The propionate-GPR41 axis in infancy protects from subsequent bronchial asthma onset.

Evidence has accumulated that gut microbiota and its metabolites, in particular the short-chain fatty acid propionate, are significant contributors to the pathogenesis of a variety of diseases. However, little is known regarding its impact on pediatric bronchial asthma, one of the most common allergic diseases in childhood. This study aimed to elucidate whether, and if so how, intestinal propionate during lactation is involved in the development of bronchial asthma. We found that propionate intake through breast milk during the lactation period resulted in a significant reduction of airway inflammation in the offspring in a murine house dust mite-induced asthma model. Moreover, GPR41 was the propionate receptor involved in suppressing this asthmatic phenotype, likely through the upregulation of Toll-like receptors. In translational studies in a human birth cohort, we found that fecal propionate was decreased one month after birth in the group that later developed bronchial asthma. These findings indicate an important role for propionate in regulating immune function to prevent the pathogenesis of bronchial asthma in childhood.

Microbiome analysis of thai traditional fermented soybeans reveals short-chain fatty acid-associated bacterial taxa.

Thua Nao is a Thai traditional fermented soybean food and low-cost protein supplement. This study aimed to evaluate the bacterial community in Thua Nao from northern Thailand and assess potentially active short-chain fatty acids (SCFAs)-related bacteria. Sixty-five Thua Nao consisting of 30 wet and 35 dried samples were collected from six provinces: Chiang Rai, Chiang Mai, Mae Hong Son, Lampang, Lamphun, and Phayao. Bacterial diversity was significantly higher in the wet samples than in the dried samples. The dominant phyla were Firmicutes (92.7%), Proteobacteria (6.7%), Actinobacteriota (0.42%), and Bacteroidota (0.26%). The genus Bacillus (67%) was the most represented in all samples. Lactobacillus, Enterococcus, and Globicatella were enriched in the wet samples. Assessment of the SCFA-microbiota relationships revealed that high butyrate and propionate concentrations were associated with an increased Clostridiales abundance, and high acetate concentrations were associated with an increased Weissella abundance. Wet products contained more SCFAs, including acetate (P = 2.8e-08), propionate (P = 0.0044), butyrate (P = 0.0021), and isovalerate (P = 0.017), than the dried products. These results provide insight into SCFA-microbiota associations in Thua Nao, which may enable the development of starter cultures for SCFA-enriched Thua Nao production.

Evaluation of Biological Activity of New 1,2,4-Triazole Derivatives Containing Propionic Acid Moiety.

To this day, the quest to find new drugs is still a challenge due to the growing demands of patients suffering from chronic inflammatory diseases and the need for the individualization of therapy. The aim of this research was to synthesize new 1,2,4-triazole derivatives containing propanoic acid moiety and to investigate their anti-inflammatory, antibacterial and anthelmintic activity. Compounds 3a-3g were obtained in reactions of amidrazones 1a-1g with succinic anhydride. Several analyses of proton and carbon nuclear magnetic resonance (1H NMR, 13C NMR, respectively), as well as high-resolution mass spectra (HRMS), confirmed the structures of 1,2,4-triazole derivatives 3a-3g. Toxicity, antiproliferative activity and influence on cytokine release (TNF-α: Tumor Necrosis Factor-α, IL-6: Interleukin-6, IFN-γ: Interferon-γ, and IL-10: Interleukin-10) of the compounds 3a-3g were evaluated in peripheral blood mononuclear cells culture. Moreover, mitogen-stimulated cell culture was used for biological activity tests. The antimicrobial and anthelmintic activity of derivatives 3a-3g were studied against Gram-positive and Gram-negative bacterial strains and Rhabditis sp. culture. Despite the lack of toxicity, compounds 3a-3g significantly reduced the level of TNF-α. Derivatives 3a, 3c and 3e also decreased the release of IFN-γ. Taking all of the results into consideration, compounds 3a, 3c and 3e show the most beneficial anti-inflammatory effects.

Emerging Strategies for Enhancing Propionate Conversion in Anaerobic Digestion: A Review.

Anaerobic digestion (AD) is a triple-benefit biotechnology for organic waste treatment, renewable production, and carbon emission reduction. In the process of anaerobic digestion, pH, temperature, organic load, ammonia nitrogen, VFAs, and other factors affect fermentation efficiency and stability. The balance between the generation and consumption of volatile fatty acids (VFAs) in the anaerobic digestion process is the key to stable AD operation. However, the accumulation of VFAs frequently occurs, especially propionate, because its oxidation has the highest Gibbs free energy when compared to other VFAs. In order to solve this problem, some strategies, including buffering addition, suspension of feeding, decreased organic loading rate, and so on, have been proposed. Emerging methods, such as bioaugmentation, supplementary trace elements, the addition of electronic receptors, conductive materials, and the degasification of dissolved hydrogen, have been recently researched, presenting promising results. But the efficacy of these methods still requires further studies and tests regarding full-scale application. The main objective of this paper is to provide a comprehensive review of the mechanisms of propionate generation, the metabolic pathways and the influencing factors during the AD process, and the recent literature regarding the experimental research related to the efficacy of various strategies for enhancing propionate biodegradation. In addition, the issues that must be addressed in the future and the focus of future research are identified, and the potential directions for future development are predicted.

