Acid Production Research Articles

Enhancing D-lactic acid production from methane through metabolic engineering of Methylomonas sp. DH-1

BackgroundMethane is an abundant and low-cost carbon source with great potential for conversion into value-added chemicals. Methanotrophs, microorganisms that utilize methane as their sole carbon and energy source, present a promising platform for biotechnological applications. This study aimed to engineer Methylomonas sp. DH-1 to enhance D-LA production through metabolic pathway optimization during large-scale cultivation.ResultsIn this study, we regulated the expression of D-lactate dehydrogenase (D-LDH) using a Ptac promoter with IPTG induction to mitigate the toxic effects of lactate accumulation. To further optimize carbon flow away from glycogen, the glgA gene was deleted. However, this modification led to growth inhibition, especially during scale-up, likely due to the accumulation of ADP-glucose caused by the rewired carbon flux under carbon-excess conditions. Deleting the glgC gene, which encodes glucose 1-phosphate adenylyltransferase, alleviated this issue. The final optimized strain, JHM805, achieved a D-LA production of 6.17 g/L in a 5-L bioreactor, with a productivity of 0.057 g/L/h, marking a significant improvement in D-LA production from methane.ConclusionsThe metabolic engineering strategies employed in this study, including the use of an inducible promoter and alleviation of ADP-glucose accumulation toxicity, successfully enhanced the ability of the strain to produce D-LA from methane. Furthermore, optimizing the bioreactor fermentation process through methane and nitrate supplementation resulted in a significant increase in both the titer and productivity, exceeding previously reported values.

Functional Component Production Capabilities in Milk Fermentation of Some Featured Lactic Acid Bacteria Species for Use in Different Food Processes

This study examines the fermentation performance of featured bacteria (Lactobacillus acidophilus-ATCC-4356, Lactobacillus helveticus-ATCC-15009, Lactobacillus delbrueckii subsp. bulgaricus-ATCC-11842, Lacticaseibacillus casei-ATCC-393, Streptococcus thermophilus-ATCC-19258 (ST), and Bifidobacterium bifidum-ATCC-29521 (BB)) used in fermented dairy products and their impact on product quality. The main focus is on evaluating the metabolic activities, organic acid production, viscosity values, and sensory properties of probiotic strains such as L. acidophilus, L. bulgaricus, L. casei, L. helveticus, B. bifidum, and S. thermophilus. The strains were activated in a sterile milk medium and incubated until they reached a pH of 4.6. Then, pH, microbial enumeration, organic acid, sugar composition, vitamins A, D, E, K1, and K2 (menaquinone-7), and viscosity values were measured in the bacteria. Organic acid, sugar composition, and vitamins A, D, E, K1, and K2 (menaquinone-7) were analyzed with the HPLC method. Additionally, sensory analyses were performed, and volatile compounds were examined. L. casei demonstrated superiority in lactic acid production, while L. helveticus showed high lactose consumption. L. bulgaricus stood out in galactose metabolism. The highest viscosity was observed in products produced by B. bifidum. Differences in viscosity were attributed to exopolysaccharide (EPS) production and acid production capacity. A total of 62 volatile compounds were identified, with the highest levels of aromatic components found in products containing B. bifidum. The most preferred product, based on panel evaluations, was the fermented dairy product produced with L. acidophilus. As for aroma profiles, it was determined that the phenethyl alcohol, 3-methyl-1 butanol, and ethanol compounds are associated with B. bifidum, the hexanoic acid and 2-methylbutanal compounds are associated with the L. acidophilus, the hexanoic acid, 2-methylbutanal, 2-furanmethanol, and acetaldehyde compounds are associated with the L. bulgaricus, and the hexanoic acid, 2-methylbutanal, 2-heptanone, acetoin, and d-limonene are associated with the L. casei. On the other hand, the L. helveticus strain is associated with the hexanoic acid, 2-methylbutanal, and 2-heptanone, and the S. termophilus strain is associated with the hexanoic acid, hexanol, acetoin, 2,3-pentanedione, 1-butanol, and 3-methyl-2-butanone volatile aroma compounds. The determination of fat-soluble vitamins is particularly important for vitamin K1 and vitamin K2. In this study, the bacterial sources of these vitamins were compared for the first time. The menaquinone-7 production by L. helveticus was determined to be the highest at 0.048 µg/mL. The unique metabolic capacities of these prominent cultures have been revealed to play an important role in determining the aroma, organic acid content, viscosity, and overall quality of the products as a whole. Therefore, the findings of this study will provide the right strain selection for a fermented dairy product or a different non-dairy-based fermented product according to the desired functional properties. It also provides a preliminary guide for inoculation in the right ratios as an adjunct culture or co-culture for a desired property.

