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PloS One 2023Tributyrin (TB) is a butyric acid precursor and has a key role in anti-inflammatory and intestinal barrier repair effects by slowly releasing butyric acid. However, its...
Tributyrin (TB) is a butyric acid precursor and has a key role in anti-inflammatory and intestinal barrier repair effects by slowly releasing butyric acid. However, its roles in gut microbiota disorder caused by antibiotics remain unclear. Herein, we established an intestinal microbiota disorder model using ceftriaxone sodium via gavage to investigate the effects of different TB doses for restoring gut microbiota and intestinal injury. First, we divided C57BL/6 male mice into two groups: control (NC, n = 8) and experimental (ABx, n = 24) groups, receiving gavage with 0.2 mL normal saline and 400 mg/mL ceftriaxone sodium solution for 7 d (twice a day and the intermediate interval was 6 h), respectively. Then, mice in the ABx group were randomly split into three groups: model (M, 0.2 mL normal saline), low TB group (TL, 0.3 g/kg BW), and high TB group (TH, 3 g/kg BW) for 11 d. We found that TB supplementation alleviated antibiotics-induced weight loss, diarrhea, and intestinal tissue damage. The 16S rRNA sequence analysis showed that TB intervention increased the α diversity of intestinal flora, increased potential short-chain fatty acids (SCFAs)-producing bacteria (such as Muribaculaceae and Bifidobacterium), and inhibited the relative abundance of potentially pathogenic bacteria (such as Bacteroidetes and Enterococcus) compared to the M group. TB supplementation reversed the reduction in SCFAs production in antibiotic-treated mice. Additionally, TB downregulated the levels of serum LPS and zonulin, TNF-α, IL-6, IL-1β and NLRP3 inflammasome-related factors in intestinal tissue and upregulated tight junction proteins (such as ZO-1 and Occludin) and MUC2. Overall, the adjustment ability of low-dose TB to the above indexes was stronger than high-dose TB. In conclusion, TB can restore the dysbiosis of gut microbiota, increase SCFAs, suppress inflammation, and ameliorate antibiotic-induced intestinal damage, indicating that TB might be a potential gut microbiota modulator.
Topics: Male; Animals; Mice; Gastrointestinal Microbiome; Anti-Bacterial Agents; Ceftriaxone; Dysbiosis; RNA, Ribosomal, 16S; Saline Solution; Mice, Inbred C57BL; Fatty Acids, Volatile; Butyric Acid
PubMed: 37523400
DOI: 10.1371/journal.pone.0289364 -
Nutrients Oct 2023Chemokine-driven leukocyte infiltration and sustained inflammation contribute to alcohol-associated liver disease (ALD). Elevated hepatic CCL2 expression, seen in ALD,...
PURPOSE
Chemokine-driven leukocyte infiltration and sustained inflammation contribute to alcohol-associated liver disease (ALD). Elevated hepatic CCL2 expression, seen in ALD, is associated with disease severity. However, mechanisms of CCL2 regulation are not completely elucidated. Post-translational modifications (PTMs) of proteins, particularly acetylation, modulate gene expression. This study examined the acetylation changes of promoter-associated histone-H3 and key transcription factor-NFκB in regulating hepatic CCL2 expression and subsequent inflammation and injury. Further, the effect of therapeutic modulation of the acetylation state by tributyrin (TB), a butyrate prodrug, was assessed.
METHODS
Hepatic CCL2 expression was assessed in mice fed control (PF) or an ethanol-containing Lieber-DeCarli (5% /, EF) diet for 7 weeks with or without oral administration of tributyrin (TB, 2 g/kg, 5 days/week). A chromatin immunoprecipitation (ChIP) assay evaluated promoter-associated modifications. Nuclear association between SIRT1, p300, and NFκB-p65 and acetylation changes of p65 were determined using immunoprecipitation and Western blot analyses. A Student's -test and one-way ANOVA determined the significance.
RESULTS
Ethanol significantly increased promoter-associated histone-H3-lysine-9 acetylation (H3K9Ac), reflecting a transcriptionally permissive state with a resultant increase in hepatic CCL2 mRNA and protein expression. Moreover, increased lysine-310-acetylation of nuclear RelA/p65 decreased its association with SIRT1, a class III HDAC, but concomitantly increased with p300, a histone acetyltransferase. This further led to enhanced recruitment of NF-κB/p65 and RNA polymerase-II to the CCL2 promoter. Oral TB administration prevented ethanol-associated acetylation changes, thus downregulating CCL2 expression, hepatic neutrophil infiltration, and inflammation/ injury.