[Effects of electroacupuncture at "Siguan" points on the expression of colonic 5-hydroxytryptamine and fecal short-chain fatty acids in rats with post-stroke depression].

OBJECTIVE: To observe the effects of electroacupuncture at "Siguan" points on behavior, colonic 5-hydroxytryptamine (5-HT) and fecal short-chain fatty acids (SCFAs) in rats with post-stroke depression (PSD), and explore the effect mechanism of electroacupuncture at Siguan points on PSD. METHODS: Fifty SD rats were randomly divided into a sham-operation group, a stroke group, a PSD group, a drug group and an electroacupuncture group, with 10 rats in each one. The stroke model was established by middle cerebral artery occlusion (MCAO) method in the stroke group; except for the sham-operation group, the rats in the other groups were intervened with MCAO combined with solitary and chronic unpredictable mild stress (CUMS) to establish PSD model. In the electroacupuncture group, electroacupuncture was delivered at "Hegu" (LI 4) and "Taichong" (LR 3), with disperse-dense wave, 2 Hz/10 Hz in frequency, for 30 min in each intervention, once daily, for consecutive 21 days. Simultaneously, distilled water (0.01 L•kg-1•d-1) was administrated intragastrically. Fluoxetine solution (2.33 mg•kg-1•d-1) was given by gavage , once a day and for 21 days in the drug group. The same procedure of fixation and gavage with distilled water were adopted in the sham-operation group, the stroke group and the PSD group. Separately, before stroke modeling, after PSD modeling and after 21-day intervention, the consumption of sugar water and the scores of horizontal movement and vertical movement in open-field test were observed. After 21-day intervention, the content of colonic 5-HT was detected by immunohistochemical method, and that of fecal SCFAs was determined by gas chromatography mass spectrometry. RESULTS: After PSD modeling, compared with the stroke group, the sugar water consumption, the horizontal movement scores and vertical movement scores of the open-field test were all reduced in the PSD group, the drug group and the electroacupuncture group (P<0.05). After 21-day intervention, the sugar water consumption and the scores of horizontal movement and vertical movement of the open-field test were increased in the drug group and the electroacupuncture group (P<0.05) when compared with the PSD group; and the horizontal movement score in the electroacupuncture group was lower than that of the drug group (P<0.05). Compared with the sham-operation group, the contents of total fecal SCFAs and acetic acid were lower in the stroke group (P<0.05), and the contents of colonic 5-HT and total fecal SCFAs, acetic acid, propionic acid and butyric acid were reduced in the PSD group (P<0.05). In comparison with the PSD group, the contents of colonic 5-HT and total fecal SCFAs, acetic acid and propionic acid were increased in the drug group and the electroacupuncture group (P<0.05); and the content of colonic 5-HT in the electroacupuncture group was lower than that of the drug group (P<0.05). The level of colonic 5-HT was positively correlated with the contents of total fecal SCFAs and propionic acid (r=0.424, P=0.005; r=0.427, P=0.004). CONCLUSION: Electroacupuncture at "Siguan" points can relieve the depression-like behavior of PSD rats, and its underlying mechanism may be related to the regulation of fecal SCFAs, which affects the release of colonic 5-HT.

Synthesis and Evaluation of Hypoglycemic Activity of Structural Isomers of ((Benzyloxy)phenyl)propanoic Acid Bearing an Aminobornyl Moiety.

Free fatty acid receptor-1 (FFAR1) agonists are promising candidates for therapy of type 2 diabetes because of their ability to normalize blood sugar levels during hyperglycemia without the risk of hypoglycemia. Previously, we synthesized compound QS-528, a FFA1 receptor agonist with a hypoglycemic effect in C57BL/6NCrl mice. In the present work, structural analogs of QS-528 based on (hydroxyphenyl)propanoic acid bearing a bornyl fragment in its structure were synthesized. The seven novel compounds synthesized were structural isomers of compound QS-528, varying the positions of the substituents in the aromatic fragments as well as the configuration of the asymmetric center in the bornyl moiety. The studied compounds were shown to have the ability to activate FFAR1 at a concentration of 10 µM. The cytotoxicity of the compounds as well as their effect on glucose uptake in HepG2 cells were studied. The synthesized compounds were found to increase glucose uptake by cells and have no cytotoxic effect. Two compounds, based on the meta-substituted phenylpropanoic acid, 3-(3-(4-(((1R,2R,4R)-1,7,7-trimethylbicyclo-[2.2.1]heptan-2-ylamino)methyl)benzyloxy)phenyl)propanoic acid and 3-(3-(3-(((1R,2R,4R)-1,7,7-trimethylbicyclo [2.2.1]heptan-2-ylamino)methyl)benzyloxy)phenyl)propanoic acid, were shown to have a pronounced hypoglycemic effect in the oral glucose tolerance test with CD-1 mice.

