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The objective of this study was to determine the in vitro antimicrobial activity of several organic acids and their derivatives against Gram-positive (G+) and Gram-negative (G−) bacteria. Butyric acid, valeric acid, monopropionin, monobutyrin, valerate glycerides, monolaurin, sodium formate, and ProPhorce—a mixture of sodium formate and formic acid (40:60 w/v)—were tested at 8 to 16 concentrations from 10 to 50,000 mg/L. The tested bacteria included G− bacteria (Escherichia coli, Salmonella enterica Typhimurium, and Campylobacter jejuni) and G+ bacteria (Enterococcus faecalis, Clostridium perfringens, Streptococcus pneumoniae, and Streptococcus suis). Antimicrobial activity was expressed as minimum inhibitory concentration (MIC) of tested compounds that prevented growth of tested bacteria in treated culture broth. The MICs of butyric acid, valeric acid, and ProPhorce varied among bacterial strains with the lowest MIC of 500–1000 mg/L on two strains of Campylobacter. Sodium formate at highest tested concentrations (20,000 mg/L) did not inhibit the growth of Escherichia coli, Salmonella Typhimurium, and Enterococcus faecalis, but sodium formate inhibited the growth of other tested bacteria with MIC values from 2000 to 18,800 mg/L. The MIC values of valerate glycerides, monolaurin, and monobutyrin ranged from 2500 to 15,000 mg/L in the majority of bacterial strains. Monopropionin did not inhibit the growth of all tested bacteria, with the exception that the MIC of monopropionin was 11,300 mg/L on Clostridia perfringens. Monolaurin strongly inhibited G+ bacteria, with the MIC value of 10 mg/L against Streptococcus pneumoniae. The MIC tests indicated that organic acids and their derivatives exhibit promising antimicrobial effects in vitro against G− and G+ bacteria that are resistant to antimicrobial drugs. The acid forms had stronger in vitro antimicrobial activities than ester forms, except that the medium chain fatty acid ester monolaurin exhibited strong inhibitory effects on G+ bacteria.

The potential for mitigating intestinal inflammation through the gut-bone axis in the treatment of osteoporosis is significant. While various gut-derived postbiotics or bacterial metabolites have been created as dietary supplements to prevent or reverse bone loss, their efficacy and safety still need improvement. Herein, a colon-targeted drug delivery system is developed using surface engineering of polyvinyl butyrate nanoparticles by shellac resin to achieve sustained release of postbiotics butyric acid at the colorectal site. These engineered postbiotics nanoparticles can effectively suppress macrophage inflammatory activation, modulate the redox balance, and regulate the composition of the gut microbiota, thereby restoring epithelial barriers, inhibiting bacterial invasion, and down-regulating pro-inflammatory responses. As a result, the remission of systemic inflammation is accompanied by a rebalancing of osteoblast and osteoclast activity, alleviating inflammatory bowel disease-related and post-menopausal bone loss. Specifically, the treatment of engineered postbiotics nanoparticles can also improve the quality and quantity of bone with restoration of deteriorative mechanical properties, which indicating a therapeutic potential on fracture prevention. This study provides valuable insights into the gut-bone axis and establishes a promising and safe therapeutic strategy for osteoporosis. Gut inflammation and bone loss have previously been linked. Here, the authors show colon-targeted engineered postbiotics can protect the gut and reduce systemic inflammation, which rebalances inflammation disturbed osteoblast-osteoclast levels restoring bone homeostasis.

Background Macrophages play an important role in the pathogenesis of ulcerative colitis (UC). We will explore the effects of sodium butyrate (SB) on macrophage function. Methods The targets of butyric acid were identified using SwissTargetPrediction database and surface plasmon resonance (SPR). Limited proteolysis mass spectrometry (Lip-MS) was used to further investigate the binding sites of butyric acid with its targets and molecular docking was employed to simulate their binding modes. Macrophage polarization model was established with lipopolysaccharide (LPS) in vitro. Takeda G protein-coupled receptor 5 (TGR5) and β-arrestin2 expression and macrophage polarization markers were detected with or without SB. Results TGR5 was identified as the target of butyric acid. Moreover, the amino acid regions 275–286 and 321–330 of TGR5 (GPBAR1 [275–286] and GPBAR1 [321–330]) were the potential binding regions for butyric acid. Based on molecular docking analysis, butyric acid formed effective hydrogen-bonding interactions with ASP-284 and TYR-287 of TGR5. In cell experiments, LPS inhibited the expression of TGR5, β-arrestin2, IL-10, ARG1, and CD206 and increased the expression of IL-1β, iNOS, and CD86, while SB reversed the effect of LPS. SBI-115, a TGR5 antagonist, and knockdown of β-arrestin2 inhibited the effect of sodium butyrate. INT-777, a TGR5 agonist, reversed the inhibitory effect of knockdown of β-arrestin2. Conclusion SB inhibited M1-like polarization and promoted M2-like polarization induced by LPS via TGR5/β-arrestin2 in RAW264.7 cells and TGR5 was the target of SB.

