Tributyrin Supplementation Research Articles

Dietary Tributyrin Improves Growth Performance, Meat Quality, Muscle Oxidative Status, and Gut Microbiota in Taihe Silky Fowls under Cyclic Heat Stress.

Heat stress adversely affects poultry production and meat quality, leading to economic losses. This study aimed to investigate the effects of adding tributyrin on growth performance, meat quality, muscle oxidative status, and gut microbiota of Taihe silky fowls under cyclic heat stress (CHS) conditions. In this study, 120-day-old Taihe silky fowls (male) were randomly divided into six dietary treatments. These treatments included a normal control treatment (NC, fed a basal diet), a heat stress control treatment (HS, fed a basal diet), and HS control treatments supplemented with 0.04%, 0.08%, 0.16%, and 0.32% tributyrin, respectively. The NC treatment group was kept at 24 ± 1 °C, while the HS treatment birds were exposed to 34 ± 1 °C for 8 h/d for 4 weeks. Results showed that CHS decreased growth performance and compromised the meat quality of broilers (p < 0.05). However, tributyrin supplementation improved ADG and FCR in broilers exposed to CHS (p < 0.05). Additionally, tributyrin supplementation resulted in increased shear force value and GSH-Px activity, as well as a decrease in drip loss, ether extract content, and MDA content of the breast muscle in broilers under CHS (p < 0.05). Furthermore, tributyrin supplementation up-regulated the mRNA expressions of Nrf2, NQO1, HO-1, SOD, and GSH-Px of the breast muscle in broilers exposed to CHS (p < 0.05). Based on these positive effects, the study delved deeper to investigate the impact of 0.16% tributyrin supplementation (HS + 0.16%T) on the cecum microbiota. The HS + 0.16%T treatment showed an increase in the relative abundance of Rikenellaceae_RC9_gut_group (p < 0.05) and a trend towards an increase in Lactobacillus (p = 0.096) compared to the HS treatment. The results indicate that supplementation successfully improved the growth performance and meat quality of Taihe silky fowls. Furthermore, tributyrin supplementation, particularly at levels of 0.16%, improved meat quality by enhancing muscle antioxidant capacity, which is believed to be associated with activation of the Nrf2 signaling pathway.

Investigation of the tolerability and potential health benefits of a novel butyrate generating supplement in a pilot human study

BACKGROUND: Butyrate is a health promoting short-chain fatty acid (SCFA) metabolite of fiber fermentation in the gut. Supplementing directly with a butyrate generator may be a dietary alternative with health benefits. OBJECTIVE: To evaluate the effect of tributyrin, a butyrate generator, on tolerability, gut microbiome composition, gut permeability, inflammation and metabolic markers in healthy adults at two dose levels. METHODS: Healthy adults (n = 29) were randomized to this single-blinded, two-arm, 28-day parallel design pilot study. Participants ingested one or two placebo capsules for 7 days followed by one or two (200 or 400 mg, respectively) ButyraGen® capsules, a novel tributyrin complex, daily for 21 days. Tolerability was assessed weekly by questionnaire. Blood and stool were collected at baseline and weekly for metabolic and inflammation markers, gut microbiome composition and SCFA concentrations, respectively. Urine was collected at baseline and end of the study for permeability assays. RESULTS: Twenty-four participants (n = 24, 25±8 years; 24.0±2.8 kg/m2; 66% male) completed the study. ButyraGen® was well-tolerated, with less than 10% (n = 2) reporting gastrointestinal-related discomfort. Fecal acetic (p = 0.03) and propionic (p = 0.03) acids decreased after supplementation (p = 0.03 and p = 0.03, respectively, n = 24) compared to baseline, and triglycerides increased (p = 0.02, 400 mg only, n = 11). Trends in decreased hs-CRP after 200 mg (p = 0.08) and 400 mg (p = 0.07) supplementation and decreased glucose (p = 0.10) after 200 mg supplementation was observed. No other changes in endpoints were observed. CONCLUSIONS: Tributyrin supplementation using ButyraGen® was safe and tolerable at the doses provided. Biological effects were observed suggesting butyrate generation and absorption in the small intestine followed by activity in the liver, though further investigation on mechanism of action is needed for confirmation.