Pseudovitamin B12 producing Loigolactobacillus coryniformis enhances soy milk fermentation by Lactobacillus delbrueckii subsp. bulgaricus.

Fermenting soy milk with lactic acid bacteria is challenging. Generally, carbohydrates are added to enhance the acid production in soy milk. However, the yoghurt starter Lactobacillus delbrueckii subsp. bulgaricus did not succeed in fermenting soy milk supplemented with carbohydrates. If this yoghurt starter could be used with soy milk, it is expected that it would produce a yoghurt-like flavour, making soy yoghurt more appealing. In this study, we aimed to ferment soy milk using Lb. delbrueckii subsp. bulgaricus and pseudovitamin B12-producing lactic acid bacteria. Loigolactobacillus coryniformis SAB01 was found to produce corrinoid in soy milk, with the highest production being observed at 20 °C. The produced corrinoid was identified as pseudovitamin B12 using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Another bacterial strain, Lb. delbrueckii subsp. bulgaricus NBRC 13953, was examined for its ability to produce lactic acid in soy milk. Compared with soy milk supplemented with glucose or cyanocobalamin alone, the highest lactic acid production was observed in soy milk supplemented with both glucose and cyanocobalamin. These findings indicate that the combined addition of glucose and cyanocobalamin enhances lactic acid production by strain NBRC 13953 in soy milk. We accordingly examined lactic acid production in soy milk inoculated with strains SAB01 and NBRC 13953, and found that a substantial quantity of lactic acid was produced when glucose was added to soy milk. Our findings in this study indicate that the growth of Lb. delbrueckii subsp. bulgaricus NBRC 13953 was promoted by the pseudovitamin B12 produced by Loigolactobacillus coryniformis SAB01, thereby suggesting a novel symbiotic relationship between these two lactic acid bacteria in soy milk. © 2025 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Corrigendum: Production of biopolyamide precursors 5-amino valeric acid and putrescine from rice straw hydrolysate by engineered Corynebacterium glutamicum

Corrigendum: Production of biopolyamide precursors 5-amino valeric acid and putrescine from rice straw hydrolysate by engineered Corynebacterium glutamicum

Protective Effect of Dietary Fiber on Blood Pressure and Vascular Dysfunction Through Regulation of Sympathetic Tone and Immune Response in Genetic Hypertension.

