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Fish Oil-Based Fat Emulsion Reduces Acute Kidney Injury and Inflammatory Response in Antibiotic-Treated Polymicrobial Septic Mice.

ABSTRACT: Acute kidney injury (AKI) is a common complication in sepsis. This study compared the effects of a fish oil-based with a mixed oil fat emulsion on remote renal injury in an antibiotic-treated septic murine model. Mice were randomly assigned to a normal control (NC) group and three septic groups. Sepsis was induced by cecal ligation and puncture (CLP). The antibiotic was injected intraperitoneally (IP) after CLP and then daily till the time of sacrifice. Three hours after antibiotic treatment, one of the septic groups was injected IP with a fish oil-based emulsion (FO), while the other two groups were given either a mixed oil emulsion (MO) or saline (SC). The septic groups were further divided into two separate time groups, with blood and kidneys samples collected at 24 h or 72 h post-CLP. The results showed that sepsis leads to the activation of neutrophils, T helper (Th)1/Th-2/Th-17 and Treg cells (p < 0.05). Plasma NGAL and mRNA expressions of renal MyD88 and TLR4 were also enhanced (p < 0.05). Compared to the SC group, the group given the fish oil-based emulsion had decreased plasma NGAL by 22% and Treg by 33%. Furthermore, renal gene expressions of MyD88 and TLR4 reduced by 46% and 62%, respectively, whereas heat shock protein 70 and peroxisome proliferator-activated receptor-? increased by 158% and 69%, respectively (p < 0.05), at Day 3 after CLP. These results suggest that administration of a fish oil-based emulsion has favorable effects, maintaining blood T cell percentage, downregulating Treg expression, attenuating systemic and local inflammation and offering renal protection under conditions of antibiotic-treated polymicrobial sepsis.

SUBMITTER: Shih JM

PROVIDER: S-EPMC4808893 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Fish Oil-Based Fat Emulsion Reduces Acute Kidney Injury and Inflammatory Response in Antibiotic-Treated Polymicrobial Septic Mice.

Shih Juey-Ming JM Shih Yao-Ming YM Pai Man-Hui MH Hou Yu-Chen YC Yeh Chiu-Li CL Yeh Sung-Ling SL

Nutrients 20160315 3

Acute kidney injury (AKI) is a common complication in sepsis. This study compared the effects of a fish oil-based with a mixed oil fat emulsion on remote renal injury in an antibiotic-treated septic murine model. Mice were randomly assigned to a normal control (NC) group and three septic groups. Sepsis was induced by cecal ligation and puncture (CLP). The antibiotic was injected intraperitoneally (IP) after CLP and then daily till the time of sacrifice. Three hours after antibiotic treatment, on ...[more]

PMID: 26999192

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Project description:BackgroundSepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Mortality of patients with sepsis is high and largely unchanged throughout the past decades. Animal models have been widely used for the study of sepsis and septic shock, but translation into effective treatment regimes in the clinic have mostly failed. Pigs are considered as suitable research models for human diseases due to their high comparability and similarity to human anatomy, genetics, and the immune system. We here evaluated the previously reported models of septic shock in pigs and established a novel model of polymicrobial sepsis that meets the clinical criteria of septic shock in pigs.Materials and methodsThe literature search was performed using the keywords "pig", "sepsis" and "septic shock". For the establishment of septic shock in n = 10 German landrace pigs, mechanical ventilation was initiated, central venous and arterial lines and invasive hemodynamic monitoring via pulse contour cardiac output measurement (PiCCO) established. Peritoneal polymicrobial faecal sepsis was induced by application of 3 g/kg body weight faeces into the abdominal cavity. Septic shock was defined according to the third international consensus definitions (Sepsis-3). Upon shock, pigs underwent the 1-h bundle for the treatment of human sepsis. Cytokine levels were measured by ELISA.ResultsPublished porcine sepsis models exhibited high methodological variability and did not meet the clinical criteria of septic shock. In our model, septic shock developed after an average of 4.8 ± 0.29 h and was associated with a reproducible drop in blood pressure (mean arterial pressure 54 ± 1 mmHg) and significant hyperlactatemia (3.76 ± 0.65 mmol/L). Septic shock was associated with elevated levels of interleukin-6 (IL6) and initial cardiac depression followed by a hyperdynamic phase with significant loss of systemic vascular resistance index after initial resuscitation. In addition, organ dysfunction (acute kidney injury) occurred.ConclusionsWe here established a model of septic shock in pigs that meets the clinical criteria of septic shock utilized in human patients. Our model may thus serve as a reference for clinically relevant sepsis research in pigs.

