Propionic Research Articles

Effects of Lagenaria siceraria (Molina) Standl polysaccharides on growth performance, immune function, cecum microorganisms and short-chain fatty acids in broilers.

In this study, Lagenaria siceraria (Molina) Standl polysaccharides (LSP) was prepared using the water-alcohol precipitation method to evaluate its effects on growth performance, slaughter performance, cytokines, immune organ indices, cecal short-chain fatty acids (SCFAs), and microbial community structure in broiler chickens when added to the basal diet. Seventy-five broiler chickens were selected and randomly divided into five groups, with 15 chickens per group. All groups were fed a basal diet for 7 days. From 7 days of age, the control group continued to receive the basal diet, while the positive drug group was fed a diet supplemented with Astragalus polysaccharides (APS, 100 g/kg) in addition to the basal diet. The experimental groups were fed diets containing different concentrations of LSP (50, 100, and 200 g/kg) in addition to the basal diet, and the supplementation continued for 42 days. The findings indicated that the incorporation of LSP into the feed significantly enhanced average daily weight gain (ADWG), average daily feed intake (ADFI), feed to gain ratio (F/G), dressing percentage, percentage of breast muscle, percentage of leg muscle, and percentage of abdominal fat while concurrently reducing drip loss rate and cooking loss rate (p < 0.01) in comparison to the control group. Additionally, it significantly augmented the levels of interleukin-4 (IL-4) and interleukin-12 (IL-12) in cytokines, secreted immunoglobulin A (SIgA) and immunoglobulin G (IgG) in immunoglobulins, as well as immune organ indicators (p < 0.05). Furthermore, LSP also modulated the intestinal microbiome composition by increasing the abundance of Bacteroides species and significantly changing concentrations of specific short-chain fatty acids (SCFAs) such as propionic acid, isobutyric acid, acetic acid, and isovaleric acid (p < 0.01). These results suggest that dietary supplementation with LSP can effectively regulate intestinal microbiome composition while promoting short-chain fatty acid production. The alterations in microbial characteristics ultimately contribute to improved intestinal immunity and immune organ development as well as enhanced production performance and immune function in broilers.

Intratumoural microorganism can affect the progression of hepatocellular carcinoma.

Several recent studies have confirmed that intratumoural microorganisms can affect the occurrence and development of hepatocellular carcinoma (HCC); however, their role in tumor progression remains unclear. Hence, there is a need for further research on the role of intratumoural microorganisms in HCC. To investigate the changes in intratumoural microorganisms in HCC and the effect of Propionibacterium on HCC progression. HCC and normal liver tissue specimens were subjected to fluorescence in situ hybridization (FISH). After performing 16S rRNA sequencing on HCC and peritumoral tissues to analyze the differences between the two groups. Propionibacterium was cocultured with HCC cells in vitro. Changes in cell proliferation and migration capacity were evaluated. The expression of NF-κB pathway related proteins in tumor cells was compared. The orthotopic liver implantation model and the subcutaneous xenograft model were constructed. liver tissues and subcutaneous tumors were collected 2 weeks later. FISH demonstrated the presence of microorganisms in HCC and normal liver tissues. 16S rRNA sequencing revealed an abundance of Lysobacter, Lachnospiraceae, Pseudomonas, and Lactobacillus in HCC tissues. The distribution and abundance of Propionibacterium showed differences between HCC and peritumoral tissues (P < 0.05). In vitro studies demonstrated that Propionibacterium and its metabolite propionic acid (PA) inhibited the proliferation and migration of HCC cells (P < 0.05). The expression of the proteins in NF-κB signaling pathway also decreased in HCC cells (P < 0.05). Microorganisms in HCC and normal liver tissues displayed significant disparities. The PA-producing bacterium Propionibacterium in HCC exerts an effect on the NF-κB pathway, thereby affecting the biological behavior of HCC.

Characterization of patients with major psychiatric disorders with AMPA receptor positron emission tomography.

