Effects Of Butyrate Supplementation Research Articles

Effects of Butyrate Supplementation on Inflammation and Kidney Parameters in Type 1 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Trial.

Type 1 diabetes is associated with increased intestinal inflammation and decreased abundance of butyrate-producing bacteria. We investigated the effect of butyrate on inflammation, kidney parameters, HbA1c, serum metabolites and gastrointestinal symptoms in persons with type 1 diabetes, albuminuria and intestinal inflammation. We conducted a randomized placebo-controlled, double-blind, parallel clinical study involving 53 participants randomized to 3.6 g sodium butyrate daily or placebo for 12 weeks. The primary endpoint was the change in fecal calprotectin. Additional endpoints were the change in fecal short chain fatty acids, intestinal alkaline phosphatase activity and immunoglobulins, serum lipopolysaccharide, CRP, albuminuria, kidney function, HbA1c, metabolites and gastrointestinal symptoms. The mean age was 54 ± 13 years, and the median [Q1:Q3] urinary albumin excretion was 46 [14:121] mg/g. The median fecal calprotectin in the butyrate group was 48 [26:100] μg/g at baseline, and the change was −1.0 [−20:10] μg/g; the median in the placebo group was 61 [25:139] μg/g at baseline, and the change was −12 [−95:1] μg/g. The difference between the groups was not significant (p = 0.24); neither did we find an effect of butyrate compared to placebo on the other inflammatory markers, kidney parameters, HbA1c, metabolites nor gastrointestinal symptoms. Twelve weeks of butyrate supplementation did not reduce intestinal inflammation in persons with type 1 diabetes, albuminuria and intestinal inflammation.

The effects of butyrate supplementation on glycemic control, lipid profile, blood pressure, nitric oxide level and glutathione peroxidase activity in type 2 diabetic patients: A randomized triple -blind, placebo-controlled trial.

This study aimed to investigate the effects of oral NaBut on metabolic parameters, blood pressure, and oxidative stress indices including glutathione peroxidase (GPx) and nitric oxide (NO) status in type 2 diabetic patients. In the current interventional trial, 42 patients with type 2 diabetes mellitus (T2DM) were randomly allocated into either NaBut (n=21) or placebo (n=21) group for six weeks. Serum concentrations of metabolic parameters, GPx, NO as well as blood pressure were assessed before and after the intervention. Within-group findings demonstrated that NaBut administration significantly reduced systolic and diastolic blood pressure (p=0.016 and p=0.002, respectively). Blood sugar 2-hr postprandial (BS2hpp) was also significantly decreased in the intervention and placebo groups (p=0.016 and p=0.019, respectively), but the between-group differences were not statistically significant. Differences in homeostatic model assessment of insulin resistance (HOMA-IR) were not significant between groups after adjustment for potential confounders (p=0.061). NaBut supplementation was also found to significantly increase total cholesterol (p=0.001), low-density lipoprotein cholesterol (p=0.005), and insulin levels (p=0.047) compared to the baseline, while decreased NO levels (p=0.040). However, there were no significant between-group differences in these parameters. No significant differences were also found in other parameters. We observed significant within-group decreases in systolic and diastolic blood pressure as well as BS2hpp following oral butyrate treatment. While no or even adverse changes in other biochemical parameters were found. Further investigations with longer durations are warranted to more vividly elucidate the effects of NaBut supplementation on patients with T2DM. Registered under Iranian Registry of Clinical Trials website (http://www.irct.ir), Identifier no. IRC T20090609002017N33.

406-P: Effects of Butyrate Supplementation on Inflammation and Kidney Parameters in Type 1 Diabetes—A Randomized, Double-Blind, Placebo-Controlled Trial

Background: Fecal calprotectin, a marker of inflammation, is increased in persons with type 1 diabetes (T1D) and kidney disease. This may be explained by a reduction of butyrate-producing bacterial species in the gut. Butyrate supplementation has beneficial effects on intestinal inflammation in inflammatory bowel disease but has never been tested in persons with T1D. Objective: To assess the effect of sodium butyrate on fecal calprotectin and other inflammatory markers, kidney parameters, hba1c and gastrointestinal symptoms in persons with T1D and intestinal inflammation. Methods: Randomized placebo-controlled, double-blind, parallel clinical study including 53 participants with T1D, albuminuria and intestinal inflammation (elevated fecal calprotectin) . Participants were assigned to receive 3.6 g sodium butyrate daily (n=28) or placebo (n=25) for 12 weeks. Primary endpoint was fecal calprotectin changes, and additional outcomes were fecal short chain fatty acids, intestinal alkaline phosphatase activity and immunoglobulins; serum lipopolysaccharide, serum C-reactive protein, albuminuria, kidney function, hba1c and gastrointestinal symptoms. Results: Mean age of the participants was 54±13 years, 43% were women, diabetes duration was 30±15 years and median [Q1:Q3] urinary albumin excretion was 46 [14:121] mg/g. Median fecal calprotectin in the butyrate group was 48 [26:100] μg/g at baseline and change was -1.0 [-20:10] μg/g, the median in the placebo group was 61 [25:139] μg/g at baseline and change was -12 [-95:1] μg/g. Difference in change between groups was not significant (p=0.24) . Neither did we find an effect of butyrate compared to placebo on the other fecal and circulating inflammatory markers, kidney parameters, hba1c or gastrointestinal symptoms. Conclusion: Oral butyrate supplementation for 12 weeks did not reduce fecal calprotectin in persons with T1D and intestinal inflammation. Disclosure N.H.Tougaard: None. P.Groop: Advisory Panel; Novo Nordisk, Sanofi, Other Relationship; Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Merck Sharp & Dohme Corp., Mundipharma, Speaker's Bureau; Medscape. M.Lehto: None. P.Rossing: Consultant; Astellas Pharma Inc., AstraZeneca, Bayer AG, Gilead Sciences, Inc., Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi, Speaker's Bureau; Eli Lilly and Company. M.Frimodt-moeller: None. H.Salmenkari: None. E.Buur stougaard: Other Relationship; Novo Nordisk. I.Mattila: None. T.W.Hansen: Stock/Shareholder; Novo Nordisk A/S. C.Legido-quigley: None. S.Hörkkö: None. C.Forsblom: None.

