• Biomolecules & Therapeutics
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• 제30권1호
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• pp.48-54
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• 2022

GPR43 (also known as FFAR2), a metabolite-sensing G-protein-coupled receptor stimulated by short-chain fatty acid (SCFA) ligands is involved in innate immunity and metabolism. GPR43 couples with Gα_i/o and Gα_q/11 heterotrimeric proteins and is capable of decreasing cyclic AMP and inducing Ca²⁺ flux. The GPR43 receptor has additionally been shown to bind β-arrestin 2 and inhibit inflammatory pathways, such as NF-κB. However, GPR43 shares the same ligands as GPR41, including acetate, propionate, and butyrate, and determination of its precise functions in association with endogenous ligands, such as SCFAs alone, therefore remains a considerable challenge. In this study, we generated novel synthetic agonists that display allosteric modulatory effects on GPR43 and downregulate NF-κB activity. In particular, the potency of compound 187 was significantly superior to that of pre-existing compounds in vitro. However, in the colitis model in vivo, compound 110 induced more potent attenuation of inflammation. These novel allosteric agonists of GPR43 clearly display anti-inflammatory potential, supporting their clinical utility as therapeutic drugs.

• Journal of Microbiology and Biotechnology
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• 제32권10호
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• pp.1234-1244
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• 2022

Oral streptococci are considered as an opportunistic pathogen associated with initiation and progression of various oral diseases. However, since the currently-available treatments often accompany adverse effects, alternative strategy is demanded to control streptococci. In the current study, we investigated whether short-chain fatty acids (SCFAs), including sodium acetate (NaA), sodium propionate (NaP), and sodium butyrate (NaB), can inhibit the growth of oral streptococci. Among the tested SCFAs, NaP most potently inhibited the growth of laboratory and clinically isolated strains of Streptococcus gordonii under anaerobic culture conditions. However, the growth inhibitory effect of NaP on six different species of other oral streptococci was different depending on their culture conditions. Metabolic changes such as alteration of methionine biosynthesis can affect bacterial growth. Indeed, NaP enhanced intracellular methionine levels of oral streptococci as well as the mRNA expression level of methionine biosynthesis-related genes. Collectively, these results suggest that NaP has an inhibitory effect on the growth of oral streptococci, which might be due to alteration of methionine biosynthesis. Thus, NaP can be used an effective bacteriostatic agent for the prevention of oral infectious diseases caused by oral streptococci.

• Molecules and Cells
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• 제44권7호
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• pp.458-467
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• 2021

GPR43 (also known as FFAR2 or FFA2) is a G-protein-coupled receptor primarily expressed in immune cells, enteroendocrine cells and adipocytes that recognizes short-chain fatty acids, such as acetate, propionate, and butyrate, likely to be implicated in innate immunity and host energy homeostasis. Activated GPR43 suppresses the cAMP level and induces Ca²⁺ flux via coupling to Gα_i and Gα_q families, respectively. Additionally, GPR43 is reported to facilitate phosphorylation of ERK through G-protein-dependent pathways and interacts with β-arrestin 2 to inhibit NF-κB signaling. However, other G-protein-dependent and independent signaling pathways involving GPR43 remain to be established. Here, we have demonstrated that GPR43 augments Rho GTPase signaling. Acetate and a synthetic agonist effectively activated RhoA and stabilized YAP/TAZ transcriptional coactivators through interactions of GPR43 with Gα_q/11 and Gα_12/13. Acetate-induced nuclear accumulation of YAP was blocked by a GPR43-specific inverse agonist. The target genes induced by YAP/TAZ were further regulated by GPR43. Moreover, in THP-1-derived M1-like macrophage cells, the Rho-YAP/TAZ pathway was activated by acetate and a synthetic agonist. Our collective findings suggest that GPR43 acts as a mediator of the Rho-YAP/TAZ pathway.

