Loss of MYO5B expression deregulates late endosome size which hinders mitotic spindle orientation.

Recycling endosomes regulate plasma membrane recycling. Recently, recycling endosome-associated proteins have been implicated in the positioning and orientation of the mitotic spindle and cytokinesis. Loss of MYO5B, encoding the recycling endosome-associated myosin Vb, is associated with tumor development and tissue architecture defects in the gastrointestinal tract. Whether loss of MYO5B expression affects mitosis is not known. Here, we demonstrate that loss of MYO5B expression delayed cytokinesis, perturbed mitotic spindle orientation, led to the misorientation of the plane of cell division during the course of mitosis, and resulted in the delamination of epithelial cells. Remarkably, the effects on spindle orientation, but not cytokinesis, were a direct consequence of physical hindrance by giant late endosomes, which were formed in a chloride channel-sensitive manner concomitant with a redistribution of chloride channels from the cell periphery to late endosomes upon loss of MYO5B. Rab7 availability was identified as a limiting factor for the development of giant late endosomes. In accordance, increasing rab7 availability corrected mitotic spindle misorientation and cell delamination in cells lacking MYO5B expression. In conclusion, we identified a novel role for MYO5B in the regulation of late endosome size control and identify the inability to control late endosome size as an unexpected novel mechanism underlying defects in cell division orientation and epithelial architecture.

Evaluation of gallnut tannin and Lactobacillus plantarum as natural modifiers for alfalfa silage: Ensiling characteristics, in vitro ruminal methane production, fermentation profile and microbiota.

AIMS: The potential of gallnut tannin (GT) and Lactobacillus plantarum (LP) on fermentation characteristics, in vitro ruminal methane (CH4 ) production and microbiota of alfalfa silage was investigated. METHODS AND RESULTS: Alfalfa was ensiled with GT (20 and 50 g kg-1 dry matter [DM]) and LP (3 × 108  CFU per gram fresh matter) alone or in combination for 60 days. The GT and LP alone or in combination decreased DM losses, pH and non-protein nitrogen contents of alfalfa silage. All additive treatments decreased ruminal CH4 production, and increased propionic acid molar proportions and Fibrobacter succinogenes numbers. The LP treatment increased nutrient degradation, cellobiase, pectinase and protease activities, and Prevotella ruminicola abundance, whereas high-dose GT treatment inhibited these variables. Importantly, LP together with GT alleviated the adverse effects of high-dose GT supply alone by enhancing pectinase and protease activities as well as Rumincoccus flavefaciens and P. ruminicola growth. CONCLUSIONS: Combination of GT and LP can be used as an efficient additive to improve silage quality and utilization by ruminants. SIGNIFICANCE AND IMPACT OF THE STUDY: Using GT-LP combination has practical implications, particularly concerning effects of tannins on ruminal CH4 mitigation, which may alleviate inhibitory effects of tannins on feed digestion through modulating ruminal microbiota.

A Molecular Mechanism Underlying Genotype-Specific Intrahepatic Cholestasis Resulting From MYO5B Mutations.

BACKGROUND AND AIMS: Progressive familial intrahepatic cholestasis (PFIC) 6 has been associated with missense but not biallelic nonsense or frameshift mutations in MYO5B, encoding the motor protein myosin Vb (myoVb). This genotype-phenotype correlation and the mechanism through which MYO5B mutations give rise to PFIC are not understood. The aim of this study was to determine whether the loss of myoVb or expression of patient-specific myoVb mutants can be causally related to defects in canalicular protein localization and, if so, through which mechanism. APPROACH AND RESULTS: We demonstrate that the cholestasis-associated substitution of the proline at amino acid position 600 in the myoVb protein to a leucine (P660L) caused the intracellular accumulation of bile canalicular proteins in vesicular compartments. Remarkably, the knockout of MYO5B in vitro and in vivo produced no canalicular localization defects. In contrast, the expression of myoVb mutants consisting of only the tail domain phenocopied the effects of the Myo5b-P660L mutation. Using additional myoVb and rab11a mutants, we demonstrate that motor domain-deficient myoVb inhibited the formation of specialized apical recycling endosomes and that its disrupting effect on the localization of canalicular proteins was dependent on its interaction with active rab11a and occurred at the trans-Golgi Network/recycling endosome interface. CONCLUSIONS: Our results reveal a mechanism through which MYO5B motor domain mutations can cause the mislocalization of canalicular proteins in hepatocytes which, unexpectedly, does not involve myoVb loss-of-function but, as we propose, a rab11a-mediated gain-of-toxic function. The results explain why biallelic MYO5B mutations that affect the motor domain but not those that eliminate myoVb expression are associated with PFIC6.

