Organ growth and fermentation profiles of broilers differing in body growth rate.

This study sought to determine the relationship among broiler performance, organ development, and indicators of microbiota colonization. A total of 1,200 two-day-old male Ross 308 broiler chicks, divided among 3 cohorts of equal size, were housed in battery cages, and allotted based on body weight. On study d 11, birds were weighed, and birds with BW gain within the 10th and 90th percentiles were assigned to the Slow and Fast groups, respectively. Birds (n = 30 for each group) selected on d 11 were provided water and a corn-soybean meal-based diet ad libitum while maintained individually through study d 25 (i.e., a 14-d growth period). Parameters regarding growth performance, organ and intestine weights and lengths, and intestinal volatile fatty acid concentrations were measured. All data were analyzed by one-way ANOVA using the Mixed procedure of SAS. Fast birds exhibited greater (P < 0.001) BW gain and feed intake than slow birds, but feed conversion ratio (FCR) did not differ (P = 0.19). Additionally, Slow birds had higher (P < 0.05) relative weights (% of BW) for nearly all organs on d 11 and 25, most notably the gizzard, proventriculus, pancreas, and liver. Conversely, intestinal sections were longer (P < 0.05) in the Fast birds. Measurement of gut histomorphology did not show any notable differences between growth rate groups in terms of villi height, crypt depth, or their ratio for either time-point (P > 0.05). In terms of volatile fatty acid concentrations of luminal contents, acetate concentrations were 10.2% higher (P < 0.001) in the ileum of the Slow birds compared with Fast birds on d 25. Overall, the findings suggest that total BW gain is influenced by the development of metabolically active organs, as supported by lower weight gain in Slow birds with relatively larger organ weights and shorter intestinal lengths than their Fast counterparts. The general lack of differences in fermentation end-product concentrations in luminal contents does not rule out influence of the microbiota on growth rate of broilers, which warrants further investigation.

Effects of lysine biomass supplementation on growth performance and clinical indicators in broiler chickens.

Production of crystalline amino acids (AA) through microbial fermentation concomitantly provides an AA-enriched biomass that may serve as a cost-effective supplement for broiler chickens. We investigated the effects of feeding a fermentation biomass product containing approximately 62% Lys on growth performance, organ growth, and clinical outcomes of broilers. Beginning at 2 d post-hatch, a total of 360 Ross 308 chicks were randomly assigned to 1 of 5 treatments provided to 12 replicate cages of 6 birds. Practical corn-soybean meal-based dietary treatments included: negative control (NC; no supplementation of L-Lys, 1.01 and 0.86% standardized ileal digestible Lys in starter and grower phases, respectively), NC + 0.23% L-Lys HCl (positive control; PC), and NC supplemented with 0.30, 0.90, or 1.50% Lys biomass (LB) in both phases. Feed and water were provided ad libitum throughout the study. Individual bird and feeder weights were recorded on study day 0, 10, 21, and 35. At study conclusion, birds from each treatment were randomly selected to collect blood and tissue samples. The PC and 0.30% LB diets elicited similar overall (day 0-35) body weight gain and birds were heavier (P < 0.001) than the NC and other LB treatments. The PC, 0.30% LB, and 0.90% LB groups had better (P < 0.001) overall feed conversion ratio than NC. Some LB-supplemented treatments elicited increased (P < 0.001) relative spleen and ileum weight compared with NC and PC. Heterophils were increased (P < 0.001) in LB treatments compared with PC and NC. Lymphocytes were decreased (P < 0.001) in LB treatments compared with NC, and 1.50% LB was similar to PC. This resulted in an increased (P < 0.001) heterophil-to-lymphocyte ratio in some LB treatments, which may have resulted from general AA supplementation or the LB product. Collectively, these results suggest that addition of up to 0.30% LB restored growth performance when added to a Lys-deficient practical diet and elicited results identical to the Lys-adequate PC diet with no negative clinical effects.

Dietary soy isoflavones reduce pathogen-related mortality in growing pigs under porcine reproductive and respiratory syndrome viral challenge.

