Autolyzed yeast and sodium butyrate supplemented alone to diets promoted improvements in performance, intestinal health and nutrient transporter in weaned piglets.

This study investigated the effects of supplemental nucleotides, autolyzed yeast (Saccharomyces cerevisiae), and sodium butyrate in diets for nursery pigs on growth performance, diarrhea incidence, blood profile, intestinal morphology, mRNA expression of nutrient transporters, inflammatory markers, antioxidant profile, and tight junction proteins in the small intestine. One hundred eighty 21-day-old pigs (5.17 ± 0.57 kg) were assigned in a randomized block design to 1 of 4 dietary treatments: (1) CON: control, basal diet, (2) NUC: CON + nucleotides, (3) YSC: CON + lysed yeast S. cerevisiae, (4) ASB: CON + acidifier sodium butyrate. Pigs were fed for 24 days, phase 1 (21-32 days) and 2 (32-45 days). During phase 1, YSC and ASB improved average daily gain (ADG) and feed conversion (FC) compared with CON. At the overall period, ASB improved ADG and YSC improved FC compared with CON. The NUC diet did not affect growth performance. The ASB increased ileal villus height compared to CON. The YSC and ASB reduced the number of Peyer's patches in the ileum compared with CON. The YSC increased mRNA expression of nutrient transporters (SMCT2, MCT1, and PepT1), tight junction proteins (OCL and ZO-1), antioxidants (GPX), and IL1-ß in the jejunum compared with CON. The ASB increased mRNA expression of nutrient transporters (SGLT1 and MCT1), tight junction proteins (OCL and ZO-1), and antioxidants (GPX and SOD) compared with CON. In conclusion, autolyzed yeast and sodium butyrate promoted growth performance by improving the integrity of the intestinal barrier, the mRNA expression of nutrient transporters, and antioxidant enzymes in the jejunum of nursery pigs whereas supplementation of nucleotides did not show such effects.

Sodium butyrate alleviates intestinal injury and microbial flora disturbance induced by lipopolysaccharides in rats.

Bacterial endotoxin invasion reduces intestinal barrier functions, such as intestinal bacterial translocation and enteric infection. In this study, we investigated whether sodium butyrate (NaB) alleviates lipopolysaccharide (LPS)-induced inflammation by reducing intestinal damage and regulating the microflora. Rats were divided into four groups for the intraperitoneal injection of LPSs and intragastric gavage with NaB: Con, LPS, LPS + NaB, and NaB. The results showed that NaB alleviated intestinal villus injury and inflammatory infiltration caused by LPS. NaB supplementation decreased the mRNA levels of toll-like receptor (TLR)-4, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and the trend was most pronounced in the jejunum. The morphology of the intestinal nucleus and mitochondria was further observed by transmission electron microscopy. The results showed that NaB supplementation alleviated LPS-induced nuclear atrophy, apoptosis, mitochondrial damage, and rupture. Moreover, NaB improved the LPS-induced inflammatory response by regulating the intestinal barrier. Furthermore, 16S rRNA sequencing showed that the LPS increased the abundance of the harmful bacterium Bacteroides, while the abundance of beneficial bacteria decreased. In the LPS + NaB group, the intestinal microbiota destroyed by the LPS was rebalanced, including a decrease in Bacteroides and an increase in Bifidobacterium and Odoribacter. In conclusion, NaB alleviates LPS-induced enteritis by regulating inflammatory cytokines, maintaining the mucosal barrier, and restoring the microbiota changes.

Intranasal curcumin and sodium butyrate modulates airway inflammation and fibrosis via HDAC inhibition in allergic asthma.

Asthma being an inflammatory disease of the airways lead to structural alterations in lungs which often results in the severity of the disease. Curcumin, diferuloylmethane, is well known for its medicinal properties but its anti-inflammatory potential via Histone deacetylase inhibition (HDACi) has not been revealed yet. Therefore, we have explored here, anti-inflammatory and anti-fibrotic potential of intranasal curcumin via HDAC inhibition and compared its potential with Sodium butyrate (SoB), a known histone deacetylase inhibitor of Class I and II series. Anti-inflammatory potential of SoB, has been investigated in cancer but not been studied in asthma before. MATERIALS AND METHODS: In present study, ovalbumin (OVA) was used to sensitize Balb/c mice and later exposed to (1%) OVA aerosol. Curcumin (5 mg/kg) and Sodium butyrate (50 mg/kg) was administered through intranasal route an hour before OVA aerosol challenge. Efficacies of SoB and Curcumin as HDAC inhibitors were evaluated in terms of different inflammatory parameters like, total inflammatory cell count, reactive oxygen species (ROS), histamine release, nitric oxide and serum IgE levels. Inflammatory cell recruitment was analyzed by H&E staining and structural alterations were revealed by Masson's Trichrome staining of lung sections. RESULTS: Enhanced Matrix Metalloproteinase-2 and 9 (MMP-2 and MMP-9) activities were observed in bronchoalveolar lavage fluid (BALF) of asthmatic mice by gelatin zymography which was inhibited in both treatment groups. Protein expressions of MMP-9, HDAC 1, H3acK9 and NF-kB p65 were modulated in intranasal curcumin and SoB pretreatment groups. CONCLUSION: This is the first report where intranasal curcumin inhibited asthma severity via affecting HDAC 1 (H3acK9) leading to NF-kB suppression in mouse model of allergic asthma.

