A prospective multicenter study of the efficacy of a fiber-supplemented dietary intervention in dogs with chronic large bowel diarrhea.

BACKGROUND: Chronic large bowel diarrhea is common in dogs and can have a significant impact on their overall health and well being. We evaluated the safety and efficacy of a therapeutic food with select dietary plant fibers known to contain antioxidant and polyphenol compounds on clinical signs in dogs with chronic diarrhea. METHODS: A prospective clinical study was conducted in 31 adult dogs currently experiencing chronic diarrhea from private veterinary practices in the United States. Enrolled dogs were switched to a complete and balanced dry therapeutic food containing whole grains and polyphenol-containing fiber sources for 56 days. Veterinarians evaluated changes from baseline in overall clinical signs, recurrence of clinical signs, and stool parameters at Days 2, 3, 4, 28, and 56. Dog owners evaluated stool consistency daily and nausea/vomiting, quality of life (QoL), and stooling behaviors at Days 1, 14, 28, and 56. Statistical analysis was performed using a mixed-effects model with Day as a fixed-effect. RESULTS: Assessments of overall clinical response and stool parameters indicated that diarrhea improved significantly within 1 day of initiating the therapeutic food. Veterinarians reported that 68% of dogs had complete resolution of their clinical signs by Day 56 and the remaining 32% experienced improvement (P < 0.05), with no cases of recurrence. Veterinarians also reported improvement in stool consistency (P < 0.001) and reductions of blood and mucus in stool (P < 0.001). Significant improvements in nausea/vomiting, stooling behaviors, and quality of life (QoL) were reported by dog owners after 28 days and were sustained through day 56 (P < 0.05). The therapeutic food was safe and well tolerated. CONCLUSIONS: In dogs with chronic large bowel diarrhea, the therapeutic food rapidly improved stool consistency, resolved clinical signs, and improved stooling behaviors and QoL. Therapeutic foods supplemented with fiber sources rich in antioxidant and anti-inflammatory compounds contribute to rapid resolution of chronic diarrhea without recurrence and may contribute to long term health.

Microbiome function underpins the efficacy of a fiber-supplemented dietary intervention in dogs with chronic large bowel diarrhea.

BACKGROUND: Chronic large bowel diarrhea is a common occurrence in pet dogs. While nutritional intervention is considered the primary therapy, the metabolic and gut microfloral effects of fiber and polyphenol-enriched therapeutic foods are poorly understood. METHODS: This prospective clinical study enrolled 31 adult dogs from private veterinary practices with chronic, active large bowel diarrhea. Enrolled dogs received a complete and balanced dry therapeutic food containing a proprietary fiber bundle for 56 days. Metagenomic and metabolomic profiling were performed on fecal samples at Days 1, 2, 3, 14, 28, and 56; metabolomic analysis was conducted on serum samples taken at Days 1, 2, 3, 28, and 56. RESULTS: The dietary intervention improved clinical signs and had a clear effect on the gut microfloral metabolic output of canines with chronic diarrhea, shifting gut metabolism from a predominantly proteolytic to saccharolytic fermentative state. Microbial metabolism of tryptophan to beneficial indole postbiotics and the conversion of plant-derived phenolics into bioavailable postbiotics were observed. The intervention altered the endocannabinoid, polyunsaturated fatty acid, and sphingolipid profiles, suggesting a modulation in gastrointestinal inflammation. Changes in membrane phospholipid and collagen signatures were indicative of improved gut function and possible alleviation of the pathophysiology related to chronic diarrhea. CONCLUSIONS: In dogs with chronic diarrhea, feeding specific dietary fibers increased gut saccharolysis and bioavailable phenolic and indole-related compounds, while suppressing putrefaction. These changes were associated with improved markers of gut inflammation and stool quality.

Adding a polyphenol-rich fiber bundle to food impacts the gastrointestinal microbiome and metabolome in dogs.