Effect of butyrate sources in a high-concentrate diet on rumen structure and function in growing rams

Dietary butyrate is considered to have mostly positive impacts on the ruminal epithelium. However, its supplementation in a high-concentrate diet may not be justified as excessive ruminal butyrate may negatively affect the rumen. Furthermore, butyrate impact on the rumen may depend on its source. Thirty-two Świniarka growing rams (30.6 ± 2.5 kg; 11–14 months of age) were used to investigate the effect of a high-concentrate diet and sodium butyrate (SB) or tributyrin (TB) supplementation in a high-concentrate diet on the rumen structure and selected functions. The rams were allocated to four treatments and fed diets with: (1) low concentrate inclusion (22.5% of diet DM; L); (2) high concentrate inclusion (60% of diet DM; H); (3) H with SB (3.2% of diet DM; H+SB); and (4) H with TB (2.93% of diet DM; H+TB). The preplanned contrasts were used for treatment comparisons (L vs H treatments (H, H+SB, and H+TB), H vs H+SB, and H vs H+TB). The BW, BW gain and DM intake did not differ between treatments. In the atrium ruminis, epithelium thickness did not differ between the L and H treatments (P = 0.46), tended to be higher for H+SB than for H (P = 0.09) but did not differ between H+TB and H (P = 0.61). The expression of downregulated in adenoma was higher for L than for H treatments (P = 0.03) but was not affected by SB or TB supplementation (P ≥ 0.26). In the ventral rumen, the mucosa surface and epithelium thickness were lower for L than for H treatments (P < 0.01), were or tended to be higher for H+SB than for H (P ≤ 0.06) but did not differ between H+TB and H (P ≥ 0.26). The expression of monocarboxylate transporter 1 was lower for L than for H treatments (P = 0.02) but was not affected by SB or TB supplementation (P ≥ 0.28). The expression of putative anion transporter-1 and downregulated in adenoma did not differ between the L and H treatments (P ≥ 0.76); however, expression of the former tended to be higher and the latter tended to be lower for H+SB than for H (P ≤ 0.09), whereas no differences were observed between H+TB and H (P ≥ 0.14). In summary, SB supplementation, but not TB supplementation, in a high-concentrate diet stimulated ruminal epithelium growth and affected short-chain fatty acid transporters expression in the ruminal epithelium.

PSV-4 Exposure to prenatal tributyrin improved pre-weaning growth performance and reduced fat deposition in the muscle of market age pigs

Abstract Organic acids, including short chain fatty acids, medium chain fatty acids, and tricarboxylic acid, are used as alternatives to antibiotics for the purpose of growth promotion in livestock species. Butyric acid has been used extensively for its various functions in intestinal health and barrier function, as well as its actions as a histone deacetylase inhibitor. Many of the issues relating to using butyric acid as a feed supplement are overcome by utilizing tributyrin (TB), a butyrate prodrug. Dietary supplementation of TB to sows during gestation was able to improve pre-weaning litter performance. Sows (n = 52, 42 gestational days) were randomly assigned to either a control diet or control diet supplemented with 2% TB. All diets were made isocaloric with the addition of oil and wheat flour. Dietary treatments continued until 112 d of gestation. After farrowing, piglet growth performance was monitored. Once offspring reached 6 mo of age, 30 gilts from the most median performing litters were identified for tissue collection and evaluation of meat characteristics. Sows that received tributyrin during gestation tended to have greater total litter weights at birth (P &amp;lt; 0.1); however, average individual birthweights were not statistically different between control and TB litters. The TB piglets tended to be heavier at weaning (P &amp;lt; 0.1). Pre-weaning average daily gains were higher in piglets exposed to prenatal TB (P &amp;lt; 0.01). Body weights and hot carcass weights did not differ significantly in gilts at market age. There was, however, a trend of increased dressing percentage from TB treated offspring, accompanied by significantly reduced back fat at the 10th rib (P &amp;lt; 0.1 and P &amp;lt; 0.05 respectively). These data suggest that TB supplementation results in both temporary and permanent improvements to growth and development. This study provides further evidence that prenatal TB can have long term effects on muscle growth and meat quality. Further studies are needed to ultimately determine whether prenatal or postnatal supplementation is ideal for improving long-term growth performance.