Combined analysis of microbial community and microbial metabolites based on untargeted metabolomics during pig manure composting.

Compost has been widely used in agriculture in recent years, but the nutrients it provides are far from enough for plant growth. Therefore, it is necessary to systematically explore the fermentation process of composting. In this study, the succession of microbial community and metabolite characteristics in compost were analyzed by using microbial sequencing and metabolomics techniques. The results showed that compared with mesophilic phase and cooling phase, the richness and diversity of bacterial community decreased in thermophilic phase. At the genus level, Pseudomonas (8.90%), Lactobacillus (3.99%), Bacteroidetes (3.39%), Flavobacterium (3.25%) and Prevotella (Prevotella_9, 2.33%, Prevotellaceae_NK3B31_group, 2.44%) were the dominant genera in the pig manure composting. The abundance of Pseudomonas and Flavobacterium increased significantly while Lactobacillus and Prevotella were significantly decreased after composting, and the abundance of Bacteroidetes increased first and then decreased. Fatty acyls, sterol lipids, glycerophospholipids, polyketides and prenol lipids were common microbial metabolites in compost. Moreover, the linoleic acid metabolic pathway was significantly enriched in the three stages of composting, and linoleic acid metabolism might be the primary function of the microbial community in composting. The network analysis showed that between the microbial communities or between the microbial community and metabolites were closely related to each other.

Dietary intervention reduces left atrial enlargement in dogs with early preclinical myxomatous mitral valve disease: a blinded randomized controlled study in 36 dogs.

BACKGROUND: Myxomatous mitral valve disease (MMVD), the most common naturally-occurring heart disease in dogs, is associated with alterations in energy metabolism, oxidative stress and inflammation. Energy deprivation plays a causal role in the development of heart failure. This study was designed to determine if a cardiac protection blend (CPB) of nutrients containing medium-chain triglycerides as an alternative energy source, fish oil to reduce inflammation, antioxidants, and other key nutrients important to cardiac health and function could slow or prevent MMVD progression. Nineteen dogs with early stage MMVD and 17 breed-, age-, and sex-matched healthy dogs were enrolled for a 6-month blinded, placebo-controlled study. Dogs in each cardiac health group were randomly assigned to either control diet (CON) or CPB-supplemented diet. Echocardiography was performed at baseline, 3 months and 6 months. RESULTS: No changes were found in healthy dogs. While MMVD-CON dogs had an average 10% increase over baseline in left atrial diameter (LAD) and left atrial to aortic root ratio (LA/Ao) at 6 months, MMVD-CPB dogs showed 3% decreases, resulting significant diet by time interactions (P = 0.037, P = 0.005, respectively). More MMVD-CON dogs progressed from stage B1 to B2 during the study. A positive correlation was found between 6-month changes in LAD and blood pressures in MMVD-CPB dogs (systolic: P = 0.050, diastolic: P = 0.035) but not MMVD-CON dogs. CONCLUSIONS: Our results demonstrated efficacy of CPB-based dietary intervention in reducing LA size and mitral regurgitation, and in slowing or preventing the progression of early MMVD in dogs.

Alterations of Group I mGluRs and BDNF Associated with Behavioral Abnormity in Prenatally Stressed Offspring Rats.