Introduction: Pet foods fortified with fermentable fibers are often indicated for dogs with gastrointestinal conditions to improve gut health through the production of beneficial post-biotics by the pet's microbiome. Methods: To evaluate the therapeutic underpinnings of pre-biotic fiber enrichment, we compared the fecal microbiome, the fecal metabolome, and the serum metabolome of 39 adult dogs with well-managed chronic gastroenteritis/enteritis (CGE) and healthy matched controls. The foods tested included a test food (TF1) containing a novel pre-biotic fiber bundle, a control food (CF) lacking the fiber bundle, and a commercially available therapeutic food (TF2) indicated for managing fiber-responsive conditions. In this crossover study, all dogs consumed CF for a 4-week wash-in period, were randomized to either TF1 or TF2 and fed for 4 weeks, were fed CF for a 4-week washout period, and then received the other test food for 4 weeks. Results: Meaningful differences were not observed between the healthy and CGE dogs in response to the pre-biotic fiber bundle relative to CF. Both TF1 and TF2 improved stool scores compared to CF. TF1-fed dogs showed reduced body weight and fecal ash content compared to either CF or TF2, while stools of TF2-fed dogs showed higher pH and lower moisture content vs. TF1. TF1 consumption also resulted in unique fecal and systemic metabolic signatures compared to CF and TF2. TF1-fed dogs showed suppressed signals of fecal bacterial putrefactive metabolism compared to either CF or TF2 and increased saccharolytic signatures compared to TF2. A functional analysis of fecal tryptophan metabolism indicated reductions in fecal kynurenine and indole pathway metabolites with TF1. Among the three foods, TF1 uniquely increased fecal polyphenols and the resulting post-biotics. Compared to CF, consumption of TF1 largely reduced fecal levels of endocannabinoid-like metabolites and sphingolipids while increasing both fecal and circulating polyunsaturated fatty acid profiles, suggesting that TF1 may have modulated gastrointestinal inflammation and motility. Stools of TF1-fed dogs showed reductions in phospholipid profiles, suggesting fiber-dependent changes to colonic mucosal structure. Discussion: These findings indicate that the use of a specific pre-biotic fiber bundle may be beneficial in healthy dogs and in dogs with CGE.

Successful nutritional control of scratching and clinical signs associated with adverse food reaction: A randomized controlled COSCAD'18 adherent clinical trial in dogs in the United States.

BACKGROUND: Adverse reactions to food are a common dermatological condition in dogs, requiring nutritional intervention using a novel or hydrolysate protein-based food. OBJECTIVE: To evaluate a therapeutic food containing egg and phytonutrients in dogs with food allergies using an activity monitor and core outcome set for canine atopic dermatitis (COSCAD'18) guidelines and in a controlled double-masked, multicenter, prospective clinical trial. ANIMALS: Adult dogs with a history of adverse food reaction as diagnosed by a food elimination trial were recruited from general practices. METHODS: After a 21-day baseline period, dogs were randomized to test or positive control (hydrolyzed protein) food for 21 days. Owner (pruritus visual analog score [PVAS], coat quality, food acceptance, and satisfaction) and veterinarian (canine atopic dermatitis lesion index [CADLI], physical examination) assessments were completed on days 0, 21, and 42. Dogs wore a collar-mounted activity monitor to record scratching and shaking behavior throughout the study. Statistical analysis included within-group comparison to baseline and between-group comparison at study end using a significance threshold of alpha = 0.05. RESULTS: At the end of the treatment period, all results were similar between groups for CADLI, PVAS, owner satisfaction, activity, and questionnaire data. Scores for hair dullness, brittleness, amount of dandruff, feces quality, and food acceptance were positive and not statistically different between groups. CONCLUSIONS AND CLINICAL IMPORTANCE: The therapeutic test food was well-accepted and efficacious in managing signs of adverse reactions to food compared to baseline as well as compared to the positive control food.

Successful nutritional control of scratching and clinical signs associated with adverse food reaction: A randomized controlled COSCAD'18 adherent clinical trial in dogs in the United Kingdom.