Lactobacillus paracasei L9 improves colitis by expanding butyrate-producing bacteria that inhibit the IL-6/STAT3 signaling pathway.

Inflammatory bowel disease (IBD) is a chronic intestinal inflammation that is currently incurable. Increasing evidence indicates that supplementation with probiotics could improve the symptoms of IBD. It is scientifically significant to identify novel and valid strains for treating IBD. It has been reported that the probiotic Lactobacillus paracasei L9 (L9), which is identified from the gut of healthy centenarians, can modulate host immunity and plays an anti-allergic role. Here, we demonstrated that L9 alleviates the pathological phenotypes of experimental colitis by expanding the abundance of butyrate-producing bacteria. Oral administration of sodium butyrate in experimental colitis recapitulates the L9 anti-inflammatory phenotypes. Mechanistically, sodium butyrate ameliorated the inflammatory responses by inhibiting the IL-6/STAT3 signaling pathway in colitis. Overall, these findings demonstrated that L9 alleviates the DSS-induced colitis development by enhancing the abundance of butyrate-producing bacterial strains that produce butyrate to suppress the IL-6/STAT3 signaling pathway, providing new insight into a promising therapeutic target for the remission of IBD.

Dietary sodium butyrate supplementation attenuates intestinal inflammatory response and improves gut microbiota composition in largemouth bass (Micropterus salmoides) fed with a high soybean meal diet.

The study aimed to investigate the effects of dietary sodium butyrate (NaBT) supplementation on the gut health of largemouth bass (Micropterus salmoides) fed with a high soybean meal diet. Three isonitrogenous and isolipidic diets were formulated: a high fishmeal group (Control); a high soybean meal group (SBM), in which the 30% fishmeal protein in the Control diet was replaced by soy protein; and an NaBT group, in which 0.2% NaBT was added to the SBM diet. Each diet was fed to triplicate tanks (20 fish in each tank). After 8 weeks of feeding trial, the distal intestine and intestinal digesta of the fish in each treatment were sampled. The results showed that fishmeal replacement and NaBT supplementation did not affect fish growth performance. Dietary 0.2% NaBT supplementation improved intestinal morphology, increasing the villus width and villus height and reducing the width of lamina propria. The distal intestine of fish in the control and NaBT groups demonstrated lower activities of total superoxide dismutase (T-SOD) and glutathione peroxidase (GPx) and a lower malondialdehyde (MDA) content, compared with the fish in the SBM group. Moreover, the addition of 0.2% NaBT in the feed significantly decreased the expression of tumor necrosis factor α (TNF-α) and interleukin 1ß (IL-1ß) compared to the SBM diet. PCoA and UPGMA analyses based on weighted UniFrac distances demonstrated that intestinal microbial communities in the NaBT group were closer to those in the control group than to those in the SBM group. In addition, dietary 0.2% NaBT supplementation significantly increased the abundance of Firmicutes and Bacteroidetes and decreased the abundance of Tenericutes at the phylum level. Furthermore, the abundance of Bacteroides, Lachnospiraceae_unclassified, and Lachnospiraceae_uncultured was significantly increased, while that of Mycoplasma was significantly decreased in fish intestine at NaBT group at the genus level. In conclusion, dietary NaBT supplementation had beneficial roles in protecting the gut health of largemouth bass from the impairments caused by soybean meal.

Could the use of butyric acid have a positive effect on microbiota and treatment of type 2 diabetes?

OBJECTIVE: This review focuses on the role of butyrate as one of the key metabolites of gut microbiota. Butyrate along with other short-chain fatty acids, acetate and propionate, is one of the most important regulators of human metabolism. In this review, we discuss how changes in gut microbiota triggered by type 2 diabetes mellitus and its treatment (e.g., metformin) affect butyrate synthesis, how to increase butyrate production and whether there is robust evidence for the positive effects of sodium butyrate in the treatment of diabetes mellitus. MATERIALS AND METHODS:  Literature review was conducted by all authors. Studies published until 27/03/2020 were included. Search words were: ("butyric acid" OR "butyrate") AND ("type 2 diabetes "OR "T2DM"). The articles selected for the study were not chosen in a systematic manner, so the evidence may not be comprehensive. RESULTS: Butyrate was found to effectively reduce inflammation and plays a prominent role in the function of the intestinal barrier. To date the use of sodium butyrate in the treatment of patients with T2DM is not very popular. Meanwhile, butyric acid can beneficially modulate intestinal functions, counteracting the negative effects of the disease as well as the drugs used to treat diabetes. CONCLUSIONS: T2DM is a widespread chronic disease. Understanding role of microbiota in type 2 diabetes and the mechanisms connecting T2DM and alterations in gut microbiota could be the key to improved treatment of T2DM.