CONCLUSION
The modulation of a protein acetylation state via ethanol or TB mechanistically regulates hepatic CCL2 upregulation in ALD.
Topics: Mice; Animals; Histones; NF-kappa B; Ethanol; Lysine; Sirtuin 1; Acetylation; Protein Processing, Post-Translational; Inflammation; Hepatitis
PubMed: 37892472
DOI: 10.3390/nu15204397 -
Food Science & Nutrition Sep 2023This study evaluated the effects of antimicrobial peptide (AMP) and tributyrin (TB) on dairy calves in terms of growth performance, immunity, oxidative stress, and...
This study evaluated the effects of antimicrobial peptide (AMP) and tributyrin (TB) on dairy calves in terms of growth performance, immunity, oxidative stress, and intestinal microflora. A total of 40 female calves were divided into four treatment groups ( = 10): basal diet +0.015% essential oil, basal diet +0.03% AMP, basal diet +0.15% TB, and basal diet +0.03% AMP + 0.15% TB. AMP and TB supplementation increased the average daily gain (ADG) and weaning weight, while reducing diarrhea occurrence. Additionally, AMP and TB supplementation reduced the levels of reactive oxygen species (ROS) and malonaldehyde (MDA), while increasing superoxide dismutase (SOD) levels and serum immunoglobulin M (IgM) levels. However, the combined use of AMP and TB did not significantly affect the average daily feed intake, ADG, weaning weight, or diarrhea incidence but decreased ROS levels, while increasing SOD levels as well as MDA and IgM levels. Moreover, AMP and TG supplementation increased the relative abundance of several beneficial fiber- and mucin-degrading bacteria in the gut, in contrast to combined AMP and TB supplementation. The 16S rRNA results showed that AMP supplementation significantly increased the relative abundance of , and ( < .01), and significantly decreased the relative abundance of and ( < .01). The TB supplementation significantly increased the abundances of and ( < .01), and significantly decreased the relative abundances of , and ( < .01). The combined use of AMP and TB significantly increased the relative abundance of and ( < .01), and significantly decreased the relative abundance of , and ( < .01). In summary, diets supplemented with either AMP or TB improved the intestinal microflora, growth performance, and health of weaned calves, but combined use was detrimental to calf performance.
PubMed: 37701190
DOI: 10.1002/fsn3.3483 -
Animals : An Open Access Journal From... Nov 2023This study investigated the impact of (BC) and tributyrin (TB) supplementation on the growth performance, serum antioxidant capacity, intestinal morphology, and cecal...
This study investigated the impact of (BC) and tributyrin (TB) supplementation on the growth performance, serum antioxidant capacity, intestinal morphology, and cecal microbiota of yellow-feathered broilers. Using a 2 × 2 factorial design, 480 broilers were randomly assigned to four experimental diets, comprising two levels of BC (0 and 1 g/kg) and two levels of TB (0 and 1 g/kg), over a 36-day period. A significant interaction was observed between BC and TB, impacting the average daily feed intake (ADFI) of broilers aged between 26 and 40 days ( < 0.01). BC and TB also displayed a significant interaction in relation to serum malondialdehyde levels and total antioxidant capacity ( < 0.05). Additionally, there was a significant interaction between BC and TB concerning the duodenal villus-to-crypt ratio, crypt depth, and jejunal villus-to-crypt ratio ( < 0.05). The addition of BC and TB significantly enhanced the richness and diversity of cecal microbiota, with a notable interactive effect observed for the abundance of Faecalibacterium, Ruminococcus_torques_group, and Phascolarctobacterium. In conclusion, supplementation with BC and TB can effectively improve the growth performance, serum antioxidant capacity, intestinal morphology, and cecal microbiota composition of yellow-feathered broilers, indicating the presence of an interactive effect.
PubMed: 38003151
DOI: 10.3390/ani13223534 -
Journal of Dairy Science Jul 2023This study aimed to evaluate the effects of triglycerides containing medium-chain fatty acids (MCT) and tributyrin (TB) supplementation in a milk replacer (MR) on growth...
Effects of medium-chain fatty acids and tributyrin supplementation in milk replacers on growth performance, blood metabolites, and hormone concentrations in Holstein dairy calves.