BACKGROUND: Adverse reactions to food are a common dermatological condition in dogs, requiring nutritional intervention using novel or hydrolysate protein-based foods. OBJECTIVE: To evaluate a therapeutic food containing egg and phytonutrients in dogs with food allergies using an activity monitor and core outcome set for canine atopic dermatitis (COSCAD'18) in a controlled double-masked, multicenter, prospective clinical trial. ANIMALS: Adult dogs with a history of adverse food reaction as diagnosed by a food elimination trial were recruited from general practices. METHODS: After a 21-day baseline period, dogs were randomized to test or positive control (hydrolyzed protein) food for 21 days. Owner (pruritus visual analog score [PVAS], coat quality, food acceptance, and satisfaction) and veterinarian (canine atopic dermatitis lesion index [CADLI], physical examination) assessments were completed on days 0, 21, and 42. Dogs wore a collar-mounted activity monitor to record sleep, scratching, and shaking behavior throughout the study. Statistical analysis included within-group comparison to baseline and between-group comparison at study end using a significance threshold of alpha = 0.05. RESULTS: At the end of the treatment period, all results were similar between groups for CADLI, PVAS, owner satisfaction, activity, and questionnaire data. Scores for hair dullness, brittleness, amount of dandruff, feces quality, and food acceptance were positive and were not statistically different between groups. CONCLUSIONS AND CLINICAL IMPORTANCE: The therapeutic test food was well-accepted and efficacious in managing signs of adverse reactions to food compared to baseline as well as compared to the positive control food.

The Effects of Nutrition on the Gastrointestinal Microbiome of Cats and Dogs: Impact on Health and Disease.

The gastrointestinal (GI) microbiome of cats and dogs is increasingly recognized as a metabolically active organ inextricably linked to pet health. Food serves as a substrate for the GI microbiome of cats and dogs and plays a significant role in defining the composition and metabolism of the GI microbiome. The microbiome, in turn, facilitates the host's nutrient digestion and the production of postbiotics, which are bacterially derived compounds that can influence pet health. Consequently, pet owners have a role in shaping the microbiome of cats and dogs through the food they choose to provide. Yet, a clear understanding of the impact these food choices have on the microbiome, and thus on the overall health of the pet, is lacking. Pet foods are formulated to contain the typical nutritional building blocks of carbohydrates, proteins, and fats, but increasingly include microbiome-targeted ingredients, such as prebiotics and probiotics. Each of these categories, as well as their relative proportions in food, can affect the composition and/or function of the microbiome. Accumulating evidence suggests that dietary components may impact not only GI disease, but also allergies, oral health, weight management, diabetes, and kidney disease through changes in the GI microbiome. Until recently, the focus of microbiome research was to characterize alterations in microbiome composition in disease states, while less research effort has been devoted to understanding how changes in nutrition can influence pet health by modifying the microbiome function. This review summarizes the impact of pet food nutritional components on the composition and function of the microbiome and examines evidence for the role of nutrition in impacting host health through the microbiome in a variety of disease states. Understanding how nutrition can modulate GI microbiome composition and function may reveal new avenues for enhancing the health and resilience of cats and dogs.

Use of Accelerometer Activity Monitors to Detect Changes in Pruritic Behaviors: Interim Clinical Data on 6 Dogs.

Veterinarians and pet owners have limited ability to assess pruritic behaviors in dogs. This pilot study assessed the capacity of the Vetrax® triaxial accelerometer to measure these behaviors in six dogs with pruritus likely due to environmental allergens. Dogs wore the activity monitor for two weeks while consuming their usual pet food (baseline), then for eight weeks while consuming a veterinary-exclusive pet food for dogs with suspected non-food-related skin conditions (Hill's Prescription Diet® Derm DefenseTM Canine dry food). Veterinarians and owners completed questionnaires during baseline, phase 1 (days 1-28) and phase 2 (days 29-56) without knowledge of the activity data. Continuous 3-axis accelerometer data was processed using proprietary behavior recognition algorithms and analyzed using general linear mixed models with false discovery rate-adjusted p values. Veterinarian-assessed overall clinical signs of pruritus were significantly predicted by scratching (ß 0.176, p = 0.008), head shaking (ß 0.197, p < 0.001) and sleep quality (ß -0.154, p < 0.001), while owner-assessed quality of life was significantly predicted by scratching (ß -0.103, p = 0.013) and head shaking (ß -0.146, p < 0.001). Among dogs exhibiting pruritus signs eating the veterinary-exclusive food, the Vetrax® sensor provided an objective assessment of clinically relevant pruritic behaviors that agreed with owner and veterinarian reports.

Effects of Infant Formula With Human Milk Oligosaccharides on Growth and Morbidity: A Randomized Multicenter Trial.