High doses of butyrate induce a reversible body temperature drop through transient proton leak in mitochondria of brain neurons.

AIMS: Sodium butyrate (SB) is a major product of gut microbiota with signaling activity in the human body. It has become a dietary supplement in the treatment of intestinal disorders. However, the toxic effect of overdosed SB and treatment strategy remain unknown. The two issues are addressed in current study. MATERIALS AND METHODS: SB (0.3-2.5 g/kg) was administrated through a single peritoneal injection in mice. The core body temperature and mitochondrial function in the brown adipose tissue and brain were monitored. Pharmacodynamics, targeted metabolomics, electron microscope, oxygen consumption rate and gene knockdown were employed to dissect the mechanism for the toxic effect. KEY FINDINGS: The temperature was reduced by SB (1.2-2.5 g/kg) in a dose-dependent manner in mice for 2-4 h. In the brain, the effect was associated with SB elevation and neurotransmitter reduction. Metabolites changes were seen in the glycolysis, TCA cycle and pentose phosphate pathways. Adenine nucleotide translocase (ANT) was activated by butyrate for proton transportation leading to a transient potential collapse through proton leak. The SB activity was attenuated by ANT inhibition from gene knockdown or pharmacological blocker. ROS was elevated by SB for the increased ANT activity in proton leak in Neuro-2a. SIGNIFICANCE: Excessive SB generated an immediate and reversible toxic effect for inhibition of body temperature through transient mitochondrial dysfunction in the brain. The mechanism was quick activation of ANT proteins for potential collapse in mitochondria. ROS may be a factor in the ANT activation by SB.

Combined effects of xylo-oligosaccharides and coated sodium butyrate on growth performance, immune function, and intestinal physical barrier function of broilers.

This study was conducted to investigate the effects of dietary supplementation xylo-oligosaccharides (XOS), coated sodium butyrate (CSB), and their combination on growth performance, immune parameters, and intestinal barrier of broilers. A total of 192 1-day-old chicks were assigned to a 2 × 2 factorial design including two dietary additives (0 and 150 mg/kg XOS and 0 and 400 mg/kg CSB). This trial lasted for 42 days. CSB supplementation increased the thymus and bursa index, blood myeloperoxidase (MPO) activity, and IgG and IgM concentrations, whereas adding XOS only improved IgM concentration (p < .05). A significant interaction was observed for MPO activity. Furthermore, broilers fed CSB and their interaction exhibited increased ileal villus height/crypt depth (VH/CD) and goblet cells numbers in the ileum, as well as decreased ileal CD (p < .05). Broilers fed XOS and CSB individually showed higher ileal VH, the number of goblet cells in the duodenum and jejunum (p < .05). Moreover, XOS and CSB individual supplementation upregulated the expression of claudin3 in the ileum (p < .05). Simultaneously, a significant interaction was found for the ileal expression of claudin3. Overall, XOS and CSB supplementation could improve the development of immune organs, the small intestine morphology, and the intestinal physical barrier of broilers. Although no clear synergy of XOS and CSB was detected, the combination had positively affect broilers intestinal barrier and immune parameters.

Sodium butyrate relieves lung ischemia-reperfusion injury by inhibiting NF-κB and JAK2/STAT3 signaling pathways.

OBJECTIVE: Ischemia-reperfusion (IR) is the main cause of acute lung injury (ALI) in clinical lung transplantation, extracorporeal circulation, lung sleeve resection, trauma and cardiopulmonary resuscitation. The inflammatory response and oxidative stress following IR are factors that cause and aggravate its secondary damage. The purpose of this study was to investigate the efficacy and mechanism of sodium butyrate (NaB) on lung ischemia-reperfusion injury (LIRI). MATERIALS AND METHODS: We used male C57BL/6 mice to construct the LIRI model and administered the mice with NaB. By examining the expression of inflammatory factors and oxidative stress-related molecules in mouse lung tissue, we investigated the effects of NaB on inflammation and oxidative stress in lung tissue after IR. In addition, the changes in the activity of the NF-κB and JAK2/STAT3 signaling pathways were also examined to determine the mechanism of NaB. RESULTS: The expression levels of the inflammatory factors (IL-1ß, IL-6 and TNF-α) in lung tissue of mice after IR were significantly increased, while NaB reduced the expression of inflammatory factors. In addition, the oxidative stress level of mouse lung tissue after IR increased significantly, showing the decrease of antioxidant molecules SOD1/2, catalase (CAT), and Peroxiredoxin 1 (Prdx1), while the intake of NaB increased the antioxidant level of mouse lung tissue. The activities of NF-κB and JAK2/STAT3 signaling pathways were significantly increased in lung tissue after IR, whereas NaB inhibited the activity of NF-κB and JAK2/STAT3 signaling pathways. CONCLUSIONS: NaB relieves LIRI by inhibiting NF-κB and JAK2/STAT3 signaling pathways to reduce inflammation and oxidative stress levels in lung tissue of mice after IR.

Sodium butyrate attenuated iE-DAP induced inflammatory response in the mammary glands of dairy goats fed high-concentrate diet.

