Betaine and Soluble Fiber Improve Body Composition and Plasma Metabolites in Cats with Chronic Kidney Disease.

BACKGROUND: Chronic kidney disease (CKD) is a common condition in cats and cachexia (loss of lean body mass) is a concern. A nutrition-based intervention was investigated in cats with CKD for its effects on body composition, the plasma metabolome, and possible implications on health. METHODS: After a 4-week prefeed period with the control food, cats with CKD (N = 24) were randomized to one of six groups to consume a control food; a food supplemented with 0.5% betaine, 0.39% oat beta-glucan, and 0.27% short-chain fructooligosaccharides (scFOS, test food 1); and a food supplemented with 0.5% betaine, 0.59% oat beta-glucan, and 0.41% scFOS (test food 2) in a William's Latin Square design, each for 10 weeks. Body composition was assessed via dual-energy X-ray absorptiometry measurements, and the plasma metabolome was characterized. RESULTS: Despite no significant differences in daily intake among the three foods, significant increases in total body mass, lean body mass, and lean plus bone mineral composition were observed when cats with CKD consumed test food 1 compared with the control food; numerical increases were seen with test food 2 versus the control food. Plasma metabolomics indicated increased one-carbon metabolism following consumption of test food 1 and/or 2, with significant increases in sarcosine and numerical increases in methionine. Lower levels of plasma trans-4-hydroxyproline and N-methylproline following consumption of test foods 1 and 2 indicates reduced collagen breakdown and perhaps reduced fibrosis. Several acylcarnitines and branched-chain fatty acids associated with CKD were also reduced when cats ate test food 1 or 2 versus the control food. Higher plasma levels of sphingomyelins with consumption of test food 1 or 2 may reflect less severe CKD. CONCLUSIONS: Consumption of foods with supplemental betaine and fibers by cats with CKD led to improvements in body composition and changes in the plasma metabolome that correspond to better kidney health.

A Diet Supplemented with Polyphenols, Prebiotics and Omega-3 Fatty Acids Modulates the Intestinal Microbiota and Improves the Profile of Metabolites Linked with Anxiety in Dogs.

A nutrition-based approach was utilized to examine the effects of fish oil and a polyphenol blend (with or without tomato pomace) on the fecal microbiota and plasma/fecal metabolomes. Forty dogs, aged 5-14 years, were fed a washout food, then randomized to consume a control (fish oil and polyphenol blend without tomato pomace) or test (fish oil and polyphenol blend with tomato pomace) food, then the washout food, and crossed over to consume the test or control food; each for 30 days. Several metabolites differed when comparing consumption of the washout with either the control or test foods, but few changed significantly between the test and control foods. Plasma levels of 4-ethylphenyl sulfate (4-EPS), a metabolite associated with anxiety disorders, demonstrated the largest decrease between the washout food and the control/test foods. Plasma 4-EPS levels were also significantly lower after dogs ate the test food compared with the control food. Other plasma metabolites linked with anxiety disorders were decreased following consumption of the control/test foods. Significant increases in Blautia, Parabacteroides, and Odoribacter in the fecal microbiota correlated with decreases in 4-EPS when dogs ate the control/test foods. These data indicate that foods supplemented with polyphenols and omega-3 fatty acids can modulate the gut microbiota to improve the profile of anxiety-linked metabolites.

Feeding cats with chronic kidney disease food supplemented with betaine and prebiotics increases total body mass and reduces uremic toxins.

