Blood Metabolite Profiles Research Articles

Cord blood metabolite profiles and childhood cardio-metabolic outcomes in a population-based cohort.

Adverse exposures in utero might cause adaptations of cardiovascular and metabolic organ development, predisposing individuals to an adverse cardio-metabolic risk profile from childhood onwards. We hypothesized that adaptations in metabolic pathways underlie these associations and examined associations of metabolite profiles at birth with childhood cardio-metabolic risk factors. The study included 763 mother-child pairs participating in an ongoing population-based prospective cohort study with an overall low disease risk. Cord blood serum concentrations of amino acids (AA), non-esterified fatty acids (NEFA), phospholipids (PL) and carnitines (Carn) were obtained using a liquid chromatography coupled with tandem mass-spectrometry. We measured android/gynoid fat mass ratio, blood pressure, insulin, and lipid concentrations at the children's age of 5.9 (0.3) and 9.8 (0.9) years. We did not observe associations of cord blood metabolites with systolic or diastolic blood pressure, insulin, triglycerides and android/gynoid fat mass ratio at both ages and cardio-metabolic risk clustering at age 10 years. Five short- and medium-chain Carn.a metabolites were positively associated with cardio-metabolic risk clustering at age 6 but did not survive more stringent confounder adjustment. No consistent associations between cord blood metabolites and cardiovascular risk factors at school age were observed.

Effects of Lactiplantibacillus plantarum CBT LP3 and Bifidobacterium breve CBT BR3 supplementation on weight loss and gut microbiota of overweight dogs

The prevalence of obesity in dogs is increasing worldwide. This study evaluated the effects of a mixed probiotic formula on the weight, body condition score (BCS), blood metabolite profiles, and gut microbiota of overweight and obese dogs over a 12-week supplementation period to determine the anti-obesity effects of Lactiplantibacillus plantarum CBT LP3 and Bifidobacterium breve CBT BR3. This was a community-based, randomized study that sampled 41 overweight and obese dogs with a veterinarian-determined BCS of 6 or more. The physical activity of all the subjects was measured using a pedometer designed exclusively for dogs. The food intake was measured using the developed application. Only the treatment group received the mixed probiotic formula twice daily (3 g per dose). A significant decrease in body weight (p < 0.0001), BCS (p < 0.0001), serum TG (p < 0.0001), serum TC (p = 0.0400), and serum leptin (p = 0.0252), and a significantly increased serum adiponectin levels (p = 0.0007) were observed in the treatment group compared with the values in the control group. Microbiota analysis showed that Lactiplantibacillus increased and Erysipelatoclostridium, Staphylococcus, and Gemella decreased more significantly in the treatment group than in the control group. These results suggested that Lactiplantibacillus plantarum CBT LP3 and Bifidobacterium breve CBT BR3 may be effective in alleviating obesity in dogs.

Effects of pre- and postpartum dietary fat sources (soybean oil versus linseed oil) on lactation performance and blood metabolites in transition dairy cows

This study investigated the effects of supplementation with two calcium salt fatty acid sources (soybean oil (CaSO) and linseed oil (CaLN)) before and after parturition on lactation performance and blood metabolite profiles in dairy cows. A study was conducted with twenty-four multiparous Holstein cows (parity = 3.12 ± 0.9 and Backfat thickness = 21.77 ± 1.98) that were divided into a 2 × 2 factorial design 21 days before expected calving. The aim was to investigate the interplay between prepartum (CaSO or CaLN, at 2 % of dry matter) and postpartum (at 1.4 % of dry matter) fat supplementation on lactation performance and blood metabolite profiles. Initially, cows were grouped according to the source of prepartum fat (either CaSO or CaLN, with 12 cows in each group). Postpartum, these groups were further subdivided according to whether the fat source was administered continuously (LN-LN, SO-SO) or alternately (LN-SO, SO-LN) over a 28-day period. This resulted in four different treatment groups, each with six cows. The fat supplements contained 84 % fat and 9 % Ca. No statistically significant differences were found in dry matter intake (DMI), colostrum yield or most concentrations of blood metabolites (insulin, cholesterol, glucose, triglycerides, total protein, albumin, β-hydroxybutyric acid (BHB), non-esterified fatty acids (NEFA), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and urea-N). However, cows fed CaSO prepartum had a significantly higher plasma concentration of insulin-like growth factor-1 (IGF-1) than cows fed CaLN. Cows fed CaSO had higher backfat thickness (BFT) from day −21–0 than those fed CaLN (P = 0.05). Notably, cows in the SO-SO group lost the most weight, while cows in the SO-LN group lost the least, especially on days 21 and 28 postpartum (P = 0.05). Switching from soybean oil prepartum to linseed oil postpartum (SO-LN) significantly increased milk production in the first 28 days of lactation compared to other diets. In addition, the fat content in milk was influenced by the type of fat supplementation prepartum, with cows receiving CaSO having a lower milk fat percentage than those receiving CaLN (P < 0.05). The results on blood parameters suggest potential benefits of the SO-LN diet for postpartum cows, as emphasized by stable BHB concentrations and the highest IGF-1 concentrations, especially without the elevated BHB concentrations typically associated with the SO-SO diet. The blood concentrations of total protein, urea-N, triglycerides and NEFA were not affected by the treatments. Also, the dietary change did not adversely affect liver function, as shown by unchanged AST and ALT concentrations. Therefore, the results suggest that a dietary intervention involving the administration of soybean oil prepartum and switching to linseed oil postpartum (SO-LN strategy) has the potential to improve milk yield during the early lactation period.

