RESUMEN

Large dog breeds commonly produce unformed faeces. The present study hypothesised that foods for large dog breeds require higher starch gelatinisation (SG) to reduce organic matter flow to colon. Fifteen Rottweilers (Ro; 49.4 ± 6.12 kg), 18 Beagles (Be; 12.13 ± 1.75 kg) and 20 Shih-Tzus (ST; 4.62 ± 1.15 kg) were fed one of three diets, all based on the same sorghum formulation, processed to obtain three levels of SG: SG90 (91.8% SG), SG50 (50.7% SG) and SG30 (27.4% SG). Foods were provided for 23 days, and the coefficient of total tract apparent digestibility (CTTAD) of nutrients, faecal production and fermentation products, Na, K and Cl apparent absorption and gastrointestinal transit time (GTT) were evaluated. Results were submitted to analysis of variance considering SG, breed and their interactions, and means compared by the Tukey test (p < 0.05). All dogs promptly ate the foods. Faeces scores were lower for Ro than for Be and ST, and lower for SG30 than SG90 (p < 0.05). Faeces pH was higher, and total short-chain fatty acids were lower for SG90 than for SG50 and SG30 (p < 0.01), regardless of breed. No diet effect was observed for GTT (p > 0.05), but it was lower for Ro (41.7 ± 6.2 h) than for ST (48.7 ± 8.6 h). The CTTAD of nutrients was lower for SG30, intermediary for SG50 and higher for SG90 (p < 0.05), and among breeds CTTAD was higher for Be than ST and Ro (p < 0.05), which did not differ from each other, except for crude protein CTTAD which was lower for Ro (p < 0.05). The apparent absorption of Na and K was higher for the SG90 treatment, and for Be in comparison with Ro and ST (p < 0.05). Food SG had a remarkable influence on Ro faeces formation and on the CTTAD in all breeds. Greater fermentation in the colon and lower protein CTTAD may be involved in Ro unformed faeces formation.

RESUMEN

Objective: The objective of this study was to evaluate the use of condensed tannin from black acacia (Acacia mearnsii) as a substitute additive for zinc oxide and growth-promoting antibiotics on the performance, digestibility, and intestinal health of piglets in the nursery phase. Methods: A total of 200 PIC® piglets that were 22 days old and weighed 6.0±0.9 kg were subjected to four treatments in the nursery phase (22 to 64 days of age): CONTR (control diet); ENR+ZnO (control diet + 10 mg/kg of enramycin + 2,500 mg/kg of zinc oxide during the first 21 days); BUT (control diet + 900 mg/kg of sodium butyrate) and TAN (control diet + 2,000 mg/kg of condensed tannin). The experimental design was a randomized block with 4 treatments and 10 replicates, with a pen of five animals each as the experimental unit. The zootechnical performance, diarrhea index score, dietary digestibility and metagenomics of the deep rectum microbiota were evaluated. Results: The TAN had greater weight gain in the nursery phase and final weight (p<0.05) than the CONTR (394 vs. 360 g/d, and 22.6 vs. 21.1 kg, respectively), with these values being intermediate for the ENR+ZnO and BUT (365 and 382 g/d, and 21.3 and 22.1 kg, respectively). There was no difference between treatments for semi-liquid diarrhea (score 2), but CONTR had more cases of severe diarrhea (score 3; p<0.05) than ENR+ZnO, BUT and TAN, with 42, 18, 29 and 21 cases, respectively. The treatments had no impact on rare taxa or the relative abundances of taxonomic groups (uniformity), but the use of TAN promoted an increase in the abundances of Brevibacillus spp. and Enterococcus spp. compared to the other treatments (p<0.05). Conclusion: The use of condensed tannin from black wattle as a performance-enhancing additive was effective, with effects on performance and intestinal health, demonstrating its potential as a substitute for zinc oxide and enramycin in the diets of piglets in nursery phase.