Synaptic phenotypes in living patients with psychiatric disorders are poorly characterized. Excitatory glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) is a fundamental component for neurotransmission. We recently developed a positron emission tomography (PET) tracer for AMPAR, [11C]K-2, the first technology to visualize and quantify AMPARs density in living human brain. In this study, we characterized patients with major psychiatric disorders with [11C]K-2. One hundred forty-nine patients with psychiatric disorders (schizophrenia, n = 42; bipolar disorder, n = 37; depression, n = 35; and autism spectrum disorder, n = 35) and 70 healthy participants underwent a PET scan with [11C]K-2 for measurement of AMPAR density. We detected brain regions that showed correlation between AMPAR density and symptomatology scores in each of four disorders. We also found brain areas with significant differences in AMPAR density between patients with each psychiatric disorder and healthy participants. Some of these areas were observed across diseases, indicating that these are commonly affected areas throughout psychiatric disorders. Schizophrenia, bipolar disorder, depression, and autism spectrum disorder are uniquely characterized by AMPAR distribution patterns. Our approach to psychiatric disorders using [11C]K-2 can elucidate the biological mechanisms across diseases and pave the way to develop novel diagnostics and therapeutics based on the synapse physiology.

Effects of Boron on Learning and Behavioral Disorders in Rat Autism Model Induced by Intracerebroventricular Propionic Acid.

Autism spectrum disorder is a neurodevelopmental disorder in which learning, communication, and social interaction are impaired. Research has sought to minimize the neural impairments associated with autism spectrum disorder and improve the quality of life. Recent studies suggest that boron may benefit nerve cells, with effects varying depending on the dosage. This study explored the impact of boron, administered as boric acid, on behavioral, biochemical, and histopathological parameters in a rat model of autism induced by propionic acid (PPA). Thirty-two male Sprague-Dawley rats were divided into control, autism model, and boron-treated groups. Behavioral tests were conducted pre- and post-PPA induction, with brain tissue analyzed post-euthanasia. Proinflammatory cytokines (tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), interleukin 6 (IL-6)) and brain-derived neurotrophic factor (BDNF) levels were assessed in the hippocampus. Histopathological evaluations were conducted on the hippocampus and cerebellum. Autism model rats displayed impaired learning, elevated BDNF and cytokine levels, microglial and astrocytic activation, and decreased Purkinje cell count. The boron-treated groups showed improvements, particularly with the 4mg/kg dose. This dose enhanced learning and social interaction, reduced proinflammatory cytokine levels, prevented microglial and astrocytic activation, and increased Purkinje cell count. Boron treatment exhibited neuroprotective potential, ameliorating autism spectrum disorder deficits by modulating cytokines, BDNF, microglia, and astrocytes, with low doses yielding pronounced effects.

Potential Prebiotic Effects of Artemisia capillaris-Derived Transglycosylated Product.

This study investigated the impact of a transglycosylated product (ACOD) catalyzed by Leuconostoc mesenteroides MKSR dextransucrase using sucrose as a glucosyl donor and both maltose and Artemisia capillaris as acceptors on gut microbiota through fecal fermentation. ACOD promoted the growth of probiotics such as Lactiplantibacillus plantarum, Lacticaseibacillus casei, Lacticaseibacillus rhamnosus GG, and Leuconostoc mesenteroides MKSR, while inhibiting the growth of pathogenic bacteria such as Escherichia coli, E. coli O157:H7, Enterococcus faecalis, Listeria monocytogenes, Staphylococcus aureus, Shigella flexneri, Streptococcus mutans, Pseudomonas aeruginosa, and Bacillus cereus during independent cultivation. Fecal fermentation for 24 h revealed that ACOD significantly increased the production of short-chain fatty acids (SCFAs) compared to the blank and fructoooligosaccharide (FOS) groups. Specifically, ACOD led to a 4.5-fold increase in acetic acid production compared to FOSs and a 3.3-fold increase in propionic acid production. Both the ACOD and FOS groups exhibited higher levels of butyric acid than the blank. Notably, ACOD significantly modulated the composition of the gut microbiota by increasing the relative abundances of Lactobacillus and decreasing Escherichia/Shigella and Salmonella. In contrast, FOSs remarkably promoted the growth of Salmonella. These findings suggest that ACOD is a potential candidate for prebiotics that improve the intestinal environment by being actively used by beneficial bacteria.