Cats with chronic kidney disease (CKD) have a decreased ability to maintain body weight. As CKD advances, loss of body weight contributes to morbidity and mortality. The goal of this study was to evaluate the combined effects of feeding betaine and prebiotics on body weight of both CKD and healthy cats. The pre-trial food (control food) was a complete and balanced dry food designed to aid in the management of CKD. Test food was the control food supplemented with betaine (0.500%) and prebiotics: long-chain oat beta-glucan (0.586%) and 0.407% short chain fructooligosaccharides (scFOS). The CKD cats (n = 7) were fed pre-trial food for 28 days and then randomly assigned to control food or test food. Each food was fed for 8 weeks in a cross-over study design. In a second study, healthy cats received control food or test food for 8 weeks (n = 8 each group). Blood, urine, and fecal samples were collected to evaluate concentrations of relevant kidney function biomarkers and metabolites at the end of each feeding period for CKD cats, and blood samples were collected monthly to evaluate concentrations of plasma metabolites for healthy cats. Body weight and composition were measured using dual-energy X-ray absorptiometry (DEXA) scan at baseline and after each feeding period. Total body mass was significantly higher in CKD cats after consuming test food compared with control food (P = 0.004), with no significant difference in food intake while consuming test or control food (P = 0.34). Test food did not affect total body mass or composition of healthy cats. Indole compounds produced by bacterial metabolism were decreased in urine and increased in feces of CKD cats fed test food, and plasma concentrations were negatively correlated with the level of kidney function, indicating a potential benefit of consuming test food. In healthy cats, consuming test food resulted in significantly decreased concentrations of plasma P-cresol sulfate (P = 0.004) and increased concentrations of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA; both P < 0.05), despite the fact that both control and test foods had similar concentrations of these long-chain fatty acids, 0.03% and 0.02%, respectively. These results suggest that the addition of betaine and prebiotics to the control food formula may have increased total body mass in CKD cats by enhancing one-carbon metabolism and by modulating the gut microbiome.

Effect of Nutrition on Age-Related Metabolic Markers and the Gut Microbiota in Cats.

Age-related changes in the gut microbiota and metabolites are associated with the increased risk of detrimental conditions also seen with age. This study evaluated whether a test food with potential anti-aging benefits results in favorable changes in plasma and fecal metabolites and the fecal microbiota in senior cats. Forty healthy domestic cats aged 8.3-13.5 years were fed a washout food for 30 days, then control or test food for 30 days. After another 30-day washout, cats were switched to the other study food for 30 days. Assessment of plasma and fecal metabolites showed lower levels of metabolites associated with detrimental processes (e.g., uremic toxins) and higher levels of metabolites associated with beneficial processes (e.g., tocopherols) after cats consumed the test food compared with the control food. A shift toward proteolysis with the control food is supported by higher levels of amino acid metabolites and lower levels of carbohydrate metabolites. Operational taxonomic units of greater abundance with the test food positively correlated with carbohydrate and nicotinic acid metabolites, and negatively correlated with uremic toxins, amino acid metabolism, secondary bile salts, and branched-chain fatty acids. Taken together, the test food appears to result in greater levels of metabolites and microbiota associated with a healthier state.

Effect of Added Dietary Betaine and Soluble Fiber on Metabolites and Fecal Microbiome in Dogs with Early Renal Disease.

Renal diets are recommended for dogs with chronic kidney disease (CKD). This study examined the effects of foods with added betaine and fiber on the plasma and fecal metabolome and fecal microbiome in dogs with early stage CKD. At baseline, several metabolites differed between healthy dogs and those with CKD. Dogs with CKD (n = 28) received a control food, low soluble fiber plus betaine food (0.5% betaine, 0.39% oat beta-glucan, and 0.27% short-chain fructooligosaccharides (scFOS)), or high soluble fiber plus betaine food (0.5% betaine, 0.59% oat beta-glucan, and 0.41% scFOS) each for 10 weeks in different sequences. Consumption of test foods led to several favorable, significant changes in the plasma metabolome, including decreases of several uremic toxins and other deleterious metabolites, and increases in favorable metabolites compared with the control food. Only 7 fecal metabolites significantly changed with consumption of the test foods compared with the control food, largely increases in polyphenols and lignans. Few changes were seen in the fecal microbiome, though some taxa that significantly changed in response to the test foods have beneficial effects on health, with some negatively correlating with uremic toxins. Overall, foods with added betaine and soluble fiber showed positive effects on the plasma and fecal metabolomes.

