Host-mediated effects of phytonutrients in ruminants: A review.

Plants produce an extensive array of organic compounds derived from secondary metabolism that may be useful in animal nutrition because of their chemical makeup. These plant-derived bioactive compounds, also referred to as phytonutrients (PN) or phytobiotics, have been shown to express antimicrobial activities against a wide range of bacteria, yeast, and fungi and have been investigated as rumen modifiers in ruminant nutrition. Studies have reported that PN may inhibit deamination of AA and methanogenesis in the rumen and shift fermentation toward propionate and butyrate. Most of the experiments, however, have been conducted in vitro, and responses have been highly variable and inconsistent in animal experiments. In addition, some studies have reported that PN had positive effects on productivity, although rumen fermentation was not affected. Other than antimicrobial effects in the gut, PN are known to bind specific receptors expressed in neurons, intestines, and other cells and exhibit related physiological effects in nonruminants. The receptor-mediated effects include immune responses, oxidative stress, and insulin secretion and activity. Some PN, due to their phenolic nature, are likely less susceptible to microbial degradation in the rumen and may exhibit activities postruminally, similar to their mode of action in nonruminant species. This opens a new area of research in ruminants, including effects of PN on the animal's immune system, postruminal nutrient use, and animal physiology. Although limited, studies with ruminants provide first evidence of PN's regulatory effects on the host responses. For example, PN were reported to regulate immune cells related to adaptive and innate immunity in challenged or nonchallenged dairy cows. Supplementation of PN reduced oxidative stress by decreasing lipid peroxidation and increasing endogenous antioxidants in ruminants. Additionally, insulin secretion and sensitivity were reportedly regulated by PN in dairy cows. The regulatory effects of PN on immunity may be beneficial for immune suppression and inflammation in dairy cows. In addition, PN could positively affect energy partitioning for milk production through their effects on insulin secretion and sensitivity. Further research is needed to elucidate the effect and mode of action of PN on immune function and animal energetics.

Effects of rumen-protected Capsicum oleoresin on productivity and responses to a glucose tolerance test in lactating dairy cows.

The objective of this experiment was to investigate the effects of rumen-protected Capsicum oleoresin (RPC) supplementation on feed intake, milk yield and composition, nutrient utilization, fecal microbial ecology, and responses to a glucose tolerance test in lactating dairy cows. Nine multiparous Holstein cows were used in a replicated 3 × 3 Latin square design balanced for residual effects with three 28-d periods. Each period consisted of 14 d for adaptation and 14 d for data collection and sampling. Treatments were 0 (control), 100, and 200 mg of RPC/cow per day. They were mixed with a small portion of the total mixed ration and top-dressed. Glucose tolerance test was conducted once during each experimental period by intravenous administration of glucose at a rate of 0.3 g/kg of body weight. Dry matter intake was not affected by RPC. Milk yield tended to increase for RPC treatments compared to the control. Feed efficiency was linearly increased by RPC supplementation. Concentrations of fat, true protein, and lactose in milk were not affected by RPC. Apparent total-tract digestibility of dry matter, organic matter, and crude protein was linearly increased, and fecal nitrogen excretion was linearly decreased by RPC supplementation. Rumen-protected Capsicum oleoresin did not affect the composition of fecal bacteria. Glucose concentration in serum was not affected by RPC supplementation post glucose challenge. However, compared to the control, RPC decreased serum insulin concentration at 5, 10, and 40 min post glucose challenge. The area under the insulin concentration curve was also decreased 25% by RPC. Concentration of nonesterified fatty acids and ß-hydroxybutyrate in serum were not affected by RPC following glucose administration. In this study, RPC tended to increase milk production and increased feed efficiency in dairy cows. In addition, RPC decreased serum insulin concentration during the glucose tolerance test, but glucose concentration was not affected by treatment.

Effects of rumen-protected Capsicum oleoresin on immune responses in dairy cows intravenously challenged with lipopolysaccharide.