OBJECTIVES: The aim of the study was to evaluate the effects of infant formula supplemented with 2 human milk oligosaccharides (HMOs) on infant growth, tolerance, and morbidity. METHODS: Healthy infants, 0 to 14 days old, were randomized to an intact-protein, cow's milk-based infant formula (control, n = 87) or the same formula with 1.0 g/L 2'fucosyllactose (2'FL) and 0.5 g/L lacto-N-neotetraose (LNnT) (test, n = 88) from enrollment to 6 months; all infants received standard follow-up formula without HMOs from 6 to 12 months. Primary endpoint was weight gain through 4 months. Secondary endpoints included additional anthropometric measures, gastrointestinal tolerance, behavioral patterns, and morbidity through age 12 months. RESULTS: Weight gain was similar in both groups (mean difference [95% confidence interval] test vs control: -0.30 [-1.94, 1.34] g/day; lower bound of 95% confidence interval was above noninferiority margin [-3 g/day]). Digestive symptoms and behavioral patterns were similar between groups; exceptions included softer stool (P = 0.021) and fewer nighttime wake-ups (P = 0.036) in the test group at 2 months. Infants receiving test (vs control) had significantly fewer parental reports (P = 0.004-0.047) of bronchitis through 4 (2.3% vs 12.6%), 6 (6.8% vs 21.8%), and 12 months (10.2% vs 27.6%); lower respiratory tract infection (adverse event cluster) through 12 months (19.3% vs 34.5%); antipyretics use through 4 months (15.9% vs 29.9%); and antibiotics use through 6 (34.1% vs 49.4%) and 12 months (42.0% vs 60.9%). CONCLUSIONS: Infant formula with 2'FL and LNnT is safe, well-tolerated, and supports age-appropriate growth. Secondary outcome findings showing associations between consuming HMO-supplemented formula and lower parent-reported morbidity (particularly bronchitis) and medication use (antipyretics and antibiotics) warrant confirmation in future studies.

Macro- and micronutrient intakes in picky eaters: a cause for concern?

BACKGROUND: Picky eating (PE) is characterized by an unwillingness to eat certain foods and by strong food preferences. PE may result in lower intakes of energy and nutrients, which may compromise health. OBJECTIVES: We quantified nutrient and food group intakes in children identified as picky eaters or nonpicky eaters and compared intakes between groups and with United Kingdom reference nutrient intakes. DESIGN: PE was identified in an observational cohort (Avon Longitudinal Study of Parents and Children) from questionnaires administered when children were aged 2, 3, 4.5, and 5.5 y. Dietary intake was assessed at 3.5 and 7.5 y with a 3-d food record. The dietary assessment at 3.5 y compared picky eaters with nonpicky eaters identified at age 3 y, and the assessment at 7.5 y compared longitudinally defined PE groups. RESULTS: Picky eaters aged 3 y had lower mean carotene, iron, and zinc intakes than nonpicky eaters. There were similar differences between the longitudinally defined PE groups. Iron and zinc intakes were most likely to be below recommended amounts, with free sugar intake much higher than recommended. There were no significant differences in energy intakes between the groups, and intakes were adequate relative to estimated average requirements. Nutrient differences were explained by lower intakes of meat, fish, vegetables, and fruits in picky eaters than in nonpicky eaters. There were higher intakes of sugary foods and drinks in older picky eaters. CONCLUSIONS: PE did not result in compromised macronutrient intakes, although intakes of zinc and iron were more likely to be below recommendations for picky eaters than for nonpicky eaters. Emphasis should be placed on allaying parental concerns about picky eaters being prone to inadequate nutrient intakes and on encouraging all parents to extend their child's diet to include more nutrient-rich items, especially fruits and vegetables, and less nutrient-poor sugary foods.

Picky eating in preschool children: Associations with dietary fibre intakes and stool hardness.