Effect of different genetic backgrounds on rumen microbiota and serum metabolic phenotypes in beef cattle

Species with different genetic backgrounds exhibit distinct metabolic traits. Nine beef cattle were selected for the experiment to study changes in serum metabolic phenotypes, rumen microbiota diversity, and composition in beef cattle from different genetic backgrounds. Three groups were Chinese Simmental (S group), Simmental×Chinese Holstein (SH group), and Simmental × Mongolian (SM group) cattle. We used ELISA to detect serum biochemical indicators. The Short-chain fatty acids (SCFAs) in the rumen were examined, and a significant difference was observed in the acetic acid content of the three experimental groups (p < 0.01). The propionic acid content in the rumen of the S group was significantly higher than that of the SH and SM groups (p < 0.05). The A/P ratios of both the S and SM groups were significantly higher than that of the SH group (p < 0.05). We analyzed rumen microbiota composition and diversity in each group of cattle using 16 S rRNA sequencing and found that their composition was generally similar in the three groups of crossbred fattening cattle; however, the f_Bacteroidales_RF16_group and g_norank_f_Bacteroidales_RF16_group were significantly enriched in the SH group, whereas Treponema and Spirochaetia were significantly enriched in the SM group. Spirochaetia was significantly enriched in the SM group. Differences in rumen bacterial enrichment indicated that starch, protein, and cellulolytic abilities differed among the S, SH, and SM groups. The results of Spearman correlation analysis confirmed the correlation between rumen genera and serum biochemical indices. Overall, differences in rumen microflora play an important role in influencing the serum metabolic phenotype.

Hazard assessment of fenozan, a released non-intentionally added substance from polyester-based can coating

Since the safety of new-generation polyester-based internal coatings regarding the migration of non-intentionally added substances (NIAS) is poorly documented, studies are needed to identify NIAS originating from these food-contact materials (FCM). The aim of this study was to identify volatile and semi-volatile NIAS from polyester-based coatings in order to assess their hazard and ensure consumers’ safety with regard to exposure from canned food. Extraction and migration tests were carried out on a single polyester-coated tin plate (5 batches) using two solvents: acetonitrile and ethanol 95%, then FCM’s extracts and migrates were analysed by GC-MS. An antioxidant degradation (hydrolysis) product, 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionic acid or fenozan (CAS RN: 20170-32-5), was identified and confirmed by reference standard in all migrates. To assess fenozan’s toxicity, several in vitro bioassays, such as the Ames test (to assess point mutation), the micronucleus assay (to detect chromosomal aberrations), and the iodide uptake assay (to study one mode of action for thyroid disruption) were conducted. Fenozan was negative in the Ames test on three strains of S. typhimurium (TA98, TA100, and TA1535) and on one strain of E.coli (WP2), with and without metabolic activation system (S9 mix) using direct incorporation and pre-incubation methods. The in vitro micronucleus assay conducted on HepG2 cells also exhibited a negative response following a 4-hour treatment with the S9 mix, and a 48-hour treatment without the S9 mix. A weak inhibitory effect was obtained when testing fenozan in the iodide uptake assay using rat thyroid FRTL-5 cells. Significant inhibition started from 800 µM of fenozan, with a maximal inhibition of almost 47% at 1000 µM. The findings indicate that fenozan exhibits an anti-thyroid activity in vitro.

The Effect of Adding Green and Black Tea Waste Extracts on Rumen Fermentation Parameters by In Vitro Techniques

The increase in global temperatures over the past few decades due to greenhouse gas emissions has raised concerns and necessitated further research in climate change mitigation and adaptation. Methane is a prominent greenhouse gas that significantly contributes to climate change, with a substantial amount generated through fermentation processes occurring in the rumen of ruminant animals. The potential of plant secondary metabolites, especially those derived from tannin-rich plants, warrants investigation to modify rumen fermentation and mitigate methane emissions in livestock diets. The objective of this study was to assess the impact of extracts obtained from green and black tea waste on rumen fermentation dynamics and gas (methane) production, utilizing in vitro methods. For this purpose, rumen fluid was collected from two fistulated sheep and subjected to three treatments: (1) a basal diet (control), (2) a basal diet + green tea waste extract (5% of dry matter), (3) a basal diet + black tea waste extract (5% of dry matter). The study assessed the effects of incorporating extracts from green and black tea waste on various parameters, including digestibility, protozoa population, ammonia nitrogen levels, volatile fatty acids, and methane gas production following a 24-h incubation period. Statistical analysis of the data was conducted using SAS software within a completely randomized design framework. The findings indicated that the addition of green and black tea waste extracts significantly decreased methane gas production (p &lt; 0.05), protozoa count (p &lt; 0.05), and ammonia nitrogen concentrations in rumen fluid (p &lt; 0.05) when compared to the control group. The addition of green and black tea waste extracts has significantly altered the concentration of VFAs in rumen fluid (p &lt; 0.05). Specifically, the addition of green tea waste extract has led to a highly significant reduction in acetic acid, (p &lt; 0.01) and the addition of both extracts has resulted in a significant increase in propionic acid (p &lt; 0.05). Consequently, the results suggest that the inclusion of green and black tea waste extracts in livestock diets may effectively mitigate methane emissions in the rumen, thereby reducing feed costs and reducing environmental pollution.

