Galacto-oligosaccharides alleviate lung inflammation by inhibiting NLRP3 inflammasome activation in vivo and in vitro

Introduction: The lack of effective anti-inflammatory therapies for pneumonia represents a challenge for identifying new alternatives. Non-digestible galacto-oligosaccharides (GOS) are attractive candidates due to their anti-inflammatory and immunomodulatory effects both locally and systemically. Objectives: The anti-inflammatory properties of GOS were investigated in calves with lung infections and in calf primary bronchial epithelial cells (PBECs) and human lung epithelial cells (A549). To delineate the mechanism, the potential capacity of GOS to inhibit the NLR family pyrin domain containing 3 (NLRP3) inflammasome has been investigated. Methods: GOS were administrated orally to calves with naturally occurring lung infections during early life or used as pretreatments in cell cultures exposed to M. haemolytica, lipopolysaccharides (LPS), leukotoxin or ATP. The cell composition, cytokine/chemokine concentrations, and M. haemolytica-LPS lgG levels in broncho-alveolar lavage fluid (BALF) and blood were investigated, while the M. haemolytica positivity in BALF and bronchial mucosa was detected in vivo. Key markers of NLRP3 inflammasome activation were measured in vivo and in vitro. Results: GOS reduced M. haemolytica positivity and M. haemolytica-LPS lgG levels in calves with lung infections. Regulation of immune function and suppression of inflammatory response by GOS is related to the inhibition of NLRP3 inflammasome as observed in bronchial mucosal tissue of infected calves. The M. haemolytica-induced IL-1β production in PBECs was lowered by GOS, which was associated with NLRP3 inflammasome inhibition caused by the decreased reactive oxygen species and ATP production. GOS inhibited leukotoxin-induced ATP production in PBECs. The LPS- and ATP-induced NLRP3 inflammasome activation in PBECs and A549 cells was suppressed by GOS. Conclusion: GOS exert anti-inflammatory properties by inhibiting the NLRP3 inflammasome activation in vitro and in vivo, suggesting a potential role for GOS in the prevention of lung infections

Dietary diversity affects feeding behaviour of suckling piglets

Stimulating solid feed intake in suckling piglets is important to facilitate the weaning transition, exemplified by the positive correlation between pre- and post-weaning feed intake. The present study compared the effect of dietary diversity (i.e. offering two feeds simultaneously) and flavour novelty (i.e. regularly changing the flavour of one feed) on the feeding behaviour and performance of suckling piglets until weaning at day 22. It was hypothesized that presentation of the feed in a more diverse form, by varying multiple sensory properties of the feed, stimulates pre-weaning feed intake. Piglets received ad libitum feed from 2 days of age in two feeders per pen (choice feeding set-up). One group of piglets (dietary diversity (DD), n = 10 litters) were given feed A and feed B which differed in production method, size, flavour, ingredient composition and nutrient profile, smell, texture and colour. The other group of piglets (flavour novelty (FN), n = 9 litters) received feed A plus feed A to which one of 4 flavours were added from day 6 in a daily sequential order. Feeding behaviour was studied by weighing feed remains (d6, 12, 16, 22) and by live observations (4-min scan sampling, 6 h/d; d9, 14, 21; n = 6 litters per treatment). Observations were also used to discriminate ‘eaters’ from ‘non-eaters’. All piglets were weighed at d2, 6 and 22. Piglets did not prefer feed A (d2–22: 1.4 ± 0.16 kg/litter) over B (1.6 ± 0.18) within DD nor had a preference for feed A with (d6–22: 1.1 ± 0.06 kg/litter) or without additional flavours (0.9 ± 0.07) within FN. Nevertheless, DD-litters (d2–22: 3.0 ± 0.32 kg) ate significantly more than FN-litters (2.0 ± 0.12 kg; P = 0.02) and explored the feed 2.6 times more at d14 (P = 0.001). Furthermore feed A, the common feed provided in DD and FN, was more consumed in DD (d2–22: 1.4 ± 0.16 kg) compared to FN (1.0 ± 0.07 kg; P = 0.04). The percentage of eaters within a litter did not differ over time between DD (d9: 26%, d14: 78%, d21: 94%) and FN (20%, 71% and 97%) and no effect was found on pre-weaning weight gain. In conclusion, this study showed that provision of dietary diversity to suckling piglets stimulated their feed exploration and intake more than dietary flavour novelty only, but did not enhance the percentage of piglets within a litter that consume the feed or their growth performance. These data suggest that dietary diversity could be an innovative feeding strategy to stimulate solid feed intake in suckling piglets.</p

Lactose and Digestible Maltodextrin in Milk Replacers Differently Affect Energy Metabolism and Substrate Oxidation : A Calorimetric Study in Piglets