Project description:Prophylactic antibiotics in the aquaculture and ornamental fish industry are intended to prevent the negative impacts of disease outbreaks. Research in mice and humans suggests that antibiotics may disturb microbiome communities and decrease microbiome-mediated disease resistance, also known as "colonization resistance." If antibiotics impact fish as they do mice and humans, prophylactic administrations on aquaculture farms may increase downstream disease susceptibility in target hosts, despite short-term pathogen control benefits. We tested the effects of antibiotics on mortality after a pathogen challenge in the Poecilia sphenops black molly and subsequently tested if probiotic inoculations could reverse any antibiotic-induced losses of disease resistance. We found that antibiotic treatment significantly increased fish mortality. We further found that our two candidate probiotic bacterial species, Phaeobacter inhibens S4Sm and Bacillus pumilus RI06-95Sm, were able to colonize black molly microbiomes and reverse the negative impacts of antibiotics. Despite the positive impact on survival, probiotic treatment did not influence overall microbiome community structure or diversity. Our results suggest that subtle manipulations of microbiome composition can have dramatic impacts on host phenotype. The results of this study have implications for how antibiotic-treated microbiomes can be restored and suggest that small-scale additions may be as effective as wholesale transplants. IMPORTANCE Prophylactic antibiotics are widespread in the aquaculture industry and are used where vaccination is impossible or overly expensive. If antibiotics impact fish as they do mice and humans, prophylactic administrations in aquaculture and ornamental fish farms may increase downstream disease susceptibility in target hosts, despite short-term pathogen control benefits. Recent research has suggested that their use exacerbates bacterial outbreaks by creating sterile, nutrient-rich environments for invading pathogens to colonize and could help to explain rising economic costs of bacterial outbreaks in aquaculture. Our findings suggest a long-term cost of prophylactic antibiotic use and demonstrate a probiotic-based solution that does not rely on full microbiome community transplantation.

Project description:SUMMARY Research background Formulations based on vegetable or fish oil and modifications in the production technology of dry fermented sausages have emerged in recent years aiming to achieve the desirable target of reducing the fat content of these meat products. However, previous efforts have confronted many difficulties, such as high mass loss and unacceptable appearance due to intensely wrinkled surfaces and case hardening. The objective of this study is to produce and evaluate dry fermented sausages by utilising a meat protein-olive oil emulsion as fat substitute and indigenous lactic acid bacteria (LAB) with probiotic properties isolated from traditional Greek meat products. Experimental approach A novel formulation with extra virgin olive oil and turkey protein was developed to totally replace the conventionally added pork fat. Probiotic and safety characteristics of autochthonous LAB isolates from spontaneously fermented sausages were evaluated and three LAB isolates were finally selected as starter cultures. Physicochemical, microbiological and sensory analyses were carried out in all treatments (control, Lactobacillus acidophilus, L. casei, L. sakei and Pediococcus pentosaceus) during fermentation. Results and conclusions Ready-to-eat sausages were found to be microbiologically stable. The olive oil-based formulation produced in this study generated a mosaic pattern visible in the sliced product simulating the fat in conventional fermented sausages and was regarded as an ideal fat substitute for the production of fermented sausages. An autochthonous isolate of Lactobacillus casei adapted the best to the final products as it was molecularly identified to be present in the highest counts among the LAB isolates used as starter cultures. Novelty and scientific contribution Α novel and high-quality dry fermented meat product was produced by replacing the added pork fat with a fat substitute based on a meat protein-olive oil emulsion. Autochthonous LAB with in vitro probiotic properties could have a potential use in large-scale novel dry fermented sausage production. Such isolates could be used as starters in an effort to standardise the production process and retain the typical organoleptic and sensory characteristics. Moreover, isolates like L. casei 62 that survived in high counts in the final products can increase the safety of fermented sausages by competing not only with pathogens but also with the indigenous microbiota and could have a potential functional value for the consumer.

Dataset Information

Fish Oil-Based Fat Emulsion Reduces Acute Kidney Injury and Inflammatory Response in Antibiotic-Treated Polymicrobial Septic Mice.

Publications

Fish Oil-Based Fat Emulsion Reduces Acute Kidney Injury and Inflammatory Response in Antibiotic-Treated Polymicrobial Septic Mice.

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