This study aimed to evaluate the effects of triglycerides containing medium-chain fatty acids (MCT) and tributyrin (TB) supplementation in a milk replacer (MR) on growth performance, plasma metabolites, and hormone concentrations in dairy calves. Sixty-three Holstein heifer calves (body weight at 8 d of age, 41.1 ± 2.91 kg; mean ± SD) were randomly assigned to 1 of 4 experimental MR (28% crude protein and 18% fat): (1) containing 3.2% C8:0 and 2.8% C10:0 (in fat basis) without TB supplementation (CONT; n = 15), (2) containing 6.7% C8:0 and 6.4% C10:0 without TB supplementation (MCT; n = 16), (3) containing 3.2% C8:0 and 2.8% C10:0 with 0.6% (dry matter basis) TB supplementation (CONT+TB; n = 16), (4) containing 6.7% C8:0 and 6.4% C10:0 with 0.6% TB supplementation (MCT+TB; n = 16). The MR were offered at 600 g/d (powder basis) from 8 to 14 d, up to 1,300 g/d from 15 to 21 d, 1,400 g/d from 22 to 49 d, down to 700 g/d from 50 to 56 d, 600 g/d from 57 to 63 d, and weaned at 64 d of age. All calves were fed calf starter, chopped hay, and water ad libitum. The data were analyzed using a 2-way ANOVA via the fit model procedure of JMP Pro 16 (SAS Institute Inc.). Medium-chain fatty acid supplementation did not affect the total dry matter intake. However, calves that were fed MCT had greater feed efficiency (gain/feed) before weaning (0.74 ± 0.098 vs. 0.71 ± 0.010 kg/kg) compared with non-MCT calves. The MCT calves also had a lower incidence of diarrhea compared with non-MCT calves during 23 to 49 d of age and the weaning period (50 to 63 d of age; 9.2% vs. 18.5% and 10.5% vs. 17.2%, respectively). Calves fed with TB had a greater total dry matter intake during postweaning (3,465 vs. 3,232 g/d). Calves fed TB also had greater body weight during the weaning (90.7 ± 0.97 vs. 87.9 ± 1.01 kg) and postweaning period (116.5 ± 1.47 vs. 112.1 ± 1.50 kg) compared with that of non-TB calves. The plasma metabolites and hormone concentrations were not affected by MCT or TB. These results suggest that MCT and TB supplementation in the MR may improve the growth performance and gut health of dairy calves.
Topics: Animals; Cattle; Female; Fatty Acids; Diet; Milk; Weaning; Body Weight; Triglycerides; Dietary Supplements; Hormones; Animal Feed
PubMed: 37225581
DOI: 10.3168/jds.2022-22957 -
Animal Nutrition (Zhongguo Xu Mu Shou... Dec 2023This study aimed to determine the effects of tributyrin on growth performance, gastrointestinal tract development, ruminal bacteria and volatile fatty acid (VFA)...
This study aimed to determine the effects of tributyrin on growth performance, gastrointestinal tract development, ruminal bacteria and volatile fatty acid (VFA) formation. Thirty healthy weaned Small-Tailed Han female lambs at 3 months old with BW 27.5 ± 4.1 kg (mean ± SD) were randomly assigned to five groups of six lambs each, and each group received tributyrin at 0, 0.5, 1.0, 2.0 and 4.0 g/kg in feed. Weights were measured before the start and end of the study. After 15 d adaptation, DMI, feed, faeces and urine were recorded every week. Lambs were sacrificed at d 75. Compared to lambs fed no tributyrin, lambs fed 4.0 g/kg tributyrin had higher average daily BW gain ( = 0.04) and DMI ( < 0.01). Tributyrin reduced nitrogen ( < 0.01), Ca ( < 0.01) and P ( < 0.01) losses derived from faeces and urine. The mostly important, tributyrin increased dorsal sac thickness ( < 0.01), papillae length ( = 0.04) and width ( < 0.01), ventral sac papillae length ( < 0.01) and width ( < 0.01), caudodorsal blind sac thickness ( = 0.02), papillae length ( < 0.01) and width ( < 0.01). Furthermore, tributyrin increased thicknesses of both the duodenum ( < 0.01) and ileum ( = 0.01), and villus heights of the duodenum ( = 0.01), ileum ( < 0.01), jejunum ( < 0.01) and caecum ( = 0.02), but tributyrin decreased duodenal ( < 0.01) and caecal crypt depths ( < 0.01). Tributyrin reduced rumen pH ( < 0.01) while promoting total VFA concentration ( < 0.01). Tributyrin improved the structure of rumen bacteria by enhancing ( = 0.04), ( < 0.01), ( = 0.04), ( = 0.04), ( = 0.02) and ( = 0.03). In conclusion, tributyrin could stimulate gastrointestinal tract development by enhancing colonization of rumen VFA-producing bacteria, and dietary supplementation of tributyrin at 4.0 g/kg of DM was recommended for the weaned lambs.