Wheat Peptides as Catalysts for Athletic Performance Improvement in Cross-Country Skiers: A Randomized Controlled Trial.

This study investigated the efficacy of wheat peptide supplementation compared to regular proteins in elite cross-country skiers, providing insights into the metabolic and performance effects of these supplements in order to guide athletes in selecting optimal energy sources for training and competition. Nineteen healthy male cross-country skiers were enrolled and assigned to either the peptide group (PEP, n = 9) or the protein group (PRO, n = 10). A four-week intervention study involving supplementation with wheat peptides/regular proteins was conducted, and pre- and post-intervention assessments were performed to evaluate exercise capacity and metabolic profiles. The study found that the PEP group and the PRO group showed distinct within-group effects on exercise performance. The PEP group demonstrated improved aerobic capacity, including better performance in 10 km roller skating, an increased lactate threshold, and reduced resting blood lactate levels. The PRO group enhanced anaerobic capacity, such as improved sprint time, hexagon test performance, and lactate clearance. Metabolomic analysis revealed specific metabolic pathways affected in each group, with the PEP group showing impacts on the α-linolenic acid pathway and the PRO group on ketone body synthesis and degradation as well as vitamin B6 metabolism. Our findings indicate that wheat oligopeptides and regular proteins have comparable effects on exercise performance. However, the wheat peptides may offer greater advantages in enhancing aerobic capacity. No significant variations were observed in blood metabolite profiles between the two groups, but distinct metabolic pathways exhibited different responses.

Different Flushing Frequency on Blood Metabolites Profile of Ewes and Their Lambs at Pre-Weaning Period

Different Flushing Frequency on Blood Metabolites Profile of Ewes and Their Lambs at Pre-Weaning Period

Metabolomics and amino acid profiling of plasma reveals the metabolite profiles associated with nitrogen utilisation efficiency in primiparous dairy cows

Nitrogen (N) utilisation efficiency (NUE, milk N yield [g/d]/N intake [g/d]) is an important performance indicator in dairy farming. Determining the NUE-associated blood metabolite profile will contribute to the optimisation of nutritional strategies to further improve NUE among dairy cows. Here, 20 primiparous lactating cows with days in milk ranging from 95 to 115 days were selected from a total of 1 221 cows. Each cow’s N intake and milk N yield were measured for 7 days. Subsequently, blood samples were collected before morning feeding. Based on analysis and calculations, cows were retrospectively classified into two groups based on their NUE values, namely, a low NUE group (LNUE, NUE = 24.8 ± 1.6%, n = 10, mean ± SD) and a high NUE group (HNUE, NUE = 35.2 ± 1.7%, n = 10, mean ± SD). Plasma samples were selected from six cows in each group for metabolomics and amino acid profiling. Among the 41 differential metabolites (DMs) identified in the metabolomic analysis, sucrose, MG(0:0/22:1(13Z)/0:0), 2-amino-6-hydroxyhexanoic acid, and L-glutamine exhibited significant correlations with NUE, milk yield, and BW (P < 0.05). Moreover, the five differential amino acids and amino acid metabolites (DAAs) identified in the amino acid profiling and 5 of the 6 differential amino acids and amino acid conjugates identified by plasma metabolomics were found to be less abundant in the HNUE group (P < 0.05). Specifically, there was a 39.4% decrease in L-arginine content and a 29.2% decrease in L-glutamine content (P < 0.05). Pathway analysis indicated that the DMs and DAAs were mainly involved in arginine biosynthesis, glutathione metabolism, arginine and proline metabolism, and tryptophan metabolism (pathway impact > 0.1). These results provided new insights into the new blood metabolite profile associated with NUE in dairy cows. These new insights can provide foundational information for the formulation of new strategies to further enhance NUE in dairy cows.