BACKGROUND: Long-term high-concentrate (HC) diet feeding increased bacterial endotoxins, which translocated into the mammary glands of dairy goats and induced inflammatory response. γ-d-Glutamyl-meso-diaminopimelic acid (iE-DAP), bacterial peptidoglycan component, triggered inflammatory response through activating nucleotide oligomerization domain protein 1 (NOD1) signaling pathway. While dietary supplemented with sodium butyrate (SB) relieved inflammatory response and improved animal health and production. To investigate the effects and the mechanisms of action of SB on the inflammatory response in the mammary glands of dairy goats fed HC diet, 12 Saanen dairy goats were randomly assigned into HC group and SB regulated (BHC) group. RESULTS: The results showed that SB supplementation attenuated ruminal pH decrease caused by HC diet in dairy goats resulting in a decrease of proinflammatory cytokines and iE-DAP plasma concentration and the mRNA expression of NOD1 and other inflammation-related genes. The protein levels of NOD1, NF-κB p65 and NF-κB pp65 were decreased by the SB supplementation. The expression of histone deacetylase 3 (HDAC3) was also inhibited by the SB supplementation. Meanwhile, the chromatin compaction ratios and DNA methylation levels of NOD1 and receptor-interacting protein 2 (RIP2) of BHC group were upregulated. CONCLUSION: Collectively, the SB supplementation mitigated the inflammatory response in the mammary glands of dairy goats during HC-induced subacute ruminal acidosis (SARA) by inhibiting the activation of the NOD1/NF-κB signaling pathway through the decrease of the iE-DAP concentration in the rumen fluid and plasma and HDAC3 expression. DNA methylation and chromatin remodeling also contributed to the anti-inflammatory effect of SB. © 2020 Society of Chemical Industry.

GPR43 regulates sodium butyrate-induced angiogenesis and matrix remodeling.

Butyrate is a short-chain fatty acid (SCFA) derived from microbiota and is involved in a range of cell processes in a concentration-dependent manner. Low concentrations of sodium butyrate (NaBu) were shown to be proangiogenic. However, the mechanisms associated with these effects are not yet fully known. Here, we investigated the contribution of the SCFA receptor GPR43 in the proangiogenic effects of local treatment with NaBu and its effects on matrix remodeling using the sponge-induced fibrovascular tissue model in mice lacking the Gpr43 gene (Gpr43-KO) and the wild-type (WT) mice. We demonstrated that NaBu (0.2 mM intraimplant) treatment enhanced the neovascularization process, blood flow, and VEGF levels in a GPR43-dependent manner in the implants. Moreover, NaBu was able to modulate matrix remodeling aspects of the granulation tissue such as proteoglycan production, collagen deposition, and α-smooth muscle actin (α-SMA) expression in vivo, besides increasing transforming growth factor (TGF)-ß1 levels in the fibrovascular tissue, in a GPR43-dependent manner. Interestingly, NaBu directly stimulated L929 murine fibroblast migration and TGF-ß1 and collagen production in vitro. GPR43 was found to be expressed in human dermal fibroblasts, myofibroblasts, and endothelial cells. Overall, our findings evidence that the metabolite-sensing receptor GPR43 contributes to the effects of low dose of NaBu in inducing angiogenesis and matrix remodeling during granulation tissue formation. These data provide important insights for the proposition of new therapeutic approaches based on NaBu, beyond the highly explored intestinal, anti-inflammatory, and anticancer purposes, as a local treatment to improve tissue repair, particularly, by modulating granulation tissue components.NEW & NOTEWORTHY Our data show the contribution of the metabolite-sensing receptor GPR43 in the effects of low dose of sodium butyrate (NaBu) on stimulating angiogenesis and extracellular matrix remodeling in a model of granulation tissue formation in mice. We also show that human dermal fibroblasts, myofibroblasts, and endothelial cells express the receptor GPR43. These data provide important insights for the use of NaBu in local therapeutic approaches applicable to tissue repair in sites other than the intestine.

Effects of diet fermentability and supplementation of 2-hydroxy-4-(methylthio)-butanoic acid and isoacids on milk fat depression: 2. Ruminal fermentation, fatty acid, and bacterial community structure.