RESUMEN

HIV infection results in marked alterations in the gut microbiota (GM), such as the loss of microbial diversity and different taxonomic and metabolic profiles. Despite antiretroviral therapy (ART) partially ablating gastrointestinal alterations, the taxonomic profile after successful new ART has shown wide variations. Our objective was to determine the GM composition and functions in people living with HIV (PLWHIV) under ART in comparison to seronegative controls (SC). Fecal samples from 21 subjects (treated with integrase strand-transfer inhibitors, INSTIs) and 18 SC were included. We employed 16S rRNA amplicon sequencing, coupled with PICRUSt2 and fecal short-chain fatty acid (SCFA) quantification by gas chromatography. The INSTI group showed a decreased α-diversity (p < 0.001) compared to the SC group, at the expense of increased amounts of Pseudomonadota (Proteobacteria), Segatella copri, Lactobacillus, and Gram-negative bacteria. Concurrently, we observed an enrichment in Megasphaera and Butyricicoccus, both SCFA-producing bacteria, and significant elevations in fecal butyrate in this group (p < 0.001). Interestingly, gut dysbiosis in PLWHIV was characterized by a proinflammatory environment orchestrated by Pseudomonadota and elevated levels of butyrate associated with bacterial metabolic pathways, as well as the evident presence of butyrogenic bacteria. The role of this unique GM in PLWHIV should be evaluated, as well as the use of butyrate-based supplements and ART regimens that contain succinate, such as tenofovir disoproxil succinate. This mixed profile is described for the first time in PLWHIV from Mexico.

Asunto(s)

RESUMEN

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.

Asunto(s)

RESUMEN

Diarrhea and respiratory diseases pose significant challenges in the rearing of pre-weaned calves, motivating the investigation of tools to improve gastrointestinal tract development, health, and overall performance in young calves. Consequently, the primary objective of this study was to assess the effectiveness of an additive incorporated into milk replacer to promote the development and health of the animals. Forty-six dairy calves were randomly assigned into two treatments: control (CON, n = 23; with 15 females and 8 males), and sodium butyrate (SB, n = 23; with 15 females and 8 males). The calves in the SB treatment group were supplemented with 4 g/d of unprotected sodium butyrate (Adimix, Adisseo, China), added to the milk replacer from 4 to 60 days of age. Water and starter were fed ad libitum. The study evaluated several parameters, including feed intake, nutrient digestibility, ruminal pH, ammonia and volatile fatty acids, blood metabolites (glucose, insulin-like growth factor type 1, urea, ß-hydroxybutyrate), hemogram, health scores, performance, and feed efficiency. Bull calves were euthanized at 60 days of age for organ comparison, while heifer calves were assessed for carryover effects up to 90 days of age. Data were analyzed independently using linear mixed models using the nlme package in R, and the Artools package for non-parametric categorical outcomes. Although the feed intake and performance variables exhibited differences within weeks, no divergence was observed between treatment groups. Notably, a positive treatment-by-week interaction was identified for starter feed intake (p = 0.02) and total dry matter intake (p = 0.04) during pre-weaning for CON animals. Ruminal parameters, blood metabolites, and hemogram values such as glucose, urea, insulin-like growth factor type 1, mean corpuscular value, lymphocytes, and neutrophils displayed differences within weeks during the pre-weaning stage, but similar results within groups. No differences between supplemented and non-supplemented calves were found across nutrient digestibility, organ development, and histology. Regarding health scores, differences were noted within weeks for fecal and respiratory scores during the pre-weaning stage, and only the respiratory score during the post-weaning stage. Consequently, butyrate supplementation did not elicit improvements or negative effects in the body development or health status of dairy calves.

RESUMEN

Macauba (Acrocomia aculeata) is a palm tree native from Brazil, whose pulp is rich in oil that has a high content of oleic acid and carotenoids. Macauba pulp oil can bring health benefits due to its bioactive compounds; however, its effects on gut health are unknown. Thus, the objective of this study was to evaluate the effect of macauba pulp oil on the intestinal health in mice fed a high-fat (HF) diet. Male C57BL1/6 mice were randomly divided into three groups (10 animals/group): control diet, HF diet and HF diet with 4 % of macauba pulp oil (HFM). Concentration of short-chain fatty acids (SCFA), faecal pH and histomorphometric analysis of the colon were performed. Content of colon samples was used on microbiome analysis using 16S rRNA amplicon sequencing. Animals from the HFM group had higher butyric acid content and goblet cells number, greater circular and longitudinal muscle layer and higher α-diversity compared with the HF group. Moreover, consumption of MPO reduced Desulfobacterota phylum, Ruminococcaceae, Oscillospiraceae, Prevotellaceae, Bifidobacteriaceae family, Faecalibacterium, Prevotella, Ruminococcus and Enterorhabdus genus. Therefore, macauba pulp oil was able to modulate the gut microbiota and enhance intestinal barrier morphology, showing preventive effects on gut dysbiosis in mice fed a HF diet.

