Genetic control of susceptibility to experimental Lyme arthritis is polygenic and exhibits consistent linkage to multiple loci on chromosome 5 in four independent mouse crosses.

C3H/He mice infected with Borrelia burgdorferi develop severe arthritis and are high antibody responders, while infected C57BL/6 and BALB/c mice develop mild arthritis and less robust humoral responses. Genetic analysis using composite interval mapping (CIM) on reciprocal backcross populations derived from C3H/HeN and C57BL/6N or C3H/HeJ and BALB/cAnN mice identified 12 new quantitative trait loci (QTL) linked to 10 murine Lyme disease phenotypes. These QTL reside on chromosomes 1, 2, 4, 6, 7, 9, 10, 12, 14, 15, 16, and 17. A reanalysis of an F(2) intercross between C57BL/6N and C3H/HeN mice using CIM identified two new QTL on chromosomes 4 and 15 and confirmed the location of seven previously identified loci. Two or more experimental crosses independently verified six QTL controlling phenotypes after B. burgdorferi infection. Additionally, Bb2 on chromosome 5 was reproduced in four experimental populations and was linked to the candidate locus Cora1. Evidence of four distinct QTL residing within the 30-cM region of chromosome 5 encompassing the previously mapped Bb2 and Bb3 loci was shown by CIM. Interestingly, some alleles contributing to susceptibility to Lyme arthritis were derived from C57BL/6N and BALB/cAnN mice, showing that disease-resistant strains harbor susceptibility alleles.

Malnutrition modifies pig small intestinal inflammatory responses to rotavirus.

Infectious diarrheal diseases and malnutrition are major causes of child morbidity and mortality. In this study, malnutrition was superimposed on rotavirus infection in neonatal piglets to simulate the combined intestinal stress of viral enteritis in malnourished infants. Two-day-old piglets were assigned to three treatment groups as follows: 1) noninfected, fully nourished; 2) infected, fully nourished; and 3) infected, malnourished. Intestinal indices of inflammation were monitored over the subsequent 2-wk period. Intestinal damage and diarrhea were observed within 2 d of rotavirus infection and began to subside in nourished piglets by d 9 but persisted through d 16 postinfection in malnourished piglets. Rotavirus upregulated small intestinal expression of major histocompatibility complex (MHC) class I and class II genes; malnutrition intensified MHC class I gene expression and suppressed MHC class II expression. Jejunal CD4(+) and CD8(+) T-lymphocyte numbers were elevated for infected, nourished piglets on d 2, 9 and 16 postinfection. Malnutrition did not significantly affect the local expansion of T cell subsets in response to rotavirus. Intestinal prostaglandin E2 (PGE2) concentrations were elevated early after rotavirus infection independent of nutritional state. By d 9, PGE2 concentrations returned to baseline in infected, nourished piglets but remained elevated in malnourished piglets, corresponding to diarrhea observations. Together, the results identify intestinal indices of inflammation that are modulated by malnutrition and prompt reconsideration of current models of rotavirus pathophysiology.

Weaning anorexia may contribute to local inflammation in the piglet small intestine.

Compromising alterations in villus-crypt structure are common in pigs postweaning. Possible contributions of local inflammatory reactions to villus-crypt alterations during the weaning transition have not been described. This study evaluated local inflammatory responses and their relationship with morphological changes in the intestine in 21-d-old pigs (n = 112) killed either at weaning (Day 0) or 0.5, 1, 2, 4 or 7 d after weaning to either milk- or soy-based pelleted diets. Cumulative intake averaged <100 g during the first 2 d postweaning, regardless of diet. During this period of weaning anorexia, inflammatory T-cell numbers and local expression of the matrix metalloproteinase stromelysin increased while jejunal villus height, crypt depth and major histocompatibility complex (MHC) class I RNA expression decreased. Upon resumption of feed intake by the fourth d postweaning, villus height and crypt depth, CD8(+) T cell numbers, MHC class I RNA expression and local expression of stromelysin returned to Day 0 values. Together the results indicate that inadequate feed intake during the immediate postweaning period may contribute to intestinal inflammation and thereby compromise villus-crypt structure and function.

Identification of quantitative trait loci governing arthritis severity and humoral responses in the murine model of Lyme disease.