Effects of chicken slurry inclusion on apparent total tract macronutrient digestibility, palatability, and fecal characteristics, microbiota, and metabolites of healthy adult dogs.

"Premium" pet foods are often formulated with meat slurries. Meat slurries are believed to be of higher quality than rendered meals, but inadequate research has been performed to test how their inclusion affects palatability, digestibility, or indicators of gastrointestinal health. Therefore, the objectives of this study were to determine how chicken slurry inclusion affected the palatability and apparent total tract macronutrient digestibility (ATTD) of dog foods and to assess their effects on the fecal characteristics, metabolites, and microbiota of dogs. A replicated 3x3 Latin square design digestibility study was conducted using 9 healthy adult dogs (age = 5.44 ± 0.53 yr) to test diets containing 0% (control; CON), 8% (low inclusion; LOW), and 16% (high inclusion; HIGH) chicken slurry. The experiment comprised three 21-day experimental periods (14 days of adaptation, 5 days of total fecal collection (used for ATTD calculations), and 2 days of blood collection). On the first day of fecal collections, one fresh sample was collected for measurement of pH, dry matter (DM) content, fermentative metabolite concentrations, and microbiota populations. A 2-day palatability study (n=20 dogs) was also conducted to compare CON vs. HIGH. Data were analyzed statistically by Mixed Models using SAS 9.4, with P<0.05 being significant. In the palatability study, dogs were shown to prefer (P<0.05) the HIGH diet by a ratio of 2:1. In the digestibility study, fecal output, scores, pH, and DM percentage were not different among diets. The ATTD of protein was higher (P<0.05) for the HIGH diet (84.6%) than for the LOW (82.7%) or CON (82.6%) diets. The ATTD of other nutrients and energy were not different among diets (all over 80%). Fecal propionate, butyrate, and total short-chain fatty acid concentrations were higher (P<0.05) in dogs fed the LOW diet (122.0, 67.4, and 408.2 βmol/g, respectively) than those fed the HIGH diet (89.0, 46.9, and 338.2 βmol/g, respectively). The other fecal metabolites (acetate, branched-chain fatty acids, ammonia, phenol, and indole) were not different among treatments. Few changes to the fecal microbiota were noted. However, the relative abundance of fecal Fusobacterium was higher (P<0.05) in dogs fed the CON diet than those fed the HIGH diet (25.% vs. 20.0% relative abundance). In summary, chicken slurry inclusion improved palatability but had minimal effects on nutrient digestibility and fecal characteristics, metabolites, and microbiota.

Use of embedding immobilized biofillers to improve hydrolysis acidification efficiency in domestic wastewater treatment

This study evaluated the effectiveness of embedding immobilization technology in wastewater treatment and its capacity to enhance the hydrolysis acidification process. Based on this technology, a stable anaerobic environment has been maintained. Results showed that the rates of dissolved organic nitrogen (DON) and dissolved organic phosphorus (DOP) conversion both exceeded 98 % under short hydraulic retention time (HRT = 2h) and ambient temperature. Notably, acetic acid and propionic acid comprised up to 90.9 % of the total volatile fatty acids in the effluent, providing suitable carbon sources for downstream denitrification. 16S rRNA gene sequencing indicated that biofillers effectively enriched and retained functional bacteria, causing norank_Anaerolineaceae (11.6 %-29.7 %) and norank_Bacteroidetes_vadinHA17 (10.8 %-14.9 %) as the dominant genera in the reactor, which were crucial for refractory organic matter degradation. Immobilized biofillers effectively improved wastewater biodegradability, supporting a stable microbial community with high DON and DOP conversion rates as well as increased VFA accumulation.

Diethyl aminoethyl hexanoate reprogramed accumulations of organic metabolites associated with water balance and metabolic homeostasis in white clover under drought stress.