It has been suggested that constipation may be associated with picky eating. Constipation is a common condition in childhood and a low intake of dietary fibre may be a risk factor. Differences in fibre intake between picky and non-picky children and its relation to stool consistency is currently not well-understood. Children enrolled in the Avon Longitudinal Study of Parents and Children identified as picky eaters (PE) were compared with non-picky eaters (NPE): (1) to determine dietary fibre intake at 38 months; (2) to investigate whether any difference in dietary fibre intake was predictive of usual stool hardness at 42 months. PE was identified from questionnaires at 24 and 38 months. Usual stool hardness was identified from a questionnaire at 42 months. Dietary intake was assessed at 38 months with a food frequency questionnaire. Dietary fibre intake was lower in PE than NPE (mean difference -1.4 (95% CI -1.6, -1.2) g/day, p < 0.001). PE was strongly associated with dietary fibre intake (adjusted regression model; unstandardised B -1.44 (95% CI -1.62, -1.24) g/day, p < 0.001). PE had a lower percentage of fibre from vegetables compared with NPE (8.9% vs 15.7%, respectively, p < 0.001). There was an association between PE and usually having hard stools (adjusted multinomial model; OR 1.31, 95% CI 1.07, 1.61; p = 0.010). This was attenuated when dietary fibre was included in the model, suggesting that fibre intake mediated the association (OR 1.16, 95% CI 0.94, 1.43, p = 0.180). Picky eating in 3-year-old children was associated with an increased prevalence of usually having hard stools. This association was mediated by low dietary fibre intake, particularly from vegetables, in PE. For children with PE, dietary advice aimed at increasing fibre intake may help avoid hard stools.

Picky/fussy eating in children: Review of definitions, assessment, prevalence and dietary intakes.

Picky eating (also known as fussy, faddy or choosy eating) is usually classified as part of a spectrum of feeding difficulties. It is characterised by an unwillingness to eat familiar foods or to try new foods, as well as strong food preferences. The consequences may include poor dietary variety during early childhood. This, in turn, can lead to concern about the nutrient composition of the diet and thus possible adverse health-related outcomes. There is no single widely accepted definition of picky eating, and therefore there is little consensus on an appropriate assessment measure and a wide range of estimates of prevalence. In this review we first examine common definitions of picky eating used in research studies, and identify the methods that have been used to assess picky eating. These methods include the use of subscales in validated questionnaires, such as the Children's Eating Behaviour Questionnaire and the Child Feeding Questionnaire as well as study-specific question(s). Second, we review data on the prevalence of picky eating in published studies. For comparison we present prevalence data from the UK Avon Longitudinal Study of Parents and Children (ALSPAC) in children at four time points (24, 38, 54 and 65 months of age) using a study-specific question. Finally, published data on the effects of picky eating on dietary intakes (both variety and nutrient composition) are reviewed, and the need for more health-related data and longitudinal data is discussed.

Effect of an α-lactalbumin-enriched infant formula supplemented with oligofructose on fecal microbiota, stool characteristics, and hydration status: a randomized, double-blind, controlled trial.

AIMS: To evaluate the impact of oligofructose (OF)-supplemented infant formula on fecal microbiota, stool characteristics, and hydration. METHODS: Ninety-five formula-fed infants were randomized to α-lactalbumin-enriched control formula (CF) or identical formula with 3.0 g/L OF (EF) for 8 weeks; 50 infants fed human milk (HM) were included. RESULTS: Eighty-four infants completed the study, 70 met per-protocol criteria. Over 8 weeks, bifidobacteria increased more in EF than CF group (0.70 vs. 0.16 log10 bacterial counts/g dry feces, P = .008); EF was not significantly different from HM group (P = .32). EF group stool consistency was intermediate between CF and HM groups; at week 8, EF group had softer stools than CF (5-point scale: 1 = hard, 5 = watery; consistency score 3.46 vs. 2.82, P = .015) without significant differences in stool frequency. Physician-assessed hydration status was normal for all infants. CONCLUSIONS: Infant formula with 3.0 g/L OF promoted bifidobacteria growth and softer stools without adversely affecting stool frequency or hydration.

Folate network genetic variation predicts cardiovascular disease risk in non-Hispanic white males.