A spectrum of disease severity has been observed in patients with Lyme disease, with approximately 60% of untreated individuals developing arthritis. The murine model of Lyme disease has provided strong evidence that the genetic composition of the host influences the severity of arthritis following infection with Borrelia burgdorferi: infected C3H mice develop severe arthritis while infected C57BL/6N mice develop mild arthritis. Regions of the mouse genome controlling arthritis severity and humoral responses during B. burgdorferi infection were identified in the F2 intercross generation of C3H/HeNCr and C57BL/6NCr mice. Rear ankle swelling measurements identified quantitative trait loci (QTL) on chromosomes 4 and 5, while histopathological scoring identified QTL on a unique region of chromosome 5 and on chromosome 11. The identification of QTL unique for ankle swelling or histopathological severity suggests that processes under distinct genetic control are responsible for these two manifestations of Lyme arthritis. Additional QTL that control the levels of circulating Igs induced by B. burgdorferi infection were identified on chromosomes 6, 9, 11, 12, and 17. Interestingly, the magnitude of the humoral response was not correlated with the severity of arthritis in infected F2 mice. This work defines several genetic loci that regulate either the severity of arthritis or the magnitude of humoral responses to B. burgdorferi infection in mice, with implications toward understanding the host-pathogen interactions involved in disease development.

Neither intact nor hydrolyzed soy proteins elicit intestinal inflammation in neonatal piglets.

BACKGROUND: Efficacy of feeding hydrolyzed soy proteins to infants intolerant to cow milk proteins has not been determined fully. This study compared growth and intestinal responses of neonatal piglets fed formulas with hydrolyzed soy protein to piglets fed formulas with intact soy or cow milk (casein-whey) proteins. METHODS: Piglets (n = 40, day 2 postpartum) were fed commercial milk replacer until day 7 postpartum (designated day 0) and then were assigned randomly to casein-whey (CW) or soy (intact, SI; hydrolyzed SH) formulas to evaluate intestinal responses on days 0, 2, 5, and 10. RESULTS: Average daily gain was higher for CW (121 g/d; p < .05) compared with SI piglets 85 g/d); SH pig weight gain was intermediate (109 g/d). Villus height-to-crypt depth ratio in proximal jejunum was lower (p < .05) on day 2 than day 0 in soy-fed pigs and lower (p < .05) on day 5 than day 0 in CW pigs. Mucosal mast cells were generally higher in CW pigs compared with soy-fed pigs. Villus goblet cell numbers in the midjejunum of SH-fed piglets were lower (p < .05) on day 5 compared with day 0. On day 5, crypt goblet cell numbers were higher (p < .05) in the midjejunum of CW-fed piglets compared with SH-fed piglets with numbers intermediate for SI-fed piglets. Intestinal differences were not detected among dietary treatments for major histocompatibility complex class I and II gene expression, tissue concentrations of prostaglandin E2, or CD8+ T-cell numbers. CONCLUSIONS: Hydrolyzed soy proteins do not elicit intestinal inflammatory responses in piglets and may be viable alternatives to milk and intact soy proteins for feeding infants.

Short-term metabolic responses do not differ between neonatal piglets fed formulas containing hydrolyzed or intact soy proteins.

Hydrolyzed soy protein (SH) could be used as a protein source in formulas for infants with intolerance to cow's milk protein and may be preferable to intact soy protein (SI). However, metabolic responses to SH are poorly defined. Because of their partially hydrolyzed nature, nonphysiological elevations in either plasma amino acids or regulatory hormones may occur. Therefore, we evaluated effects of SH on plasma nutrient and pancreatic hormone (insulin, glucagon) concentrations. In Experiment 1, 24 newborn pigs were fitted with umbilical arterial and portal catheters, fed formula for 36 h and food deprived for 12 h. Pigs were then fed formula including either SH or SI with glucose polymers or casein-whey proteins (CW) containing lactose, and serial blood samples were taken for 2 h postprandially. Peak portal exceeded peak arterial amino acid concentrations within each treatment, and peak amino acid concentrations in CW-fed pigs exceeded those of SH- and SI-fed pigs. However, only SH formula-fed piglets had higher postprandial portal minus arterial amino acid concentrations (P < 0.05) throughout Experiment 1, suggesting that SH was well digested and absorbed. In Experiment 2, arterial catheters were inserted in 24 piglets. Previous procedures were followed except dietary carbohydrate was standardized to glucose polymers for all three diets, and sampling was extended to 3 h. Overall, portal or arterial nutrient and hormone concentrations were not different in the SI and SH groups (P > 0.05), indicating that hydrolyzed soy protein did not cause abnormal plasma concentrations. In conclusion, hydrolyzed soy protein did not result in elevated nutrient concentrations or hormone responses compared with intact soy or cow's milk protein.

Diet-dependent and diet-independent metabolic responses underlie growth stasis of pigs at weaning.