Vitamin and mineral supplementation to beef heifers during gestation: impacts on morphometric measurements of the neonatal calf, vitamin and trace mineral status, blood metabolite and endocrine profiles, and calf organ characteristics at 30h after birth.

To examine the effects of feeding a vitamin and mineral supplement to beef heifers throughout gestation on mineral status and hormone/endocrine profiles in the dam and calf, and morphometric characteristics and organ mass of the calf at 30h after birth, Angus-based heifers (n = 72, 14 to 15mo of age, initial body weight [BW] = 380.4 ± 50.56kg) were estrus synchronized and artificially inseminated (AI) with female-sexed semen. Heifers were blocked by BW and randomly assigned to receive either a basal diet (CON; n = 36) or a basal diet plus a vitamin and mineral supplement (VTM; n = 36) via an individual feeding system beginning at breeding, with both diets targeting BW gains of 0.45kg heifer-1·d-1. Heifers not pregnant after the first AI (CON, n = 19; VTM, n = 18) were rebred via AI 60d after treatment initiation, and heifers gestating female fetuses (CON, n = 7; VTM, n = 7) received treatments throughout gestation and were experimental units for this study. Calves were separated from their dams and fed colostrum replacer within 2h of birth and euthanized 30h after the first feeding. Calf morphometrics were recorded, and tissues were weighed and sampled. Serum from the dam at calving and serum, liver, and muscle from the calf at 30h were analyzed for concentrations of minerals. Serum from the dam and calf were analyzed for concentrations of leptin, vitamins A, D, and E, cortisol, growth hormone, and insulin-like growth factor 1. All response variables were analyzed using the MIXED procedure of SAS. Calf body morphometrics and BW of the dam at calving (P ≥ 0.32), calf organ weights (P ≥ 0.21), and calf ovarian follicle counts (P ≥ 0.13) were not affected by maternal treatment. Concentrations of Se and Co in calf serum and Se in calf liver were increased (P ≤ 0.02) in VTM. Serum concentrations of Co and vitamin A in the dam were greater (P ≤ 0.01) in supplemented compared with nonsupplemented dams, and serum concentrations of vitamin D were greater (P ≤ 0.0003) in supplemented dams and calves compared with the nonsupplemented cohort. Maternal supplementation supported vitamin and mineral status in the neonate, yet had no discernable impact on BW, organ mass, or circulating hormones/metabolites in the calf. Evaluating offspring at later postnatal time points is warranted to determine if prenatal vitamin and mineral supplementation affects performance, health, metabolism, and efficiency of energy utilization in key metabolic tissues in the calf.

Metabolit dan Profil Darah Ayam Akhir Periode Bertelur yang Disuplementasi Enzim Bromelin dalam Ransumnya

This experiment aimed to evaluate the effect of bromelain enzyme supplementation in a late-laying period diet on blood metabolite and blood profile parameters. A total of 200 Isa Brown at late laying period hens, 85 weeks of age, were randomly distributed into four dietary treatments and fed for eight weeks. The bromelain enzyme was used at the level of 0% (control diet), 0.025%, 0.050%, and 0.075%. Each treatment was replicated five times. Experimental design data were analyzed using ANOVA and Duncan multiple range test. Bromelain supplementation had a significant effect on the concentration of blood protein (p&lt;0.01), reduced blood cholesterol (p&lt;0.05), and increased concentration of immunoglobulin Y (IgY) (p&lt;0.05). It is concluded that supplementation at dosages 0.05% and 0.075% of bromelain can improve the birds' immunity by increasing the IgY content in blood serum. supplementation at 0.05% reduces blood cholesterol and increases blood protein.&#x0D; Key words: blood metabolite, blood profile, bromelain, IgY, late laying period

Cord Blood Metabolite Profiles and Their Association with Autistic Traits in Childhood.