Genes functioning in folate-mediated 1-carbon metabolism are hypothesized to play a role in cardiovascular disease (CVD) risk beyond the current narrow focus on the MTHFR 677 C→T (rs1801133) polymorphism. Using a cohort study design, we investigated whether sequence variants in the network of folate-related genes, particularly in genes encoding proteins related to SHMT1, predict CVD risk in 1131 men from the Normative Aging Study. A total of 330 single nucleotide polymorphisms (SNPs) in 52 genes, selected for function and gene coverage, were assayed on the Illumina GoldenGate platform. Age- and smoking-adjusted genotype-phenotype associations were estimated in regression models. Using a nominal P ≤ 5.00 × 10(-3) significance threshold, 8 SNPs were associated with CVD risk in single locus analyses. Using a false discovery rate (FDR) threshold (P-adjusted ≤1.00 × 10(-1)), a SNP in the GGH gene remained associated with reduced CVD risk, with a stronger association in early onset CVD cases (<55 y). A gene × folate interaction (MAT2B) and 2 gene × vitamin B-12 interactions (BHMT, SLC25A32) reached the FDR P-adjusted ≤2.00 × 10(-1) threshold. Three biological hypotheses related to SHMT1 were explored and significant gene × gene interactions were identified for TYMS by UBE2N, FTH1 by CELF1, and TYMS by MTHFR. Variations in genes other than MTHFR and those directly involved in homocysteine metabolism are associated with CVD risk in non-Hispanic white males. This work supports a role for SHMT1-related genes and nuclear folate metabolism, including the thymidylate biosynthesis pathway, in mediating CVD risk.

Folate network genetic variation, plasma homocysteine, and global genomic methylation content: a genetic association study.

BACKGROUND: Sequence variants in genes functioning in folate-mediated one-carbon metabolism are hypothesized to lead to changes in levels of homocysteine and DNA methylation, which, in turn, are associated with risk of cardiovascular disease. METHODS: 330 SNPs in 52 genes were studied in relation to plasma homocysteine and global genomic DNA methylation. SNPs were selected based on functional effects and gene coverage, and assays were completed on the Illumina Goldengate platform. Age-, smoking-, and nutrient-adjusted genotype--phenotype associations were estimated in regression models. RESULTS: Using a nominal P ≤ 0.005 threshold for statistical significance, 20 SNPs were associated with plasma homocysteine, 8 with Alu methylation, and 1 with LINE-1 methylation. Using a more stringent false discovery rate threshold, SNPs in FTCD, SLC19A1, and SLC19A3 genes remained associated with plasma homocysteine. Gene by vitamin B-6 interactions were identified for both Alu and LINE-1 methylation, and epistatic interactions with the MTHFR rs1801133 SNP were identified for the plasma homocysteine phenotype. Pleiotropy involving the MTHFD1L and SARDH genes for both plasma homocysteine and Alu methylation phenotypes was identified. CONCLUSIONS: No single gene was associated with all three phenotypes, and the set of the most statistically significant SNPs predictive of homocysteine or Alu or LINE-1 methylation was unique to each phenotype. Genetic variation in folate-mediated one-carbon metabolism, other than the well-known effects of the MTHFR c.665C>T (known as c.677 C>T, rs1801133, p.Ala222Val), is predictive of cardiovascular disease biomarkers.

Polymorphisms in serine hydroxymethyltransferase 1 and methylenetetrahydrofolate reductase interact to increase cardiovascular disease risk in humans.

The enzymes serine hydroxymethyltransferase 1 (gene name SHMT1) and methylenetetrahydrofolate reductase (gene name MTHFR) regulate key reactions in folate-mediated one-carbon metabolism. Common genetic variants with the potential to influence disease risk exist in both genes. A prior report from the Normative Aging Study indicated no association of the SHMT1 rs1979277 SNP with cardiovascular disease (CVD), but a strong gene-gene interaction was detected with MTHFR rs1801133. We investigated the effect of the SHMT1 rs1979277 SNP and the SHMT1 rs1979277-MTHFR rs1801133 interaction in 2 epidemiologic cohort studies. In the Nurses' Health Study (NHS), the MTHFR rs1801133 variant genotypes were associated with an increased CVD risk and there was an interaction between SHMT1 and MTHFR such that the association of the MTHFR rs1801133 CT genotype (vs. CC; the TT genotype could not be evaluated) was stronger in the presence of the SHMT1 rs1979277 TT genotype (OR = 4.34, 95% CI = 1.2, 16.2; P = 0.049). In the Health Professionals Follow-Up Study, the MTHFR rs1801133 genotype was not associated with CVD risk, nor was there an interaction with SHMT1 rs1979277. The association of genetic variation in the SHMT1 gene, alone and in interaction with MTHFR, in relation to CVD risk is relatively understudied at the population level and results in the NHS confirmed a past report of gene-gene interaction, which is consistent with mechanisms suggested by basic science studies.