens ( Arsenault et al, 2013 ; Kogut et al, 2016 ; Swaggerty et al, 2017 ) demonstrating the usefulness of the technology to provide detailed mechanistic insight into the host:pathogen interaction. Several studies have begun to identify specific host signaling pathways impacted by NE including MAPK signaling ( Pham et al, 2020 ), JAK-STAT signaling ( Truong et al, 2017a , b ), and peroxisome proliferator-1 activated receptors ( PPAR ) signaling ( Gharib-Naseri et al, 2021 ) pathways. Despite experimental model variations and the diversity of the tools used to determine the mode-of-action, all of these signaling pathways were also significantly different in the current study ( Table 4 ) suggesting their overall importance in the underlying disease and the host:pathogen interaction(s) associated with NE in broilers.…”

Development and Functional Properties of Intestinal Mucus Layer in Poultry

“…However, the intracellular fatty acid-binding proteins (FABPs) have been subject of several studies. In poultry, FABPs modulate lipid metabolism via regulation in the fatty acid uptake (in line with the concentration gradient) into the cell ( 140 ). Several FABPs including FABP1, FABP2, and FABP6 have been identified to be predominantly expressed in the digestive tract of chickens ( 140 , 141 ).…”

“…In poultry, FABPs modulate lipid metabolism via regulation in the fatty acid uptake (in line with the concentration gradient) into the cell ( 140 ). Several FABPs including FABP1, FABP2, and FABP6 have been identified to be predominantly expressed in the digestive tract of chickens ( 140 , 141 ). It has been shown that, enhancing the dietary fat level in poultry feed could increase the concentration of FABPs in the intestine ( 142 ).…”

“…It was suggested that necrotic enteritis infection in broilers caused downregulation of FABP1 and FABP2 in the small intestine. These downregulations were assumed to be attributed to structural damage and intestinal epithelium loss in the small intestine and lead to reduction in fatty acid utilization ( 140 ). However, to the best of our knowledge, no direct interaction between FABPs and mucus production and/or quality has been reported so far.A downregulation in mRNA expression of FABP2 occurred in compromised gut barrier chickens (challenged with coccidiosis vaccine) along with decreased MUC2 and occludin expression, which indicate the role of FABP2 in maintaining intestinal integrity in chicken ( 141 ).…”

“…However, to the best of our knowledge, no direct interaction between FABPs and mucus production and/or quality has been reported so far.A downregulation in mRNA expression of FABP2 occurred in compromised gut barrier chickens (challenged with coccidiosis vaccine) along with decreased MUC2 and occludin expression, which indicate the role of FABP2 in maintaining intestinal integrity in chicken ( 141 ). It was suggested that the downregulation of FABP1, FABP2 and other genes that are related to reduced fatty acid utilization may be also associated with intestinal inflammation and structural damage of the epithelium ( 140 ). The concentration of lipids in poultry feed is considerably lower than carbohydrates and proteins, but they still influence gut microbiota ( 143 , 144 ).…”