Diurnal variation of NMR based blood metabolites in calves fed a high plane of milk replacer: a pilot study.

BACKGROUND: Blood profiles have been used to monitor herd health status, diagnose disorders, and predict the risk of diseases in cattle and calves. Characterizing plasma metabolites in dairy calves could provide further insight into daily metabolic variations and the mechanisms that lead to metabolic diseases. In addition, by understanding physiological ranges of plasma metabolites relative to meal and the time of feeding in healthy animals, veterinarians can accurately diagnose abnormalities with a blood test. For diagnostic purposes, nuclear magnetic resonance (NMR) spectroscopy shows promise as a new and reliable method to determine a large number of blood metabolites simultaneously. RESULTS: Results demonstrated that the concentration of specific metabolites in plasma (i.e., lysine, isoleucine, leucine, tyrosine, glutamine, creatine, and 1-methylhistidine) fluctuated around meal times, while others (i.e., glutamic acid, methanol, formic acid, and acetic acid) maintained a stable temporal concentration. In addition to temporal changes in concentration, results also characterized differences for overall plasma metabolite concentrations; for example, methionine had the lowest (38 µM) while glutamine had the highest concentration (239 µM) amongst plasma AA. This is the first report describing how the plasma metabolome changes during 24-h period in young calves fed an elevated plane of milk replacer twice daily. CONCLUSIONS: Data from this pilot study will help to establish reference standards for future metabolic diagnostics in dairy calves. In addition, this pilot study illustrated that feeding milk replacer may influence plasma metabolite concentrations. With the rapid implementation of blood metabolomics in monitoring animal health, it is then important to consider the time of feeding during the day when interpreting metabolomics analysis results.

Immunosuppressive Treatment Alters Secretion of Ileal Antimicrobial Peptides and Gut Microbiota, and Favors Subsequent Colonization by Uropathogenic Escherichia coli.

BACKGROUND: Transplant recipients are treated with immunosuppressive (IS) therapies, which impact host-microbial interactions. We examined the impact of IS drugs on gut microbiota and on the expression of ileal antimicrobial peptides. METHODS: Mice were treated for 14 days with prednisolone, mycophenolate mofetil, tacrolimus, a combination of these 3 drugs, everolimus, or water. Feces were collected before and after treatment initiation. Ileal samples were collected after sacrifice. Fecal and ileal microbiota were analyzed by pyrosequencing of 16S rRNA genes and enumeration of selected bacteria by culture, and C-type lectins were assessed in ileal tissues by reverse transcriptase-quantitative polymerase chain reaction. RESULTS: Prednisolone disrupted fecal microbiota community structure, decreased Bacteroidetes, and increased Firmicutes in the feces. Prednisolone, tacrolimus, and mycophenolate mofetil modified fecal microbiota at the family level in each experimental replicate, but changes were not consistent between the replicates. In ileal samples, the genus Clostridium sensu stricto was dramatically reduced in the prednisolone and combined IS drug groups. These modifications corresponded to an altered ileal expression of C-type lectins Reg3γ and Reg3ß, and of interleukin 22. Interestingly, the combined IS treatment enabled a commensal Escherichia coli to flourish, and dramatically increased colonization by uropathogenic E. coli strain 536. CONCLUSIONS: IS treatment alters innate antimicrobial defenses and disrupts the gut microbiota, which leads to overgrowth of indigenous E. coli and facilitates colonization by opportunistic pathogens.

Lipid Emulsion Formulation of Parenteral Nutrition Affects Intestinal Microbiota and Host Responses in Neonatal Piglets.

BACKGROUND: Total parenteral nutrition (TPN) is a cause of intestinal microbial dysbiosis and impaired gut barrier function. This may contribute to life-threatening parenteral nutrition-associated liver disease and sepsis in infants. We compared the effects of a lipid emulsion containing long-chain ω-3 polyunsaturated fatty acids (PUFAs; SMOFlipid) and a predominantly ω-6 PUFA emulsion (Intralipid) on microbial composition and host response at the mucosal surface. MATERIALS AND METHODS: Neonatal piglets were provided isocaloric, isonitrogenous TPN for 14 days versus sow-fed (SF) controls. Equivalent lipid doses (10 g/kg/d) were given of either SMOFlipid (ML; n = 10) or Intralipid (SO; n = 9). Ileal segments and mucosal scrapings were used to characterize microbial composition by 16S rRNA gene sequencing and quantitative gene expression of tight junction proteins, mucins, antimicrobial peptides, and inflammatory cytokines. RESULTS: The microbial composition of TPN piglets differed from SF, while ML and SO differed from each other (analysis of molecular variance; P < .05); ML piglets were more similar to SF, as indicated by UniFrac distance ( P < .05). SO piglets showed a specific and dramatic increase in Parabacteroides ( P < .05), while ML showed an increase in Enterobacteriaceae ( P < .05). Gene expression of mucin, claudin 1, ß-defensin 2, and interleukin 8 were higher in TPN; overall increases were significantly less in ML versus SO ( P < .05). CONCLUSION: The formulation of parenteral lipid is associated with differences in the gut microbiota and host response of TPN-fed neonatal piglets. Inclusion of ω-3 long-chain PUFAs appears to improve host-microbial interactions at the mucosal surface, although mechanisms are yet to be defined.

A Mechanistic Model of Intermittent Gastric Emptying and Glucose-Insulin Dynamics following a Meal Containing Milk Components.

To support decision-making around diet selection choices to manage glycemia following a meal, a novel mechanistic model of intermittent gastric emptying and plasma glucose-insulin dynamics was developed. Model development was guided by postprandial timecourses of plasma glucose, insulin and the gastric emptying marker acetaminophen in infant calves fed meals of 2 or 4 L milk replacer. Assigning a fast, slow or zero first-order gastric emptying rate to each interval between plasma samples fit acetaminophen curves with prediction errors equal to 9% of the mean observed acetaminophen concentration. Those gastric emptying parameters were applied to glucose appearance in conjunction with minimal models of glucose disposal and insulin dynamics to describe postprandial glycemia and insulinemia. The final model contains 20 parameters, 8 of which can be obtained by direct measurement and 12 by fitting to observations. The minimal model of intestinal glucose delivery contains 2 gastric emptying parameters and a third parameter describing the time lag between emptying and appearance of glucose in plasma. Sensitivity analysis of the aggregate model revealed that gastric emptying rate influences area under the plasma insulin curve but has little effect on area under the plasma glucose curve. This result indicates that pancreatic responsiveness is influenced by gastric emptying rate as a consequence of the quasi-exponential relationship between plasma glucose concentration and pancreatic insulin release. The fitted aggregate model was able to reproduce the multiple postprandial rises and falls in plasma glucose concentration observed in calves consuming a normal-sized meal containing milk components.