Varying Protein Levels Influence Metabolomics and the Gut Microbiome in Healthy Adult Dogs.

The optimal ranges of protein for healthy adult dogs are not known. This study evaluated the impact of long-term consumption of foods containing low, medium, and high levels of protein on serum, urine, and fecal metabolites, and gut microbiome in beagles. Following maintenance on a prefeed food for 14 days, dogs (15 neutered males, 15 spayed females, aged 2-9 years, mean initial weight 11.3 kg) consumed the low (18.99%, dry matter basis), medium (25.34%), or high (45.77%) protein foods, each for 90 days, in a William's Latin Square Design sequence. In serum and/or urine, metabolites associated with inflammation (9,10-dihydroxyoctadecanoic acid (DiHOME)), 12,13-DiHOME) and kidney dysfunction (urea, 5-hydroxyindole sulfate, 7-hydroxyindole sulfate, p-cresol sulfate) increased with higher protein levels in food, while one-carbon pathway metabolites (betaine, dimethylglycine, sarcosine) decreased. Fecal pH increased with protein consumed, and levels of beneficial indoles and short-chain fatty acids decreased while branched-chain fatty acids increased. Beta diversity of the fecal microbiome was significantly different, with increased abundances of proteolytic bacteria with higher protein food. Feeding dogs a high amount of protein leads to a shift to proteolytic gut bacteria, higher fecal pH, and is associated with increased levels of metabolites linked with inflammation and kidney dysfunction.

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.

Chronic kidney disease in cats alters response of the plasma metabolome and fecal microbiome to dietary fiber.

METHODS: A cross-over study within a split-plot design was performed using healthy (n = 10) and CKD cats [IRIS Stage 1 and 2; n = 10]. Cats were fed dry Prescription Diet® k/d® Feline with chicken, during a pre-trial period and then randomly assigned to two fiber treatments for 4 weeks each. Treatment foods were formulated similar to pre-trial food, with the exception that they contained 0.500% betaine, 0.586% oat beta glucan, and either 0.407% short chain fructooligosaccharides (scFOS) fiber or 3.44% apple pomace. Both foods had similar crude fiber percent (2.0 and 2.1% for scFOS and apple pomace, respectively) whereas soluble fiber was 0.8 and 1.6%, respectively. RESULTS: Plasma metabolites separated cats based on health status. At baseline, cats with CKD had significantly higher circulating concentrations of creatinine, urea, and some microbial and host tryptophan metabolites including several indole sulfates and kynurenate. Healthy cats had higher concentrations of the antioxidant α-tocopherol after consuming apple pomace; alternatively, they had higher concentrations of inflammatory sphingolipid metabolites after consuming scFOS, but not after consuming apple pomace. The CKD cats had higher concentrations of the more oxidized glutathione metabolites after consuming apple pomace compared with scFOS, as well as higher concentrations of inflammatory sphingolipid metabolites after consuming apple pomace, but not scFOS. After consuming scFOS, CKD cats had lower concentrations of the phenolic uremic toxins guaiacol sulfate and 4-vinylphenol sulfate compared with after consuming apple pomace. At baseline, there were five significant microbiota OTU differences in CKD cats compared with healthy cats. Overall, the OTUs in CKD cats were more resistant to change after feeding either fiber source. Counts of an unclassified genus in the family S24-7 in the order Bacteroidales (OTU 100296), were lower in CKD cats compared with healthy cats at baseline (P = 0.001), but increased after consumption of food containing scFOS (P = 0.006). Linear regression analysis showed that this genus had significant negative correlations with several microbial uremic toxins. None of the baseline differences in OTUs between healthy and CKD cats changed after CKD cats consumed food containing apple pomace. CONCLUSIONS: Health status impacts the influence of dietary fermentable fibers on the feline plasma metabolome and fecal microbiome. A more readily fermented fiber such as scFOS is preferable to apple pomace as a fiber source for cats with CKD.