Evaluation of the One-Hour ¹³C-Propionate Breath Test in 49 Patients from a Single Center in Japan to Detect Vitamin B12 Deficiency.

BACKGROUND Given the unavailability of reliable biomarkers for vitamin B12 (VB12) deficiency in clinical settings, the usefulness of the ¹³C-propionate breath test (PBT), utilizing VB12 as a coenzyme of methylmalonyl-CoA in propionate metabolism, as a diagnostic modality for VB12 deficiency has been studied. However, a collection time of 2 h reduces its convenience. Hence, we evaluated the effectiveness of 1-h PBT for detecting VB12 deficiency in 49 patients with suspected VB12 deficiency. MATERIAL AND METHODS We collected 100-200 mL breath gas every 10 min until 1 h after the administration of 1 g of ¹³C-propionate from 49 patients (31 men, 18 women; median age, 70 years) with clinically suspected VB12 deficiency and calculated the ¹³CO2 recovered in the breath per hour as the recovery rate (RR [%dose/h]) from ¹³CO2/¹²CO2 using infrared isotope spectrometry. We compared the RRs between groups: (1) with serum VB12 levels ≥145 pg/mL and <145 pg/mL, (2) with mean corpuscular volume ≤100 fL and >100 fL, and 3) pre- and post-VB12 supplementation. RESULTS The RRs peaked within 30 min. The RRs at 20 min (RR20) and 30 min (RR30) were significantly lower in macrocytotic patients (41.28 vs 50.07, p=0.026 and 37.82 vs 43.93, P=0.003). The RR30 was higher in the supplemented patients (41.93 vs 32.84, P=0.024). There was no significant difference in RRs between the patients with normal and low serum VB12 levels. CONCLUSIONS The 1-h PBT can be a diagnostic modality for VB12 deficiency because 1 h is a sufficient collection time.

Discovery of Potent Tetrazole Free Fatty Acid Receptor 2 Antagonists.

The free fatty acid receptor 2 (FFA2), also known as GPR43, mediates effects of short-chain fatty acids and has attracted interest as a potential target for treatment of various metabolic and inflammatory diseases. Herein, we report the results from bioisosteric replacement of the carboxylic acid group of the established FFA2 antagonist CATPB and SAR investigations around these compounds, leading to the discovery of the first high-potency FFA2 antagonists, with the preferred compound TUG-2304 (16l) featuring IC50 values of 3-4 nM in both cAMP and GTPγS assays, favorable physicochemical and pharmacokinetic properties, and the ability to completely inhibit propionate-induced neutrophil migration and respiratory burst.

Fermentation of increasing ratios of grain starch and straw fiber: effects on hydrogen allocation and methanogenesis through in vitro ruminal batch culture.

Grain starch has a faster rate of rumen fermentation than straw fiber and causes a rapid increase in ruminal molecular hydrogen (H2) partial pressure, which may promote other H2 sinks to compete H2 away from methanogenesis. The study was designed to investigate the effects of increasing ratios of grain starch to straw fiber on hydrogen allocation and methanogenesis through in vitro ruminal batch incubation. Corn grain and corn straw were employed as starch and fiber source respectively. Seven treatments were the ratios of corn grain to corn straw (RGS) being 0:6, 1:5, 2:4, 3:3, 4:2, 5:1, and 6:0. Elevating RGS increased dry matter (DM) degradation and decreased methane (CH4) and hydrogen gas (gH2) production relative to DM degraded. Elevating RGS increased volatile fatty acid (VFA) concentration, propionate molar percentage and microbial protein (MCP) concentration, decreased acetate molar percentage, acetate to propionate ratio and estimated net metabolic hydrogen ([H]) production relative to DM degraded. Elevating RGS decreased the molar percentage of [H] utilized for CH4 and gH2 production. In summary, increasing ratios of grain starch to straw fiber altered rumen fermentation pathway from acetate to propionate production, reduced the efficiency of [H] production with the enhancement of MCP synthesis, and led to a reduction in the efficiency of CH4 and gH2 production.

Reprogramming Effects of Postbiotic Butyrate and Propionate on Maternal High-Fructose Diet-Induced Offspring Hypertension.