Asunto(s)

RESUMEN

This study aimed to determine whether the addition of butyric acid glycerides as substitutes to conventional growth promoters can provide adequate zootechnical performance and intestinal health in healthy piglets in the nursery phase. We used 90 male piglets (average weight of 6.5 kg) subdivided into five treatments with six replicates per treatment. The treatments had the same basal diet: NC-negative control (without growth promoter), PC-positive control (with gentamicin, oral), PSB-protected sodium butyrate, FSB-free sodium butyrate, and TRI-tributyrin. In these animals, zootechnical performance was evaluated on days 1, 10, 20 and 39, microbiological analysis on days 14 and 39, hematocrit, blood biochemistry and intestinal histology, intestinal oxidation and antioxidation on day 39. The average daily weight gain was higher in the TRI group on days 21 to 39 in the nursery (P = 0.03), with more significant weight gain from 1 to 39 days (P = 0.05). There were higher leukocyte counts in the PC group than in the TRI group and higher lymphocyte counts in the PC treatment than in the NC or TRI groups. Escherichia coli counts were lower in the PC, followed by the PSB and TRI groups on day 39 (P = 0.01). Lower crypt depths were found in the TRI and FSB groups, followed by PC, than in the NC group (P = 0.01). Higher values for crypt villosity ratio were found in the FSB and TRI groups than in the NC group (P = 0.05). Lower lipid peroxidation was found in analyzes of serum oxidative status (LPO: P = 0.01), associated with greater activities of superoxide dismutase - SOD (P = 0.08), glutathione S-transferase - GST (P = 0.09) in PSB and TRI groups than in the NC group. In conclusion, the use of butyric acid in the form of tributyrin can be used as growth enhancers in piglets in the nursery phase.

Asunto(s)

RESUMEN

Degenerative Cervical Myelopathy (DCM) is the most common cause of spinal cord impairment in elderly populations. It describes a spectrum of disorders that cause progressive spinal cord compression, neurological impairment, loss of bladder and bowel functions, and gastrointestinal dysfunction. The gut microbiota has been recognized as an environmental factor that can modulate both the function of the central nervous system and the immune response through the microbiota-gut-brain axis. Changes in gut microbiota composition or microbiota-producing factors have been linked to the progression and development of several pathologies. However, little is known about the potential role of the gut microbiota in the pathobiology of DCM. Here, DCM was induced in C57BL/6 mice by implanting an aromatic polyether material underneath the C5-6 laminae. The extent of DCM-induced changes in microbiota composition was assessed by 16S rRNA sequencing of the fecal samples. The immune cell composition was assessed using flow cytometry. To date, several bacterial members have been identified using BLAST against the largest collection of metagenome-derived genomes from the mouse gut. In both, female and males DCM caused gut dysbiosis compared to the sham group. However, dysbiosis was more pronounced in males than in females, and several bacterial members of the families Lachnospiraceae and Muribaculaceae were significantly altered in the DCM group. These changes were also associated with altered microbe-derived metabolic changes in propionate-, butyrate-, and lactate-producing bacterial members. Our results demonstrate that DCM causes dynamic changes over time in the gut microbiota, reducing the abundance of butyrate-producing bacteria, and lactate-producing bacteria to a lesser extent. Genome-scale metabolic modeling using gapseq successfully identified pyruvate-to-butanoate and pyruvate-to-propionate reactions involving genes such as Buk and ACH1, respectively. These results provide a better understanding of the sex-specific molecular effects of changes in the gut microbiota on DCM pathobiology.