Fermented alcoholic drinks’ contribution to the gut microbiota composition is mostly unknown. However, intestinal microorganisms can use compounds present in beer. This work explored the associations between moderate consumption of beer, microbiota composition, and short chain fatty acid (SCFA) profile. Seventy eight subjects were selected from a 261 healthy adult cohort on the basis of their alcohol consumption pattern. Two groups were compared: (1) abstainers or occasional consumption (ABS) (n = 44; <1.5 alcohol g/day), and (2) beer consumption ≥70% of total alcohol (BEER) (n = 34; 200 to 600 mL 5% vol. beer/day; <15 mL 13% vol. wine/day; <15 mL 40% vol. spirits/day). Gut microbiota composition (16S rRNA gene sequencing) and SCFA concentration were analyzed in fecal samples. No differences were found in α and β diversity between groups. The relative abundance of gut bacteria showed that Clostridiaceae was lower (p = 0.009), while Blautia and Pseudobutyrivibrio were higher (p = 0.044 and p = 0.037, respectively) in BEER versus ABS. In addition, Alkaliphilus, in men, showed lower abundance in BEER than in ABS (p = 0.025). Butyric acid was higher in BEER than in ABS (p = 0.032), and correlated with Pseudobutyrivibrio abundance. In conclusion, the changes observed in a few taxa, and the higher butyric acid concentration in consumers versus non-consumers of beer, suggest a potentially beneficial effect of moderate beer consumption on intestinal health.

The present work describes the protolytic properties and in vitro biological activity of spinorphin (Leu-Val-Val-Tyr-Pro-Trp-Thr) and three spinorphin derivatives containing butyric acid residue: Butyryl-Lys-Lys-Leu-Leu-Val-Tyr-Pro-Trp-Thr, Butyryl-Lys-Lys-Leu-Val-Val-Tyr-Pro-Trp-Thr (butyric acid bound to the α-amino group of lysine), Lys(Butyryl)-Lys-Leu-Val-Val-Tyr-Pro-Trp-Thr (butyric acid bound to the ε-amino group of lysine) in an aqueous solution. The overall protonation constants and the stepwise dissociation constants of the ligands studied were calculated by the potentiometric method. The percentage of each species formed was estimated from the species distribution curves as a function of pH. The biological activity of all tested compounds was characterized in vitro, in the neutral red uptake and Griess assay tests in RAW264.7 macrophage cell line. The three protonation constants for spinorphin and four for its derivatives suggest that metal ions may bind to these peptides and form complexes by coordination with the functional groups of the respective amino acid residues. In vitro biological activity tests suggest that two peptides deserve attention for their potential anti-inflammatory role.

The aim of the present study was to investigate the effects of different dietary sustained-release microencapsulated sodium butyrate (MSB) products (0 (non-supplement), 1·5 and 3·0 h) for a control or oxidised soyabean oil (SBO) diet on fish production, intestinal mucosal condition, immunity and intestinal bacteria in juvenile common carp ( Cyprinus carpio ). Dietary MSB increased weight gain and reduced the feed conversion ratio within the control and oxidised SBO groups. Gut mucosa was damaged in the oxidised SBO group fed without MSB, in contrast to a normal appearance found in fish fed the MSB1·5 and MSB3·0 diets in the oxidised SBO group. Microvillus density increased in fish fed the MSB1·5 and MSB3·0 diets in the oxidised SBO group ( P < 0·001); however, microvillus density was affected by the different pre-fed diets in the midgut ( P < 0·001) and by the different sustained-release times of MSB in the distal gut (DG) ( P = 0·003). The interaction between the pre-fed diets and the sustained-release times of dietary MSB was significant for the relative gene expression levels of gut heat shock protein-70 ( HSP70 ), pro-inflammatory cytokines ( IL-1β and TNF-α ) and anti-inflammatory cytokines (transforming growth factor-β) within each gut segment, except for HSP70 in the DG and IL-1β in the foregut. Modulation of adherent bacterial communities within each gut segment investigated was not obvious when the common carp were fed the diets with MSB, as similarity coefficients of >0·79 were observed. These results indicated that MSB can be used as a dietary supplement to repair or prevent intestinal damage in carp fed oxidised SBO.

Although enzymes are efficient catalysts capable of converting various substrates into desired products with high specificity under mild conditions, their effectiveness as catalysts is substantially reduced when substrates are poorly water-soluble. In this study, to expedite the enzymatic conversion of a hydrophobic substrate, we use a bicontinuous interfacially jammed emulsion gel (bijel) which provides large interfacial area between two immiscible liquids: oil and water. Using lipase-catalyzed hydrolysis of tributyrin as a model reaction in a batch mode, we show that bijels can be used as media to enable enzymatic reaction. The bijel system gives a four-fold increase in the initial reaction rate in comparison to a stirred biphasic medium. Our results demonstrate that bijels are powerful biphasic reaction media to accelerate enzymatic reactions with various hydrophobic reagents. This work also demonstrates that bijels can potentially be used as reaction media to enable continuous reactive separations.