The objective of this experiment was to investigate the effects of rumen-protected Capsicum oleoresin (RPC) on productivity and immune responses including feed intake, milk yield and composition, white and red blood cells, lipid peroxidation, and blood concentration of cortisol, haptoglobin, glucose, and insulin in lactating dairy cows experimentally challenged with lipopolysaccharide (LPS). The experiment was a replicated 3 × 3 Latin square design with 9 multiparous Holstein cows in three 28-d periods. Treatments were 0 (control), 100, and 200 mg of RPC/cow per day, mixed with small portions of the total mixed ration and top-dressed. Bacterial LPS was intravenously administered at 1.0 µg/kg of body weight in the last week of each experimental period, and blood samples were collected at 0, 2, 4, 8, and 24 h after administration. Dry matter intake, milk yield, and white blood cells including neutrophils, lymphocytes, monocytes, and eosinophils were decreased, and rectal temperature, hemoglobin, and serum concentrations of cortisol and haptoglobin were increased by LPS. Red blood cells, platelets, and plasma concentration of thiobarbituric acid reactive substances were not affected by LPS. Dry matter intake, milk yield, and milk composition in the 5 d post-LPS challenge were not affected by RPC. Rectal temperature, white blood cells, red blood cells, hemoglobin, and platelets were also not affected by RPC. Compared with the control, RPC tended to decrease cortisol at 2 h following LPS challenge and decreased haptoglobin concentration in serum across sampling points. Concentration of thiobarbituric acid reactive substances in plasma was decreased by RPC at 24 h post-LPS challenge. Glucose and insulin were not affected by RPC, but serum insulin concentration at 8 h was lowered by RPC compared to the control. Collectively, RPC had no or subtle effects on feed intake, milk yield and composition, rectal temperature, white and red blood cells, and serum glucose and insulin concentration in dairy cows challenged by LPS. However, RPC tended to decrease cortisol and decreased concentrations of haptoglobin and thiobarbituric acid reactive substances in blood following LPS challenge. Data suggest that dietary supplementation of RPC may modulate acute phase responses induced by bacterial infection in lactating dairy cows.

Reducing gut effects from Cryptosporidium parvum infection in dairy calves through prophylactic glucagon-like peptide 2 therapy or feeding of an artificial sweetener.

Glucagon-like peptide 2 (GLP-2) therapy was shown previously to reduce inflammation-related gut damage from coccidiosis in dairy calves, and feeding of artificial sweetener stimulates GLP-2 secretion from intestinal L cells. The purpose of this study was to determine whether GLP-2 treatment or artificial sweetener feeding beginning 1 wk before an experimental inoculation with the coccidian parasite Cryptosporidium parvum can reduce infection-related intestinal damage in Holstein bull calves. Newborn calves were assigned to 1 of 4 treatment groups of 6 calves each, including noninfected control calves injected s.c. every 12 h with control buffer (CON), infected control calves injected s.c. every 12 h with control buffer (INF), infected calves injected s.c. every 12 h with 50 µg/kg of body weight of GLP-2 (GLP2), and infected calves injected s.c. every 12 h with control buffer and supplemented in the diet with Sucram (Pancosma, Geneva, Switzerland) at 400 mg/kg of dry matter of milk replacer (SUC). Treatments were initiated on d 1, and calves in INF, GLP2, and SUC were orally dosed on d 8 with 12,500 C. parvum oocysts. Fecal scores were recorded daily, plasma was collected on d 1, 8, 12, 15, and 18 to evaluate markers of inflammation, and fecal samples were collected on d 1, 8, and every other day thereafter to determine the presence of oocysts. Calves were euthanized on d 18 for collection of intestinal tissues and histological and gene expression analyses. Relative to CON, calves in INF exhibited an increase in diarrhea severity, increased plasma serum amyloid A concentration on d 15 and 18, reduced intestinal villus height, increased villus apoptosis and crypt cell proliferation, and increased intestinal mRNA expression of MARVELD2 and GPX2. However, calves in SUC and GLP2 had reduced diarrhea severity and fecal C. parvum oocyst shedding, reduced plasma serum amyloid A concentration on d 15 and 18, and, depending on the intestinal segment, increased villus height, reduced crypt cell proliferation, and reduced mRNA expression of MARVELD2, GPX2, and other tight junction proteins relative to INF. Lastly, GLP2 and SUC exhibited increased intestinal mass-to-length ratio and decreased length-to-empty body weight ratio relative to INF. Our findings suggest that GLP-2 and Sucram treatments administered before a low-level C. parvum exposure may contribute to fewer effects on intestinal integrity, morphology, and inflammation in response to infection, and shorter, denser intestines.