Porcine reproductive and respiratory syndrome virus (PRRSV) is an economically important disease, and ingestion of soy isoflavones (ISF) may benefit PRRSV-infected pigs due to demonstrated anti-inflammatory and antiviral properties. The objective of this experiment was to recreate immunological effects previously observed in young pigs infected with PRRSV receiving ISF and determine how those effects influence growth performance during the entire growth period from weaning to market. In total, 96 weaned barrows were group housed in a biosafety level-2 containment facility and allotted to 1 of 3 experimental treatments that were maintained throughout the study: noninfected pigs received an ISF-devoid control diet (NEG, n = 24), and infected pigs received either the control diet (POS, n = 36) or that supplemented with total ISF in excess of 1,600 mg/kg (ISF, n = 36). Following a 7-d adaptation, weanling pigs were inoculated intranasally with either a sham-control (PBS) or live PRRSV (1 × 105 TCID50/mL, strain NADC20). After inoculation, individual blood samples (n = 8 to 12/treatment) were routinely collected to monitor viral clearance and hematological parameters, including serum neutralizing anti-PRRSV antibody production. Pen-based oral fluids were used to monitor PRRSV clearance at later growth stages. A 1- or 2-way ANOVA was performed to compare experimental treatments depending on whether the outcome was repeatedly measured. In general, PRRSV infection decreased performance during early growth phases, resulting in 5.4% lower final BW for POS vs. NEG pigs (P < 0.05). Dietary ISF elicited inconsistent effects on growth performance, increased (P < 0.05) neutrophil cell counts and the relative proportion of memory T-cells, and decreased (P < 0.05) the time to full PRRSV clearance from oral fluids. Dietary ISF also elicited earlier, more robust anti-PRRSV neutralizing antibody production when compared with POS pigs. Additionally, and most notably, POS pigs experienced ~50% greater infection-related mortality rate vs. ISF pigs (P < 0.05), which may have significant economic implications for producers. Overall, dietary ISF ingestion supported immune responses and reduced mortality in PRRSV-infected pigs when fed to growing pigs though the biological mechanism of these effects remains unclear.

HFD refeeding in mice after fasting impairs learning by activating caspase-1 in the brain.

BACKGROUND: Diets that include some aspect of fasting have dramatically increased in popularity. In addition, fasting reduces inflammasome activity in the brain while improving learning. Here, we examine the impact of refeeding a low-fat diet (LFD) or high-fat diet (HFD) after fasting. METHODS: Male wildtype (WT), caspase-1 knockout (KO) and/or IL-1 receptor 1 (IL-1R1) KO mice were fasted for 24 h or allowed ad libitum access to food (chow). Immediately after fasting, mice were allowed to refeed for 2 h in the presence of LFD, HFD or chow. Mouse learning was examined using novel object recognition (NOR) and novel location recognition (NLR). Caspase-1 activity was quantified in the brain using histochemistry (HC) and image analysis. RESULTS: Refeeding with a HFD but not a LFD or chow fully impaired both NOR and NLR. Likewise, HFD when compared to LFD refeeding increased caspase-1 activity in the whole amygdala and, particularly, in the posterior basolateral nuclei (BLp) by 2.5-fold and 4.6-fold, respectively. When caspase-1 KO or IL-1R1 KO mice were examined, learning impairment secondary to HFD refeeding did not occur. Equally, administration of n-acetylcysteine to fasted WT mice prevented HFD-dependent learning impairment and caspase-1 activation in the BLp. Finally, the free-fatty acid receptor 1 (FFAR1) antagonist, DC260126, mitigated learning impairment associated with HFD refeeding while blocking caspase-1 activation in the BLp. CONCLUSIONS: Consumption of a HFD after fasting impairs learning by a mechanism that is dependent on caspase-1 and the IL-1R1 receptor. These consequences of a HFD refeeding on the BLP of the amygdala appear linked to oxidative stress and FFAR1.

Handling stress impairs learning through a mechanism involving caspase-1 activation and adenosine signaling.