Maternal nutrition has a key role in the developmental programming of adult disease. Excessive maternal fructose intake contributes to offspring hypertension. Newly discovered evidence supports the idea that early-life gut microbiota are connected to hypertension later in life. Short-chain fatty acids (SCFAs), butyrate, and propionate are microbiota-derived metabolites, also known as postbiotics. The present study aimed to determine whether maternal butyrate or propionate supplementation can protect offspring from hypertension using a maternal high-fructose (HF) diet rat model. Female Sprague Dawley rats were allocated during pregnancy and lactation to (1) regular chow (ND); (2) 60% high-fructose diet (HF); (3) HF diet plus butyrate (HFB, 400 mg/kg/day); and (4) HF diet plus propionate (HFP, 200 mmol/L). Male offspring were sacrificed at 12 weeks of age. The maternal HF diet impaired the offspring's BP, which was prevented by perinatal butyrate or propionate supplementation. Both butyrate and propionate treatments similarly increased plasma concentrations of propionic acid, isobutyric acid, and valeric acid in adult offspring. Butyrate supplementation had a more profound impact on trimethylamine N-oxide metabolism and nitric oxide parameters. Whilst propionate treatment mainly influenced gut microbiota composition, it directly altered the abundance of genera Anaerovorax, Lactobacillus, Macellibacteroides, and Rothia. Our results shed new light on targeting gut microbiota through the use of postbiotics to prevent maternal HF intake-primed hypertension, a finding worthy of clinical translation.

HMOs Exert Marked Bifidogenic Effects on Children's Gut Microbiota Ex Vivo, Due to Age-Related Bifidobacterium Species Composition.

Prebiotics are substrates that are selectively utilized by host microorganisms, thus conferring a health benefit. There is a growing awareness that interpersonal and age-dependent differences in gut microbiota composition impact prebiotic effects. Due to the interest in using human milk oligosaccharides (HMOs) beyond infancy, this study evaluated how HMOs [2'Fucosyllactose (2'FL), Lacto-N-neotetraose (LNnT), 3'Sialyllactose (3'SL), 6'Sialyllactose (6'SL)] and blends thereof affect the microbiota of 6-year-old children (n = 6) and adults (n = 6), compared to prebiotics inulin (IN) and fructooligosaccharides (FOS). The ex vivo SIFR® technology was used, given its demonstrated predictivity in clinical findings. First, HMOs and HMO blends seemed to maintain a higher α-diversity compared to FOS/IN. Further, while 2'FL/LNnT were bifidogenic for both age groups, 3'SL/6'SL and FOS/IN were exclusively bifidogenic for children and adults, respectively. This originated from age-related differences in microbiota composition because while 3'SL/6'SL stimulated B. pseudocatenulatum (abundant in children), FOS/IN enhanced B. adolescentis (abundant in adults). Moreover, all treatments significantly increased acetate, propionate and butyrate (only in adults) with product- and age-dependent differences. Among the HMOs, 6'SL specifically stimulated propionate (linked to Bacteroides fragilis in children and Phocaeicola massiliensis in adults), while LNnT stimulated butyrate (linked to Anaerobutyricum hallii in adults). Indole-3-lactic acid and 3-phenyllactic acid (linked to immune health) and gamma-aminobutyric acid (linked to gut-brain axis) were most profoundly stimulated by 2'FL and HMO blends in both children and adults, correlating with specific Bifidobacteriaceae. Finally, 2'FL/LNnT increased melatonin in children, while 3'SL remarkably increased folic acid in adults. Overall, age-dependent differences in microbiota composition greatly impacted prebiotic outcomes, advocating for the development of age-specific nutritional supplements. HMOs were shown to be promising modulators in the adult, and particularly the children's microbiota. The observed HMO-specific effects, likely originating from their structural heterogeneity, suggest that blends of different HMOs could maximize treatment effects.

Membrane Potential-requiring Succinate Dehydrogenase Constitutes the Key to Propionate Oxidation and Is Unique to Syntrophic Propionate-oxidizing Bacteria.