Glucagon-like peptide 2 and its beneficial effects on gut function and health in production animals.

Numerous endocrine cell subtypes exist within the intestinal mucosa and produce peptides contributing to the regulation of critical physiological processes including appetite, energy metabolism, gut function, and gut health. The mechanisms of action and the extent of the physiological effects of these enteric peptides are only beginning to be uncovered. One peptide in particular, glucagon-like peptide 2 (GLP-2) produced by enteroendocrine L cells, has been fairly well characterized in rodent and swine models in terms of its ability to improve nutrient absorption and healing of the gut after injury. In fact, a long-acting form of GLP-2 recently has been approved for the management and treatment of human conditions like inflammatory bowel disease and short bowel syndrome. However, novel functions of GLP-2 within the gut continue to be demonstrated, including its beneficial effects on intestinal barrier function and reducing intestinal inflammation. As knowledge continues to grow about GLP-2's effects on the gut and its mechanisms of release, the potential to use GLP-2 to improve gut function and health of food animals becomes increasingly more apparent. Thus, the purpose of this review is to summarize: (1) the current understanding of GLP-2's functions and mechanisms of action within the gut; (2) novel applications of GLP-2 (or stimulators of its release) to improve general health and production performance of food animals; and (3) recent findings, using dairy calves as a model, that suggest the therapeutic potential of GLP-2 to reduce the pathogenesis of intestinal protozoan infections.

COMPARATIVE GUT PHYSIOLOGY SYMPOSIUM: Comparative physiology of digestion.

The digestive systems of all species have been shaped by environmental pressures over long evolutionary time spans. Nevertheless, all digestive systems must achieve the same end points, the ingestion of biological material and its conversion to molecules that serve as energy substrates and structural components of tissues. A range of strategies to extract nutrients, including for animals reliant primarily on foregut fermentation, hindgut fermentation, and enzymatic degradation, have evolved. Moreover, animals have adapted to different foodstuffs as herbivores (including frugivores, folivores, granivores, etc.), carnivores, and omnivores. We present evidence that humans have diverged from other omnivores because of the long history of consumption of cooked or otherwise prepared food. We consider them to be cucinivores. We present examples to illustrate that the range of foodstuffs that can be efficiently assimilated by each group or species is limited and is different from that of other groups or species. Differences are reflected in alimentary tract morphology. The digestive systems of each group and of species within the groups are adaptable, with constraints determined by individual digestive physiology. Although overall digestive strategies and systems differ, the building blocks for digestion are remarkably similar. All vertebrates have muscular tubular tracts lined with a single layer of epithelial cells for most of the length, use closely related digestive enzymes and transporters, and control the digestive process through similar hormones and similarly organized nerve pathways. Extrapolations among species that are widely separated in their digestive physiologies are possible when the basis for extrapolation is carefully considered. Divergence is greatest at organ or organismal levels, and similarities are greatest at the cell and molecular level.

Effect of L-carnitine on exercise performance in patients with mitochondrial myopathy

Exercise intolerance due to impaired oxidative metabolism is a prominent symptom in patients with mitochondrial myopathy (MM), but it is still uncertain whether L-carnitine supplementation is beneficial for patients with MM. The aim of our study was to investigate the effects of L-carnitine on exercise performance in MM. Twelve MM subjects (mean age±SD=35.4±10.8 years) with chronic progressive external ophthalmoplegia (CPEO) were first compared to 10 healthy controls (mean age±SD=29±7.8 years) before they were randomly assigned to receive L-carnitine supplementation (3 g/daily) or placebo in a double-blind crossover design. Clinical status, body composition, respiratory function tests, peripheral muscle strength (isokinetic and isometric torque) and cardiopulmonary exercise tests (incremental to peak exercise and at 70% of maximal), constant work rate (CWR) exercise test, to the limit of tolerance [Tlim]) were assessed after 2 months of L-carnitine/placebo administration. Patients with MM presented with lower mean height, total body weight, fat-free mass, and peripheral muscle strength compared to controls in the pre-test evaluation. After L-carnitine supplementation, the patients with MM significantly improved their Tlim (14±1.9 vs 11±1.4 min) and oxygen consumption ( V ˙ O 2 ) at CWR exercise, both at isotime (1151±115 vs 1049±104 mL/min) and at Tlim (1223±114 vs 1060±108 mL/min). These results indicate that L-carnitine supplementation may improve aerobic capacity and exercise tolerance during high-intensity CWRs in MM patients with CPEO.