Acute stressors can induce fear and physiologic responses that prepare the body to protect from danger. A key component of this response is immune system readiness. In particular, inflammasome activation appears critical to linking stress to the immune system. Here, we show that a novel combination of handling procedures used regularly in mouse research impairs novel object recognition (NOR) and activates caspase-1 in the amygdala. In male mice, this handling-stress paradigm combined weighing, scruffing and sham abdominal injection once per hr. While one round of weigh/scruff/needle-stick had no impact on NOR, two rounds compromised NOR without impacting location memory or anxiety-like behaviors. Caspase-1 knockout (KO), IL-1 receptor 1 (IL-1R1) KO and IL-1 receptor antagonist (IL-RA)-administered mice were resistant to handling stress-induced loss of NOR. In addition, examination of the brain showed that handling stress increased caspase-1 activity 85% in the amygdala without impacting hippocampal caspase-1 activity. To delineate danger signals relevant to handling stress, caffeine-administered and adenosine 2A receptor (A2AR) KO mice were tested and found resistant to impaired learning and caspase-1 activation. Finally, mice treated with the ß-adrenergic receptor antagonist, propranolol, were resistant to handling stress-induced loss of NOR and caspase-1 activation. Taken together, these results indicate that handling stress-induced impairment of object learning is reliant on a pathway requiring A2AR-dependent activation of caspase-1 in the amygdala that appears contingent on ß-adrenergic receptor functionality.

Exposure to a firefighting overhaul environment without respiratory protection increases immune dysregulation and lung disease risk.

Firefighting activities appear to increase the risk of acute and chronic lung disease, including malignancy. While self-contained breathing apparatuses (SCBA) mitigate exposures to inhalable asphyxiates and carcinogens, firefighters frequently remove SCBA during overhaul when the firegrounds appear clear of visible smoke. Using a mouse model of overhaul without airway protection, the impact of fireground environment exposure on lung gene expression was assessed to identify transcripts potentially critical to firefighter-related chronic pulmonary illnesses. Lung tissue was collected 2 hrs post-overhaul and evaluated via whole genome transcriptomics by RNA-seq. Although gas metering showed that the fireground overhaul levels of carbon monoxide (CO), carbon dioxide (CO2), hydrogen cyanine (HCN), hydrogen sulfide (H2S) and oxygen (O2) were within NIOSH ceiling recommendations, 3852 lung genes were differentially expressed when mice exposed to overhaul were compared to mice on the fireground but outside the overhaul environment. Importantly, overhaul exposure was associated with an up/down-regulation of 86 genes with a fold change of 1.5 or greater (p<0.5) including the immunomodulatory-linked genes S100a8 and Tnfsf9 (downregulation) and the cancer-linked genes, Capn11 and Rorc (upregulation). Taken together these findings indicate that, without respiratory protection, exposure to the fireground overhaul environment is associated with transcriptional changes impacting proteins potentially related to inflammation-associated lung disease and cancer.

Acute fasting inhibits central caspase-1 activity reducing anxiety-like behavior and increasing novel object and object location recognition.

BACKGROUND: Inflammation within the central nervous system (CNS) is frequently comorbid with anxiety. Importantly, the pro-inflammatory cytokine most commonly associated with anxiety is IL-1ß. The bioavailability and activity of IL-1ß are regulated by caspase-1-dependent proteolysis vis-a-vis the inflammasome. Thus, interventions regulating the activation or activity of caspase-1 should reduce anxiety especially in states that foster IL-1ß maturation. METHODS: Male C57BL/6j, C57BL/6j mice treated with the capase-1 inhibitor biotin-YVAD-cmk, caspase-1 knockout (KO) mice and IL-1R1 KO mice were fasted for 24h or allowed ad libitum access to food. Immediately after fasting, caspase-1 activity was measured in brain region homogenates while activated caspase-1 was localized in the brain by immunohistochemistry. Mouse anxiety-like behavior and cognition were tested using the elevated zero maze and novel object/object location tasks, respectively. RESULTS: A 24h fast in mice reduced the activity of caspase-1 in whole brain and in the prefrontal cortex, amygdala, hippocampus, and hypothalamus by 35%, 25%, 40%, 40%, and 40% respectively. A 24h fast also reduced anxiety-like behavior by 40% and increased novel object and object location recognition by 21% and 31%, respectively. IL-1ß protein, however, was not reduced in the brain by fasting. ICV administration of YVAD decreased caspase-1 activity in the prefrontal cortex and amygdala by 55%, respectively leading to a 64% reduction in anxiety like behavior. Importantly, when caspase-1 KO or IL1-R1 KO mice are fasted, no fasting-dependent reduction in anxiety-like behavior was observed. CONCLUSIONS: Results indicate that fasting decrease anxiety-like behavior and improves memory by a mechanism tied to reducing caspase-1 activity throughout the brain.