RESUMEN

OBJECTIVE: Immunotherapy has been proven to improve the prognosis of patients with advanced malignancy but has shown limited efficacy in patients with Colorectal Cancer (CRC). Increasing evidence suggests that butyrate, a bacterial metabolite, enhances the efficacy of cancer therapies by modulating immune responses. Here, the effect and the mechanism of butyrate on anti-PD-L1 therapy were investigated in CRC. METHODS: The expression of PD-L1 and STAT1, and the lysine acetylation of STAT1 in CRC cells were observed after treatment with butyrate (2, 5, and 10 mM) for 24h or butyrate (5 mM) for 8, 16, and 24h. Site-directed mutations of STAT1 (K410R or K413R) were introduced to determine the role of STAT1 acetylation in modulating PD-L1 expression. The effect of butyrate on the cytotoxicity of CD8+ T-cells against CRC cells with or without PD-L1 overexpression was explored in vitro and in vivo. RESULTS: Butyrate could suppress IFN-γ-induced PD-L1 up-regulation in CRC cells in a dose- and time-dependent way. Butyrate promoted the lysine acetylation of STAT1 to reduce STAT1 expression. Non-acetylated mutant STAT1 not only ameliorated butyrate-induced suppression of lysine acetylation and nuclear translocation of STAT1 but also blocked the effect of butyrate on PD-L1. Butyrate attenuated the IFN-γ-induced impairment of CD8+ T-cell cytotoxicity against CRC cells. Meanwhile, butyrate suppressed CRC tumor growth by enhancing CD8+ T-cell infiltration. However, directly overexpressing PD-L1 in CRC cells could abolish the effect of butyrate. CONCLUSION: Butyrate strengthens the immune response to CRC cells by suppressing PD-L1 expression via acetylation of STAT1.

Asunto(s)

RESUMEN

Inflammatory bowel diseases (IBD) cause increased inflammatory signalling and oxidative damage. IBDs are correlated with an increased incidence of brain-related disorders suggesting that the gut-brain-axis exerts a pivotal role in IBD. Butyrate is one of the main microbial metabolites in the colon, and it can cross the blood-brain barrier, directly affecting the brain. We induced ulcerative colitis (UC) in mice utilizing dextran sodium sulfate (DSS) in the drinking water for 7 days. Animals were divided into four groups, receiving water or DSS and treated with saline or 0,066 g/kg of Sodium Butyrate for 7 days. We also used an integrative approach, combining bioinformatics functional network and experimental strategies to understand how butyrate may affect UC. Butyrate was able to attenuate colitis severity and intestinal inflammation. Butyrate protected the colon against oxidative damage in UC and protected the prefrontal cortex from neuroinflammation observed in DSS group. Immunocontent of tight junction proteins Claudin-5 and Occludin were reduced in colon of DSS group mice and butyrate was able to restore to control levels. Occludin and Claudin-5 decrease in DSS group indicate that an intestinal barrier disruption may lead to the increased influx of gut-derived molecules, causing neuroinflammation in the prefrontal cortex, observed by increased IBA-1 marker. The probable protection mechanism of butyrate treatment occurs through NRF2 through Nrf2 and HIF-1α activation and consequent activation of catalase and superoxide dismutase. Our data suggest that systemic inflammation associated with intestinal barrier disruption in UC leads to neuroinflammation in the prefrontal cortex, which was atenuated by butyrate.

Asunto(s)

RESUMEN

The enteric nervous system is affected by inflammatory bowel diseases (IBD). Gut microbiota ferments dietary fibers and produces short-chain fatty acids, such as Butyrate, which bind to G protein-coupled receptors, such as GPR41, and contribute to maintaining intestinal health. This work aimed to study the GPR41 in myenteric neurons and analyze the effect of Butyrate in mice submitted to experimental ulcerative colitis. The 2, 4, 6 trinitrobenzene sulfonic acid (TNBS) was injected intrarectally in C57BL/6 mice (Colitis). Sham group received ethanol (vehicle). One group was treated with 100 mg/kg of Sodium Butyrate (Butyrate), and the other groups received saline. Animals were euthanized 7 days after colitis induction. Analyzes demonstrated colocalization of GPR41 with neurons immunoreactive (-ir) to nNOS and ChAT-ir and absence of colocalization of the GPR41 with GFAP-ir glia. Quantitative results demonstrated losses of nNOS-ir, ChAT-ir, and GPR41-ir neurons in the Colitis group and Butyrate treatment attenuated neuronal loss. The number of GFAP-ir glia increased in the Colitis group, whereas Butyrate reduced the number of these cells. In addition, morphological alterations observed in the Colitis group were attenuated in the Butyrate group. The presence of GPR41 in myenteric neurons was identified, and the treatment with Butyrate attenuated the damage caused by experimental ulcerative colitis.