The mechanisms underlying the antihypertensive effect of dietary fibers remain poorly understood. This study investigates whether dietary fiber supplementation can prevent cardiovascular damage and high blood pressure in a genetic model of neurogenic hypertension. Six-week-old male spontaneously hypertensive rats (SHR) and their respective normotensive control, Wistar Kyoto rats (WKY), were divided into four groups: Untreated WKY, untreated SHR, SHR treated with resistant starch (SHR + RS), and SHR treated with inulin-type fructans (SHR + ITF) for 12 weeks. Additionally, a faecal microbiota transplantation (FMT) experiment was conducted, transferring faecal content from treated SHR donors to recipient SHRs. A diet rich in RS fiber reduced vascular oxidative stress, inflammation, and high blood pressure. These protective effects were associated with a reshaped gut microbiota, leading to increased short-chain fatty acid production, reduced endotoxemia, decreased sympathetic activity, and a restored balance between Th17 and Treg lymphocytes in mesenteric lymph nodes and aorta. Elevated plasma levels of acetate and butyrate in the SHR + RS group correlated with increased expression of aortic GPR41, GRP43 and PPARδ. Conversely, ITF treatment failed to prevent hypertension or endothelial dysfunction in SHR. FMT from the SHR + RS group to recipient SHR partially replicated these beneficial effects. This study highlights the antihypertensive benefits of dietary insoluble RS fiber, which are attributed to enhanced short-chain fatty acids production in the gut. This leads to improved gut permeability, reduced sympathetic tone, and diminished vascular T-cell accumulation. Therefore, dietary interventions with RS fiber may offer promising therapeutic strategies for preventing hypertension.

Use of Cocoa Pods Husks (Theobroma cacao L.) as a Potential Substrate for the Production of Lactic Acid by Submerged Fermentation Using Lactobacillus Fermentum ATCC 9338

Use of Cocoa Pods Husks (Theobroma cacao L.) as a Potential Substrate for the Production of Lactic Acid by Submerged Fermentation Using Lactobacillus Fermentum ATCC 9338

Cytosolic Peroxiredoxin TSA1 Influences Acetic Acid Metabolism and pH Homeostasis in Wine Yeasts.

Acetic acid is a key metabolite in yeast fermentation, influencing wine quality through its role in volatile acidity. In Saccharomyces cerevisiae, acetic acid production involves aldehyde dehydrogenases, primarily Ald6p during fermentation and Ald4p under respiratory conditions. However, the regulatory mechanisms of these enzymes throughout fermentation and how they differ in commonly used strains remain partially unclear. This study explores cytosolic peroxiredoxin Tsa1p as a novel regulator of acetic acid metabolism. TSA1 gene deletion revealed strain-dependent effects on acetic acid metabolism and tolerance, showing reduced production and enhanced consumption in the laboratory media. Under respiration, Ald4p-driven acetic acid production, which raises extracellular pH, was mitigated by the absence of Tsa1p. During wine fermentation, TSA1 deletion decreased the initial acetic acid surge by downregulating the ALD6 transcription and enzymatic activity. These findings establish Tsa1p as a metabolic regulator and a potential target for modulating acetic acid levels to manage volatile acidity and improve wine quality.

Global profiling of CPL3-mediated alternative splicing reveals regulatory mechanisms of DGK5 in plant immunity and phosphatidic acid homeostasis

BackgroundAlternative splicing of precursor mRNAs serves as a crucial mechanism to enhance gene expression plasticity for organismal adaptation. However, the precise regulation and function of alternative splicing in plant immune gene regulation remain elusive.ResultsHere, by deploying in-depth transcriptome profiling with deep genome coverage coupled with differential expression, differential alternative splicing, and differential transcript usage analysis, we reveal profound and dynamic changes in alternative splicing following treatment with microbial pattern flg22 peptides in Arabidopsis. Our findings highlight RNA polymerase II C-terminal domain phosphatase-like 3 (CPL3) as a key regulator of alternative splicing, preferentially influencing the splicing patterns of defense genes rather than their expression levels. CPL3 mediates the production of a flg22-induced alternative splicing variant, diacylglycerol kinase 5α (DGK5α), which differs from the canonical DGK5β in its interaction with the upstream kinase BIK1 and subsequent phosphorylation, resulting in reduced flg22-triggered production of phosphatidic acid and reactive oxygen species. Furthermore, our functional analysis suggests that DGK5β, but not DGK5α, contributes to plant resistance against virulent and avirulent bacterial infections.ConclusionsThese findings underscore the role of CPL3 in modulating alternative splicing dynamics of defense genes and DGK5 isoform-mediated phosphatidic acid homeostasis, shedding light on the intricate mechanisms underlying plant immune gene regulation.