Propionate oxidation in Pelotomaculum thermopropionicum is performed under a thermodynamic limit. The most energetically unfavorable reaction in the propionate oxidation pathway is succinate oxidation. Based on previous genomic and transcriptomic ana-lyses, succinate oxidation in P. thermopropionicum under propionate-oxidizing conditions is conducted by the membrane-bound forms of two succinate dehydrogenases (SDHs). We herein examined the activity of SDH, the mechanisms underlying the succinate oxidation reaction in P. thermopropionicum, and the importance of the protein sequences of related genes. SDH activity was highly localized to the membrane fraction. An ana-lysis of the soluble fraction revealed that fumarate reductase received electrons from NADH, suggesting the involvement of membrane-bound SDH in propionate oxidation. We utilized an uncoupler and inhibitors of adenosine triphosphate (ATP) synthase and membrane-bound SDH to investigate whether the membrane potential of P. thermopropionicum supports propionate oxidation alongside hydrogen production. These chemicals inhibited hydrogen production, indicating that membrane-bound SDH requires a membrane potential for succinate oxidation, and this membrane potential is maintained by ATP synthase. In addition, the phylogenetic distribution of the flavin adenine dinucleotide-binding subunit and conserved amino acid sequences of the cytochrome b subunit of SDHs in propionate-oxidizing bacteria suggests that membrane-bound SDHs possess specific conserved amino acid residues that are strongly associated with efficient succinate oxidation in syntrophic propionate-oxidizing bacteria.

A D-2-hydroxyglutarate dehydrogenase mutant reveals a critical role for ketone body metabolism in Caenorhabditis elegans development.

In humans, mutations in D-2-hydroxyglutarate (D-2HG) dehydrogenase (D2HGDH) result in D-2HG accumulation, delayed development, seizures, and ataxia. While the mechanisms of 2HG-associated diseases have been studied extensively, the endogenous metabolism of D-2HG remains unclear in any organism. Here, we find that, in Caenorhabditis elegans, D-2HG is produced in the propionate shunt, which is transcriptionally activated when flux through the canonical, vitamin B12-dependent propionate breakdown pathway is perturbed. Loss of the D2HGDH ortholog, dhgd-1, results in embryonic lethality, mitochondrial defects, and the up-regulation of ketone body metabolism genes. Viability can be rescued by RNAi of hphd-1, which encodes the enzyme that produces D-2HG or by supplementing either vitamin B12 or the ketone bodies 3-hydroxybutyrate (3HB) and acetoacetate (AA). Altogether, our findings support a model in which C. elegans relies on ketone bodies for energy when vitamin B12 levels are low and in which a loss of dhgd-1 causes lethality by limiting ketone body production.

Isolation and characterization of a new oxyphenisatin analogue, oxyphenisatin propionate, from a processed plum intended as a weight loss product.

A new oxyphenisatin analogue was detected from a processed plum claiming to be a weight loss product without any side effects during the daily inspecting and monitoring of illegal adulterants in health supplements. An abundant peak caused our interest firstly owing to its identical fragments of m/z 224 and 196 in the MS/MS experiments with those of oxyphenisatin acetate. The chemical structure of the unknown compound was characterized by ultra-high performance liquid chromatography equipped with diode array detector and quadrupole time-of-flight tandem mass spectrometry (UHPLC-DAD-Q-TOF/MS), followed by nuclear magnetic resonance (NMR) and infrared (IR) spectroscopy experiments. Based on the data, it was defined that the two symmetrical acetyl groups in oxyphenisatin acetate were replaced by two propionyl groups for the unknown structure. Finally, the new oxyphenisatin analogue was identified as 3,3-bis[4'-(propionyloxy)phenyl]-1,3-dihydroindole-2-one and designated as oxyphenisatin propionate. Thereafter, the content of the new analogue was quantitatively determined to be 681 mg/kg, which would inevitably cause adverse health effect because there was not specification for daily consumption of this product. To the best of our knowledge, this is the first report for identification of oxyphenisatin propionate.

Effects of adding ruminal propionate on dry matter intake and glucose metabolism in steers fed a finishing ration.

The objective of this experiment was to determine if supplying additional propionate to the rumen alters dry matter intake (DMI), feeding behavior, glucose metabolism, and rumen fluid metabolites in steers fed a finishing diet. Ruminally cannulated steers (n = 6) were fed a finishing diet ad libitum. Steers were randomly assigned to one of three treatments in a 3 × 6 Latin rectangle design with three 15 d periods. Treatments of no Ca propionate (Control), 100 g/d (Low), or 300 g/d (High) were ruminally dosed twice daily. Individual intake was measured using an Insentec feeding system. Pre-feeding blood samples were collected on day 7 and rumen fluid samples were collected on day 13. An intravenous glucose tolerance test (IVGTT) was conducted on day 14 and liver biopsies were collected on day 15. Liver samples were analyzed for expression of genes involved in gluconeogenesis. Data were analyzed using a mixed model with period, treatment, day, and their interaction included, with day and minute within period as a repeated measure and steer as a random effect. Meal size (P = 0.049), meal frequency (P = 0.046), and DMI (P < 0.001) were decreased in High steers. Day 7 plasma glucose (P = 0.23) and lactate (P = 0.47) were not affected by treatment, but insulin was decreased (P = 0.008) and non-esterified fatty acids were increased (P = 0.044) in the High treatment compared with the Control. Rumen fluid lactate was decreased (P = 0.015) in the High treatment compared with the Low treatment. Total VFA concentrations did not differ (P = 0.88) between treatments. There was treatment × time interaction for proportions of acetate and propionate (P < 0.001) and the acetate:propionate ratio (P = 0.005). The effect on acetate was due to a decrease in the High treatment 2 h after dosing the treatment. Propionate proportions were greater in the High treatment than the Control at all time points and differed from the Low except at 0 h. Propionate treatments had no major effects on the glucose and insulin parameters observed in the IVGTT other than a tendency (P = 0.09) for an increased insulin time to peak. These data indicate that exogenous propionate decreases DMI but the decrease in propionate from fermentation due to reduced DMI might negate the supply of exogenous propionate in VFA supply to the animal. Mechanisms other than hepatic oxidation of propionate might be responsible for DMI regulation.