Asunto(s)

RESUMEN

Butyrate is a microbiota-produced metabolite, sensed by host short-chain fatty acid receptors FFAR2 (Gpr43), FFAR3 (Gpr41), HCAR2 (Gpr109A), and Histone deacetylase (HDAC) that promotes microbiota-host crosstalk. Butyrate influences energy uptake, developmental and immune response in mammals. This microbial metabolite is produced by around 79 anaerobic genera present in the mammalian gut, yet little is known about the role of butyrate in the host-microbiota interaction in salmonid fish. To further our knowledge of this interaction, we analyzed the intestinal microbiota and genome of Atlantic salmon (Salmo salar), searching for butyrate-producing genera and host butyrate receptors. We identified Firmicutes, Proteobacteria, and Actinobacteria as the main butyrate-producing bacteria in the salmon gut microbiota. In the Atlantic salmon genome, we identified an expansion of genes orthologous to FFAR2 and HCAR2 receptors, and class I and IIa HDACs that are sensitive to butyrate. In addition, we determined the expression levels of orthologous of HCAR2 in the gut, spleen, and head-kidney, and FFAR2 in RTgutGC cells. The effect of butyrate on the Atlantic salmon immune response was evaluated by analyzing the pro and anti-inflammatory cytokines response in vitro in SHK-1 cells by RT-qPCR. Butyrate decreased the expression of the pro-inflammatory cytokine IL-1ß and increased anti-inflammatory IL-10 and TGF-ß cytokines. Butyrate also reduced the expression of interferon-alpha, Mx, and PKR, and decreased the viral load at a higher concentration (4 mM) in cells treated with this molecule before the infection with Infectious Pancreatic Necrosis Virus (IPNV) by mechanisms independent of FFAR2, FFAR3 and HCAR2 expression that probably inhibit HDAC. Moreover, butyrate modified phosphorylation of cytoplasmic proteins in RTgutGC cells. Our data allow us to infer that Atlantic salmon have the ability to sense butyrate produced by their gut microbiota via different specific targets, through which butyrate modulates the immune response of pro and anti-inflammatory cytokines and the antiviral response.

RESUMEN

High amounts of grains in the equine diet led to high starch intake, causing gut alterations. Aimed at reducing harmful effects, Macleaya cordata extract (MCE) is a phytogenic additive that stands out for its antibiotic and anti-inflammatory effects proven in different species. However, there is no useful information for horses. The objective of this study was to evaluate the effects of different levels of the inclusion of commercial MCE on body weight (BW), body condition score (BCS), total apparent digestibility (AD) of nutrients, faecal pH and fermentative products, on ponies fed a high-starch diet. Eight healthy gelding Mini Horse ponies were used. The study design was contemporary double Latin-square 4 × 4 in the experimental unit, with the animal inside each experimental period (n = 8 experimental units per group). The experiment was conducted over four 20-d periods. Basal diet attended 1.75% BW dry matter daily and starch intake was 2.2 g/kg BW/meal. The experimental groups were as follows: control - without food additive; S1-1 mg/kg BW MCE; S1.5-1.5 mg/kg BW MCE and S2-2 mg/kg BW MCE. The data were analysed by PROC MIXED of SAS (p < 0.05). Tendency was considered when 0.05 < p < 0.1. Our results showed higher ether extract (EE) AD for S2 group (63.75%) when compared with the control (54.55%) (p = 0.0377). Lactate was lower (p = 0.0391) in S1 (3.27 mmol/l) and S2 (3.24 mmol/l) groups, although pH was not different between groups. Iso-valerate was greater in S1 group (2.29 mmol/l; p = 0.0289), and a tendency of higher butyrate values was found for S1 and S2 groups (p = 0.0980). We concluded that MCE supplementation probably positively influences equine resident microbiota, improving EE AD and increasing iso-valerate concentration. It can also minimise harmful high-starch impact. We recommend further studies using MCE in horses for a better understanding of its local activity and possible benefits.