BACKGROUND: In recent years, lactose-free infant formulas have been increasingly used. Digestible maltodextrins are commonly used as a substitute for lactose in these formulas, but the effects on energy metabolism are unknown. OBJECTIVE: We aimed to evaluate the differences in energy metabolism and substrate oxidation in piglets fed milk replacers containing lactose compared with maltodextrin as the only source of carbohydrates. METHODS: Piglets (Tempo × Topigs 20) from 8 litters were fed milk replacers containing lactose or maltodextrin (28% w/w, milk powder basis) from 1 to 9 wk of age (n = 4 litters/milk replacer). At 5 wk of age, 4 females and 4 entire males (mean ± SEM bodyweight, 10 ± 0.3 kg) were selected per litter, and housed in 16 groups of 4 littermates, with 2 females and 2 males per pen (n = 8 groups/milk replacer). Between 7 and 9 wk of age, groups were housed for 72 h in climate respiration chambers, and fed their experimental milk replacer in 2 meals per day, at 08:30 and 16:30. Heat production data were calculated from the continuous measurement of gaseous exchanges and analyzed using general linear models in SAS. RESULTS: Resting metabolic rate was 6% less in maltodextrin- than in lactose-fed piglets, notably before the morning meal. The postprandial respiratory quotient was 13% greater in maltodextrin- than in lactose-fed piglets after both meals. Net rates of carbohydrate oxidation were on average 5% greater in maltodextrin- than in lactose-fed piglets, particularly after the afternoon meal, whereas net rates of fat oxidation were 9% less in maltodextrin- than in lactose-fed piglets, particularly after the morning meal. CONCLUSIONS: Compared with lactose, maltodextrin in milk replacers reduced resting metabolic rate in the fasting state, and induced a shift in postprandial substrate oxidation profiles in pigs. Further research is warranted to evaluate the consequences of these metabolic changes for body composition

Pigs Ferment Enzymatically Digestible Starch when it Is Substituted for Resistant Starch

<p>BACKGROUND: Feeding behavior is controlled by satiety mechanisms, which are affected by the extent of starch digestion, and thus resistant starch (RS) intake. Alterations in feeding behavior to changes in RS intake may depend on the adaptation of processes involved when shifting from starch digestion to fermentation or vice versa. OBJECTIVES: The aim of this study was to investigate how growing pigs adapt their feeding behavior in response to increasing and decreasing dietary RS concentrations. METHODS: Thirty-six groups of 6 pigs (25.4 ± 2.8 kg; Hypor Libra × Hypor Maxter; male:female, 1:1) were fed diets containing 50% high-amylose maize starch (high RS; HRS) or waxy maize starch (low RS; LRS). Over 28 d, diets were exchanged following a 5-step titration (25% per step) that was executed in the upward (LH) or downward direction (HL). Twelve groups received a control diet to correct for changes over time. Individual feeding behavior and total tract starch digestion and fermentation were evaluated. The response in each parameter to increasing dietary HRS inclusion was estimated through the use of linear regression procedures, and tested for titration direction and sex effects. RESULTS: Complete substitution of LRS with HRS increased the proportion of starch fermented, which was greater in LH pigs than in HL pigs (17.6% compared with 8.18%; P &lt; 0.001), and decreased the feed intake (106 g/d; P = 0.021) and meal size (12.6 g; P &lt; 0.001) of LH pigs, but not of HL pigs. In LH pigs, the size of the starch fermentation response positively correlated with the size of the feed intake response (r = 0.90, P &lt; 0.001). CONCLUSIONS: The attenuated response in starch fermentation in HL pigs indicates that pigs adapt more slowly to dietary supply of digestible starch than to RS, consequently resulting in fermentation of enzymatically digestible starch. Feed intake and feeding behavior only changed in pigs poorly adapting to RS, indicating that adequacy of adaptation, rather than RS itself, drives feed intake. These findings stress the importance of diet history for nutrient digestion and feeding behavior.</p

Pigs Ferment Enzymatically Digestible Starch when it Is Substituted for Resistant Starch

BACKGROUND: Feeding behavior is controlled by satiety mechanisms, which are affected by the extent of starch digestion, and thus resistant starch (RS) intake. Alterations in feeding behavior to changes in RS intake may depend on the adaptation of processes involved when shifting from starch digestion to fermentation or vice versa. OBJECTIVES: The aim of this study was to investigate how growing pigs adapt their feeding behavior in response to increasing and decreasing dietary RS concentrations. METHODS: Thirty-six groups of 6 pigs (25.4 ± 2.8 kg; Hypor Libra × Hypor Maxter; male:female, 1:1) were fed diets containing 50% high-amylose maize starch (high RS; HRS) or waxy maize starch (low RS; LRS). Over 28 d, diets were exchanged following a 5-step titration (25% per step) that was executed in the upward (LH) or downward direction (HL). Twelve groups received a control diet to correct for changes over time. Individual feeding behavior and total tract starch digestion and fermentation were evaluated. The response in each parameter to increasing dietary HRS inclusion was estimated through the use of linear regression procedures, and tested for titration direction and sex effects. RESULTS: Complete substitution of LRS with HRS increased the proportion of starch fermented, which was greater in LH pigs than in HL pigs (17.6% compared with 8.18%; P < 0.001), and decreased the feed intake (106 g/d; P = 0.021) and meal size (12.6 g; P < 0.001) of LH pigs, but not of HL pigs. In LH pigs, the size of the starch fermentation response positively correlated with the size of the feed intake response (r = 0.90, P < 0.001). CONCLUSIONS: The attenuated response in starch fermentation in HL pigs indicates that pigs adapt more slowly to dietary supply of digestible starch than to RS, consequently resulting in fermentation of enzymatically digestible starch. Feed intake and feeding behavior only changed in pigs poorly adapting to RS, indicating that adequacy of adaptation, rather than RS itself, drives feed intake. These findings stress the importance of diet history for nutrient digestion and feeding behavior.</p