Propionate metabolism by the liver is thought to be a key regulator of appetite and feed intake of animals, including cattle. Previous research has shown that providing propionate to the rumen of cattle decreases feed intake. Propionate is also a major contributor to glucose for cattle to use as an energy source for growth and maintenance. In this experiment, it was hypothesized that increasing ruminal propionate would depress feed intake and decrease insulin sensitivity. Supplying 300 g of propionate a day to the rumen decreased feed intake and increased the proportion of propionate in the rumen fluid of steers. However, when propionate production was calculated based on feed intake, there was likely no difference in propionate supply to the animal. The lack of increase in propionate supply to the animal could explain the lack of effect on glucose metabolism, insulin sensitivity, and liver gene expression. The lack of an increase in propionate also indicates that the effect of propionate on feed intake could be due to alternative mechanisms than liver metabolism of propionate.

Prevalence of Novel and Traditional Synthetic Phenolic Antioxidants in Baby Food from China: A Dominant Pathway for Infant Exposure.

Synthetic phenolic antioxidants (SPAs) are a group of ubiquitous contaminants with multiple toxicities. However, current knowledge on the occurrence of SPAs in baby food and associated infant exposure is lacking. Herein, we analyzed three categories of baby food from China: infant formula, cereal, and puree, for a broad suite of 11 traditional and 19 novel SPAs. In addition to 11 traditional SPAs, up to 13 novel SPAs were detected in the baby food samples. The median concentrations of novel SPAs for infant formula, cereal, and puree were 604, 218, and 24.1 ng/g, respectively, surpassing those of traditional SPAs (53.4, 62.1, and 10.0 ng/g). The prevalent SPAs in the samples were butylated hydroxytoluene, 2,4-di-tert-butylphenol, pentaerythritol tetrakis[3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate] (AO 1010), and octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl) propionate (AO 1076). Source analysis indicated that the prevalence of these four SPAs in baby food was associated with contamination of packaging materials, mechanical processing, or raw ingredients. Migration experiments demonstrated that contamination of plastic packaging constituted an important source. Exposure assessment suggested that there may be no appreciable health risk posed by the SPAs in baby food. Even so, baby food consumption was still a dominant pathway for infant exposure to SPAs, with a higher contribution than breast milk consumption, dust ingestion, dermal dust absorption, and air inhalation, which requires special attention.

Effect of low dietary concentrations of Acacia mearnsii tannin extract on chewing, ruminal fermentation, digestibility, nitrogen partition, and performance of dairy cows.

The supplementation of dairy cows with tannins can reduce the ruminal degradation of dietary protein and urine N excretion, but high concentration in the diet can impair ruminal function, diet digestibility, feed intake, and milk yield. This study evaluated the effect of low concentrations (0, 0.14, 0.29, or 0.43% of diet in DM basis) of a tannin extract from the bark of Acacia mearnsii (TA) on milking performance, dry matter intake (DMI), digestibility, chewing behavior, ruminal fermentation, and N partition of dairy cows. Twenty Holstein cows (34.7 ± 4.8 kg/d, 590 ± 89 kg, and 78 ± 33 d in lactation) were individually fed a sequence of 4 treatments in 5, 4 × 4 Latin squares (with 21-d treatment periods, each with a 14-d adaptation period). The TA replaced citrus pulp in the total mixed ration and other feed ingredients were kept constant. Diets had 17.1% crude protein, mostly from soybean meal and alfalfa haylage. The TA had no detected effect on DMI (22.1 kg/d), milk yield (33.5 kg/d), and milk components. The proportions in milk fat of mixed origin fatty acids (16C and 17C) and the daily secretion of unsaturated fatty acids were linearly reduced and the proportion of de novo fatty acids was increased by TA. Cows fed TA had linear increase in the molar proportion of butyrate and linear reduction in propionate in ruminal fluid, whereas acetate did not differ. There was a tendency for the ratio of acetate to propionate to be linearly increased by TA. Cows fed TA had a linear reduction in the relative ruminal microbial yield, estimated by the concentrations of allantoin and creatinine in urine and body weight. The total-tract apparent digestibility of neutral detergent fiber, starch, and crude protein also did not differ. The TA induced a linear increase in meal size and duration of the first daily meal and reduced meal frequency. Rumination behavior did not differ with treatment. Cows fed 0.43% TA selected against feed particles >19 mm in the morning. There were tendencies for linear decreases in milk urea N (16.1-17.3 mg/dL), urine N (153-168 g/d and 25.5-28.7% of N intake), and plasma urea N at 6, 18, and 21 h postmorning feeding, and plasma urea N 12 h postfeeding was reduced by TA. The proportion of N intake in milk (27.1%) and feces (21.4%) did not differ with treatment. Reductions in urine N excretion and milk and plasma urea N suggest that TA reduced ruminal AA deamination, whereas lactation performance did not differ. Overall, TA up to 0.43% of DM did not affect DMI and lactation performance, while there was a tendency to reduce urine N excretion.