Asunto(s)

RESUMEN

Short-chain fatty acids (SCFA) such as propionate and butyrate are critical metabolites produced by the gut microbiota. Microbiome dysbiosis resulting in altered SCFA profiles is associated with certain diseases, including inflammatory bowel diseases (IBD), characterized by a reduction in butyrate concentration and active intestinal inflammation. There is an increasing interest in the use of engineered bacteria as diagnostic and therapeutic tools for gut diseases. In this study, we developed genetic circuits capable of sensing SCFA concentrations to build biosensors that express a response protein (superfolder green fluorescent protein [sfGFP]) in amounts inversely proportional to the SCFA concentration. We also built biotherapeutics expressing the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) using the same logic. The propionate biotherapeutic expressed larger amounts of mouse GM-CSF in the absence of propionate. The butyrate biotherapeutics presented the expected behavior only at the beginning of the kinetics and an accelerated response in the absence of butyrate. Overall, these genetic systems may function as complementary diagnostic tools for measuring SCFAs and as delivery vehicles for biotherapeutic molecules. IMPORTANCE Short-chain fatty acids are key molecules produced by the gut microbiome. Their concentrations are altered in certain diseases. Here, we created molecular biosensors that quantify the absence of propionate and butyrate, using logic "NOT" gates and bacterial promoters. Finally, we show that these genetic systems could be useful for the delivery of therapeutic molecules in the gut, in the absence of these acids.

RESUMEN

Rheumatoid Arthritis (RA) is an autoimmune disease characterized by loss of immune tolerance and chronic inflammation. It is pathogenesis complex and includes interaction between genetic and environmental factors. Current evidence supports the hypothesis that gut dysbiosis may play the role of environmental triggers of arthritis in animals and humans. Progress in the understanding of the gut microbiome and RA. has been remarkable in the last decade. In vitro and in vivo experiments revealed that gut dysbiosis could shape the immune system and cause persistent immune inflammatory responses. Furthermore, gut dysbiosis could induce alterations in intestinal permeability, which have been found to predate arthritis onset. In contrast, metabolites derived from the intestinal microbiota have an immunomodulatory and anti-inflammatory effect. However, the precise underlying mechanisms by which gut dysbiosis induces the development of arthritis remain elusive. This review aimed to highlight the mechanisms by which gut dysbiosis could contribute to the pathogenesis of RA. The overall data showed that gut dysbiosis could contribute to RA pathogenesis by multiple pathways, including alterations in gut barrier function, molecular mimicry, gut dysbiosis influences the activation and the differentiation of innate and acquired immune cells, cross-talk between gut microbiota-derived metabolites and immune cells, and alterations in the microenvironment. The relative weight of each of these mechanisms in RA pathogenesis remains uncertain. Recent studies showed a substantial role for gut microbiota-derived metabolites pathway, especially butyrate, in the RA pathogenesis.

Asunto(s)