Substantial evidence reveals that prenatal stress is closely linked with abnormal behavior in offspring, but the mechanism remains unclear. In this study, our aim was to observe the alterations of behaviors, metabotropic glutamate receptor-1/5 (mGluR1/5) and brain-derived neurotrophic factor (BDNF) in various brain regions of prenatally stressed offspring rats. The forced swimming test (FST) and the open field test (OFT) were carried on 1-month-old offspring rats. The expression levels of mGluR1, mGluR5, and BDNF mRNA were measured in various brain regions of the offspring rats. Our results showed that the immobile time in the FST was significantly increased in the late prenatal stress (LPS) group compared with that in the control group, especially in the female rats. Similarly, in the OFT, the rats in both the mid prenatal stress (MPS) and LPS groups demonstrated anxiety-like behavior, especially the male rats in the LPS group. The expression of mGluR1 protein was increased in the hippocampus and prefrontal cortex of rats from the LPS group, as well as in the prefrontal cortex of rats from the MPS group. Meanwhile, the expression of mGluR5 protein was facilitated in the hippocampus and prefrontal cortex of rats in the LPS group. The expression of mGluR5 protein was increased in the striatum of the female rats in both MPS and LPS groups, and only in the male rats from the LPS group. In addition, the reduced BDNF mRNA level was detected in the hippocampus and prefrontal cortex in the LPS rats, and in the striatum of the female rats in LPS group. These results indicate that alterations of the mGluR1, mGluR5 and BDNF mRNA may contribute to the depression-like and anxiety-like behaviors of prenatally stressed offspring rats.

Expression Profiling of Circulating MicroRNAs in Canine Myxomatous Mitral Valve Disease.

MicroRNAs (miRNAs) are small non-coding RNAs that have shown promise as noninvasive biomarkers in cardiac disease. This study was undertaken to investigate the miRNA expression profile in dogs with myxomatous mitral valve disease (MMVD). 277 miRNAs were quantified using RT-qPCR from six normal dogs (American College of Veterinary Internal Medicine Stage A), six dogs with MMVD mild to moderate cardiac enlargement (ACVIM Stage B1/B2) and six dogs with MMVD and congestive heart failure (ACVIM Stage C/D). Eleven miRNAs were differentially expressed (False Discovery Rate < 0.05). Dogs in Stage B1/B2 or C/D had four upregulated miRNAs, including three cfa-let-7/cfa-miR-98 family members, while seven others were downregulated, compared to Stage A. Expression of six of the 11 miRNAs also were significantly different between dogs in Stage C/D and those in Stage B1/B2. The expression changes were greater as disease severity increased. These miRNAs may be candidates for novel biomarkers and may provide insights into genetic regulatory pathways in canine MMVD.

Effects of grape seed procyanidins on the lipid metabolism of growing-finishing pigs based on transcriptomics and metabolomics analyses.

This study investigated how lipid metabolism in the longissimus thoracis is influenced by the diet supplemented with grape seed procyanidins (GSPs) in growing-finishing pigs. Forty-eight crossbred pigs were randomly assigned to four groups, each receiving a basal diet, or basal diet added with 150, 200, and 250 mg/kg GSPs. Transcriptomics and metabolomics were employed to explore differential gene and metabolite regulation. The expression of key lipid metabolism-related genes was tested via qRT-PCR, and the lipid and fatty acid composition of the longissimus thoracis were determined. Dietary GSPs at different concentrations upregulated lipoprotein lipase (LPL), which is involved in lipolysis, and significantly increased the mRNA expression levels of carnitine palmitoyltransferase-1B (CPT1B) and cluster of differentiation 36 (CD36), implicated in transmembrane transport of fatty acids. Dietary supplementation of GSPs at 200 or 250 mg/kg markedly reduced total cholesterol and triglyceride content in longissimus thoracis. Dietary GSPs significantly decreased the contents of low-density lipoprotein cholesterol and saturated fatty acids, while increasing unsaturated fatty acids. In conclusion, GSPs may regulate lipid metabolism, reducing cholesterol level, and improving fatty acid composition in the longissimus thoracis of growing-finishing pigs. Our findings provide evidence for the beneficial effects of GSPs as pig feed additives for improving lipid composition.