Effects of calcium supplementation on the composition and activity of in vitro simulated gut microbiome during inulin fermentation.

The gut microbiome influences the availability of micronutrients in the gastrointestinal tract. However, our insights into how colonic fermentation of prebiotic fibers and lactose is modulated by the presence of micronutrients and local pH environment are limited. Here, we investigated the influence of different calcium salts (calcium phosphate (CaPi), calcium citrate (CaCi), and calcium carbonate (CaCa)) on gut microbiome composition and metabolism using inulin and lactose as carbohydrate sources under low, medium, and high in vitro colonic pH gradients. Our results showed that in vitro colonic pH gradient had a significant effect on gut microbiome diversity (observed ASVs and Shannon diversity index, p < 0.05). After 24 hours of fermentation, the calcium sources had a significant effect on beta diversity at all colonic pH gradients (adjusted p < 0.05). Although changes in GM composition were more pronounced after 24 hours, after 6 hours of fermentation, the CaPi group exhibited a higher abundance of Leuconostoc than other groups. After 24 hours of fermentation, the CaPi group exhibited a higher Blautia abundance at high colonic pH gradient and lower Bacteroides abundance at all colonic pH gradient levels. The CaCi and CaCa groups exhibited a pH-dependent decrease in the abundance of Bacteroides. In addition, Bifidobacterium abundance remained over 1% regardless of colonic pH gradient, calcium source, or fermentation time. In addition, short-chain fatty acid (SCFA) production was dependent on the calcium source. For instance, compared to the control group, the CaCi group exhibited higher acetate production at low and high colonic pH gradients, while the CaPi and CaCa groups showed enhanced lactate production at medium and low pH gradients. These findings can increase our understanding of the impacts of calcium-rich diets on the human gut microbiome and its metabolic activity.

Construction and Characterization of Polyethylene Glycol/Sodium Alginate Hydrogel Loaded With Zirconia Nanoparticles: Potential Antibacterial and Antibiofilm Agent to Inhibit Dental Caries InVitro and InVivo.

Biofilm formation on tooth surfaces is a primary contributor to dental caries and periodontal diseases. Streptococcus mutans is recognized for its role in biofilm production, significantly influencing the development of dental caries. Key virulence factors associated with S. mutans biofilms include acid production, acid tolerance, and the synthesis of exopolysaccharides (EPS). This study presents a novel approach by focusing on the loading of biosynthesized zirconia nanoparticles (ZrO2 NPs) onto polyethylene glycol/sodium alginate (PEG/SA) hydrogel nanocomposite, evaluating their effects on the biofilm-forming ability of S. mutans both invivo and invitro. ZrO2 NPs were biosynthesized using Citrus aurantifolia (C. aurantifolia) extract and incorporated into the PEG/SA hydrogel beads through a sol-gel process. The formation of ZrO2 NPs and the PEG/SA/ZrO2 NPs hydrogel nanocomposite was confirmed through diverse analyzes, including UV-visible spectroscopy, particle size measurement, morphology examination, spectral analysis, thermal gravimetric analysis (TGA) and hemolysis studies. The average particle size of the ZrO2 NPs was approximately 26 nm, while the PEG/SA/ZrO2 NPs hydrogel beads exhibited a highly porous, sheet-like surface structure. Invitro results demonstrated inhibition zones of 30 and 28 mm for ZrO2 NPs and PEG/SA/ZrO2 NPs hydrogel beads against S. mutans, respectively, with a minimum inhibitory concentration (MIC) of 12.5 mg/mL. The growth curve analysis indicated a complete decline in S. mutans growth with an 87% reduction in biofilm formation when treated with PEG/SA/ZrO2 NPs hydrogel beads. SEM analysis revealed that S. mutans cells appeared lysed or crumpled, losing their characteristic coccal shape after exposure to the hydrogel beads. Additionally, SEM images confirmed the effective prevention of S. mutans attachment to teeth when encapsulated with PEG/SA/ZrO2 NPs hydrogel, altering the morphology of mature biofilms that developed on the teeth after treatment. Finally, the incorporation of biosynthesized ZrO2 NPs into PEG/SA hydrogels demonstrates significant potential as an effective strategy for inhibiting S. mutans biofilm formation and may serve as a promising topical agent for reducing dental caries. Further studies could explore the long-term efficacy and potential clinical applications of this nanocomposite in oral health care.