RESUMEN

The effects of yeast cell wall compounds (YCWs) being added to cat food on hindgut fermentation metabolites and fecal microbiota were assessed in in vivo Experiment 1 (Exp. 1) and in vitro Experiments 2 and 3 (Exp. 2 and 3). In Exp. 1, the cats' diets were supplemented with two dietary concentrations (46.2 and 92.4 ppm) of YCWs (YCW-15 and YCW-30, respectively), and a negative control diet with no compound in three groups (six cats per group) was used to assess the fecal score, pH, digestibility, fermentation products, and microbiota. In Exp. 2, feces from the cats that were not supplemented with YCWs (control) were used as an inoculum. A blend of pectin, amino acids, and cellulose was used as a substrate, and the YCW compound was added at two levels (5 and 10 mg). In Exp. 3, feces from cats fed YCWs were used as an inoculum to test three different substrates (pectin, amino acids, and cellulose). In Exp. 2 and 3, the gas production, pH, and fermentation products (ammonia, SCFAs, and BCFAs) were assessed. YCW-30 resulted in a higher digestibility coefficient of the crude protein, organic matter (OM) (p < 0.05), and energy of the diet (p < 0.10). Regarding the fermentation products, YCW-15 showed a trend toward higher concentrations of propionate, acetate, lactate, ammonia, isobutyrate, and valerate, while YCW-30 showed a trend (p < 0.10) toward higher levels of butyrate and pH values. The bacteroidia class and the genus Prevotella were increased by using YCW-30 and the control. At the gender level, decreased (p < 0.01) Megasphaera was observed with YCW inclusion. The microbiota differed (p < 0.01) among the groups in their Shannon indexes. For beta diversity, YCW-30 showed higher indexes (p = 0.008) than the control. The microbiota metabolic profile differed in the pathway CENTFERM-PWY; it was more expressed in YCW-30 compared to the control. In Exp. 2, the YCWs showed a higher ratio (p = 0.006) of the fermentation products in the treatments with additives with a trend towards a high dose of the additive (10 mg). In Exp. 3, the effects of the substrates (p < 0.001), but not of the YCWs, on the fermentation products were observed, perhaps due to the low dietary concentrations we used. However, the marked responses of the fermentation products to the substrates validated the methodology. We could conclude that the YCWs, even at low dietary concentrations, affected fecal SCFA production, reduced the fecal pH, and modulated the fecal microbiota in the cats. These responses were more pronounced under in vitro conditions.

RESUMEN

The objective of this study was to determine the effect of a dry versus a molasses-based liquid supplement on ruminal butyrate concentration, gastrointestinal tract (GIT) barrier function, inflammatory status, and performance of newly received feedlot cattle. In experiment 1, 60 mixed breed steers (234 ±â€…2.1 kg) were weaned, held overnight at a sale barn, then transported 14 h to Purdue University. After arrival, steers were weighed, blocked by body weight, and allotted within block to treatments (six pens per treatment and five steers per pen). Diets consisted of 45% roughage and 55% concentrate (dry matter basis). Treatments differed in the supplement source as follows: DRY: 10% dry supplement or LIQUID: 10% liquid molasses-based supplement. Feed intake, average daily gain (ADG), and gain:feed were determined for the three 21-d periods and overall. In experiment 2, 16 crossbred heifers (246 ±â€…7.5 kg) were used (8 heifers per treatment). Diets were the same as in experiment 1 and were fed for 60 d. On d 56 ruminal fluid samples were collected at 0, 3, 6, and 9 h after feeding. To mimic a stress event, heifers were transported for 4 h on d 61, rested overnight, and transported 12 h on d 62. Blood was collected from heifers immediately prior to transport and immediately upon their return. Gut barrier function using a Cr-EDTA marker was determined after transportation. Data were analyzed using the GLIMMIX procedure of SAS. Steers fed the liquid supplement had greater (P ≤ 0.03) ADG through d 42 and overall compared to steers fed the dry supplement. Feed intake did not differ (P = 0.25) between treatments from d 0 to d 21. However, steers fed the liquid supplement showed greater (P < 0.001) dry matter intake after d 21 and overall compared to those fed the dry supplement. Steers fed the liquid supplement tended (P < 0.09) to have reduced serum haptoglobin and lipopolysaccharide-binding protein (LBP) compared to those fed the dry supplement. Heifers fed the liquid supplement had greater (P = 0.02) Cr in urine and tended (P = 0.07) to have lower serum LBP after transport compared to those fed the dry supplement. Heifers fed the liquid supplement had 72% lower serum haptoglobin before, but only a 19% lower serum haptoglobin after transport compared to animals fed the dry supplement (treatment × time; P = 0.07). Therefore, the liquid supplement altered GIT barrier function, and improved inflammatory status, resulting in increased growth of receiving cattle.