Uncovering the Relationship Between Genes and Phenotypes Beyond the Gut in Microvillus Inclusion Disease.

Microvillus inclusion disease (MVID) is a rare condition that is present from birth and affects the digestive system. People with MVID experience severe diarrhea that is difficult to control, cannot absorb dietary nutrients, and struggle to grow and thrive. In addition, diverse clinical manifestations, some of which are life-threatening, have been reported in cases of MVID. MVID can be caused by variants in the MYO5B, STX3, STXBP2, or UNC45A gene. These genes produce proteins that have been functionally linked to each other in intestinal epithelial cells. MVID associated with STXBP2 variants presents in a subset of patients diagnosed with familial hemophagocytic lymphohistiocytosis type 5. MVID associated with UNC45A variants presents in most patients diagnosed with osteo-oto-hepato-enteric syndrome. Furthermore, variants in MYO5B or STX3 can also cause other diseases that are characterized by phenotypes that can co-occur in subsets of patients diagnosed with MVID. Recent studies involving clinical data and experiments with cells and animals revealed connections between specific phenotypes occurring outside of the digestive system and the type of gene variants that cause MVID. Here, we have reviewed these patterns and correlations, which are expected to be valuable for healthcare professionals in managing the disease and providing personalized care for patients and their families.

Ensiling pretreatment fortified with laccase and microbial inoculants enhances biomass preservation and bioethanol production of alfalfa stems.

This study investigated the potential of ensiling pretreatment fortified with laccase and a lactic acid bacteria (LAB) inoculant on improving the utilization of alfalfa stems for bioethanol production. The alfalfa stems were ensiled with no additives (Con), 0.04 % laccase (LA), a LAB inoculant containing Pediococcus pentosaceus at 1 × 106 fresh weight (FW) and Pediococcus acidilactici at 3 × 105 cfu/g FW (PP), and a combination of LA and PP (LAP) for 120 days. By reshaping the bacterial community structure of alfalfa stem silages toward a higher abundance of Lactobacillus, the addition of laccase and LAB inoculant either alone or in combination facilitated lactic acid fermentation to reduce fermentation losses, as evidenced by low concentrations of ammonia nitrogen (53.7 to 68.9 g/kg total nitrogen) and ethanol (2.63 to 3.55 g/kg dry matter). All additive treatments increased lignocellulose degradation and soluble sugars concentrations of alfalfa stem silages. Due to delignification and polyphenol removal, glucan and xylan conversion (70.3 % vs. 35.7 % and 51.6 % vs. 27.9 %, respectively) and ethanol conversion efficiency (53.9 % vs. 26.4 %) of alfalfa stems were greatly increased by ensiling fortified with LA versus Con, and these variables (79.8 % for glucan, 58.7 % for xylan, and 60.1 % for ethanol conversion efficiency) were further enhanced with a synergistic effect of LA and PP fortification. The spearman correlation analysis revealed that bioethanol fermentation of silage biomass was closely related to ensiling parameters and total phenols. In conclusion, ensiling pretreatment with LA and PP combination offered a feasible way to efficient utilization of alfalfa stems for bioethanol production.

Effects of grape seed procyanidins on antioxidant function, barrier function, microbial community, and metabolites of cecum in geese.