Exposure to Prenatal Tributyrin Improved Pre-Weaning Growth Performance and Reduced Fat Deposition in the Muscle of Market Age Pigs

Organic acids, including short chain fatty acids, medium chain fatty acids, and tricarboxylic acid, are used as alternatives to antibiotics for the purpose of growth promotion in livestock species. Butyric acid has been used extensively for its various functions in intestinal health and barrier function, as well as its actions as a histone deacetylase inhibitor. Many of the issues related to using butyric acid as a feed supplement are overcome by utilizing tributyrin (TB), a butyrate prodrug. Dietary supplementation of TB to sows during gestation was able to improve pre-weaning litter performance. Sows (n=52, 42 gestational days) were randomly assigned to either a control diet or control diet supplemented with 2% TB. All diets were made isocaloric with the addition of oil and wheat flour. Dietary treatments continued until 112 days of gestation. After farrowing, piglet growth performance was monitored. Once offspring reached 6 months of age, 30 gilts from the most median performing litters were identified for tissue collection and evaluation of meat characteristics. Sows that received tributyrin during gestation tended to have higher total litter weights at birth (P value &lt; 0.1), however, average individual birthweights were not statistically different between control and TB litters. TB piglets tended to be heavier at weaning (P value &lt; 0.1). Pre-weaning average daily gains were higher in piglets exposed to prenatal TB (P value &lt; 0.01). Live weights and hot carcass weights did not differ significantly in gilts at market age. There was, however, a trend of increased dressing percentage from TB treated offspring, accompanied by significantly reduced back fat at the 10th rib (P value &lt; 0.1 and P value &lt; 0.05 respectively). This data suggests that TB supplementation results in both temporary and permanent improvements to growth and development. This study provides further evidence that prenatal TB can have long term effects on muscle growth and meat quality. Further studies are needed to ultimately determine whether prenatal or postnatal supplementation is ideal for improving long-term growth performance. USDA Grant Funded. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Beneficial effects of the butanoic acid derivative tributyrin on the growth, immunity and intestinal health of large mouth bass (Micropterus salmoides)

Tributyrin (TB) is a novel butanoic acid derivative with potent bioactive functions. In this study, an eight-week feeding trial aimed to investigate the effects of dietary TB on the growth, immunity and intestinal health of large mouth bass (Micropterus salmoides). Five experimental diets containing 0, 0.5, 1.0, 1.5 or 2.0 g/kg tributyrin were formulated and were regarded as TB0 (control), TB0.5, TB1.0, TB1.5 and TB2.0, respectively. Quadruplicate groups (four tanks per group, 30 fish per tank) of juvenile M. salmoides (initial weight: 20.00 ± 1.00 g) were fed to apparent satiation two times daily. After the feeding trial,Aeromonas hydrophila challenge tests were conducted and the A. hydrophila strains were subsequently sampled. As a result, the weight gain rate (WGR) was increased in the TB supplementation groups, and the TB1.5 group obtained the highest value. Furthermore, TB administration improved immune function. The content of serum complement 4 in the TB1.5 group was significantly higher than that in the control group. Increase of lysozyme activity and immunoglobulin M were significant in TB1.0 group than the control group. After A. hydrophila injection, TB1.0, TB1.5 and TB2.0 groups presented markedly higher survival rates than did the control group. Additionally, TB markedly enhanced the activities of amylase and lipase in the gut. Moreover, 16S rRNA sequencing revealed that TB could affect the intestinal microflora composition. Compared to those in the control group, the abundance of Fusobacteria were lower in the TB1.0 and TB1.5 groups. In conclusion, this study demonstrated that TB can improve the growth, immunity and intestinal health of M. salmoides, and the optimal dietary level of TB is determined to be 0.15%.

Tributyrin Supplementation Rescues Chronic-Binge Ethanol-Induced Oxidative Stress in the Gut-Lung Axis in Mice.

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 (p < 0.05), small intestinal barrier integrity, and immune responses, as well as reducing both Ly6G mRNA (p < 0.05) and lipocalin-2 mRNA (p < 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.