The weaning transition in domestic animals involves profound environmental and nutritional changes. Growth stasis is commonly observed in pigs during this period, resulting in significant losses to the swine industry. It has been suggested that the reduced growth rate reflects immune sensitivity to soy antigens in commercial diets; however, few studies have defined metabolic responses in pigs weaned to diets containing soybean meal. The impact of environmental and social changes at weaning on physiological functions, i.e., the metabolic adjustment to new nutritional substrates, has also been overlooked. Accordingly, the aim of this study was to distinguish diet-dependent and diet-independent metabolic responses in pigs weaned to a commercially available corn-soy diet. Focus was on the endocrine pancreas and cytokines associated with stress responses. Three-week-old crossbred pigs were weaned to a corn-soy (cereal) or a milk-based (milk) diet. Blood samples taken 0 (weaning), 1, 2, 5 and 7 d post-weaning demonstrated diet-independent responses including increased (P < 0.05) plasma glucagon concentrations, decreased (P < 0.05) glucose concentrations, increased (P < 0.05) interleukin-1 (IL-1) concentrations during the first 2 d post-weaning, and increased (P < 0.05) fibrinogen concentrations during the latter part of the study. In response to dietary treatment, milk-fed pigs had higher (P < 0.05) plasma insulin and glucose concentrations, reflective of higher food intake during the early post-weaning period. This clear distinction between diet-dependent and diet-independent metabolic responses at weaning suggests consideration of novel strategies to overcome the characteristic weanling growth stasis in pigs.

Supplemental protein for beef cattle grazing dormant intermediate wheatgrass pasture: effects on nutrient quality, forage intake, digesta kinetics, grazing behavior, ruminal fermentation, and digestion.

Sixteen ruminally cannulated yearling beef cattle (British x British; average BW = 295 +/- 25 kg; three steers and one heifer per treatment) grazing dormant intermediate wheatgrass (Thinopyrum intermedium Host) were allotted to four treatments: 1) no supplement (CON); 2) alfalfa hay (ALF; .52% of BW); 3) cottonseed meal (CSM; .22% of BW); and 4) corn gluten meal-wheat bran feed (CGMWBF; .36% of BW). Supplements were formulated (DM basis) so that intakes were isonitrogenous and were provided once daily (0700). Sampling periods were in February (FEB; .96% N in masticate), March (MAR; 1.06% N in masticate), and April (APR; 1.12% N in masticate) following an initial 21-d adaptation period. Daily grazing time was 1.1 to 1.5 h longer (P < .05) for CON cattle than for supplemented cattle. Forage OM intake (OMI) was not altered (P > .15) by supplemental protein; however, total OMI was greater (P < .04) for supplemented than for unsupplemented cattle. Harvesting efficiency (grams of OM intake-kilogram of BW-1.minute spent grazing-1) was greater (P < .05) for cattle fed CSM than for those fed CGF or CON; cattle fed ALF were intermediate in harvesting efficiency. Ruminal fluid kinetics, in situ rate and extent of NDF digestion, and total VFA concentration were not influenced (P > .10) by type of supplemental protein. Ruminal NH3 N concentration exhibited a treatment x sampling time interaction (P < .05). Type of protein supplement did not seem to affect most digestion measures; however, harvesting efficiency was influenced by supplement type.

Steers grazing intermediate wheatgrass at various stages of maturity: effects on nutrient quality, forage intake, digesta kinetics, ruminal fermentation, and serum hormones and metabolites.

Six ruminally cannulated Holstein steers (average BW of 495 +/- 5 kg) grazed a 32-ha, nonirrigated, intermediate wheatgrass (Thinopyrum intermedium Host) pasture from April 10 through December 7. Sample collections were conducted in May, June, September, and November 1989. Total masticate N decreased (P < .05) and bound N increased (P < .05) with advancing forage maturity. Masticate in vitro OM disappearance was lower (P < .05) in November (40.5%) than in May (62.0%). Organic matter intake (grams/kilogram of BW) decreased (P < .05) at each sampling date (May = 35.7, June = 26.8, September = 20.0, November = 14.9). Correspondingly, particulate passage rate decreased and gastrointestinal mean retention time increased (P < .05) with advancing forage maturity. Extent and rate of NDF digestion were greater (P < .05) during May and June than during September and November. Ruminal NH3 N and total VFA concentrations were greater (P < .05) during May and June than during September and November. Advancing forage maturity did not alter (P > .10) serum growth hormone concentrations; however, nonesterified fatty acid concentrations were greater (P < .05) during September and November than during May and June. Serum insulin-like growth factor I decreased (P < .05) with advancing forage maturity. Seasonal changes in forage intake and ruminal fermentation suggest that animal performance might be increased if supplemental energy is provided early in the growing season of intermediate wheatgrass; however, supplemental protein would likely be needed as wheatgrass matures.