The gut is the first line of defense for body health and is essential to the overall health of geese. Grape seed procyanidins (GSPs) are proverbial for their antioxidant, anti-inflammatory, and microflora-regulating capabilities. This study aimed to inquire into the influences of dietary GSPs on the intestinal antioxidant function, barrier function, microflora, and metabolites of geese based on 16S rRNA sequencing and metabolomics. In total, 240 twenty-one-day-old Sichuan white geese were randomly divided into 4 groups, each of which was supplied with 1 of 4 diets: basal diet or a basal diet supplemented with 50, 100, or 150 mg/kg GSPs. Diets supplemented with GSPs at different concentrations significantly increased the total antioxidant capacity and superoxide dismutase activity in cecal mucosa (P < 0.001). Dietary supplementation with 50 or 100 mg/kg GSPs significantly increased catalase activity (P < 0.001). The serum diamine oxidase, D-lactic acid, and endotoxin concentrations were decreased by GSP supplementation in the goose diet. Dietary GSP supplementation increased microbial richness and diversity, enhanced the relative abundance of Firmicutes, and decreased that of Bacteroidetes in the cecum. Diets supplemented with 50 or 100 mg/kg GSPs enriched Eubacterium coprostanoligenes and Faecalibacterium. Dietary GSPs substantially raised the acetic and propionic acid concentrations in the cecum. The butyric acid concentration increased when the GSP dosage was 50 or 100 mg/kg. Additionally, dietary GSPs increased the levels of metabolites that belong to lipids and lipid-like molecules or organic acids and derivatives. Dietary GSP supplementation at 100 or 150 mg/kg reduced the levels of spermine (a source of cytotoxic metabolites) and N-acetylputrescine, which promotes in-vivo inflammation. In conclusion, dietary supplementation with GSPs was beneficial to gut health in geese. Dietary GSPs improved antioxidant activity; protected intestinal barrier integrity; increased the abundance and diversity of cecal microflora; promoted the proliferation of some beneficial bacteria; increased the production of acetic, propionic, and butyric acids in the cecum; and downregulated metabolites associated with cytotoxicity and inflammation. These results offer a strategy for promoting intestinal health in farmed geese.

Investigation of Catalytic Co-Pyrolysis Characteristics and Synergistic Effect of Oily Sludge and Walnut Shell.

The co-pyrolysis of oily sludge and walnut shell is a reliable method for solid waste treatment and waste recycling. In this paper, a thermogravimetric analysis was used to study the thermodynamics and synergy effect of oily sludge (OS) and walnut shell (WS) at four heating rates (10, 20, 30, and 40 °C/min) in the temperature range from 50-850 °C. Two model-free methods (FWO and KAS) were used to calculate the activation energy. The results showed that the heating rate had no significant effect on the pyrolysis process. The addition of walnut shell improved the pyrolysis process of the samples. Mixture 1OS3WS had a synergy effect, while other blends showed an inhibitory effect. The synergy effect of co-pyrolysis was strongest when the mass ratio of oily sludge was 25%. The activation energy of the Zn-ZSM-5/25 catalyst was the lowest, and the residual substances were the least, indicating that the Zn-ZSM-5/25 was beneficial to the co-pyrolysis of oily sludge and walnut shell. The analysis of catalytic pyrolysis products by Py-GC/MS found that co-pyrolysis was beneficial to the generation of aromatic hydrocarbons. This study provided a method for the resource utilization of hazardous waste and biomass waste, which was conducive to the production of aromatic chemicals with added value while reducing environmental pollution.

The effect of prenatal stress on offspring depression susceptibility in relation to the gut microbiome and metabolome.