Dietary tributyrin supplementation promotes the growth by improving intestinal digestive and antioxidant capacity and the abundance of intestinal beneficial bacteria for swimming crab (Portunus trituberculatus)

This study aimed to evaluate the effects of tributyrin (TB) supplementation on the growth, digestive enzyme activity, lipid metabolism, and intestinal health of swimming crab (Portunus trituberculatus) with an initial weight of 12.50 ± 0.02 g. Six experimental diets were formulated, which containing 0%, 0.025%, 0.05%, 0.10%, 0.20%, and 0.40% of TB, respectively. Results showed that crabs fed the diet containing 0.10% TB had significantly higher values of percent weight gain (PWG) and specific growth rate (SGR) than those in other treatments. Crabs fed the diet without TB supplementation showed dramatically higher contents of T-CHO, TG, and MDA in serum than those in other treatments, opposite patterns were recorded for the activities of T-SOD, PPO, NO, ACP, and AKP. The activities of antioxidant enzyme including T-AOC, T-SOD, ACP, AKP and GSH-Px in hepatopancreas were significantly affected by dietary TB levels. Meanwhile, crabs fed the diet without TB supplementation had significantly lower activities of trypsin, lipase, and amylase in the intestine than those in other treatments. The relative expression levels of genes related to antioxidant capacity in the hepatopancreas and intestine were markedly decreased when crabs fed the diet without TB supplementation; however, crabs fed the diet without TB supplementation exhibited the highest expression of genes linked to inflammation among treatments, and the expression levels of crustin and lyso in the intestine were significantly affected by dietary TB levels. The expression levels of genes related to energy metabolism and intestinal immune barrier in the intestine were also influenced by dietary TB levels. Dietary TB supplementation could reduce lipid accumulation in hepatopancreas by upregulating lipid catabolism related genes expression levels and decreasing lipid anabolism related gene expression levels. Muscularis thickness, fold width, and fold height in the intestine were significantly increased with dietary TB increasing from 0% to 0.10%; moreover, lipid droplets, the diameter of R cells and the area of R cells in the hepatopancreas significantly decreased with an increase of dietary TB levels. Additionally, the number of Actinobacteria and Bacteroides significantly increased with an increase of dietary TB levels. To sum up, the TB requirement of swimming crab was 0.089% based on two slope broken-line analysis of PWG. The findings of the current study indicate that TB is an effective growth promoter that can serve as a nutritional supplement to improve the growth performance, promote health and regulate lipid metabolism of swimming crab.

Effects of tributyrin supplementation in calf starter on growth, blood parameters and development of rumen and small intestine in Holstein calves fed milk replacers with different fatty acid profile

The objective of this study was to evaluate the effects of tributyrin (TB) supplementation in calf starter on development of the rumen and small intestine for calves fed two milk replacers differing in fatty acid composition. Fifty-four Holstein calves (38 heifers and 16 bull calves) were assigned to one of the four treatments: (1) milk replacer containing 31 g/kg C8:0 and 29 g/kg C10:0 in total fatty acids (MR-) and calf starter without TB (ST-) (MR-ST-; n = 14), (2) MR- and calf starter with a TB supplement (600 g/kg TB and 400 g/kg silicon dioxide) at 6 g/kg of DM (ST+) (MR-ST+; n = 13), (3) milk replacer containing 26 g/kg C4:0, 57 g/kg C8:0, and 56 g/kg C10:0 in total fatty acids (MR+) and ST- (MR+ST-; n = 13), and (4) MR+ and ST+ (MR+ST+; n = 14). Milk replacers were offered at 600 g/d (powder basis) from 8 to 14 d, increased up to 1300 g/d from 15 to 21 d, 1400 g/d from 22 to 49 d, decreased down to 700 g/d from 50 to 56 d, and 600 g/d from 57 to 63 d, and then weaned at 64 d of age. Data and samples were collected until 91 d of age. All the calves were fed one of the calf starters and chopped hay ad libitum from 8 d of age. Bull calves were euthanized at weaning to determine weights of digestive organs and evaluate ruminal and small intestinal morphology. Calf starter and milk replacer treatments did not affect dry matter intake, growth performance, digestive organs weights (kg/100 kg of body weight), and rumen papillae length. However, calves fed ST+ had greater ratio of villus height to crypt depth (2.20 vs. 1.84; P < 0.01) in the ileum compared to those fed ST-. In addition, calves fed MR+ had less crypt depth (240 vs. 298 µm; P = 0.02) and greater ratio of villus height to crypt depth (2.22 vs. 1.91; P < 0.01) in the ileum compared to those fed MR-. A tendency for interaction between milk replacer and calf starter treatments was observed for the ratio of villus height to crypt depth in the jejunum, in which TB in calf starter increased the ratio only for calves fed MR-. Milk replacer treatment did not affect plasma glucagon-like peptide-2 (GLP-2) concentration. However, calves fed ST+ had greater plasma GLP-2 concentration compared to those fed ST- after weaning (1.16 vs. 0.80 ng/mL; P < 0.02). These results suggest that TB supplementation for dairy calves may affect small intestinal morphology at weaning, and increase plasma GLP-2 concentration after weaning.