Diethyl aminoethyl hexanoate (DA-6) serving as a non-toxic and low-cost plant growth regulator is used for improving plant growth and stress tolerance, but the DA-6-mediated organic metabolites remodeling in relation to drought tolerance is not well documented in crops. The aims of the present study were to evaluate impacts of DA-6 on physiological functions including osmotic adjustment, photochemical efficiency, oxidative damage, and cell membrane stability as well as organic metabolites remodeling in white clover (Trifolium repens) leaves based on the analysis of metabolomics. Plants were foliarly treated with or without DA-6 and subsequently exposed to drought stress for 8 days. Results demonstrated that foliar application of DA-6 (1.5 mM) could significantly ameliorate drought tolerance, which was linked with better leaf water status, photosynthetic performance, and cell membrane stability as well as lower oxidative injury in leaves. Metabolic profiling of organic metabolites identified a total of 59 metabolites including 17 organic acids, 20 sugars, 12 alcohols, and 10 other metabolites. In response to drought stress, the DA-6 induced accumulations of many sugars and sugar alcohols (erythrulose, arabinose, xylose, inosose, galactose, talopyranose, fucose, erythritol, and ribitol), organic acids (propanoic acid, 2,3-dihydroxybutanoic acid, palmitic acid, linolenic acid, and galacturonic acid), and other metabolites (2-oxazoline, silane, and glycine) in white clover. These altered metabolites induced by the DA-6 could perform critical functions in maintenances of osmo-protection, osmotic adjustment, redox homeostasis, cell wall structure and membrane stability when white clover suffered from water deficit. In addition, the campesterol and stigmasterol significantly accumulated in all plants in spite of the DA-6 pretreatment under drought stress, which could be an important adaptive response to water deficit due to beneficial roles of those two metabolites in regulating cell membrane stability and antioxidant defense. Present findings provide new evidence of DA-6-regulated metabolic homeostasis contributing to drought tolerance in leguminous plants.

Fecal Microbiota Transplantation Induced by Wumei Pills Improves Chemotherapy-Induced Intestinal Mucositis in BALB/c Mice by Modulating the TLR4/MyD88/NF-κB Signaling Pathway.

Our previous studies have found that Wumei Pills can regulate the intestinal flora to inhibit chemotherapy-induced intestinal mucositis (CIM). However, there is still insufficient evidence to confirm that intestinal flora is the main link in the regulation of CIM by Wumei Pills, and its downstream mechanism is still unclear. We first obtained the signal pathway of the intervention of Wumei Pill on CIM through network pharmacological analysis and then transplanted the bacterial solution into CIM mice, combined with Western Blot, HE, ELISA and other biological technology-related proteins and inflammatory factors. It showed that 97 kinds of effective ingredients and 205 kinds of targets of Wumei pills were screened out and the potential mechanism of Wumei Pills on CIM may be the NF-κB signaling pathway. In contrast with the control group, the results displayed that the weight, food intake, and mice's colon length were apparently decreased in the 5-Fu group, while the diarrhea score was increased. However, FMT reversed this change, and the difference was statistically significant. Additionally, FMT could improve the pathological state of inflammatory cell infiltration in mice, reduce histopathological scores of colon and jejunum, decrease the expression levels of IL-1β, MPO, TNF-α, and IL-6, reverse the activation of signaling pathway named TLR4/Myd88/ NF-κB and down-regulate protein expression, thereby exerting its anti-inflammatory activities. Further experiments have found that FMT could reverse the decreasing of tight junction proteins and mucins caused by 5-Fu, thereby repairing the intestinal mucosal barrier, and FMT could also increase the content of acetic acid, propanoic acid, and butanoic acid in the feces of 5-Fu group. FMT can defend the intestinal mucosal barrier integrality by increasing the content of exercise fatty acids, and its mechanism may be in connection with its inhibition of TLR4/My- D88/NF-κB signal pathway to relieve inflammation.

Blackcurrant Anthocyanins Attenuate Estrogen -Deficiency-Induced Bone Loss through Modulating Microbial-Derived Short-Chain Carboxylic Acids and Phytoestrogen Metabolites in Peri- and Early Postmenopausal Women.