• Journal of Animal Science and Technology
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• 제64권6호
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• pp.1077-1091
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• 2022

This study was conducted to determine the rumen fermentation dynamics of lupin flakes and elucidate the effects of lupin flake supplementation on the growth performance, blood metabolites, and carcass characteristics of Hanwoo steers. In vitro and in situ trials of lupin grains and lupin flakes were conducted using three Hanwoo cows with rumen fistulas. The feeding trial included 40 early-fattening Hanwoo steers randomly divided into four groups: control, T1, T2, and T3. Their formula feed contained 0%, 3%, 6%, and 9% lupin flakes, respectively. In vitro rumen pH and ammonia concentrations were lower in the lupin flake group than in the lupin grain group after 6 and 24 h of incubation, respectively (p < 0.05). Concentrations of propionate, butyrate, and total volatile fatty acids were higher in the lupin flake group than in the lupin grain group after 12 h of incubation (p < 0.05), as was the crude protein disappearance rate at 9 and 12 h of rumen fermentation (p < 0.05). Supplementation with lupin flakes did not affect the average daily gain. Compared to that in the control group, dry matter intake was lower in the lupin flake-supplemented groups (p < 0.05); the feed conversion ratio was lower in T2 and T3 (p < 0.05); and plasma total protein concentration in 29-month-old steers was lower in T1 and T3 (p < 0.05). Plasma triglyceride concentration was lower in the lupin flake-supplemented groups than in the control group (p < 0.05). The incidence rate of yield grade A was higher in T1 and T2 than in the control group; the incidence rate of meat quality 1⁺ grade or higher was highest in T2. The carcass auction price was higher in T2 than in the other groups. Overall, compared to whole lupin grains, lupin flakes seem to more substantially affect rumen ammonia concentrations and crude protein disappearance rate. Additionally, we suggest that supplementation with 6% lupin flake formula feed exerts positive effects on the feed conversion ratio, yield grade, and quality grade of Hanwoo steers.

• Animal Bioscience
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• 제36권8호
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• pp.1199-1208
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• 2023

Objective: The purpose of this study was to perform a comparative analysis of metabolite levels in serum and milk obtained from cows fed on different concentrate to forage feed ratios. Methods: Eight lactating Holstein cows were divided into two groups: a high forage ratio diet (HF; 80% Italian ryegrass and 20% concentrate of daily intake of dry matter) group and a high concentrate diet (HC; 20% Italian ryegrass and 80% concentrate) group. Blood was collected from the jugular vein, and milk was sampled using a milking machine. Metabolite levels in serum and milk were estimated using proton nuclear magnetic resonance and subjected to qualitative and quantitative analyses performed using Chenomx 8.4. For statistical analysis, Student's t-test and multivariate analysis were performed using Metaboanalyst 4.0. Results: In the principal component analysis, a clear distinction between the two groups regarding milk metabolites while serum metabolites were shown in similar. In serum, 95 metabolites were identified, and 13 metabolites (include leucine, lactulose, glucose, betaine, etc.) showed significant differences between the two groups. In milk, 122 metabolites were identified, and 20 metabolites (include urea, carnitine, acetate, butyrate, arabinitol, etc.) showed significant differences. Conclusion: Our results show that different concentrate to forage feed ratios impact the metabolite levels in the serum and milk of lactating Holstein cows. A higher number of metabolites in milk, including those associated with milk fat synthesis and the presence of Escherichia coli in the rumen, differed between the two groups compared to that in the serum. The results of this study provide a useful insight into the metabolites associated with different concentrate to forge feed ratios in cows and may aid in the search for potential biomarkers for subacute ruminal acidosis.