Effect of L-carnitine on exercise performance in patients with mitochondrial myopathy.

Exercise intolerance due to impaired oxidative metabolism is a prominent symptom in patients with mitochondrial myopathy (MM), but it is still uncertain whether L-carnitine supplementation is beneficial for patients with MM. The aim of our study was to investigate the effects of L-carnitine on exercise performance in MM. Twelve MM subjects (mean age±SD=35.4±10.8 years) with chronic progressive external ophthalmoplegia (CPEO) were first compared to 10 healthy controls (mean age±SD=29±7.8 years) before they were randomly assigned to receive L-carnitine supplementation (3 g/daily) or placebo in a double-blind crossover design. Clinical status, body composition, respiratory function tests, peripheral muscle strength (isokinetic and isometric torque) and cardiopulmonary exercise tests (incremental to peak exercise and at 70% of maximal), constant work rate (CWR) exercise test, to the limit of tolerance [Tlim]) were assessed after 2 months of L-carnitine/placebo administration. Patients with MM presented with lower mean height, total body weight, fat-free mass, and peripheral muscle strength compared to controls in the pre-test evaluation. After L-carnitine supplementation, the patients with MM significantly improved their Tlim (14±1.9 vs 11±1.4 min) and oxygen consumption ( V ˙ O 2 ) at CWR exercise, both at isotime (1151±115 vs 1049±104 mL/min) and at Tlim (1223±114 vs 1060±108 mL/min). These results indicate that L-carnitine supplementation may improve aerobic capacity and exercise tolerance during high-intensity CWRs in MM patients with CPEO.

Effects of in ovo injection with selenium on immune and antioxidant responses during experimental necrotic enteritis in broiler chickens.

This study was conducted to investigate the effects of in ovo injection of Se on modulating the immune system and antioxidant responses in broiler chickens with experimental necrotic enteritis. Broiler eggs were injected at 18 d of embryo age with either 100 µL of PBS alone or sodium selenite (Na2SeO3) in PBS, providing 0 (SS0), 10 (SS10), or 20 (SS20) µg of Se/egg. At 14 d posthatch, PBS-treated and uninfected chickens were kept as the control group, whereas the remaining chickens were orally infected with 1.0 × 10(4) sporulated oocysts of Eimeria maxima (SS0, SS10, SS20). At 18 d posthatch, E. maxima-infected chickens were orally infected with 1.0 × 10(9) cfu of Clostridium perfringens. Infected control SS0 group showed significantly decreased BW compared with the uninfected control. However, SS20 group showed significantly increased BW compared with the infected control SS0 group, whereas the BW were similar among uninfected control and infected SS10 and SS20 groups. The SS10 group showed significantly lower intestinal lesions compared with the SS0 group, and oocyst production was decreased in both SS10 and SS20 groups. Serum malondialdehyde level and catalase activity were also decreased in both SS10 and SS20 groups, whereas the superoxide dismutase level was significantly lower in the SS10 group compared with the SS0 group. The SS20 group showed significantly higher levels of transcripts for IL-1ß and IL-6 in intestine, and SS10 and SS20 groups had higher levels of transcripts for IL-8 and inducible nitric oxide synthase expression and decreased glutathione peroxidase 7 mRNA levels compared with the SS0 group. The SS10 and SS20 groups also showed increased serum antibody levels to C. perfringens α-toxin and NetB toxin compared with the SS0 group. These collective results suggest that the injection of Se into the amniotic cavity of developing eggs may be beneficial for enhancing immune and antioxidant responses in the hatched chickens exposed to the necrotic enteritis-causing pathogens.