The present study aimed to assess the effects of blackcurrant (BC) anthocyanins on concentrations of microbial-derived short-chain carboxylic acids (SCCAs) and metabolites of phytoestrogens. We then examined their associations with six-month changes in whole-body bone mineral density (BMD) and biomarkers of bone metabolism. Fecal and blood samples from a pilot randomized controlled trial were collected and analyzed from 37 eligible peri- and early postmenopausal women aged 45-60 years who were randomized into one of three treatment groups consuming one placebo capsule (control), 392 mg BC (low BC) or 784 mg BC (high BC) daily for six months. Significant differences were observed between groups at baseline in acetic, propionic, valeric, caproic and heptanoic acids (p < 0.05). Isobutyric acid significantly decreased from baseline (0 months) to six months in the control group (p < 0.05) and the high BC group had a significantly greater concentration than the control group at six months (p < 0.05). Butyric acid was significantly greater in the high BC group than low BC at six months (p < 0.05). Six-month changes in caproic and isobutyric acids showed weak correlations with changes in whole-body BMD (r = 0.3519, p < 0.05 and r = 0.3465, p < 0.05, respectively). Isovaleric and valeric acids displayed weak correlations with BALP (r = 0.3361, p < 0.05) and OPG (r = 0.3593, p < 0.05), respectively. Enterodiol was positively correlated with BALP (r = 0.6056, p < 0.01) while enterolactone was positively correlated with osteocalcin (r = 0.5902, p < 0.001) and negatively correlated with sclerostin (r = -0.3485, p < 0.05). The results suggest that BC may be a potential dietary agent to reduce postmenopausal bone loss through modulating microbially-derived SCCAs and phytoestrogen metabolites.

Lacticaseibacillus paracasei 207-27 alters the microbiota-gut-brain axis to improve wearable device-measured sleep duration in healthy adults: a randomized, double-blind, placebo-controlled trial.

Objective: Probiotics have been reported to exert beneficial effects on sleep through the gut-brain axis. Therefore, this randomized, double-blind, placebo-controlled trial assessed the effects of Lacticaseibacillus paracasei 207-27 supplementation on sleep quality and its safety and potential mechanisms. Method and study design: Healthy adults under mild stress aged 18-35 years consumed low or high doses of L. paracasei 207-27 or a placebo for 28 days. Fecal samples, blood samples, and questionnaires were collected at the baseline and the end of the intervention. Sleep quality was measured using wearable devices and Pittsburgh sleep quality index (PSQI) questionnaire. Serum inflammatory markers, corticotropin-releasing hormone, adrenocorticotropic hormone (ACTH), cortisol (COR), γ-aminobutyric acid, and 5-hydroxytryptamine levels were detected using enzyme-linked immunosorbent assay. The gut microbiota was analyzed using 16S rRNA sequencing and bioinformatics. Short-chain fatty acids levels were detected using gas chromatography-mass spectrometry. Results: Both the low-dose and high-dose groups exhibited significant improvements in wearable device- measured sleep duration compared to the placebo group. The global scores of PSQI in three groups significantly decreased after intervention without statistical difference between groups. At the phylum level, the low-dose group exhibited a higher relative abundance of Bacteroidota and a lower Firmicutes-to-Bacteroidetes (F/B) ratio. At the genus level, two treatment groups had higher relative abundance of Bacteroides and Megamonas, alongside lower levels of Escherichia-Shigella. Furthermore, the low-dose group exhibited significant increases in acetic acid, propionic acid, butyric acid, and valeric acid levels, while two treatment groups exhibited a significant decrease in COR levels. Correlation analysis revealed that the increased levels of acetic acid and butyric acid in the low-dose group may be associated with decreased ACTH. Conclusion: L. paracasei 207-27 administration in healthy adults resulted in improvements in gut microbiota community and sleep duration. The mechanisms might involve modulation of the gut microbiota structure to regulate the function of the gut-brain axis, including increases in SCFA levels and decreases in hypothalamic-pituitary-adrenal axis activity. The Chinese clinical trial registry number is ChiCTR2300069453 (https://www.chictr.org.cn/showproj.html?proj=191193, registered 16 May 2023 - retrospectively registered).

Discovery of Propionic Acid Derivatives with a 5-THIQ Core as Potent and Orally Bioavailable Keap1-Nrf2 Protein-Protein Interaction Inhibitors for Acute Kidney Injury.