Prenatal stress (PS) increases offspring susceptibility to depression, but the underlying mechanism remains unclear. Our previous results showed that PS can affect depression-like behavior in offspring through neurotransmitters and neuroinflammatory substances in the hippocampus and frontal cortex. In recent years there has been increasing evidence for a role of the gut microbiome in depression. The brain-gut axis theory suggests there is a need to further explore the mechanism involving the gut microbiome in the susceptibility of offspring to depression caused by PS. In the present study we used a stress model relevant to depression in which pregnant female rats undergo prenatal restraint stress and the offspring show susceptibility to depression. High-resolution gene sequencing for 16S ribosomal RNA markers and non-targeted metabolomic analysis were used to evaluate the fecal microbiome and the availability of metabolites, respectively. PS was found to induce depressive-like behavior in susceptible offspring (PS-S), as detected by the sucrose preference and forced swimming tests, as well as altering Alpha and Beta diversity. The different microbiota between the PS-S and control groups were mainly involved in membrane transport, carbohydrate metabolism, amino acid metabolism, and replication and repair pathways. In total, 237 and 136 important differential metabolites with significant influence on modeling analysis were obtained under positive and negative modes, respectively. The main canonical pathways found to be altered were glycerophospholipid metabolism and glycerolipid metabolism. These results suggest that gut microbiota might contribute to the onset of PS-induced depression-like behavior by affecting the glycerophospholipid and glycerolipid metabolic pathways.

The effectiveness of combination therapy with interferon and nucleoside analogs in pediatric patients with chronic hepatitis B: a systematic review and meta-analysis.

BACKGROUND: It is a challenging issue regarding the optimal antiviral treatment of children with chronic hepatitis B (CHB). The efficacy comparison of interferon (IFN) or nucleos(t)ide analogs (NAs) monotherapy with their combination could better understand this issue. METHODS: PubMed, EMBASE, Cochrane Library, Wanfang, CNKI, and abstracts of major international hepatology meetings were searched from inception to Feb 8, 2022. Randomized control trials and observational studies reporting the efficacy of combination therapy with IFN and NAs in children with CHB were eligible. RESULTS: A total of 17 studies were included. Compared with IFN monotherapy, combination therapy with IFN and NAs was significantly associated with increased rates of HBV DNA undetectable, HBeAg clearance, HBeAg seroconversion, alanine transaminase (ALT) normalization as well as the composite treatment response both at the end of treatment and during the follow-up period (RRs ranged from 1.23 to 1.75). A favorable trend for HBsAg seroconversion was found in IFN plus NAs-treated children, but not for the HBsAg clearance at the end of treatment. Although a similar trend towards the superiority of the combination therapy versus NAs monotherapy was observed (RRs ranged from 1.24 to 2.33) except for the HBV DNA undetectable rate at the end of treatment, the number of reported studies was limited. CONCLUSIONS: Combination therapy with IFN and NAs is more effective than IFN monotherapy in viral suppression and serological response for children with CHB. More studies were still needed to reveal the efficacy of this combination therapy compared with NAs monotherapy.

Tomato LysM receptor kinase 4 mediates chitin-elicited fungal resistance in both leaves and fruit.

Fungal infection is a major cause of crop and fruit losses. Recognition of chitin, a component of fungal cell walls, endows plants with enhanced fungal resistance. Here, we found that mutation of tomato LysM receptor kinase 4 (SlLYK4) and chitin elicitor receptor kinase 1 (SlCERK1) impaired chitin-induced immune responses in tomato leaves. Compared with the wild type, sllyk4 and slcerk1 mutant leaves were more susceptible to Botrytis cinerea (gray mold). SlLYK4 extracellular domain showed strong binding affinity to chitin, and the binding of SlLYK4 induced SlLYK4-SlCERK1 association. Remarkably, qRT-PCR analysis indicated that SlLYK4 was highly expressed in tomato fruit, and ß-GLUCURONIDASE (GUS) expression driven by the SlLYK4 promoter was observed in tomato fruit. Furthermore, SlLYK4 overexpression enhanced disease resistance not only in leaves but also in fruit. Our study suggests that chitin-mediated immunity plays a role in fruit, providing a possible way to reduce fungal infection-related fruit losses by enhancing the chitin-induced immune responses.

Reversible phosphorylation of a lectin-receptor-like kinase controls xylem immunity.