Autism Spectrum Disorder (ASD) is a diverse neurodevelopmental condition. Gene-environmental interactions in early stages of life might alter metabolic pathways, possibly contributing to ASD pathophysiology. Metabolomics may serve as a tool to identify underlying metabolic mechanisms contributing to ASD phenotype and could help to unravel its complex etiology. In a population-based, prospective cohort study among 783 mother-child pairs, cord blood serum concentrations of amino acids, non-esterified fatty acids, phospholipids, and carnitines were obtained using liquid chromatography coupled with tandem mass spectrometry. Autistic traits were measured at the children's ages of 6 (n = 716) and 13 (n = 648) years using the parent-reported Social Responsiveness Scale. Lower cord blood concentrations of SM.C.39.2 and NEFA16:1/16:0 were associated with higher autistic traits among 6-year-old children, adjusted for sex and age at outcome. After more stringent adjustment for confounders, no significant associations of cord blood metabolites and autistic traits at ages 6 and 13 were detected. Differences in lipid metabolism (SM and NEFA) might be involved in ASD-related pathways and are worth further investigation.

CRISPR/Cas9-based double-strand oligonucleotide insertion strategy corrects metabolic abnormalities in murine glycogen storage disease type-Ia.

Glycogen storage disease type-Ia (GSD-Ia), characterized by impaired blood glucose homeostasis, is caused by a deficiency in glucose-6-phosphatase-α (G6Pase-α or G6PC). Using the G6pc-R83C mouse model of GSD-Ia, we explored a CRISPR/Cas9-based double-strand DNA oligonucleotide (dsODN) insertional strategy that uses the nonhomologous end-joining repair mechanism to correct the pathogenic p.R83C variant in G6pc exon-2. The strategy is based on the insertion of a short dsODN into G6pc exon-2 to disrupt the native exon and to introduce an additional splice acceptor site and the correcting sequence. When transcribed and spliced, the edited gene would generate a wild-type mRNA encoding the native G6Pase-α protein. The editing reagents formulated in lipid nanoparticles (LNPs) were delivered to the liver. Mice were treated either with one dose of LNP-dsODN at age 4 weeks or with two doses of LNP-dsODN at age 2 and 4 weeks. The G6pc-R83C mice receiving successful editing expressed ~4% of normal hepatic G6Pase-α activity, maintained glucose homeostasis, lacked hypoglycemic seizures, and displayed normalized blood metabolite profile. The outcomes are consistent with preclinical studies supporting previous gene augmentation therapy which is currently in clinical trials. This editing strategy may offer the basis for a therapeutic approach with an earlier clinical intervention than gene augmentation, with the additional benefit of a potentially permanent correction of the GSD-Ia phenotype.

Blood metabolites profile and Growth Hormone mRNA expression of Peranakan Ongole cattle fed with finishing ration containing Vinasse-molasses

&lt;p class="MDPI17abstract"&gt;&lt;strong&gt;Objective: &lt;/strong&gt;This study aimed to investigate effects of Molasses replacement with Vinasse-molasses in ration on the blood metabolite profiles and mRNA expression of &lt;em&gt;Growth Hormone 1&lt;/em&gt; (&lt;em&gt;GH1)&lt;/em&gt; of finishing Peranakan Ongole (PO) Cattle.&lt;/p&gt;&lt;p class="MDPI17abstract"&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Ten male PO cattle in averaged 209 ± 21 kg of body weight were equally allocated to receive either molasses or Vinasse-molasses dietary treatments. The concentrate diet was contained of either 15% of molasses (control) or Vinasse-molasses. This study observed the nutrient intake, percentage of weight gain, blood metabolite profiles and &lt;em&gt;GH1&lt;/em&gt; mRNA expression of PO cattle.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p class="MDPI17abstract"&gt;&lt;strong&gt;Results: &lt;/strong&gt;The result showed that replacing molasses with vinasse-molasses reduced (P&amp;lt;0.05) dry matter intake (DMI) and intakes of crude protein (CP), ether extract (EE), crude fiber (CF), and total digestible nutrient (TDN). Nevertheless, Vinasse-molasses inclusion did not change (P&amp;gt;0.05) percentage of weight gain. Vinasse-molasses increased (P&amp;lt;0.05) the blood urea nitrogen level, while it did not affect (P&amp;gt;0.05) the &lt;em&gt;GH1 &lt;/em&gt;mRNA levels.&lt;/p&gt;&lt;p class="MDPI17abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; It can be concluded that replacing molasses with vinasse-molasses does not change blood metabolite profile, &lt;em&gt;GH1&lt;/em&gt; mRNA expression and performance of PO cattle. Vinasse-molasses could be applied as energy sources ingredient to replace molasses in finishing cattle feed.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;