Keap1 plays a crucial role in regulating the Nrf2-mediated cytoprotective response and is increasingly targeted for oxidative stress-related diseases. Using small molecules to disrupt the Keap1-Nrf2 protein-protein interaction (PPI) has emerged as a new strategy for developing Nrf2 activators. Through extensive structure-activity relationship studies, we identified compound 56, which features a unique 5-tetrahydroisoquinoline scaffold and acts as a potent inhibitor of the Keap1-Nrf2 PPI. Compound 56 exhibited significant inhibitory activity (IC50 = 16.0 nM) and tight Keap1 binding affinity (Kd = 3.07 nM), along with acceptable oral bioavailability (F = 20%). Notably, 56 enhanced antioxidant defenses in HK-2 renal tubular epithelial cells and significantly reduced plasma creatinine and blood urea nitrogen levels in acute kidney injury (AKI) mice. These findings collectively position compound 56 as a promising candidate for the treatment of AKI.

Christensenellaceae minuta modulates epithelial healing via PI3K-AKT pathway and macrophage differentiation in the colitis

Ulcerative colitis (UC) is a chronic inflammatory disorder with an unsatisfactory cure rate and mucosal healing is a key treatment objective. Christensenellaceae minuta (C. minuta) has emerged as a next-generation of probiotic for maintaining intestinal health. We investigated the therapeutic efficacy of C. minuta in dextran sulfate sodium (DSS)-induced colitis, focusing on mucosal healing and the underlying mechanisms. C. minuta effectively alleviated colitis and promoted the regeneration of intestinal epithelial cells (IECs). Using 16S rRNA sequencing and metabolomics, we found that C. minuta administration increased beneficial bacteria, decreased pathogenic bacteria, and significantly elevated propionic acid levels. Additionally, C. minuta activated the PI3K-AKT pathway by upregulating systemic and local IGF-1 expression. Inhibiting the PI3K-AKT pathway reduced the therapeutic effects of C. minuta and impaired IEC regeneration. Furthermore, C. minuta promoted macrophage differentiation into the M2 phenotype and decreased proinflammatory factors. We propose that C. minuta alleviates colitis by regulating the gut microbiota, modulating macrophage differentiation, and enhancing mucosal healing by activating the PI3K-AKT pathway via IGF-1 secretion induced by short-chain fatty acids. Our findings provide evidence from animal experiments to support future clinical trials and the therapeutic translation of C. minuta.

Effects of Prebiotic Dietary Fibers on the Stimulation of the Mucin Secretion in Host Cells by In Vitro Gut Microbiome Consortia.

The gastrointestinal microbiota are important for human health. Dietary intake may modulate the composition and metabolic function of the gut microbiome. We examined how the breakdown of prebiotic dietary fibers by the gut microbiome affects mucin secretion by intestinal epithelial cells. Metagenomic analyses of in vitro gut microbiome consortia revealed taxonomic profiles and genetic diversity of carbohydrate-active enzymes that digest polysaccharides. Two independent consortia exhibited different abilities to produce acetic acid, propionic acid, and butyric acid via the fermentation of polysaccharides derived from dietary fibers of grains and mushrooms. Although acetic acid generally had the highest concentration, the ratios of butyric acid and propionic acid to acetic acid varied depending on the polysaccharide source. These short-chain fatty acids affected morphological differentiation and mucin secretion in HT-29 human intestinal epithelial cells. These results suggest that prebiotic dietary fibers can be digested and metabolized by the gut microbiome to short-chain fatty acids, which can affect gut epithelial cells both directly and indirectly via the modulation of the gut microbiota and their enzymes.

Polyphenol composition and antioxidant activity of fermentation combined with enzymatic hydrolysis modified Astragalus membranaceus stems

Astragalus membranaceus (AM) roots are a well-known homologous medicine and food in China. AM stems, which are discarded and not used effectively, also contain many active compounds and exhibit beneficial effects. It has the potential to be explored as antibiotic alternative. Fermentation combined with enzymatic hydrolysis (FEH) is an effective strategy for extracting polyphenol and improving the usage of AM stems. Therefore, in this study, the conditions of FEH and extraction for polyphenol in AM stems were screened. The antioxidant activity of extract from AM stems without and with FEH (AMSE and FAMSE) was evaluated. The metabolite profiles of phenolic acids and flavonoids in AMSE and FAMSE were characterized by ultra-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (UPLC–ESI-MS/MS). The results showed that the highest polyphenol content from AM stems was obtained with cellulase and pectinase (1:1, 2000 U/g), moisture content 43%, fermentation temperature 30 °C, and fermentation time 7 days. Selected extraction conditions of polyphenol were ethanol concentration 50%, ultrasonic power 500 W, extraction temperature 35 °C, and extraction time 40 min. On this condition, compared with AMSE, the polyphenol and flavonoid contents in FAMSE were significantly higher. FAMSE exhibited stronger DPPH, hydroxyl radical scavenging rate and reducing power than AMSE. The relative content of 3-(4-hydroxyphenyl)-propionic acid, dihydroferulic acid, isoferulic acid, 4-hydroxybenzoic acid, 4-hydroxyphenyllactic acid, ferulic acid, vanillic acid, syringic acid, gentisic acid, sinapic acid, apigenin, tricin, acacetin, daidzein, genistein, formononetin, prunetin, pratensein, rhamnocitrin and galangin were significantly upregulated in FAMSE.Graphical