• Animal Bioscience
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• 제36권6호
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• pp.879-890
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• 2023

Objective: This study was conducted to evaluate the use of Megasphaera elsdenii (M. elsdenii) as a probiotic on rumen fermentation, production performance, carcass traits and health of ruminants by integrating data from various related studies using meta-analysis. Methods: A total of 32 studies (consisted of 136 data points) were obtained and integrated into a database. The parameters integrated were fermentation products, rumen microbes, production performance, carcass quality, animal health, blood and urine metabolites. Statistical analysis of the compiled database used a mixed model methodology. Different studies were considered random effects, while M. elsdenii supplementation doses were considered fixed effects. p-values and the Akaike information criterion were employed as model statistics. The model was deemed significant at p<0.05 or had a tendency to be significant when p-value between 0.05<p<0.10. Results: Supplementation with M. elsdenii increased (p<0.05) some proportion of fermented rumen products such as propionate, butyrate, isobutyrate, and valerate, and significantly reduced (p<0.05) lactic acid concentration, acetate proportion, total bacterial population and methane emission. Furthermore, the probiotic supplementation enhanced (p<0.05) livestock production performance, especially in the average daily gain and body condition score. Regarding the carcass quality, hot carcass weight and carcass gain were elevated (p< 0.05) due to the M. elsdenii supplementation. Animal health also showed improvement as indicated by the lower (p<0.05) diarrhoea and bloat incidences as well as the liver abscess. However, M. elsdenii supplementation had negligible effects on blood and urine metabolites of ruminants. Conclusion: Supplementation of M. elsdenii is capable of decreasing ruminal lactic acid concentration, enhancing rumen health, elevating some favourable rumen fermentation products, and in turn, increasing production performance of ruminants.

• 한국축산식품학회지
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• 제43권4호
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• pp.659-673
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• 2023

Compared to infant formula, breast milk is the best source of nutrition for infants; it not only improves the neonatal intestinal function, but also regulates the immune system and gut microbiota composition. However, probiotic-fortified infant formula may further enhance the infant gut environment by overcoming the limitations of traditional infant formula. We investigated the probiotic formula administration for one month by comparing 118 Korean infants into the following three groups: infants in each group fed with breast milk (50), probiotic formula (35), or placebo formula-fed group (33). Probiotic formula improved stool consistency and defecation frequency compared to placebo formula-fed group. The probiotic formula helped maintaining the level of secretory immunoglobulin A (sIgA), which had remarkably decreased over time in placebo formula-fed infants (compared to weeks 0 and 4). Moreover, probiotic formula decreased the acidity of stool and considerably increased the butyrate concentration. Furthermore, the fecal microbiota of each group was evaluated at weeks 0 and 4. The microbial composition was distinct between each groups, and the abundance of health-promoting bacteria increased in the probiotic formula compared to the placebo formula-fed group. In summary, supplementation of probiotic infant formula can help optimize the infant gut environment, microbial composition, and metabolic activity of the microbiota, mimicking those of breast milk.

• Animal Bioscience
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• 제37권4호
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• pp.655-667
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• 2024

Objective: This study aimed to assess the impact of a hydroethanolic extract of walnut green husks (WGH) on rumen fermentation and the diversity of bacteria, methanogenic archaea, and fungi in sheep fed a high-concentrate diet. Methods: Five healthy small-tailed Han ewes with permanent rumen fistula were selected and housed in individual pens. This study adopted a self-controlled and crossover design with a control period and an experimental period. During the control period, the animals were fed a basal diet (with a ratio of concentrate to roughage of 65:35), while during the treatment period, the animals were fed the basal diet supplemented with 0.5% hydroethanolic extract of WGH. Fermentation parameters, digestive enzyme activities, and microbial diversity in rumen fluid were analyzed. Results: Supplementation of hydroethanolic extract of WGH had no significant effect on feed intake, concentrations of total volatile fatty acids, isovalerate, ammonia nitrogen, and microbial protein (p>0.05). However, the ruminal pH, concentrations of acetate, butyrate and isobutyrate, the ratio of acetate to propionate, protozoa count, and the activities of filter paper cellulase and cellobiase were significantly increased (p<0.05), while concentrations of propionate and valerate were significantly decreased (p<0.05). Moreover, 16S rRNA gene sequencing revealed that the relative abundance of rumen bacteria Christensenellaceae R7 group, Saccharofermentans, and Ruminococcaceae NK4A214 group were significantly increased, while Ruminococcus gauvreauii group, Prevotella 7 were significantly decreased (p<0.05). The relative abundance of the fungus Pseudomonas significantly increased, while Basidiomycota, Fusarium, and Alternaria significantly decreased (p<0.05). However, there was no significant change in the community structure of methanogenic archaea. Conclusion: Supplementation of hydroethanolic extract of WGH to a high-concentrate diet improved the ruminal fermentation, altered the structure of ruminal bacterial and fungal communities, and exhibited beneficial effects in alleviating subacute rumen acidosis of sheep.