PubMed: 38023378
DOI: 10.1016/j.aninu.2023.08.006 -
International Journal of Molecular... Jan 2024We aimed to test how the postbiotic butyrate impacts select gut bacteria, small intestinal epithelial integrity, and microvascular endothelial activation during acute...
We aimed to test how the postbiotic butyrate impacts select gut bacteria, small intestinal epithelial integrity, and microvascular endothelial activation during acute ethanol exposure in mice and primary human intestinal microvascular endothelial cells (HIMECs). Supplementation during an acute ethanol challenge with or without tributyrin, a butyrate prodrug, was delivered to C57BL/6 mice. A separate group of mice received 3 days of clindamycin prior to the acute ethanol challenge. Upon euthanasia, blood endotoxin, cecal bacteria, jejunal barrier integrity, and small intestinal lamina propria dendritic cells were assessed. HIMECs were tested for activation following exposure to ethanol ± lipopolysaccharide (LPS) and sodium butyrate. Tributyrin supplementation protected a butyrate-generating microbe during ethanol and antibiotic exposure. Tributyrin rescued ethanol-induced disruption in jejunal epithelial barrier, elevated plasma endotoxin, and increased mucosal vascular addressin cell-adhesion molecule-1 (MAdCAM-1) expression in intestinal microvascular endothelium. These protective effects of tributyrin coincided with a tolerogenic dendritic response in the intestinal lamina propria. Lastly, sodium butyrate pre- and co-treatment attenuated the direct effects of ethanol and LPS on MAdCAM-1 induction in the HIMECs from a patient with ulcerative colitis. Tributyrin supplementation protects small intestinal epithelial and microvascular barrier integrity and modulates microvascular endothelial activation and dendritic tolerizing function during a state of gut dysbiosis and acute ethanol challenge.
Topics: Mice; Humans; Animals; Ethanol; Endothelial Cells; Butyric Acid; Lipopolysaccharides; Mice, Inbred C57BL; Intestinal Mucosa
PubMed: 38338944
DOI: 10.3390/ijms25031665 -
Journal of Veterinary Science Mar 2024The widespread use of antimicrobials causes antibiotic resistance in bacteria. The use of butyric acid and its derivatives is an alternative tactic. This review... (Review)
Review
The widespread use of antimicrobials causes antibiotic resistance in bacteria. The use of butyric acid and its derivatives is an alternative tactic. This review summarizes the literature on the role of butyric acid in the body and provides further prospects for the clinical use of its derivatives and delivery methods to the animal body. Thus far, there is evidence confirming the vital role of butyric acid in the body and the effectiveness of its derivatives when used as animal medicines and growth stimulants. Butyric acid salts stimulate immunomodulatory activity by reducing microbial colonization of the intestine and suppressing inflammation. Extraintestinal effects occur against the background of hemoglobinopathy, hypercholesterolemia, insulin resistance, and cerebral ischemia. Butyric acid derivatives inhibit histone deacetylase. Aberrant histone deacetylase activity is associated with the development of certain types of cancer in humans. Feed additives containing butyric acid salts or tributyrin are used widely in animal husbandry. They improve the functional status of the intestine and accelerate animal growth and development. On the other hand, high concentrations of butyric acid stimulate the apoptosis of epithelial cells and disrupt the intestinal barrier function. This review highlights the biological activity and the mechanism of action of butyric acid, its salts, and esters, revealing their role in the treatment of various animal and human diseases. This paper also discussed the possibility of using butyric acid and its derivatives as surface modifiers of enterosorbents to obtain new drugs with bifunctional action.
Topics: Humans; Animals; Butyric Acid; Salts; Anti-Infective Agents; Epithelial Cells; Histone Deacetylases
PubMed: 38568825
DOI: 10.4142/jvs.23230 -
Microbiology Spectrum Apr 2024With almost a quadrillion individuals, the Antarctic krill processes five million tons of organic carbon every day during austral summer. This high carbon flux requires...