Pattern-recognition receptors (PRRs) mediate basal resistance to most phytopathogens. However, plant responses can be cell type specific, and the mechanisms governing xylem immunity remain largely unknown. We show that the lectin-receptor-like kinase LORE contributes to xylem basal resistance in Arabidopsis upon infection with Ralstonia solanacearum, a destructive plant pathogen that colonizes the xylem to cause bacterial wilt. Following R. solanacearum infection, LORE is activated by phosphorylation at residue S761, initiating a phosphorelay that activates reactive oxygen species production and cell wall lignification. To prevent prolonged activation of immune signaling, LORE recruits and phosphorylates type 2C protein phosphatase LOPP, which dephosphorylates LORE and attenuates LORE-mediated xylem immunity to maintain immune homeostasis. A LOPP knockout confers resistance against bacterial wilt disease in Arabidopsis and tomatoes without impacting plant growth. Thus, our study reveals a regulatory mechanism in xylem immunity involving the reversible phosphorylation of receptor-like kinases.

Effect of a specially formulated diet on progression of heart enlargement in dogs with subclinical degenerative mitral valve disease.

BACKGROUND: Previous studies in dogs with degenerative mitral valve disease (DMVD) have identified altered myocardial energy metabolism and oxidation, which might contribute to cardiac hypertrophy. Diets rich in medium chain fatty acids and antioxidants are a potential means of treatment. A previous clinical study found significantly smaller left atrial diameter (LAD) and left atrium-to-aorta diameter ratio (LA : Ao) in dogs with subclinical DMVD fed a specially formulated diet vs control diet for 6 months. HYPOTHESIS/OBJECTIVES: A specially formulated diet will slow or arrest left heart enlargement in dogs with subclinical DMVD over 365 days. ANIMALS: One hundred twenty-seven dogs with unmedicated subclinical DMVD; 101 dogs in the per protocol cohort. METHODS: Randomized double-blinded controlled multicenter clinical trial. RESULTS: The study's primary composite outcome measure was the sum of percentage change in LAD and left ventricular internal dimension at end-diastole (LVIDd) at day 365. In the per protocol cohort, the outcome measure increased by 8.0% (95% confidence interval [CI], 2.9%-13.1%) in dogs receiving the test diet vs 8.8% (95% CI, 5.1%-12.5%) in dogs receiving control diet (P = .79). Neither component of the primary outcome measure was significantly different between groups (LAD, P = .65; LVIDd, P = .92). No difference was found in mitral valve E wave velocity (P = .36) or the proportion of dogs withdrawn from the study because of worsening DMVD and heart enlargement (P = .41). CONCLUSIONS AND CLINICAL IMPORTANCE: Feeding a specially formulated diet for 365 days was not associated with a significantly different rate of change of left heart size in dogs with subclinical DMVD as compared to control.

Metabolic Reprogramming, Gut Dysbiosis, and Nutrition Intervention in Canine Heart Disease.

This review provides a state-of-the-art overview on recent advances in systems biology in canine cardiac disease, with a focus on our current understanding of bioenergetics and amino acid metabolism in myxomatous mitral valve disease (MMVD). Cross-species comparison is drawn to highlight the similarities between human and canine heart diseases. The adult mammalian heart exhibits a remarkable metabolic flexibility and shifts its energy substrate preference according to different physiological and pathological conditions. The failing heart suffers up to 40% ATP deficit and is compared to an engine running out of fuel. Bioenergetics and metabolic readaptations are among the major research topics in cardiac research today. Myocardial energy metabolism consists of three interconnected components: substrate utilization, oxidative phosphorylation, and ATP transport and utilization. Any disruption or uncoupling of these processes can result in deranged energy metabolism leading to heart failure (HF). The review describes the changes occurring in each of the three components of energy metabolism in MMVD and HF. It also provides an overview on the changes in circulating and myocardial glutathione, taurine, carnitines, branched-chain amino acid catabolism and tryptophan metabolic pathways. In addition, the review summarizes the potential role of the gut microbiome in MMVD and HF. As our knowledge and understanding in these molecular and metabolic processes increase, it becomes possible to use nutrition to address these changes and to slow the progression of the common heart diseases in dogs.