The experiment was conducted to understand ruminal effects of diet modification during moderate milk fat depression (MFD) and ruminal effects of 2-hydroxy-4-(methylthio)-butanoic acid (HMTBa) and isoacids on alleviating MFD. Five ruminally cannulated cows were used in a 5 × 5 Latin square design with the following 5 dietary treatments (dry matter basis): a high-forage and low-starch control diet with 1.5% safflower oil (HF-C); a low-forage and high-starch control diet with 1.5% safflower oil (LF-C); the LF-C diet supplemented with HMTBa (0.11%; 28 g/d; LF-HMTBa); the LF-C diet supplemented with isoacids [(IA) 0.24%; 60 g/d; LF-IA]; and the LF-C diet supplemented with HMTBa and IA (LF-COMB). The experiment consisted of 5 periods with 21 d per period (14-d diet adaptation and 7-d sampling). Ruminal samples were collected to determine fermentation characteristics (0, 1, 3, and 6 h after feeding), long-chain fatty acid (FA) profile (6 h after feeding), and bacterial community structure by analyzing 16S gene amplicon sequences (3 h after feeding). Data were analyzed using the MIXED procedure of SAS (SAS Institute Inc., Cary, NC) in a Latin square design. Preplanned comparisons between HF-C and LF-C were conducted, and the main effects of HMTBa and IA and their interaction within the LF diets were examined. The LF-C diet decreased ruminal pH and the ratio of acetate to propionate, with no major changes detected in ruminal FA profile compared with HF-C. The α-diversity for LF-C was lower compared with HF-C, and ß-diversity also differed between LF-C and HF-C. The relative abundance of bacterial phyla and genera associated indirectly with fiber degradation was influenced by LF-C versus HF-C. As the main effect of HMTBa within the LF diets, HMTBa increased the ratio of acetate to propionate and butyrate molar proportion. Ruminal saturated FA were increased and unsaturated FA concentration were decreased by HMTBa, with minimal changes detected in ruminal bacterial diversity and community. As the main effect of IA, IA supplementation increased ruminal concentration of all branched-chain volatile FA and valerate and increased the percentage of trans-10 C18 isomers in total FA. In addition, α-diversity and the number of functional features were increased for IA. Changes in the abundances of bacterial phyla and genera were minimal for IA. Interactions between HMTBa and IA were observed for ruminal variables and some bacterial taxa abundances. In conclusion, increasing diet fermentability (LF-C vs. HF-C) influenced rumen fermentation and bacterial community structure without major changes in FA profile. Supplementation of HMTBa increased biohydrogenation capacity, and supplemental IA increased bacterial diversity, possibly alleviating MFD. The combination of HMTBa and IA had no associative effects in the rumen and need further studies to understand the interactive mechanism.

Effects of diet fermentability and supplementation of 2-hydroxy-4-(methylthio)-butanoic acid and isoacids on milk fat depression: 1. Production, milk fatty acid profile, and nutrient digestibility.

The objectives of this experiment were to determine the effects of increased diet fermentability and polyunsaturated fatty acids (FA) with or without supplemental 2-hydroxy-4-(methylthio)-butanoic acid (HMTBa), isoacids (IA; isobutyrate, 2-methylbutyrate, isovalerate, and valerate) or the combination of these on milk fat depression (MFD). Ten Holstein cows (194 ± 58 DIM, 691 ± 69 kg BW, 28 ± 5 kg milk yield) were used in a replicated 5 × 5 Latin square design. Treatments included a high-forage control diet (HF-C), a low-forage control diet (LF-C) causing MFD by increasing starch and decreasing neutral detergent fiber (NDF), the LF-C diet supplemented with HMTBa at 0.11% (28 g/d), the LF-C diet supplemented with IA at 0.24% of dietary dry matter (60 g/d), and the LF-C diet supplemented with HMTBa and IA. Preplanned contrasts were used to compare HF-C versus LF-C and to examine the main effects of HMTBa or IA and their interactions within the LF diets. Dry matter intake was greater for LF-C versus HF-C, but milk yield remained unchanged. The LF-C diet decreased milk fat yield (0.87 vs. 0.98 kg/d) but increased protein yield compared with HF-C. As a result, energy-corrected milk was lower (28.5 vs. 29.6 kg/d) for LF-C versus HF-C. Although the concentration of total de novo synthesized FA in milk fat was not affected, some short- and medium-chain FA were lower for LF-C versus HF-C, but the concentrations of C18 trans-10 isomers were not different. Total-tract NDF apparent digestibility was numerically lower (42.4 vs. 45.6%) for LF-C versus HF-C. As the main effects, the decrease in milk fat yield observed in LF-C was alleviated by supplementation of HMTBa through increasing milk yield without altering milk fat content and by IA through increasing milk fat content without altering milk yield so that HMTBa or IA, as the main effects, increased milk fat yield within the LF diets. However, interactions for milk fat yield and ECM were observed between HMTBa and IA, suggesting no additive effect when used in combination. Minimal changes were found on milk FA profile when HMTBa was provided. However, de novo synthesized FA increased for IA supplementation. We detected no main effect of HMTBa, IA, and interaction between those on total-tract NDF digestibility. In conclusion, the addition of HMTBa and IA to a low-forage and high-starch diet alleviated moderate MFD. Although the mechanism by which MFD was alleviated was different between HMTBa and IA, no additive effects of the combination were observed on milk fat yield and ECM.

Butyrate enhances the efficacy of radiotherapy via FOXO3A in colorectal cancer patient­derived organoids.