With almost a quadrillion individuals, the Antarctic krill processes five million tons of organic carbon every day during austral summer. This high carbon flux requires a broad range of hydrolytic enzymes to decompose the diverse food-derived biopolymers. While krill itself possesses numerous such enzymes, it is unclear, to what extent the endogenous microbiota contribute to the hydrolytic potential of the gut environment. Here we applied amplicon sequencing, shotgun metagenomics, cultivation, and physiological assays to characterize the krill gut microbiota. The broad bacterial diversity (273 families, 919 genera, and 2,309 species) also included a complex potentially anaerobic sub-community. Plate-based assays with 198 isolated pure cultures revealed widespread capacities to utilize lipids (e.g., tributyrin), followed by proteins (casein) and to a lesser extent by polysaccharides (e.g., alginate and chitin). While most isolates affiliated with the genera and , also spp. (Verrucomicrobia) were observed. The krill gut microbiota growing on marine broth agar plates possess 13,012 predicted hydrolyses; 15-fold more than previously predicted from a transcriptome-proteome compendium of krill. Cultivation-independent and -dependent approaches indicated members of the families and to dominate the capacities for lipid/protein hydrolysis and to provide a plethora of carbohydrate-active enzymes, sulfatases, and laminarin- or porphyrin-depolymerizing hydrolases. Notably, also the potential to hydrolyze plastics such as polyethylene terephthalate and polylactatide was observed, affiliating mostly with Moraxellaceae. Overall, this study shows extensive microbial diversity in the krill gut, and suggests that the microbiota likely play a significant role in the nutrient acquisition of the krill by enriching its hydrolytic enzyme repertoire.IMPORTANCEThe Antarctic krill () is a keystone species of the Antarctic marine food web, connecting the productivity of phyto- and zooplankton with the nutrition of the higher trophic levels. Accordingly, krill significantly contributes to biomass turnover, requiring the decomposition of seasonally varying plankton-derived biopolymers. This study highlights the likely role of the krill gut microbiota in this ecosystem function by revealing the great number of diverse hydrolases that microbes contribute to the krill gut environment. The here resolved repertoire of hydrolytic enzymes could contribute to the overall nutritional resilience of krill and to the general organic matter cycling under changing environmental conditions in the Antarctic sea water. Furthermore, the krill gut microbiome could serve as a valuable resource of cold-adapted hydrolytic enzymes for diverse biotechnological applications.
Topics: Humans; Animals; Euphausiacea; Ecosystem; Seasons; Hydrolases; Biopolymers
PubMed: 38466097
DOI: 10.1128/spectrum.04035-23 -
Antioxidants (Basel, Switzerland) Apr 2024Excessive alcohol consumption increases the severity and worsens outcomes of pulmonary infections, often due to oxidative stress and tissue damage. While the mechanism...
Excessive alcohol consumption increases the severity and worsens outcomes of pulmonary infections, often due to oxidative stress and tissue damage. While the mechanism behind this relationship is multifaceted, recent evidence suggests ethanol-induced changes to the gut microbiome impact the gut-lung axis. To assess this, a chronic-binge ethanol feeding mouse model was used to determine how ethanol altered the gut microbiome, small intestinal epithelial barrier, and immune responses, as well as neutrophil abundance and oxidative stress in the lungs, and how supporting gut health with tributyrin supplementation during chronic-binge ethanol exposure affected these responses. We found that ethanol consumption altered gut bacterial taxa and metabolic processes, distorted small intestinal immune responses, and induced both bacteria and endotoxin translocation into the lymphatic and circulatory systems. These changes were associated with increased neutrophil (Ly6G) presence and markers of oxidative stress, lipocalin-2 and myeloperoxidase, in the lungs. Importantly, tributyrin supplementation during ethanol exposure rescued gut bacterial function ( < 0.05), small intestinal barrier integrity, and immune responses, as well as reducing both Ly6G mRNA ( < 0.05) and lipocalin-2 mRNA ( < 0.01) in the lungs. These data suggest ethanol-associated disruption of gut homeostasis influenced the health of the lungs, and that therapeutics supporting gut health may also support lung health.
PubMed: 38671919
DOI: 10.3390/antiox13040472