Gut microbiome combined with metabolomics reveals biomarkers and pathways in central precocious puberty

BackgroundCentral precocious puberty (CPP) is a common disease in prepubertal children and results mainly from disorders in the endocrine system. Emerging evidence has highlighted the involvement of gut microbes in hormone secretion, but their roles and downstream metabolic pathways in CPP remain unknown.MethodsTo explore the gut microbes and metabolism alterations in CPP, we performed the 16S rRNA sequencing and untargeted metabolomics profiling for 91 CPP patients and 59 healthy controls. Bioinformatics and statistical analyses, including the comparisons of alpha and beta diversity, abundances of microbes, were undertaken on the 16S rRNA gene sequences and metabolism profiling. Classifiers were constructed based on the microorganisms and metabolites. Functional and pathway enrichment analyses were performed for identification of the altered microorganisms and metabolites in CPP.ResultsWe integrated a multi-omics approach to investigate the alterations and functional characteristics of gut microbes and metabolites in CPP patients. The fecal microbiome profiles and fecal and blood metabolite profiles for 91 CPP patients and 59 healthy controls were generated and compared. We identified the altered microorganisms and metabolites during the development of CPP and constructed a machine learning-based classifier for distinguishing CPP. The Area Under Curves (AUCs) of the classifies were ranged from 0.832 to 1.00. In addition, functional analysis of the gut microbiota revealed that the nitric oxide synthesis was closely associated with the progression of CPP. Finally, we investigated the metabolic potential of gut microbes and discovered the genus Streptococcus could be a candidate molecular marker for CPP treatment.ConclusionsOverall, we utilized multi-omics data from microorganisms and metabolites to build a classifier for discriminating CPP patients from the common populations and recognized potential therapeutic molecular markers for CPP through comprehensive analyses.

Effect of Nutrient Improvement and Mineral Premix Supplementation on Weight, Average Daily Gain, and Metabolite Profile of Repeat Breeder Cows

Nutrient overload, deficiency, or imbalance are fundamental issues that frequently arises in breeder cows. Malnutrition in cattle can cause delayed puberty, an increased risk of pregnancy failure, and infertility. This study aimed to determine the effect of nutrient improvement and mineral premix supplementation on body weight, average daily gain, and blood metabolite profile of repeat breeder cattle. Sixteen Simmental Cross cattle aged 4 to 5 years (calved at least once) with an average S/C of 5 and an average body weight of 400 kg were used. The feed provided was forage, Profeed® concentrate, High Quality Feed Supplement (HQFS) and mineral premix. This study was initiated by selecting repeat breeder cattle of smallholder farmers. The selected cattle were reared for three months in the research cage with a predetermined feed for each group. During the research period, four weighings were carried out to determine the body weight of the cattle. Blood samples were taken for testing of the blood metabolite profile; at the beginning and end of the study. The collected samples were then analyzed in the laboratory, and the resulting data was analyzed for variance using the independent-t-test and paired t-test. The results showed that the addition of 0.5% mineral premix had no significant effect (P > 0.05) on body weight gain. In the blood metabolite profile, the improvement in nutrition had a significant effect (P<0.05) on glucose levels (H-0 and H-71). It can be concluded that the supplementation of 0.5% mineral premix has no effect on body weight and blood metabolite profiles. Repeat breeder cattle on smallholder farmers have low glucose levels, so improving nutrition (quality and quantity) is a matter of concern to support pregnancy.