Enhancing the radioresponsiveness of colorectal cancer (CRC) is essential for local control and prognosis. However, consequent damage to surrounding healthy cells can lead to treatment failure. We hypothesized that short­chain fatty acids (SCFAs) could act as radiosensitizers for cancer cells, allowing the administration of a lower and safer dose of radiation. To test this hypothesis, the responses of three­dimensional­cultured organoids, derived from CRC patients, to radiotherapy, as well as the effects of combined radiotherapy with the SCFAs butyrate, propionate and acetate as candidate radiosensitizers, were evaluated via reverse transcription­quantitative polymerase chain reaction, immunohistochemistry and organoid viability assay. Of the three SCFAs tested, only butyrate suppressed the proliferation of the organoids. Moreover, butyrate significantly enhanced radiation­induced cell death and enhanced treatment effects compared with administration of radiation alone. The radiation­butyrate combination reduced the proportion of Ki­67 (proliferation marker)­positive cells and decreased the number of S phase cells via FOXO3A. Meanwhile, 3/8 CRC organoids were found to be non­responsive to butyrate with lower expression levels of FOXO3A compared with the responsive cases. Notably, butyrate did not increase radiation­induced cell death and improved regeneration capacity after irradiation in normal organoids. These results suggest that butyrate could enhance the efficacy of radiotherapy while protecting the normal mucosa, thus highlighting a potential strategy for minimizing the associated toxicity of radiotherapy.

Consecutive intra-gingival injections of lipopolysaccharide and butyric acid to mice induce abnormal behavior and changes in cytokine concentrations.

BACKGROUND: Periodontopathic bacteria such as Porphyromonas gingivalis produce several metabolites, including lipopolysaccharide (LPS) and n-butyric acid (BA). Past work suggested that periodontal infection may cause cognitive impairment in mice. AIMS: To elucidate the mechanisms by which metabolites such as LPS and BA, resulting from Porphyromonas gingivalis activity, induce immunological and physiological abnormalities in mice. METHODS: In the present work, 28 male ICR mice were placed in an open-field arena and the total distance (cm/600 s) they covered was recorded. Based on their moving distances, mice were divided into 4 groups (n = 7) and injected the following substances into their gingival tissues for 32 consecutive days: saline (C), 5 mmol/L of BA (B), 1 µg/mouse of LPS (L), and BA-LPS (BL) solutions. Distances covered by mice were also measured on days 14 and 21, with their habituation scores considered as "(moving distance on day 14 or 21)/(moving distance on day 0)". Afterwards, mice were dissected, and hippocampal gene expression and the concentrations of short-chain fatty acids, neurotransmitters and cytokines in their blood plasma and brains were analyzed. In addition, mouse brain and liver tissues were fixed and visually assessed for histopathological abnormalities. RESULTS: Group BL had significantly higher habituation scores than C and B on day 14. LPS induced higher habituation scores on day 21. LPS induced significant decreases in the mRNA levels of interleukin (IL)-6 and brain-derived neurotrophic factors, and an increase in neurotrophic tyrosine kinase receptor type 2. In both plasma and brain, LPS induced a significant acetate increase. Moreover, LPS significantly increased acetylcholine in brain. In plasma alone, LPS and BA significantly decreased monocyte chemoattractant protein 1 (MCP-1). However, while LPS significantly decreased tyrosine, BA significantly increased it. Lastly, LPS significantly decreased IL-6 and tumor necrosis factor in plasma. No histopathological abnormalities were detected in liver or brain tissues of mice. CONCLUSION: We showed that injections of LPS and/or BA induced mice to move seemingly tireless and that both LPS and BA injections strongly induced a reduction of MCP-1 in blood plasma. We concluded that LPS and BA may have been crucial to induce and/or aggravate abnormal behavior in mice.

Sodium butyrate and monensin supplementation to postweaning heifer diets: Effects on growth performance, nutrient digestibility, and health.

The objective of this study was to evaluate growth and performance of postweaning heifers supplemented with monensin (MON), sodium butyrate (SB), or the combination of MON and SB (MSB) compared with heifers not receiving these feed additives. Forty Holstein heifers [mean age 84.2 ± 1.2 d; body weight (BW) 99.8 ± 10.8 kg (mean ± SD)] were housed in a freestall barn, blocked by birth date, and randomly assigned to 1 of 4 treatments in a randomized complete block design. Treatments were (1) 100 g of soybean meal carrier (control; CON); (2) 0.75 g of SB/kg of BW + carrier (SB); (3) 1 mg of MON/kg of BW + carrier (MON); (4) 1 mg of MON/kg of BW + 0.75 g of SB/kg of BW (MSB). Data were analyzed using single degree of freedom contrasts evaluating CON versus additives (ADD), SB versus MON, and SB and MON versus MSB. Treatments were hand-mixed daily. Feed and orts were measured daily and frozen at -20°C. Orts samples were subsampled for dry matter (DM) determination, and total mixed ration samples were taken weekly and composited monthly for DM and nutrient analysis. Initial BW, heart and paunch girths, body length, blood samples, and fecal coccidia counts were measured before the start and weekly during the 12-wk trial. Blood samples were analyzed for glucose, plasma urea nitrogen (PUN), and ketone concentrations. Apparent total-tract nutrient digestibility was determined from d 21 to 27 and from d 63 to 69 using acid detergent insoluble ash as a marker. Daily dry matter intake (DMI) and metabolizable energy intake were increased in ADD compared with CON, and average BW, final BW, and heart girth tended to increase. Whereas MSB tended to be greater than SB and MON for heart girth, feed efficiency was greater with MON compared with SB. Compared with CON, ADD decreased coccidia counts. No effect of treatment on PUN was detected. Monensin and SB tended to have greater plasma glucose than MSB did. Average blood ketone concentrations were greater with ADD versus CON, in SB versus MON, and in MSB versus SB and MON. During the wk-3 digestibility phase, DMI tended to be greater in heifers fed SB versus MON, as well as in heifers fed MSB versus SB and MON. Digestibility of nutrients were similar, except that starch digestibility was increased in heifers fed MSB versus SB and MON. During the wk-9 digestibility phase, DMI and digestibility of nutrients were similar, except NDF, which tended to be greater in CON than in ADD. Overall, ADD resulted in positive growth and reduced coccidia compared with CON.