Alleviation effects of Lactobacillus plantarum in colitis aggravated by a high-salt diet depend on intestinal barrier protection, NF-κB pathway regulation, and oxidative stress improvement.

A high-salt diet (HSD) can result in numerous health issues, including exacerbation of intestinal inflammation. Therefore, there is an immediate necessity of developing dietary supplements that can mitigate colitis exacerbated by a HSD. This study examined the impact of Lactobacillus plantarum HGD228 on colitis exacerbated by a HSD and the mechanisms underlying its alleviation. HGD228 treatment significantly enhanced colonic goblet cells and MUC2, upregulated ZO-1 and occludin, inhibited epithelial cell apoptosis, and mitigated colitis exacerbated by a HSD. Moreover, HGD228 significantly regulated oxidative stress-related enzymes, including SOD, GSH-PX, and CAT. HGD228 treatment significantly suppressed the NF-κB pathway induced by a HSD and regulated the levels of cytokines, including TNF-α, IL-10, and IL-1β. Furthermore, HGD228 reestablished the gut microbiota altered by HSDDSS, increasing Bifidobacterium while decreasing Escherichia-Shigella and Clostridium sensu stricto 1. HGD228 treatment also enhanced the production of butyric acid and acetic acid, suppressed pro-inflammatory cytokines, and strengthened the intestinal mucosal barrier. Therefore, HGD228 enhanced the production of beneficial metabolites by regulating inflammatory cytokines and oxidative stress, preserving the mucosal barrier, and enhancing gut microbiota, and mitigated colitis aggravated by a HSD. These results will aid in clinical trials of probiotics and the development of dietary supplements for colitis, with promising application value.

Interaction between Bacteroides and HG-type pectins with different molecular weights.

Interaction between Bacteroides and HG-type pectins with different molecular weights.

Effects of replacing barley grain with corn grain on performance, rumen and blood parameters in dairy cows fed alfalfa hay or corn silage.

Different grain sources in the diet have shown varying effects on performance of dairy cows. Also, the variability in response to different starch sources is influenced by the type of forage used. This study investigates the combined effects of two forage (alfalfa hay vs. corn silage) and grain (barley vs. corn) sources on dry matter intake (DMI), feed efficiency, milk production and composition, apparent nutrient digestibility, blood metabolites, and ruminal metabolism of dairy cows. Eight second-parity early lactation Holstein cows (63 ± 5 d in milk) were used in a replicated 4 × 4 Latin square with a 2 × 2 factorial design. Diets were iso-energetic and iso-nitrogenous and were based on either corn (CG) or barley (BG) grains, and corn silage (CS) or alfalfa hay (AH). Diets with CS had more long (108 vs. 68 g/kg DM) and medium particles (369 vs. 331 g/kg DM), and thus, longer mean particle size (5.4 vs. 4.6 mm) compared to diets with AH. Cows fed BG had less DMI and lower actual and energy-corrected milk (ECM) yield than CG-fed cows. The total tract digestibility of starch (952 vs. 987 g/kg) and crude protein (CP) (687 vs. 743 g/kg) were lower in CG cows than cows fed BG. Additionally, cows fed CG tended to have lower ruminal propionate concentrations than those fed BG, suggesting differences in ruminal fermentability between BG and CG. Milk fat content (30.6 vs. 29.2 g/kg) and ECM production (42.6 vs. 40.7 kg/d) tended to be greater in cows fed diets containing AH rather than CS. Furthermore, despite similar nutrient digestibility and total volatile fatty acid production, AH-fed cows had a higher ruminal acetate-to-propionate ratio compared to those fed CS. Replacement of BG with CG improved performance by increasing DMI; however, the expected positive effects of substituting CS with AH in BG-based diets may be obscured by the impact of differences in forage particle size (PS). These results indicated that inclusion of CG might be an optimum choice for modulating ruminal condition and enhancing performance compared to BG during early lactation.