Stress from weaning, feed restriction, transportation, and gastrointestinal acidosis can cause inflammation and intestinal damage, resulting in decreased absorptive capacity and immune defense capability. Gastrointestinal inflammation has a significant catabolic cost and causes nutritional resources to be directed away from anabolic processes. Molasses-based liquid supplements have the potential to improve gastrointestinal tract (GIT) barrier function in stressed, newly received feedlot cattle through increased ruminal production of butyrate from sugar. Therefore, the objective of this study was to determine the effect of a dry versus a molasses-based liquid supplement on ruminal butyrate production, GIT barrier function, inflammatory status, and performance of newly received feedlot cattle. We demonstrate that a molasses-based liquid supplement increased ruminal butyrate concentrations, altered GIT barrier function, decreased serum haptoglobin and lipopolysaccharide-binding protein, and improved the growth of stressed receiving cattle compared to a dry supplement.

Asunto(s)

RESUMEN

Abstract Objective Immunotherapy has been proven to improve the prognosis of patients with advanced malignancy but has shown limited efficacy in patients with Colorectal Cancer (CRC). Increasing evidence suggests that butyrate, a bacterial metabolite, enhances the efficacy of cancer therapies by modulating immune responses. Here, the effect and the mechanism of butyrate on anti-PD-L1 therapy were investigated in CRC. Methods The expression of PD-L1 and STAT1, and the lysine acetylation of STAT1 in CRC cells were observed after treatment with butyrate (2, 5, and 10 mM) for 24h or butyrate (5 mM) for 8, 16, and 24h. Site-directed mutations of STAT1 (K410R or K413R) were introduced to determine the role of STAT1 acetylation in modulating PD-L1 expression. The effect of butyrate on the cytotoxicity of CD8+ T-cells against CRC cells with or without PD-L1 overexpression was explored in vitro and in vivo. Results Butyrate could suppress IFN-γ-induced PD-L1 up-regulation in CRC cells in a dose- and time-dependent way. Butyrate promoted the lysine acetylation of STAT1 to reduce STAT1 expression. Non-acetylated mutant STAT1 not only ameliorated butyrate-induced suppression of lysine acetylation and nuclear translocation of STAT1 but also blocked the effect of butyrate on PD-L1. Butyrate attenuated the IFN-γ-induced impairment of CD8+ T-cell cytotoxicity against CRC cells. Meanwhile, butyrate suppressed CRC tumor growth by enhancing CD8+ T-cell infiltration. However, directly overexpressing PD-L1 in CRC cells could abolish the effect of butyrate. Conclusion Butyrate strengthens the immune response to CRC cells by suppressing PD-L1 expression via acetylation of STAT1.

RESUMEN

Studies in human microbiota dysbiosis have shown that short-chain fatty acids (SCFAs) like propionate, acetate, and particularly butyrate, positively affect energy homeostasis, behavior, and inflammation. This positive effect can be demonstrated in the reduction of butyrate-producing bacteria observed in the gut microbiota of individuals with type 2 diabetes (T2DM) and other energy-associated metabolic alterations. Butyrate is the major end product of dietary fiber bacterial fermentation in the large intestine and serves as the primary energy source for colonocytes. In addition, it plays a key role in reducing glycemia and improving body weight control and insulin sensitivity. The major mechanisms involved in butyrate regulation include key signaling pathways such as AMPK, p38, HDAC inhibition, and cAMP production/signaling. Treatment strategies using butyrate aim to increase its intestine levels, bioavailability, and improvement in delivery either through direct supplementation or by increasing dietary fiber in the diet, which ultimately generates a higher production of butyrate in the gut. In the final part of this review, we present a summary of the most relevant studies currently being carried out in humans.

RESUMEN

Short-chain fatty acids (SCFAs) are metabolites released by bacterial components of the microbiota. These molecules have a wide range of effects in the microbiota itself, but also in host cells in which they are known for contributing to the regulation of cell metabolism, barrier function, and immunological responses. Recent studies indicate that these molecules are important players in the gut-lung axis and highlight the possibility of using strategies that alter their intestinal production to prevent or treat distinct lung inflammatory diseases. Here, we review the effects of the SCFA butyrate and its derivatives in vitro and in vivo on murine models of respiratory disorders, besides discussing the potential therapeutic use of butyrate and the other SCFAs in lung diseases.