Review of the effects of sodium butyrate on obesity, inflammatory bowel disease, pregnancy and colorectal cancer

Introduction and Purpose: Short-chain fatty acids (SCFAs), including butyric acid, acetic acid and propionic acid, are naturally produced in the large intestine by bacterial fermentation of insoluble carbohydrates and oligosaccharides. Butyric acid, which is the main source of energy for colon cells, has regenerative, cytoprotective and anti-inflammatory effects. Its physiological importance lies in maintaining the integrity and function of the intestinal epithelium, which protects the body against pathogens and oxidative stress. SCFA deficiencies resulting from low dietary fiber supply can lead to intestinal disorders. Supplementation with sodium butyrate, particularly using micro-encapsulation technology, enables efficient delivery of butyric acid to the gut, which may be beneficial in the treatment of inflammatory bowel disease and in the prevention of obesity and insulin resistance. Sodium butyrate (NaB) also has promising potential in the treatment of colorectal cancer (CRC), inducing apoptosis of cancer cells, increasing sensitivity to radiotherapy and chemotherapy and protecting healthy cells. SCFAs, especially butyrate, play a key role in reproductive medicine, oncology and gastroenterology, contributing to the maintenance of health and being potential therapeutic targets. The aim of this paper is to review the available literature on this topic. Material and methods: The review was based on articles obtained from PubMed scientific database published from 2014-2024, using the following keywords: sodium butyrate, obesity, pregnancy, inflammatory bowel disease, colorectal cancer, SCFA. Conclusions: Studies confirm the beneficial effects of sodium butyrate on metabolism, intestinal integrity and reduction of inflammation, opening up new possibilities in the treatment of metabolic disorders and intestinal diseases. However, further clinical studies conducted on humans are still needed, as most of the work to date has been conducted on mice and/or rats.

Dietary Bacteriophage Administration Alleviates Enterotoxigenic Escherichia coli-Induced Diarrhea and Intestinal Impairment through Regulating Intestinal Inflammation and Gut Microbiota in a Newly Weaned Mouse Model

This study aimed to investigate the effects of dietary bacteriophage administration on diarrhea and intestinal impairment induced by enterotoxigenic Escherichia coli (ETEC) in a newly weaned mouse model. Forty-four newly weaned C57BL/6 mice were divided into four treatment groups, where they were provided either the control diet or the bacteriophage-supplemented diet, with or without ETEC infection. The results show that the bacteriophage administration resulted in increased body weight, decreased diarrhea score, and improved jejunal histopathology in ETEC-infected mice. The bacteriophage administration enhanced the intestinal barrier function of the ETEC-infected mice, as indicated by the reduced serum DAO level and the increased expression of Claudin-1, Occludin, and ZO-1 at both the mRNA and protein levels in the jejunum. Also, the bacteriophage administration resulted in a decrease in serum TNF-α and IL-1β levels, a down-regulation of TNF-α and IL-6 mRNA levels in the jejunum, and the inhibition of jejunal TLR-4/NF-κB pathway activation induced by ETEC infection. Moreover, the bacteriophage administration increased the levels of acetic acid, propionic acid, butyric acid, and total short-chain fatty acids in the caecum content. The bacteriophage administration increased the Shannon index, increased the abundance of Bacteroidota and Muribaculaceae, and decreased the abundance of Verrucomicrobiota and Akkermansiaceae in the colon contents of the ETEC-infected mice. Spearman’s correlation analysis indicates that the protective effects of bacteriophage on ETEC-induced intestinal impairment, inflammation, and intestinal barrier function are associated with regulating the abundance of Bacteroidota and Muribaculaceae in the colon contents of mice. Collectively, bacteriophage administration alleviates ETEC-induced diarrhea and intestinal impairment through regulating intestinal inflammation and gut microbiota in newly weaned mice.