Isorhamnetin ameliorates hyperuricemia by regulating uric acid metabolism and alleviates renal inflammation through the PI3K/AKT/NF-κB signaling pathway.

Hyperuricemia is a chronic metabolic disease with high incidence, and it has become a severe health risk in modern times. Isorhamnetin is a natural flavonoid found in a variety of plants, especially fruits such as buckthorn. The in vivo hyperuricemia ameliorating effect of isorhamnetin and the specific molecular mechanism were profoundly investigated using a hyperuricemia mouse model in this study. Results indicated that isorhamnetin showed a significant uric acid-lowering effect in mice. Isorhamnetin was able to reduce uric acid production by inhibiting XOD activity. Furthermore, it reduced the expression of GLUT9 to inhibit uric acid reabsorption and enhanced the expression of ABCG2, OAT1, and OAT3 to promote uric acid excretion. Metabolomics analysis revealed that gavage administration of isorhamnetin restored purine metabolism and riboflavin metabolism disorders and thus significantly alleviated hyperuricemia in mice. Furthermore, the alleviating effect of isorhamnetin on hyperuricemia-induced renal inflammation and its specific mechanism were explored through network pharmacology and molecular validation experiments. Network pharmacology predicted that seven targets were enriched in the PI3K/AKT pathway (CDK6, SYK, KDR, RELA, PIK3CG, IGF1R, and MCL1) and four targets were enriched in the NF-κB pathway (SYK, PARP1, PTGS2, and RELA). Western blot analysis validated that isorhamnetin inhibited the phosphorylation of PI3K and AKT and down-regulated the expression of NF-κB p65. It indicated that isorhamnetin could inhibit the PI3K/AKT/NF-κB signaling pathway to reduce the levels of renal inflammatory factors (TNF-α, IL-β and IL-6) and ultimately ameliorate hyperuricemia-induced renal inflammation in mice. This study provides a comprehensive and strong theoretical basis for the application of isorhamnetin in the field of functional foods or dietary supplements to improve hyperuricemia.

Efficient downstream processing of second-generation lactic acid from lignocellulosic waste using aqueous two-phase extraction

The utilization of low-cost, waste-derived lignocellulosic biomass for biotechnological lactic acid production is an area of significant interest. Although numerous attempts have been made to develop novel processes using second-generation feedstocks, the downstream recovery processes for second-generation lactic acid are still relatively uncharted. In this context, this study explores a two-step method for retrieving second-generation lactic acid from a fermented olive leaves medium. The initial step involves an aqueous two-phase extraction using an ethanol/ammonium sulfate system, a method first applied here to lactic acid derived from second-generation raw materials. This is followed by a purification step using activated carbon. The process succeeded in extracting second-generation lactic acid with a yield of 70.02 ± 2.29% in the first extraction stage, followed by a yield of 88.91 ± 0.49% in the second purification step. The lactic acid purity level at the end of the downstream process was 90.17 ± 1.55%, as confirmed by the HPLC data. Furthermore, the study examined the feasibility of direct lactic acid extraction from unfiltered, fermented olive leaves medium, revealing that up to 95.23 ± 0.42% of bacterial cells could be eliminated. The purified lactic acid underwent qualitative identification through FT-IR and 1H-NMR analysis, with the spectra showing a high degree of similarity to a standard reference substance, thus demonstrating the use of low-cost waste lignocellulosic biomass for the biotechnological production of lactic acid is a topic of great interest.Graphical