Lactate-utilizing bacteria play important roles in the production of Chinese strong-flavored liquor (CSFL). However, the identity of these bacteria and their lactate-utilizing properties are largely unknown. Here, a lactate-utilizing, butyrate-producing bacterium BPY5 was isolated from an old fermentation pit for CSFL production. The isolate represented a novel species belonging to Clostridium cluster XIVa of family Lachnospiraceae based on phylogenetic analysis using 16S rRNA gene sequences. Strain BPY5 could ferment lactate into butyrate as the major metabolic product. Butyrate was significantly formed at initial lactate concentration from 66 to 104 mM, but substantially declined when initial lactate exceeded 133 mM. At initial lactate concentration of 66 mM, lactate conversion was independent on initial pH from 5.5 to 7.0, but the conversion was completely inhibited when pH dropped below 4.8. Nevertheless, the inhibition on lactate conversion was largely relieved by the addition of acetate, suggesting that exogenous acetate could enhance lactate conversion at low pH condition. Additionally, lactate in CSFL-brewing wastewater was dramatically removed when inoculated with strain BPY5. These results implicate that the isolate may be applied for the industrial production of butyrate or the recovery of butyrate from lactate-containing wastewater.

The non-collagenous domain 1 of the α3 chain of type IV collagen (α3(IV)NC1) is the primary autoantigen in anti-glomerular basement membrane (anti-GBM) disease. We previously developed a modified antigen-specific peptide, m-P14, derived from the nephritogenic epitope α3 , which ameliorated experimental anti-GBM nephritis. However, its short half-life limits clinical translation. This study evaluated a butyrate-conjugated derivative (m-P14-BA) to improve pharmacokinetic properties while preserving therapeutic efficacy. M-P14-BA and m-P14 were administered to α3 immunized Wistar Kyoto rats in early and late treatment settings. Renal injury parameters and intrarenal inflammation were assessed, and pharmacokinetic profiles were evaluated following intraperitoneal administration in beagle dogs. M-P14-BA reduced proteinuria, crescent formation, glomerular IgG deposition, complement activation, and inflammatory cell infiltration, with overall efficacy comparable to m-P14 in early treatment settings. In late treatment settings, m-P14-BA was associated with a significant improvement in blood urea nitrogen levels and modest reductions in proteinuria and histopathological injury. Butyrate conjugation markedly improved pharmacokinetics, prolonging plasma elimination half-life by approximately 2.8-fold and increasing systemic exposure nearly fourfold. These pharmacokinetic improvements were associated with maintained therapeutic efficacy at a reduced dose, with 10 mg/kg m-P14-BA achieving effects broadly similar to those observed with 30 mg/kg m-P14. In summary, butyrate conjugation improves the pharmacokinetic profile of an antigen-specific therapeutic peptide while preserving therapeutic activity, suggesting a potential strategy to enhance the translational feasibility of peptide-based immunotherapy in anti-GBM disease.

Background Oxaliplatin (OXA) is a commonly used drug for the treatment of rectal cancer (RC). However, traditional administration methods are plagued by low efficiency, high systemic side effects, and poor patient tolerance. Therefore, there is an urgent need to develop a targeted drug delivery system to enhance efficacy and reduce toxicity. Methods A strain of Clostridium butyricum with anti-cancer properties was screened, and outer membrane vesicles (OMVs) rich in sodium butyrate (NaB) were prepared. These OMVs (NaB-OMVs, NOMVs) were used to address the challenge of combined administration caused by differences in the administration methods and physicochemical properties of OXA and NaB. OXA was encapsulated into NOMVs via sonication to obtain OXA-loaded NaB-OMVs (OXA@NOMVs, ONOMVs). To improve stability and enable targeted delivery, a dissolving microneedle (MNs) system (ONOMVs@MNs) was developed using PVP K90 and sodium hyaluronate via the mold method. The system was characterized for morphology, size, zeta potential, mechanical strength, and rectal mucosa permeability. Additionally, targeted therapy advantages were evaluated using methods including anal microneedle administration in mice and fluorescence labeling of vesicles. Results Characterization showed that ONOMVs exhibit a saucer-like morphology with a diameter of 100 nm and a zeta potential of 20 mV. The ONOMVs@MNs were conically shaped and possessed sufficient mechanical strength to penetrate the anal mucosa. In rectal mucosa permeability experiments, the 2-hour permeability of the MNs group was 1.78 times higher than that of the liquid (liquor) group. Anal microneedle administration in mice and fluorescence labeling confirmed the targeted therapy advantages of NOMVs@MNs. Conclusions ONOMVs@MNs is an efficient local drug delivery platform that combines NaB and OXA, providing a potential therapeutic approach for RC. Graphical abstract