Effects of lasalocid, narasin, or virginiamycin supplementation on rumen parameters and performance of beef cattle fed forage-based diet.

Two experiments were designed to evaluate the impacts of supplementing lasalocid (LAS), narasin (NAR), or virginiamycin (VRM) on rumen fermentation parameters, apparent nutrient digestibility, and blood parameters (Exp. 1), as well as feed intake and performance (Exp. 2) of Nellore cattle consuming a forage-based diet. In Exp. 1, 32 rumen-fistulated Nellore steers (initial shrunk body weight [BW] = 355 ± 4.4 kg) were assigned to a randomized complete block design. Within block, animals were randomly assigned to one of four treatments: 1) forage-based diet without feed additives (CON), 2) CON diet plus 13 mg/kg of dry matter (DM) of NAR, 3) CON diet plus 20 mg/kg of DM of sodium LAS, or 4) CON diet plus 20 mg/kg of DM of VRM. No treatment effects were detected (P ≥ 0.32) for intake and apparent digestibility of nutrients. Steers fed NAR had the lowest (P ≤ 0.01) molar proportion of acetate on day 28, 56, and 112 vs. CON, LAS, and VRM steers, whereas acetate did not differ (P ≥ 0.25) between LAS, VRM, and CON steers from day 28 to 84. On day 112, steers fed LAS had a lower (P < 0.02) molar proportion of acetate vs. VRM and CON, whereas it did not differ between CON and VRM (P > 0.33). Steers receiving NAR had a greater (P ≤ 0.04) ruminal propionate vs. CON, LAS, and VRM, whereas LAS steers had greater (P < 0.04) propionate vs. CON and VRM steers on day 28 and 112, and it did not differ (P > 0.22) between CON and VRM. In Exp. 2, 160 Nellore bulls were blocked by initial shrunk BW (212 ± 3.1 kg) in a 140-d feedlot trial. Diets contained the same treatments used in Exp. 1. Bulls fed NAR had greater (P < 0.02) average daily gain (ADG) vs. CON and VRM, and similar (P = 0.17) ADG between NAR and LAS, whereas ADG did not differ (P > 0.28) between LAS, VRM, and CON bulls. A treatment effect was detected (P = 0.03) for dry matter intake, being greater in NAR vs. CON, LAS, and VRM bulls, and similar (P > 0.48) between CON, LAS, and VRM bulls. A tendency was detected (P = 0.09) for feed efficiency, which was greater (P < 0.02) in NAR bulls vs. CON and VRM, and similar (P = 0.36) between NAR and LAS bulls. From day 112 to 140, bulls receiving NAR were heavier (P < 0.03) vs. CON, LAS, and VRM bulls, but no differences were observed (P > 0.51) between CON, LAS, and VRM bulls. Collectively, ruminal fermentation profile and intake were impacted by NAR supplementation, which partially contributed to the enhanced performance of Nellore bulls receiving a forage-based diet.

Feed additives are nutritional tools that benefit dietary digestibility and nutrient utilization, alter ruminal fermentation routes, and improve cattle growth and efficiency, thus increasing productivity and profitability in beef cattle systems. Nonetheless, most of the current research focuses on supplementing feed additives in high-concentrate diets. Leaving a significant gap in understanding the influence of feed additives in cattle consuming forage-based diets, especially molecules capable of altering the fermentation process and, consequently, beef cattle performance. Therefore, this experiment aimed to evaluate the impacts of supplementing narasin (NAR), lasalocid (LAS), or virginiamycin (VRM) on rumen fermentation parameters, apparent nutrient digestibility, feed intake, and performance of Bos indicus Nellore cattle consuming a forage-based diet. Including commercially available feed additives into forage-based diets did not impact nutrient intake and digestibility of nutrients. The inclusion of NAR affected ruminal fermentation parameters toward propionate production, positively contributing to animal performance. Ruminal fermentation characteristics and animal growth were not impacted by dietary LAS and VRM, which could be attributed to the dose used in the current experiment, despite the manufacturer's recommendation. This research provides insights into NAR as an important feed additive for forage-based beef cattle diets.