Metabolic Engineering and Adaptive Evolution of Escherichia coli for Enhanced Conversion of D‑Xylose to D-Glucaric Acid Mediated by Methanol.

d-Glucaric acid is a value-added dicarboxylic acid that can be utilized in the chemical, food, and pharmaceutical industries. Due to the complex process and environmental pollution associated with the chemical production of d-glucaric acid, bioconversion for its synthesis has garnered increasing attention in recent years. In this study, a novel cell factory was developed for the efficient production of d-glucaric acid using d-xylose and methanol. Mdh, Hps, Phi, Miox, Ino1, Suhb, and Udh were first co-expressed in E. coli JM109 to construct the d-glucaric acid synthesis pathway. The deletion of FrmRAB, RpiA, PfkA, and PfkB was then performed to block or weaken the endogenous competitive pathways. Next, adaptive evolution was carried out to improve cell growth and substrate utilization. With the purpose of further increasing the product titer, the NusA tag and myo-inositol biosensor were introduced into engineered E. coli to enhance Miox expression. After medium optimization and fermentation process control, 3.0 g/L of d-glucaric acid was finally obtained in the fed-batch fermentation using modified Terrific Broth medium.

Characterization and In Vitro Prebiotic Activity of Pterostilbene/β-Cyclodextrin Inclusion Complexes

Pterostilbene (PTS) has multiple benefits, but poor water solubility and bioavailability limit its application. PTS/β-CD inclusion complexes were synthesized through the phase solubility method to enhance their water solubility. The inclusion complexes were characterized through Fourier transform infrared spectroscopy, scanning electron microscopy, X-ray diffraction, nuclear magnetic resonance, and molecular docking techniques. The results demonstrated that PTS and β-CD successfully created inclusion complexes with a host–guest ratio of 1:1 and a stability constant of 166.7 M−1. To further investigate its prebiotic function, simulated digestion experiments revealed that β-CD exhibited resistance to digestion, allowing it to reach the colon intact. During gastrointestinal digestion, PTS in the PTS/β-CD inclusion complexes was gradually released. Following digestion, the in vitro fermentation of healthy human feces further confirmed the probiotic properties. Compared to the β-CD and fructooligosaccharide (FOS) groups, the PTS/β-CD group significantly increased the production of acetic acid, butyric acid, and lactic acid, respectively. Additionally, beneficial bacteria, such as Bifidobacterium and Lactobacillus, proliferated in the PTS/β-CD group, while the relative abundance of potential pathogenic bacteria, such as Lactococcus, Streptococcus, and Klebsiella, was significantly reduced. Compared to the blank group, propionic acid and butyric acid concentrations in the β-CD group were significantly higher. The abundance of Lactobacillus and other key bacterial species in the β-CD group increased, while the relative abundance of Klebsiella and other pathogens decreased significantly. In conclusion, PTS/β-CD inclusion complexes altered the composition of intestinal flora, promoting the proliferation of beneficial bacteria and inhibiting the growth of harmful bacteria, thereby demonstrating dual probiotic functionality.

Anticonstipation Activity of Garlic Fructans in Loperamide-Induced Constipated Mice: Impact of Polymerization Degree.

Constipation severely affects the quality of life, and current treatment strategies may cause adverse effects. Garlic fructans have shown great potential for improving gastrointestinal health. This study aimed to elucidate the protective effects and mechanisms of three garlic fructans with different degrees of polymerization (DPs) against loperamide (Lop)-induced constipated mice. The results showed that garlic fructans accelerated intestinal motility (0.57-1.05-fold) and alleviated colonic crypt shortening (1.42-1.97-fold). Furthermore, dysregulation of excitatory/inhibitory gastrointestinal hormones was significantly alleviated, accompanied by restored propionic and butyric acid production and ameliorated bile acid metabolism disorders. Garlic fructans also improved gut microbiota homeostasis in constipated mice by inhibiting harmful bacteria and promoting the growth of beneficial bacteria. Compared with high-DP garlic fructans, low-DP fructans exhibited stronger relieving effects on Lop-induced constipation symptoms in mice. In conclusion, this study demonstrated the anticonstipation activity of garlic fructans and revealed that low-DP garlic fructans were more effective in alleviating Lop-induced constipation.