Oral tributyrin supplementation attenuates Alzheimer’s disease‐associated neuropathology and prevents cognitive and behavioral deficits in the 3xTg‐AD mouse model

AbstractBackgroundDysbiosis of the gut microbiome is associated with various diseases, including Alzheimer’s Disease (AD). A decrease in intestinal butyrate‐producing bacteria has been indicated by pre‐clinical and clinical studies in AD; therefore, we assessed the effects of long‐term oral administration of tributyrin (TB: a butyrate pro‐drug) on the development of memory and neuromuscular deficits, and CNS pathology in 3xTg‐AD (3xTg) mice.MethodOral gavage with tributyrin (2 mg/kg) was given twice weekly to female 3xTg mice between 6‐ and 17‐months of age. Treatment was stopped and mice were tested for spatial memory (Y‐maze and novel object recognition test‐NORT) and neuromuscular function (RotaRod and grip tests). Brains from untreated (2‐, 12‐, or 18‐month‐old untreated or TB treated 18‐month‐old mice were formalin‐fixed, paraffin‐embedded for microscopic analysis of AD‐associated pathology, neuroinflammation, and oxidative stress markers.ResultShort‐term, episodic memory and spatial memory along with balance and coordination and grip strength were all significantly decreased in untreated 3xTg mice at 17‐months of age compared to 2‐ or 10‐month‐old mice. TB treatment, however, attenuated these effects in 17‐month mice. TB treatment did not affect the accumulation of either Aβ or Tau in the subiculum at 18‐months. However, pTau hyperphosphorylation—as indicated by co‐staining with both pTau(Ser404) and AT‐8 pTau (Ser202/Thr205) mAb—was effectively prevented with TB treatment. Similarly, significant age‐dependent neuroinflammation indicated by IBA1 (microglia) and GFAP (astrocytes) staining was increased in the hippocampus of 18‐month 3xTg mice and was effectively prevented by TB treatment. Additionally, markers of oxidative stress, 4‐HNE and acrolein adducts, were also increased in the molecular layer of the hippocampus and attenuated in TB treated mice.ConclusionThese studies demonstrate that TB treatment after initiation of Aβ deposition in the subiculum dramatically abrogates the loss of neurologic function in 3xTg mice as demonstrated by increased memory, cognition, and neuromuscular function. Moreover, these increases coincide with attenuated AD‐associated pathology in the hippocampus of TB‐treated 3xTg mice. Importantly, these data indicate that treatment with a butyrate pro‐drug can be integrated into treatment strategies to preserve cognitive and neuromuscular functions in patients in the prodromal phase of AD.

Effects of Dietary Bacillus coagulans and Tributyrin on Growth Performance, Serum Antioxidants, Intestinal Morphology, and Cecal Microbiota of Growing Yellow-Feathered Broilers.

This study investigated the impact of Bacillus coagulans (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 (p < 0.01). BC and TB also displayed a significant interaction in relation to serum malondialdehyde levels and total antioxidant capacity (p < 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 (p < 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.

Dietary tributyrin supplementation enhances the immune and antioxidant responses of rainbow trout (Oncorhynchus mykiss) without changes in fish performance

Dietary supplementation with tributyrin (TBT), a source of butyric acid, has been shown to improve growth performance and health status when high levels of plant ingredients are included in aquafeeds. Here, we investigated the response of rainbow trout (Oncorhynchus mykiss) to a plant-based diet supplemented with TBT aiming to improve fish performance and welfare. Juvenile rainbow trout (19.0 ± 0.19 g, mean ± SEM) were divided into 12 tanks (210 L, 40 fish/tank) connected to a RAS system and fed four experimental diets in triplicate to apparent satiety. Diets tested comprised a basal diet (CTR) including 10% fishmeal and 10% fish oil, plus 83% plant-derived ingredients (44% crude protein, 18% crude fat, gross energy 21.8 MJ kg−1) with increasing inclusion levels of TBT (55% purity), supplying 0.05% (TBT1), 0.1% (TBT2) and 0.2% (TBT4) of this compound. Fish performance was evaluated after 44 days. Following the growth trial, the effect of the diets on selected plasma innate immune and hepatic antioxidant parameters of trout was investigated at 3 h and 24 h after feeding. TBT supplementation had no significant impact on growth performance, feed efficiency, feed intake, or proximal composition in rainbow trout (P > 0.05). However, the plasma lysozyme activity was higher in fish fed the TBT2 diet than in those fed CTR or TBT4 diets after 3 h (P = 0.021). In addition, the plasma antiprotease activity in fish fed the TBT2 and TBT4 diets was higher than those fed the CTR diet after 24 h (P = 0.010 and 0.013, respectively). Catalase activity in the liver of trout fed the TBT4 diet was higher than in fish fed CTR or TBT2 diets after 3 h (P = 0.016 and 0.019). Results showed that effective levels of dietary TBT supplementation at 0.1% and 0.2% could result in improved immune and antioxidant responses in trout, respectively. Therefore, dietary TBT supplementation in this carnivorous species may result in enhanced welfare when high levels of plant-derived ingredients are used in aquafeeds.