• Animal Bioscience
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• 제37권3호
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• pp.536-546
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• 2024

Objective: This experiment was conducted to investigate the effect of grain-based pecking blocks on productivity and welfare status at two commercial broiler welfare-certified farms. Methods: Production and welfare indicators were assessed at two farms (designated Farm A and B). Both farms had two windowless houses with forced tunnel-type ventilation and housed broilers at stocking densities of approximately 16.7 birds/m² (Farm A) and 16.8 birds/m² (Farm B). Each house was divided into two or three equal sections and was provided with or without pecking blocks. Grain-based pecking blocks, measuring 25 × 25 × 25 cm, were given to broilers in both farms at 1 block per 1,000 birds. Various parameters including productivity (body weight and flock uniformity), corticosterone levels (in fecal droppings and feathers), footpad dermatitis, hock burn, feather dirtiness, gait score, litter quality, body surface temperature, and volatile fatty acids in fecal samples were assessed at 26 days of age, whereas litter quality was analyzed at 13 and 26 days of age. Results: There were no significant effects of providing pecking blocks on productivity (body weight and uniformity), fecal and feather corticosterone, welfare indicators (i.e., footpad dermatitis, hock burn, feather cleanliness, and gait score), and litter quality (i.e., moisture, nitrogen, and pH). No differences in body surface temperature between the control and enrichment treatments were noted in Farm B, but body surface temperatures of the head (p = 0.029) and legs (p = 0.011) in the enrichment vs. control group were elevated in Farm A. Butyrate concentration in the enrichment vs control group was higher in Farm B (p = 0.023), but this effect was not detected in Farm A. Conclusion: It is concluded that grain-based pecking blocks did not affect performance and welfare indicators. Further studies are warranted to elucidate the potential impact of grain-based pecking blocks on gut health indicators.

• 농업과학연구
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• 제51권3호
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• pp.283-294
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• 2024

The objective of this study was to investigate the effect of supplementing concentrates in a forage-based diet on methane emissions of pregnant Hanwoo heifers. Twenty-one pregnant Hanwoo heifers (481 ± 42.4 kg) were divided into two groups: 1) a group receiving forage only (control, CON) and 2) the other group receiving forage with 4 kg of a concentrate mix (treatment, TRT). Methane (CH₄) concentration was measured using a laser methane detector, following an 18-d adaptation period, according to previously established protocols. Feed intake was recorded throughout the experimental period. Ruminal fluid was collected and analyzed for pH, ammonia-nitrogen (NH₃-N), and volatile fatty acid (VFA). The TRT exhibited higher dry matter and neutral detergent fiber intake than CON (p < 0.05) with elevated NH₃-N (p < 0.001) and total VFA concentrations (p = 0.013). The proportions of butyrate, valerate, and iso-valerate were higher in TRT than CON (p < 0.05). Notably, CH₄ concentrations per kg dry matter intake was lower in the TRT group, both from respiration and eructation (p < 0.05). In conclusion, supplementing concentrates in a low-quality forage-based diet for pregnant Hanwoo heifers fulfills nutrient requirements and reduces CH₄ emissions, suggesting a potential strategy to reduce environmental impact of Hanwoo production.