The allosterically modulated FFAR2 is transactivated by signals generated by other neutrophil GPCRs.

Positive allosteric modulators for free fatty acid receptor 2 (FFAR2/GPR43), that affect receptor function through binding to two distinct allosteric binding sites, were used to determine the correlation between the responses induced in neutrophils by two distinct activation modes; FFAR2 was activated either by the orthosteric agonist propionate or by a receptor transactivation mechanism that activated FFAR2 from the cytosolic side of the neutrophil plasma membrane by signals generated by the neutrophil PAFR (receptor for platelet activating factor), P2Y2R (receptor for ATP), FPR1 (receptor for fMLF) and FPR2 (receptor for WKYMVM). We show that the transactivation signals that activate FFAR2 in the absence of any orthosteric agonist were generated downstream of the signaling G protein that couple to PAFR and P2Y2R. This transactivation of allosterically modulated FFAR2s, by signals generated by PAFR/P2Y2R, represents a novel mechanism by which a G protein coupled receptor can be activated. Weak correlations were obtained when the FFAR2 activity was induced by the transactivation signals generated by PAFRs and P2Y2Rs were compared with the FFAR2 activity induced by the orthosteric agonist propionate. Comparison of the responses for each allosteric modulator revealed that the ratio values, calculated from the peak values of the ATP and propionate responses, varied from 0.2 to 1. Depending on the allosteric modulator, the response induced by the two different mechanisms (orthosteric activation and receptor transactivation, respectively), was equal or the propionate response was more pronounced. Importantly, we conclude that FFAR2 activation from outside (orthosteric activation) and inside (receptor cross-talk/transactivation) can be selectively affected by an allosteric FFAR2 modulator.

Interplay between the (Poly)phenol Metabolome, Gut Microbiome, and Cardiovascular Health in Women: A Cross-Sectional Study from the TwinsUK Cohort.

BACKGROUND: Dietary (poly)phenol consumption is inversely associated with cardiovascular disease (CVD) risk in epidemiological studies, but little is known about the role of the gut microbiome in this relationship. METHODS: In 200 healthy females, aged 62.0 ± 10.0 years, from the TwinsUK cohort, 114 individual (poly)phenol metabolites were measured from spot urine using ultra-high-performance liquid chromatography-mass spectrometry. The associations between metabolites, the gut microbiome (alpha diversity and genera), and cardiovascular scores were investigated using linear mixed models adjusting age, BMI, fibre, energy intake, family relatedness, and multiple testing (FDR < 0.1). RESULTS: Significant associations were found between phenolic acid metabolites, CVD risk, and the gut microbiome. A total of 35 phenolic acid metabolites were associated with the Firmicutes phylum, while 5 metabolites were associated with alpha diversity (FDR-adjusted p < 0.05). Negative associations were observed between the atherosclerotic CVD (ASCVD) risk score and five phenolic acid metabolites, two tyrosol metabolites, and daidzein with stdBeta (95% (CI)) ranging from -0.05 (-0.09, -0.01) for 3-(2,4-dihydroxyphenyl)propanoic acid to -0.04 (-0.08, -0.003) for 2-hydroxycinnamic acid (FDR-adjusted p < 0.1). The genus 5-7N15 in the Bacteroidetes phylum was positively associated with the same metabolites, including 3-(3,5-dihydroxyphenyl)propanoic acid, 3-(2,4-dihydroxyphenyl)propanoic acid, 3-(3,4-dihydroxyphenyl)propanoic acid), 3-hydroxyphenylethanol-4-sulfate, and 4-hydroxyphenylethanol-3-sulfate)(stdBeta (95% CI): 0.23 (0.09, 0.36) to 0.28 (0.15, 0.42), FDR-adjusted p < 0.05), and negatively associated with the ASCVD score (stdBeta (95% CI): -0.05 (-0.09, -0.01), FDR-adjusted p = 0.02). Mediation analysis showed that genus 5-7N15 mediated 23.8% of the total effect of 3-(3,4-dihydroxyphenyl)propanoic acid on the ASCVD score. CONCLUSIONS: Coffee, tea, red wine, and several vegetables and fruits, especially berries, are the most abundant food sources of phenolic acids that have the strongest associations with CVD risk. We found that the gut microbiome, particularly the genus 5-7N15, partially mediates the negative association between urinary (poly)phenols and cardiovascular risk, supporting a key role of the gut microbiome in the health benefits of dietary (poly)phenols.