Effects of dietary tributyrin supplementation in low fish meal diet containing high-Clostridium autoethanogenum protein on the growth performance, antioxidative capacity, lipid metabolism and intestinal microbiota of largemouth bass (Micropterus salmoides)

This study aimed to investigate the impact of dietary tributyrin (TB) in the low fish meal (high-Clostridium autoethanogenum protein, CAP) diet on the growth, antioxidation, lipid metabolism and intestinal microbiota of largemouth bass (Micropterus salmoides). For eight weeks, largemouth bass (15.05 ± 0.58 g) were fed on eight isonitrogenous and isolipid diets with graded levels of dietary TB (0 g/kg, 0.2 g/kg, 0.4 g/kg, 0.8 g/kg, 1.6 g/kg, 3.2 g/kg, 4.0 g/kg and 8.0 g/kg). The findings showed that the weight gain rate (WGR) and specific growth rate (SGR) were increased by 1.6 g/kg of dietary TB. The protein efficiency and deposition ratios were linearly affected by dietary TB. The broken-line model based on the WGR revealed that 1.617 g/kg of dietary TB was sufficient for optimal growth. The digestive enzyme activities and villus length of the intestine were increased by dietary TB (1.6 g/kg). Total antioxidant capacity (T-AOC), superoxide dismutase (SOD) and catalase (CAT) activities were significantly improved, and the malondialdehyde (MDA) and protein carbonyl (PC) contents were significantly decreased after dietary TB. The expressions of nuclear factor erythroid 2-related factor 2 (nrf2) and kelch like ech associated protein 1 (keap1) in the liver and intestine were significantly increased and decreased by 1.6 g/kg of dietary TB, respectively. The mRNA levels of copper-zinc superoxide dismutase (cuznsod), cat, heme oxygenase-1 (ho-1) and glutathione peroxidase (gpx) were significantly upregulated. Dietary TB could significantly affect the total protein (TP) and albumin (ALB) content in the serum. The aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were the lowest at 1.6 g/kg of TB group. Besides, the hepatocyte vacuolation and nuclear translocation were alleviated after supplementation of 0.2‰− 3.0‰ of dietary TB. The total cholesterol (T-CHO), high density lipoprotein cholesterol (HDLC) and low density lipoprotein cholesterol (LDLC) were significantly increased by dietary TB. The triglycerides (TG) content was decreased by dietary TB. The mRNA levels of sterol regulatory element-binding protein 1-c (srebp1-c), acetyl-coa carboxylase alpha (accα), fatty acid synthase (fasn) and accβ in the liver were significantly downregulated, and peroxisome proliferator-activated receptor alpha (pparα) and carnitine palmitoyltransferase 1 (cpt-1) were upregulated by 1.6 g/kg of dietary TB. Dietary TB had effects on the intestine microbes of largemouth bass. The Cetobacterium was present in the highest percentage and increased from 41% (0 g/kg TB) to 59% (1.6 g/kg TB). The Mycoplasmataceae was the second most predominant genus and decreased from 90% in the 0 g/kg of TB group to 10% in the 1.6 g/kg of TB group. In summary, the dietary TB could be supplemented in the CAP-based diet for better growth and antioxidation, lipid metabolism and intestinal microbiota of largemouth bass.