Feeding concentrate versus forage-based starter diets during early life to Holstein Friesian bull calves: growth, rumen fermentation, metabolic response, feed efficiency and beef production

ABSTRACT The objective of this study was to compare the effect of artificially rearing Holstein Friesian bull calves with either forage- (FS) or concentrate-based starter diets on rumen fermentation and blood metabolite profiles to 4.5 mo, residual feed intake (RFI) at 10 mo, lifetime growth, and carcass traits and meat quality at slaughter in a pastoral grazing system. Holstein-Friesian bull calves were allocated to FS or PS diets (n = 20/group). The FS calves grew slower than PS calves following MR weaning up to 100 kg BW but tended to grow faster up to 18 wks while grazing pasture with no difference in BW observed thereafter. Rumen fermentation profiles differed at wk 7 and 12 but not thereafter. Residual feed intake (RFI), age and weight at slaughter and meat yield/quality were similar between groups. These results highlight that artificially reared Friesian bulls fed a FS compared to PS starter diet take slightly longer to reach 100 kg BW but are better prepared for weaning onto pasture, with no long-term differences in RFI, growth and beef production/quality. This study highlights the opportunity for beef producers to utilise a whole of life grain-free alternative feeding system to meet specific market requirements.

Increased Amount of Polyunsaturated Fatty Acids in the Intestinal Contents of Patients with Morbid Obesity

IntroductionObesity is associated with disturbed gut microbiota homeostasis that translates into altered intestinal and blood metabolite profiles. The long-chain fatty acid (LCFA) may be absorbed in the intestine, but until now, their composition in intestinal contents of patients with obesity has not been studied. The aim of the present study was to verify whether obesity is related to any changes in fecal LCFA content and whether intestinal LCFA content may be associated with the health status of patients with obesity.MethodsThe fatty acid composition has been studied in stool samples obtained from 26 patients with morbid obesity and 25 lean subjects by gas chromatography–mass spectrometry. The dietary habits were assessed using the Food Frequency Questionnaire (FFQ-6).ResultsOur results show for the first time that lean subjects and patients with obesity differ in their stool LCFA profiles. The levels of most n-3 polyunsaturated fatty acids (PUFAs) and n-6 PUFAs were significantly higher in fecal samples from people with obesity than in those from lean controls.ConclusionsBased on the current knowledge, we have defined three hypotheses that may explain proving the cause-and-effect relationships observed differences in fecal LCFA profiles between patients with obesity and lean subjects. They may be related to alterations in fat digestion and/or LCFA absorption and diet. However, proving the cause-and-effect relationships requires further research.Graphical

Markers for obese and non-obese Type 2 diabetes identified using whole blood metabolomics

Definitive differences in blood metabolite profiles between obese and non-obese Type 2 diabetes (T2D) have not been established. We performed an LC–MS-based non-targeted metabolomic analysis of whole blood samples collected from subjects classified into 4 types, based on the presence or absence of obesity and T2D. Of the 125 compounds identified, 20, comprising mainly nucleobases and glucose metabolites, showed significant increases or decreases in the T2D group. These included cytidine, UDP-glucuronate, UMP, 6-phosphogluconate, and pentose-phosphate. Among those 20 compounds, 11 enriched in red blood cells (RBCs) have rarely been studied in the context of diabetes, indicating that RBC metabolism is more extensively disrupted than previously known. Correlation analysis revealed that these T2D markers include 15 HbA1c-associated and 5 irrelevant compounds that may reflect diabetic conditions by a different mechanism than that of HbA1c. In the obese group, enhanced protein and fatty acid catabolism causes increases in 13 compounds, including methylated or acetylated amino acids and short-chain carnitines. Our study, which may be considered a pilot investigation, suggests that changes in blood metabolism due to obesity and diabetes are large, but essentially independent.

Effects of weight loss and feeding specially formulated diets on the body composition, blood metabolite profiles, voluntary physical activity, and fecal metabolites and microbiota of overweight cats.