Effect of dialyzable leukocyte extract, sodium butyrate, and valproic acid in the development of anergy in murine leprosy.

Background: Murine leprosy is a chronic granulomatous disease caused by Mycobacterium lepraemurium (MLM) in mice and rats. The disease evolves with the development of cellular anergy that impedes the production of interferon gamma (IFNγ), tumor necrosis factor-alpha (TNFα), and nitric oxide (NO) required to kill the microorganism. In this study we investigated whether histone deacetylase inhibitors (HDACi) (valproic acid and sodium butyrate [NaB]) and the immunomodulator transfer factor in dialyzable leukocyte extracts (DLE) can prevent anergy in murine leprosy. Methods: Five groups of six Balb/c mice were intraperitoneally inoculated with 2 × 107 MLM. Thirty-days post inoculation, treatment was started; one group received no treatment, one was treated with rifampicin-clofazimine (R-C), one with sodium valproate (VPA), one with NaB, and one with DLE. The animals were monitored for the evidence of disease for 96 days. After euthanasia, their spleens were removed and processed for histologic, bacteriologic, and cytokine studies. Results: R-C completely controlled the ongoing disease. DLE and NaB significantly reduced the development of lesions, including granuloma size and the number of bacilli; VPA was less effective. DLE, NaB, and VPA reverted the anergic condition in diverse grades and allowed the expression of IFNγ, TNFα, and inducible NO synthase, also in diverse grades. Conclusion: Anergy in leprosy and murine leprosy allows disease progression. In this study, anergy was prevented, in significant degree, by DLE (an immunomodulator) and NaB (HDACi). VPA was less effective. These results suggest potential beneficial effects of DLE and NaB in the ancillary treatment of leprosy.

An indisputable role of NHE8 in mucosal protection.

The loss of the intestinal Na+/H+ exchanger isoform 8 (NHE8) results in an ulcerative colitis-like condition with reduction of mucin production and dysbiosis, indicating that NHE8 plays an important role in intestinal mucosal protection. The aim of this study was to investigate the potential rebalance of the altered microbiota community of NHE8-deficient mice via fecal microbiota transplantation (FMT) and feeding probiotic VSL#3. We also aimed to stimulate mucin production by sodium butyrate administration via enema. Data from 16S rRNA sequencing showed that loss of NHE8 contributes to colonic microbial dysbiosis with reduction of butyrate-producing bacteria. FMT increased bacterial adhesion in the colon in NHE8 knockout (NHE8KO) mice. Periodic-acid Schiff reagent (PAS) stain and quantitative PCR showed no changes in mucin production during FMT. In mice treated with the probiotic VSL#3, a reduction of Lactobacillus and segmented filamentous bacteria (SFB) in NHE8KO mouse colon was detected and an increase in goblet cell theca was observed. In NHE8KO mice receiving sodium butyrate (NaB), 1 mM NaB stimulated Muc2 expression without changing goblet cell theca, but 10 mM NaB induced a significant reduction of goblet cell theca without altering Muc2 expression. Furthermore, 5 mM and 10 mM NaB-treated HT29-MTX cells displayed increased apoptosis, while 0.5 mM NaB stimulated Muc2 gene expression. These data showed that loss of NHE8 leads to dysbiosis with reduction of butyrate-producing bacteria and FMT and VSL#3 failed to rebalance the microbiota in NHE8KO mice. Therefore, FMT, VSL#3, and NaB are not able to restore mucin production in the absence of NHE8 in the intestine.NEW & NOTEWORTHY Loss of Na+/H+ exchanger isoform 8 (NHE8), a Slc9 family of exchanger that contributes to sodium uptake, cell volume regulation, and intracellular pH homeostasis, resulted in dysbiosis with reduction of butyrate-producing bacteria and decrease of Muc2 production in the intestine in mice. Introducing fecal microbiota transplantation (FMT) and VSL#3 in NHE8 knockout (NHE8KO) mice failed to rebalance the microbiota in these mice. Furthermore, administration of FMT, VSL#3, and sodium butyrate was unable to restore mucin production in the absence of NHE8 in the intestine.