Benefits of tributyrin on growth performance, gastrointestinal tract development, ruminal bacteria and volatile fatty acid formation of weaned Small-Tailed Han lambs

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 (P = 0.04) and DMI (P < 0.01). Tributyrin reduced nitrogen (P < 0.01), Ca (P < 0.01) and P (P < 0.01) losses derived from faeces and urine. The mostly important, tributyrin increased dorsal sac thickness (P < 0.01), papillae length (P = 0.04) and width (P < 0.01), ventral sac papillae length (P < 0.01) and width (P < 0.01), caudodorsal blind sac thickness (P = 0.02), papillae length (P < 0.01) and width (P < 0.01). Furthermore, tributyrin increased thicknesses of both the duodenum (P < 0.01) and ileum (P = 0.01), and villus heights of the duodenum (P = 0.01), ileum (P < 0.01), jejunum (P < 0.01) and caecum (P = 0.02), but tributyrin decreased duodenal (P < 0.01) and caecal crypt depths (P < 0.01). Tributyrin reduced rumen pH (P < 0.01) while promoting total VFA concentration (P < 0.01). Tributyrin improved the structure of rumen bacteria by enhancing Clostridium (P = 0.04), Butyrivibrio (P < 0.01), Streptococcus (P = 0.04), Prevotella (P = 0.04), Ruminobacter (P = 0.02) and Fibrobacter (P = 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.

Tributyrin alleviates gut microbiota dysbiosis to repair intestinal damage in antibiotic-treated mice.

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.

Effects of tributyrin on the growth performance, survival, tolerance to hypoxic stress, and nutrient digestibility of Pacific white shrimp, Litopenaeus vannamei, fed different levels of soybean meal

AbstractThe study aimed to evaluate the effect of tributyrin on the growth performance, survival, hypoxia tolerance, and nutrient digestibility of Pacific white shrimp fed 25% and 50% soybean meal (SBM) diets. Six experimental diets were formulated: (1) 25% SBM without tributyrin; (2) 25% SBM with 0.05% tributyrin; (3) 25% SBM with 0.1% tributyrin; (4) 50% SBM without tributyrin; (5) 50% SBM with 0.05% tributyrin; and (6) 50% SBM with 0.1% tributyrin. The shrimp were fed the experimental diets daily for 10 weeks. Tributyrin supplementation at 0.1% diet significantly improved the weight gain of shrimp that fed 25% SBM but not the other groups. Nevertheless, shrimp that fed tributyrin had significant improvement in survival rate at both SBM levels. Significant reductions in Vibrio spp. counts in the hepatopancreas and intestine were also evident in all tributyrin‐fed groups. In addition, 0.1% tributyrin in both SBM levels significantly enhanced the shrimp tolerance to hypoxia. Lastly, the digestibilities were generally unaffected by the tributyrin except only for the lipid digestibility of the 0.1% tributyrin in 25% SBM group, which showed a significant increase. Overall, tributyrin was proven beneficial for the shrimp's health, especially for those fed diet with a moderate level of SBM (25%).

Effects of antimicrobial peptide and tributyrin on fecal microflora and blood indices of female calves.

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 (n = 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 Rikenellaceae_RC9_gut_group, Ruminococcaceae_UCG-014 and [Eubacterium]_coprostanoligenes group (p < .01), and significantly decreased the relative abundance of Ruminococcaceae_UCG-005 and Christensenellaceae_R-7_group (p < .01). The TB supplementation significantly increased the abundances of Rikenellaceae_RC9_gut_group and Ruminococcaceae_UCG-005 (p < .01), and significantly decreased the relative abundances of Ruminococcaceae_UCG-014, [Eubacterium]_coprostanoligenes group and Christensenellaceae_R-7_group (p < .01). The combined use of AMP and TB significantly increased the relative abundance of Rikenellaceae_RC9_gut_group and Bacteroides (p < .01), and significantly decreased the relative abundance of Ruminococcaceae_UCG-014, [Eubacterium]_coprostanoligenes group and Christensenellaceae_R-7_group (p < .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.

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.

Maternal tributyrin supplementation in late pregnancy and lactation improves offspring immunity, gut microbiota, and diarrhea rate in a sow model.