PFKFB4 promotes endometrial cancer by regulating glycolysis through SRC‑3 phosphorylation.

The present study aimed to investigate the role of 6‑phosphofructo‑2‑kinase/fructose‑2,6‑biphosphatase 4 (PFKFB4) in endometrial cancer cells and to explore its potential molecular mechanisms. PFKFB4 expression in endometrial cancer tissues was detected by immunohistochemistry. Cell Counting Kit‑8, Transwell assays and flow cytometry were used to detect cell proliferation, invasion and apoptosis in endometrial cancer cells after PFKFB4 knockdown. An enzyme‑linked immunosorbent assay was used to detect the glucose and lactic acid contents. Western blotting was performed to detect the levels of glycolysis‑related enzymes, steroid receptor coactivator‑3 (SRC‑3), and phosphorylated SRC‑3. In vivo experiments were performed to investigate the tumorigenic potential of PFKFB4. PFKFB4 expression was upregulated in endometrial cancer tissues compared with that in normal controls, and its upregulation was positively correlated with the depth of myometrial invasion, lymph node metastasis, surgical pathological stage and vascular invasion. PFKFB4 knockdown significantly inhibited proliferation and invasion, increased apoptosis, and decreased oxygen consumption and lactic acid production in endometrial cancer cells. PFKFB4 knockdown decreased SRC‑3 phosphorylation. After simultaneous PFKFB4 knockdown and SRC‑3 overexpression in cancer cells, oxygen consumption, lactic acid production, and glycolysis‑related protein expression were increased compared with those in control cells. PFKFB4 knockdown inhibited tumor proliferation, apoptosis and the expression of Ki‑67. PFKFB4 may regulate glycolysis in endometrial cancer cells by targeting SRC‑3, thus promoting endometrial cancer progression.

American Foregut Society White Paper Report on the Use of Potassium-Competitive Acid Blockers in the Treatment of Gastroesophageal Reflux Disease

Background: Suppression of gastric acid secretion with proton pump inhibitors (PPIs) has been the mainstay of medical treatment for gastroesophageal reflux disease (GERD) for more than 30 years. Members of a newer class of medication, the potassium-competitive acid blockers (P-CABs), can inhibit gastric acid production faster, longer, and more potently than PPIs. In November 2023, vonoprazan became the first P-CAB to receive FDA approval for GERD treatment. Methods: The American Foregut Society (AFS) convened a 13-member panel of expert gastroenterologists and foregut surgeons to produce a white paper report on how clinicians might use P-CABs to treat GERD. After conducting a comprehensive literature review, panelists proposed 20 total statements on key aspects of P-CAB pharmacokinetics, use of P-CABs for erosive esophagitis and non-erosive reflux disease, and P-CAB safety, as well as 13 recommendation statements on how to use a P-CAB in clinical practice. Using RAND/UCLA Appropriateness Methodology, panelists independently voted to rank each statement for appropriateness, and, after panel review and discussion of first-round voting results, statements were accepted, discarded, or modified for a final round of voting. Results: Twenty-three statements were finally accepted (3 on P-CAB pharmacokinetics, 5 on P-CABs for erosive esophagitis, 3 on P-CABs for non-erosive reflux disease, 4 on P-CAB safety, 8 on how to use P-CABs in clinical practice). Conclusions: This AFS white paper report provides the statements accepted by the expert panel on the use of P-CABs in the treatment of GERD, and summarizes the literature review that provided the rationale for those statements.