Increasing intake of dietary soluble nutrients affects digesta passage rate in the stomach of growing pigs

The passage rate of solids and liquids through the gastrointestinal tract differs. Increased dietary nutrient solubility causes nutrients to shift from the solid to the liquid digesta fraction and potentially affect digesta passage kinetics. We quantified: (1) the effect of three levels of dietary nutrient solubility (8, 19 and 31 % of soluble protein and sucrose in the diet) at high feed intake level (S) and (2) the effect of low v. high feed intake level (F), on digesta passage kinetics in forty male growing pigs. The mean retention time (MRT) of solids and liquids in the stomach and small intestine was assessed using TiO2 and Cr-EDTA, respectively. In addition, physicochemical properties of digesta were evaluated. Overall, solids were retained longer than liquids in the stomach (2·0 h, P<0·0001) and stomach+small intestine (1·6 h, P<0·001). When S increased, MRT in stomach decreased by 1·3 h for solids (P=0·01) and 0·7 h for liquids (P=0·002) but only at the highest level of S. When F increased using low-soluble nutrients, MRT in stomach increased by 0·8 h for solids (P=0·041) and 0·7 h for liquids (P=0·0001). Dietary treatments did not affect water-binding capacity and viscosity of digesta. In the stomach of growing pigs, dietary nutrient solubility affects digesta MRT in a non-linear manner, while feed intake level increases digesta MRT depending on dietary nutrient solubility. Results can be used to improve predictions on the kinetics of nutrient passage and thereby of nutrient digestion and absorption in the gastrointestinal tract.</p

ASAS-NANP symposium : digestion kinetics in pigs: the next step in feed evaluation and a ready-to-use modeling exercise

Growing importance of upcycling agricultural by-products, food waste, and food processing by-products through livestock production strongly increased the variation in the nutritional quality of feed ingredients. Traditionally, feed ingredients are evaluated based on their measured extent of digestion. Awareness increases that in addition to the extent, the kinetics of digestion affects the metabolic fate of nutrients after absorption. Together with a growing body of evidence of complex interactions occurring within the lumen of the digestive tract, this urges the need of developing new approaches for feed evaluation. In a recently developed approach, we propose combining in vitro and in silico methods for feed ingredient evaluation. First steps in the development of such a systems were made by (1) evaluating in vitro the digestion potential of feed ingredients, regarding this as true ingredient properties and (2) predicting in silico the digestive processes like digesta transit, nutrient hydrolysis and absorption using dynamic, mechanistic modeling. This approach allows to evaluate to what extent the digestion potential of each ingredient is exploited in the digestive tract. Future efforts should focus on modeling digesta physicochemical properties and transit, applying in vitro digestion kinetic data of feed ingredients in mechanistic models, and generating reliable in vivo data on nutrient absorption kinetics across feed ingredients. The dynamic modeling approach is illustrated by a description of a modeling exercise that can be used for teaching purposes in digestive physiology or animal nutrition courses. A complete set of equations is provided as an on-line supplement, and can be built in modeling software that is freely available. Alternatively, the model can be constructed using any modeling software that enables the use of numerical integration methods.</p

The importance of amylase action in the porcine stomach to starch digestion kinetics

Starch digestion in the proximal small intestine of pigs exceeds in vitro predictions, suggesting a currently underestimated role for the stomach in starch digestion kinetics. This study aimed to investigate the role of amylase action in the porcine stomach on starch digestion kinetics, including hydrolysis by porcine saliva and degradation by bacterial enzymes present in the stomach. We studied the hydrolysis of starch in pigs fed barley based diets, in which starch was included as isolated powder, ground barley, or extruded barley. We identified soluble maltodextrins originating from starch breakdown in stomach digesta, especially in pigs fed extruded barley. Furthermore, we observed bacterial cells embedded in granular starch with electron microscopy, for pigs fed diets containing isolated barley starch. These observations lead us to measure starch hydrolysis in a dynamic stomach model over the course of a 225 min incubation, in which the pH was step-wise decreased from 6.5 to 2.0. Using this method, feed was either exposed to an enzyme extract obtained from stomach digesta or to porcine saliva. Up to 30 % of starch was hydrolysed into maltodextrins with a degree of polymerisation (DP) <6 when starch was incubated with the enzyme extract obtained from the stomach. Under the same conditions, saliva amylase, with an optimum pH around 7.8, hydrolysed up to 10 % of processed starch into maltodextrins with DP < 6. We conclude that a substantial part of starch may be degraded into oligomers in the porcine stomach by both salivary and bacterial amylases. This implies a considerable role for the stomach on starch digestion kinetics, which is overlooked in current feed evaluation systems.</p