Effects of pregnancy on digesta kinetics and ruminal fermentation in beef cows.

Four pregnant and four nonpregnant, ruminally cannulated beef cows were used to evaluate the effects of the last trimester of pregnancy on digesta kinetics and ruminal fermentation. Before breeding, cows were allotted randomly either to pregnant (PR) or to nonpregnant (NP) groups; PR cows were bred at the first estrus after synchronization. All cows were fed long-stem fescue hay at 15 g of DM/kg of BW based on BW 120 d before parturition of pregnant cows (average BW of 642 kg). Collection periods, each lasting 9 d, began at 96, 68, 41, and 10 +/- 1.3 d before parturition. Particulate passage rate was greater (P < .05) and retention times and gastrointestinal fill were less (P < .05) for PR than for NP cows. Apparent total tract DM digestion, rate and extent (96-h in situ incubation) of NDF disappearance, and ruminal fluid kinetics were not affected (P > .10) by pregnancy. A physiological state x sampling day interaction was noted (P < .05) for ruminal NH3 N, total VFA concentrations, and molar proportions of butyrate. Ruminal pH and individual VFA proportions, however, did not differ (P > .10) between PR and NP cows, except for valerate, which was less (P < .05) for PR than NP cows. Results suggest that in late pregnancy with restricted feeding, passage rate of particulates increases without substantial changes in fermentation or extent of digestion.

Supplemental methionine and time of supplementation effects on ruminal fermentation, digesta kinetics, and in situ dry matter and neutral detergent fiber disappearance in cattle.

Two experiments were conducted to study the effects of methionine supplementation on ruminal fermentation and digesta kinetics. In Exp. 1, nine ruminally cannulated beef heifers (average initial BW = 527 kg) in a crossover design were fed low-quality grass hay and cottonseed meal with or without 11.4 g of supplemental methionine (polysaccharide-coated). Particulate and fluid kinetics, rate of DM and NDF disappearance, ruminal VFA and NH3 N concentrations, and pH were not altered (P > .10) by supplemental methionine; however, ruminal purine concentration was greater (P < .05) in methionine-supplemented heifers than in unsupplemented heifers. In Exp. 2, 12 ruminally cannulated Holstein steers (average initial BW = 622 kg) grazing a fescue pasture were allotted to one of three groups: no supplemental methionine (CON) or 11.4 g of supplemental methionine fed at 0700 (AM) or at 1200 (PM). Forage intake, particulate kinetics, ruminal fluid kinetics, pH, VFA, and NH3 N concentrations were not altered (P > .10) by supplemental methionine or supplementation time. In situ rate of DM and NDF disappearance was greater (P < .05) in supplemented steers than in CON steers; AM steers exhibited faster (P < .05) rates than PM steers. Overall, methionine supplementation of low-quality forage increased ruminal purine concentration but did not alter in situ fermentation or digesta passage, whereas supplementation at 0700, but not at 1200, of steers grazing fescue forage increased rate of NDF fermentation.

Steers grazing endophyte-free tall fescue: seasonal changes in nutrient quality, forage intake, digesta kinetics, ruminal fermentation, and serum hormones and metabolites.

Six ruminally cannulated Holstein steers (average BW 514 kg) grazed a 33-ha, unirrigated, endophyte-free, tall fescue (Festuca arundinacea Schreb.) pasture from April 10 through December 7, 1989. Samples were collected in May, June, September, and November 1989. Total masticate N was relatively constant (P > .10) throughout the year. Masticate in vitro OM disappearance was less (P < .05) in September (48.4%) and November (50%) than in May (60.6%) and June (56%). Ruminal NH3N concentrations (milligrams/deciliter) were greater (P < .05) during May (20.5) and June (17.8) than during September (9.4) and November (5.9). Organic matter intake (grams/kilogram of BW) and particulate passage rate (percentage/hour) were least (P < .05) in November (15.3; 2.6) and not different (P > .10) during May (23.7; 3.1), June (20.7; 3.1), and September (21.0; 3.0). Extent and rate of NDF digestion and ruminal total VFA did not differ (P > .10) across sampling dates. Serum glucose concentrations were not affected (P > .10) by sampling date, but serum urea N was greater (P < .05) during May and November than during June and September. Nonesterified fatty acid concentrations increased (P < .05) with advancing plant maturity. Serum insulin concentrations were greater (P < .05) during May than during other sampling periods; however, growth hormone concentrations were not altered (P > .10) by advancing plant maturity. Unirrigated fescue pasture maintained a high nutrient level throughout the grazing season, and masticate samples did not display the decrease in nutrient content often noted with other types of pasture forage.