Feline obesity is a common and preventable disease, posing a myriad of health risks and detriments. Specially formulated diets and restricted feeding may serve as an intervention strategy to promote weight loss and improve feline health. In this study, our objective was to determine the effects of restricted feeding and weight loss on body composition, voluntary physical activity, blood hormones and metabolites, and fecal microbiota of overweight cats. Twenty-two overweight adult spayed female and neutered male cats [body weight (BW) = 5.70 ± 1.0 kg; body condition score (BCS) = 7.68 ± 0.6; age = 4 ± 0.4 yr] were used in a weight loss study. A control diet (OR) was fed during a 4-wk baseline to identify intake needed to maintain BW. After baseline (week 0), cats were allotted to OR or a test diet (FT) and fed to lose ~1.0% BW/wk for 24 wk. At baseline and 6, 12, 18, and 24 wk after weight loss, dual-energy x-ray absorptiometry scans were performed and blood samples were collected. Voluntary physical activity was measured at weeks 0, 8, 16, and 24. Fecal samples were collected at weeks 0, 4, 8, 12, 16, 20, and 24. Change from baseline data were analyzed statistically using the Mixed Models procedure of SAS, with P < 0.05 considered significant. Restricted feeding of both diets led to weight and fat mass loss, lower BCS, and lower blood triglyceride and leptin concentrations. Cats fed the FT diet had a greater reduction in blood triglycerides and cholesterol than cats fed the OR diet. Restricted feeding and weight loss reduced fecal short-chain fatty acid, branched-chain fatty acid, phenol, and indole concentrations. Fecal valerate concentrations were affected by diet, with cats fed the OR diet having a greater reduction than those fed the FT diet. Fecal bacterial alpha diversity was not affected, but fecal bacterial beta diversity analysis showed clustering by diet. Restricted feeding and weight loss affected relative abundances of 7 fecal bacterial genera, while dietary intervention affected change from baseline relative abundances of 2 fecal bacterial phyla and 20 fecal bacterial genera. Our data demonstrate that restricted feeding promoted controlled and safe weight and fat loss, reduced blood lipids and leptin concentrations, and shifted fecal metabolites and microbiota. Some changes were also impacted by diet, highlighting the importance of ingredient and nutrient composition in weight loss diets.

Effects of weight loss and feeding specially formulated diets on the body composition, blood metabolite profiles, voluntary physical activity, and fecal metabolites and microbiota of obese dogs.

Canine obesity negatively influences health and well-being, but can be managed by altering diet composition and caloric intake. Restricted feeding, dietary intervention, and consequent weight loss may be used to improve health and modify gastrointestinal microbiota. In this study, we aimed to determine the effects of restricted feeding of specially formulated foods on weight loss, body composition, voluntary physical activity, serum hormones and oxidative stress markers, and fecal metabolites and microbiota populations of obese dogs. Twenty-four obese dogs [body weight (BW) = 15.2 ± 1.7 kg; body condition score (BCS) = 8.7 ± 0.4; muscle condition score (MCS) = 3.5 ± 0.3; age = 7.2 ± 1.6 yr] were used in a 24-wk study. A control (OR) food was fed during a 4-wk baseline to identify intake needed to maintain BW. After baseline, dogs were allotted to one of two diets: OR or test (FT), and then fed to lose 1.5% BW/wk. Food intake, BW, BCS, and MCS were measured, blood and fecal samples were collected, DEXA scans were performed, and voluntary physical activity was measured over time. Microbiota data were evaluated using QIIME2 and change from baseline data from other measures were evaluated using the Mixed Models procedure of SAS, with P < 0.05 being significant. Restricted feeding led to reduced BW, BCS, fat mass, and blood cholesterol, triglyceride, glucose, and leptin concentrations, and increased MCS and lean body mass percentage. Blood cholesterol reduction was greater in dogs fed FT vs. OR. Fecal metabolites and bacterial alpha-diversity were affected by diet and weight loss. Dogs fed FT had greater reductions in fecal short-chain fatty acid, branched-chain fatty acid, and ammonia concentrations than those fed OR. Dogs fed OR had a higher alpha-diversity than those fed FT. Weight loss increased alpha-diversity (weeks 16, 20, and 24 > weeks 0 and 4). Beta-diversity showed separation between dietary groups and between week 0 and all other time points after week 8. Weight loss increased fecal Allobaculum and Ruminococcus torques. Weight loss also increased fecal Bifidobacterium, Faecalibaculum, and Parasutterella, but were greater in dogs fed OR. Weight loss decreased fecal Collinsella, Turicibacter, Blautia, Ruminococcus gnavus, Faecalibacterium, and Peptoclostridium, but were greater in dogs fed OR. In summary, restricted feeding promoted safe weight and fat loss, reduced blood lipid and leptin concentrations, and altered fecal microbiota of obese dogs.