Changes in the Fecal Metabolome Are Associated with Feeding Fiber Not Health Status in Cats with Chronic Kidney Disease.

The objective was to determine the effects of feeding different fiber sources to cats with chronic kidney disease (CKD) compared with healthy cats (both n = 10) on fecal metabolites. A cross-over within split-plot study design was performed using healthy and CKD cats (IRIS stage 1, 2, and 3). After cats were fed a complete and balanced dry food designed to aid in the management of renal disease for 14 days during a pre-trial period, they were randomly assigned to two fiber treatments for 4 weeks each. The treatment foods were formulated similar to pre-trial food and contained 0.500% betaine, 0.586% oat beta glucan, and either 0.407% short chain fructooligosaccharides (scFOS) fiber or 3.44% apple pomace. Both treatment foods had similar crude fiber (2.0 and 2.1% for scFOS and apple pomace, respectively) whereas soluble fiber was 0.8 and 1.6%, respectively. At baseline, CKD had very little impact on the fecal metabolome. After feeding both fiber sources, some fecal metabolite concentrations were significantly different compared with baseline. Many fecal uremic toxins decreased, although in healthy cats some increased; and some more so when feeding apple pomace compared with scFOS, e.g., hippurate, 4-hydroxyhippurate, and 4-methylcatechol sulfate; the latter was also increased in CKD cats. Changes in secondary bile acid concentrations were more numerous in healthy compared with CKD cats, and cats in both groups had greater increases in some secondary bile acids after consuming apple pomace compared with scFOS, e.g., tauroursodeoxycholate and hyocholate. Although changes associated with feeding fiber were more significant than changes associated with disease status, differential modulation of the gut-kidney axis using dietary fiber may benefit cats.

Antiviral activity of zinc salts against transmissible gastroenteritis virus in vitro.

Zinc has been shown to mediate antiviral effects against certain viruses. However, the underlying mechanisms are still largely unknown. We investigated the effects of the two zinc salts, zinc chloride (ZnCl(2)) and zinc sulfate (ZnSO(4)), on infection of swine testicle (ST) cells with transmissible gastroenteritis virus (TGEV) and compared it to the effects of a control salt, magnesium sulfate (MgSO(4)). Virus yield reduction experiments showed that ZnCl(2) and ZnSO(4) did not exhibit direct virucidal effects and did not affect adsorption of TGEV to ST cells. However, ZnCl(2) and ZnSO(4) markedly reduced viral titers as well as TGEV RNA and viral protein synthesis when applied during virus penetration and at different time points after viral cell entry. The results of the study suggest that zinc salts do not interfere with TGEV-cell binding but that they mediate antiviral effects through inhibition of viral penetration or egress or the intracellular phase of the viral life-cycle.

Febrile illnesses of different etiology among outpatients in four health centers in Northwestern Ethiopia.

Fever of different etiology is common in tropical and subtropical countries of the world. Etiological agents of febrile illnesses were assessed in 653 acute febrile patients aged 3 to 17 years who attended the outpatient departments of Dembecha Health Center, Jiga Health Center, Quarit Health Center, and Finoteselam Hospital in western Gojjam zone, northwestern Ethiopia. Malaria was the most prevalent illness, infecting 62% of all cases. Its prevalence varied significantly from 52% (Dembecha) to 72.7% (Quarit) (chi(2)=15.02, P=0.000). Plasmodium falciparum was the first cause of malaria (47.3%) followed by P. vivax (23%). Mixed infection of both P. falciparum and P. vivax was found in 7.2% of the cases. The other febrile infections were pneumonia (7%), typhoid (5.8%), typhus (5.1%), and brucellosis (2.6%). The availability of diagnostic facilities and the awareness of the community regarding the prevalence of non-malaria febrile illnesses are very low, and these illnesses are diagnosed clinically. As these illnesses are nonspecific, especially during the early stages of onset, misdiagnosis and mistreatment can occur. Therefore, it is recommended that the necessary diagnostic materials and awareness should be in place for prompt treatment of febrile cases in these districts.