Prebiotics and butyric acid can replace colistin as a growth promoter for nursery piglets / [Prebióticos e ácido butírico podem substituir a colistina como promotor de crescimento para leitões em fase de creche]

This study aimed to assess different prebiotic concentrations and principles, in addition to calcium butyrate, aiming to replace colistin as a growth promoter. The sample consisted of 120 piglets weaned at 22 days old with mean initial weight of 5.475 ± 0.719kg. The animals were assigned to random blocks in six treatments corresponding to the use of the following dietary additives: T1) colistin (40 ppm); T2) ß-glucan/mannan-oligosaccharides (0.2%); T3) calcium butyrate (0.1%); T4) ß-glucan/mannan-oligosaccharides (0.1%) + fructooligosaccharides (0.01%) + galactooligosaccharides (0.09%); T5) ß-glucan/mannan-oligosaccharides (0.1%) + fructooligosaccharides (0.03%) + galactooligosaccharides (0.07%); and T6) ß-glucan/mannan-oligosaccharides (0.1%) + fructooligosaccharides (0.05%) + galactooligosaccharides (0.05%). The results showed no difference among treatments for the performance parameters in any of the phases evaluated. For diarrhea incidence and intensity, the results indicated that the treatments with alternative additives had similar effects as the group treated with colistin. A significant difference was found for the profile of propionic acid (0.23% colistin and 0.32%, 0.36%, 0.37% additives) and total fatty acids (0.67% colistin and 0.97% additives) values in the caecum. The supplementation with different compositions and concentrations of prebiotics and butyric acid may viably replace colistin in controlling diarrhea and modulating volatile fatty acid production in the caecum.(AU)

O objetivo deste trabalho foi avaliar as diferentes concentrações e princípios de prebióticos e do butirato de sódio, visando substituir a colistina como promotor de crescimento. Foram utilizados 120 leitões, desmamados aos 22 dias de idade, com peso médio inicial de 5,475 ± 0,719kg. Os animais foram distribuídos em blocos ao acaso, em seis tratamentos, que corresponderam ao uso dos seguintes aditivos dietéticos: T1) colistina (40ppm); T2) ß-glucanos/mananoligossacarídeos (0,2%); T3) butirato de cálcio (0,1%); T4) ß-glucanos/mananoligossacarídeos (0,1%) + frutoligossacarídeos (0,01%) + galactoligossacarídeos (0,09%); T5) ß-glucanos/mananoligossacarídeos (0,1%) + frutoligossacarídeos (0,03%) + galactoligossacarídeos (0,07%); e T6) ß-glucanos/mananoligossacarídeos (0,1%) + frutoligossacarídeos (0,05%) + galactoligossacarídeos (0,05%). Os resultados mostraram que não houve diferença entre os tratamentos para nenhum dos parâmetros de desempenho em nenhuma das fases avaliadas. Para a incidência e a intensidade de diarreia, os resultados apontam que os tratamentos com os aditivos alternativos apresentaram efeitos semelhantes aos do grupo tratado com colistina. Foi encontrada diferença significativa para perfil dos ácidos graxos propiônicos (0,23% colistina e 0,32%, 0,36%, 0,37% aditivos) e ácidos totais (0,67% colistina e 0,97% aditivos) no ceco. A suplementação com diferentes composições e concentrações de prebióticos e do ácido butírico pode substituir a colistina de forma viável no controle da diarreia e na modulação da produção volátil de ácidos graxos no ceco.(AU)

Transcriptome analysis reveals a molecular understanding of nicotinamide and butyrate sodium on meat quality of broilers under high stocking density.

BACKGROUND: In recent years, increased attention has been focused on breast muscle yield and meat quality in poultry production. Supplementation with nicotinamide and butyrate sodium can improve the meat quality of broilers. However, the potential molecular mechanism is not clear yet. This study was designed to investigate the effects of supplementation with a combination of nicotinamide and butyrate sodium on breast muscle transcriptome of broilers under high stocking density. A total of 300 21-d-old Cobb broilers were randomly allocated into 3 groups based on stocking density: low stocking density control group (L; 14 birds/m2), high stocking density control group (H; 18 birds/m2), and high stocking density group provided with a combination of 50 mg/kg nicotinamide and 500 mg/kg butyrate sodium (COMB; 18 birds/m2), raised to 42 days of age. RESULTS: The H group significantly increased cooking losses, pH decline and activity of lactate dehydrogenase in breast muscle when compared with the L group. COMB showed a significant decrease in these indices by comparison with the H group (P < 0.05). The transcriptome results showed that key genes involved in glycolysis, proteolysis and immune stress were up-regulated whereas those relating to muscle development, cell adhesion, cell matrix and collagen were down-regulated in the H group as compared to the L group. In contrast, genes related to muscle development, hyaluronic acid, mitochondrial function, and redox pathways were up-regulated while those associated with inflammatory response, acid metabolism, lipid metabolism, and glycolysis pathway were down-regulated in the COMB group when compared with the H group. CONCLUSIONS: The combination of nicotinamide and butyrate sodium may improve muscle quality by enhancing mitochondrial function and antioxidant capacity, inhibiting inflammatory response and glycolysis, and promoting muscle development and hyaluronic acid synthesis.