Integrative metagenomic and metabolomic analyses reveal gut microbiota-derived multiple hits connected to development of gestational diabetes mellitus in humans

ABSTRACT Gestational diabetes mellitus (GDM) is characterized by the development of hyperglycemia and insulin resistance during the second or third trimester of pregnancy, associated with considerable risks to both the mother and developing fetus. Although emerging evidence suggests an association between the altered gut microbiota and GDM, remarkably little is known about the microbial and metabolic mechanisms that link the dysbiosis of the gut microbiota to the development of GDM. In this study, a metagenome-wide association study and serum metabolomics profiling were performed in a cohort of pregnant women with GDM and pregnant women with normal glucose tolerance (NGT). We identified gut microbial alterations associated with GDM and linked to the changes in circulating metabolites. Blood metabolite profiles revealed that GDM patients exhibited a marked increase in 2-hydroxybutyric acid and L-alpha-aminobutyric acid, but a decrease in methionine sulfoxide, allantoin, and dopamine and dopaminergic synapse, when compared with those in NGT controls. Short-chain fatty acid-producing genera, including Faecalibacterium, Prevotella, and Streptococcus, and species Bacteroides coprophilus, Eubacterium siraeum, Faecalibacterium prausnitzii, Prevotella copri, and Prevotella stercorea, were significantly reduced in GDM patients relative to those in NGT controls. Bacterial co-occurrence network analysis revealed that pro-inflammatory bacteria were over-represented as the core species in GDM patients. These microbial and metabolic signatures are closely associated with clinical parameters of glucose metabolism in GDM patients and NGT controls. In conclusion, we identified circulating dopamine insufficiency, imbalanced production of SCFAs, and excessive metabolic inflammation as gut microbiota-driven multiple parallel hits linked to GDM development. This work might explain in part the mechanistic link between altered gut microbiota and GDM pathogenesis, and suggest that gut microbiota may serve as a promising target to intervene in GDM.

Effect of supplementation with algae β-glucans on performance, health, and blood metabolites of Holstein dairy calves.

Studies have shown that β-glucans extracted from the cell wall of cereals, algae, and yeasts have been associated with improved immune function. However, it is unknown whether algae β-glucan supplementation affects the performance, blood metabolites, or cell counts of immune cells in dairy calves. The objective of this randomized clinical trial was to evaluate whether supplementation of β-glucans to milk replacer in dairy calves fed 6 L/d improved growth performance and fecal status and altered the blood metabolite profile. In this trial, we enrolled Holstein calves (n = 34) at birth (body weight 36.38 ± 1.33 kg; mean ± standard deviation) to receive, from 1 d of age, either 2 g/d algae β-glucans mixed into 6 L/d of milk replacer (22.4% crude protein and 16.2% fat) or an unsupplemented milk replacer (control). The calves were blocked in pairs according to birth weight, sex, and date of birth (up to 5 d difference). Calves were housed individually, and calf starter (24.7% crude protein and 13.9% neutral detergent fiber) was offered ad libitum based on orts of the previous day until 56 d of age (end of the trial). Body weight was measured weekly, and health checks and daily fecal consistency were evaluated daily in every calf by the same observer. Calves with 2 consecutive days of loose feces that sifted through bedding were considered diarrhea positive. We used a linear mixed effects model to evaluate the effects of β-glucan supplementation fed during the preweaning period on performance (average daily gain), final weight, feed efficiency (FE), white blood cell count, and selected blood metabolites, repeated by time. A generalized linear mixed effects model was also run to evaluate the likelihood of a diarrhea bout in the first 28 d of life, controlling for the calf as the subject with a logistic distribution. We included age, serum total protein at 48 h, and birth weight as covariates. At 56 d, β-glucan-supplemented calves weighed more than control calves (56.3 vs. 51.5 kg). Treatment had no effect on total starter intake, but there was a treatment by age interaction for FE, with greater FE for β-glucan-supplemented calves in wk 3 and 5 of age. There was only a tendency for average daily gain to be greater in supplemented calves than in control calves for the duration of the study. Furthermore, control calves had 14.66 [95% confidence interval (95% CI): 9.87-21.77] times greater odds of having a diarrheal bout than β-glucan-supplemented calves. Control calves had 12.70 (95% CI: 8.82-18.28) times greater odds of having an additional day with an abnormal fecal score compared with β-glucan-supplemented calves, suggesting that supplementation ameliorated diarrhea severity. We found no association of treatment with concentrations of serum total protein, albumin, creatinine, or glucose during the preweaning period. Our findings suggest that dietary supplementation of 2 g/d of algae β-glucans to milk replacer improved fecal status and may affect growth, as evidenced by a higher weaning weight, compared with control calves. Future studies should explore the effect of algae β-glucans on lower-gut physiology and digestibility in dairy calves.