Several studies have evaluated the effects of tributyrin on sow reproductive performance; however, none of these studies have investigated the effects of tributyrin on sow gut microbiota and its potential interactions with immune systems and milk composition. Therefore, we speculated that tributyrin, the combination of butyrate and mono-butyrin without odor, would reach the hindgut and affect the intestinal microbiota composition and play a better role in regulating sow reproductive performance, gut flora, and health. Thirty sows (Landrace × Yorkshire) were randomly divided into two groups: the control group (CON) and the tributyrin group (TB), which received basal diet supplemented with 0.05% tributyrin. The experimental period lasted for 35 days from late pregnancy to lactation. The results showed that TB supplementation significantly shortened the total parturition time and reduced the diarrhea rate in suckling piglets. On day 20 of lactation, the milk fat and protein levels increased by 9 and 4%, respectively. TB supplementation significantly improved the digestibility of dry material, gross energy, and crude fat in the sow diet, but had no significant effect on crude protein digestibility. Furthermore, TB supplementation increased the levels of IL-10, IL-6, and IgA in the blood of weaned piglets, but had no effect on maternal immunity. Analysis of the fecal microbial composition revealed that the addition of TB during late gestation and lactation increased the microbiota diversity in sows and piglets. At the phylum level, sows in the TB group had a slight increase in the relative abundance of Bacteroidota and Spirochaetota and a decrease in Firmicutes. At the order level, the relative abundance of Lactobacillales was increased in piglets and sows, and the TB group showed increased relative abundance of Enterobacterales and significantly decreased relative abundance of Oscillospirales in piglets. At family level, the relative abundance of Lactobacillaceae, Oscillospiraceae, and Christensenellaceae increased in sows, and the relative abundance of Enterobacteriaceae and Lactobacillaceae increased in piglets. At genus level, the relative abundance of Lactobacillus increased in sows and piglets, but the relative abundance of Subdoligranulum and Eubacterium_fissicatena_group decreased in piglets in the TB group. In conclusion, tributyrin supplementation shortened the farrowing duration and reduced the diarrhea rate of piglets by improving the inflammatory response and composition of gut microbiota in piglets and sows.

Evaluation of tributyrin supplementation in milk replacer on diarrhoea occurrence in preweaning Holstein calves

Neonatal calf diarrhoea is one of the most important health challenges in cattle herds causing substantial economic losses and antimicrobial use. Due to the raising problem of antimicrobial resistance, effective alternatives are urgently required, in line with European policies. The aim of this study was to evaluate the effect of tributyrin supplementation in milk replacer on diarrhoea, performance and metabolic status in preweaning Holstein calves. Twelve newborn calves, after colostrum administration, were randomly allotted in two experimental groups for 42 days: control (CTRL) fed milk replacer, tributyrin (TRIB) fed milk replacer supplemented with 0.3% of liquid tributyrin on milk powder weight. Calves BW was recorded on a weekly basis from day 7 to day 42, and feed intake was recorded daily to calculate zootechnical performance. Faecal consistency was assessed daily through the faecal score (0–3 scale; considering diarrhoea moderate = 2 and severe = 3). Faecal samples were collected weekly from rectal ampulla for microbiological analysis by plate counting method evaluating the number of total bacteria, lactic acid bacteria and coliform bacteria. On day 0 and day 42, individual blood samples were collected from jugular vein for metabolic profile analysis. Serum samples of day 42 were also evaluated for the antioxidant barrier using a colorimetric test, while glucagon-like peptide 2 and diamine oxidase concentrations were measured through immunoenzymatic assays. Tributyrin supplementation did not influence the zootechnical performance of calves over 42 days of trial. Diarrhoea frequency was significantly lower in TRIB compared to CTRL group (27.91 and 38.37%; P < 0.01) considering the whole experimental period. In particular, the major effect was observed for moderate diarrhoea in TRIB group that showed a significantly reduced frequency compared to CTRL (P < 0.01) thus suggesting a preventive effect of tributyrin. Faecal total bacterial, lactic acid and coliform bacteria counts did not show differences between groups. Urea serum concentrations tended to be lower in TRIB compared to CTRL, indicating an efficient utilisation of dietary protein. Antioxidant barrier and glucagon-like peptide 2 were comparable between CTRL and TRIB on day 42. Diamine oxidase concentrations were significantly decreased in TRIB compared to CTRL group after 42 days of trial (P < 0.01), suggesting a higher gut epithelial integrity probably due to lower diarrhoea frequency and the nourish effect of tributyrin on enterocytes. In conclusion, tributyrin could be considered as a valuable bioactive feed additive to decrease the neonatal diarrhoea occurrence and support intestinal integrity in preweaning calves.