The effect of sodium butyrate supplementation on ruminal and fecal pH and serum lipopolysaccharide-binding protein after ruminal acidosis challenge in nonlactating cows.

The objective of this study was to evaluate effects of sodium-butyrate supplementation on gastrointestinal function and the inflammatory response to ruminal acidosis (RA) challenge in cows. Four nonlactating cows with a rumen cannula were assigned to two treatments in a crossover design. Treatments were ruminal administration of sodium-butyrate (BUT) or control (CON). Sodium-butyrate was provided as Gustor BP70 and administered at a butyrate dose of 0.04% per kg body weight. The CON premix was made by replacing sodium-butyrate with wheat bran. Experimental periods were 28 days long with 21-day washout period separating the treatments. On Day 25 of each period, corn starch was ruminally administered at 0.7% per kg body weight as RA challenge. After RA challenge, ruminal pH was lower, and endotoxin concentration was higher for cows provided with BUT than those with CON, but the increase in fecal starch and the decrease in fecal pH were attenuated by BUT. The effect of butyrate supplementation on serum lipopolysaccharide-binding protein after RA challenge was not found. From these findings, butyrate supplementation mitigated rectal acidosis by reducing the flux of fermentable carbohydrate into the large intestine. An anti-inflammatory effect of butyrate was not observed, possibly due to lower pH and higher endotoxin concentration in the rumen.

Sa1129 – Effects of Butyrate Supplementation on Nhe8Ko Mice

Sa1129 – Effects of Butyrate Supplementation on Nhe8Ko Mice

Effects of oral butyrate supplementation on inflammatory potential of circulating peripheral blood mononuclear cells in healthy and obese males

Sodium butyrate is well-known for its immune-modulatory properties. Studies until now only focused on the in vitro effects of butyrate or assessed local effects in the gut upon butyrate administration. In this trial, we studied the systemic anti-inflammatory effects induced by sodium butyrate supplementation in humans. Nine healthy (Lean) and ten obese (metabolic syndrome group, MetSyn) males were given 4 grams sodium butyrate daily for 4 weeks. PBMCs were isolated before and after supplementation for direct stimulation experiments and induction of trained immunity by oxidized low-density lipoprotein (oxLDL), β-glucan, or Bacillus Calmette-Guérin vaccine (BCG). Butyrate supplementation moderately affected some of the cytokine responses in the MetSyn group. In the direct stimulation setup, effects of butyrate supplementation were limited. Interestingly, butyrate supplementation decreased oxLDL-induced trained immunity in the MetSyn group for LPS-induced IL-6 responses and Pam3CSK4-induced TNF-α responses. Induction of trained immunity by β-glucan was decreased by butyrate in the MetSyn group for Pam3CSK4-induced IL-10 production. In this study, while having only limited effects on the direct stimulation of cytokine production, butyrate supplementation significantly affected trained immunity in monocytes of obese individuals with metabolic complications. Therefore, oral butyrate supplementation may be beneficial in reducing the overall inflammatory status of circulating monocytes in patients with metabolic syndrome.

Effect of a butyrate-fortified milk replacer on gastrointestinal microbiota and products of fermentation in artificially reared dairy calves at weaning

Enrichment of calf diets with exogenous butyrate has shown promise as a promotor of calf growth and intestinal development. However, the impact of dietary derived butyrate on the gut microbiota and their potential role, in turn, as mediators of its effect on calf growth and development is not known. Here, the effects of butyrate supplementation on rumen and hindgut microbiota and fermentation profiles were assessed in 16 Holstein-Friesian bull calves randomly assigned to one of two groups: Control (CON) fed conventional milk replacer or Sodium-Butyrate (SB – added to milk replacer) from days 7 to 56 of life. In the colon, total short chain fatty acid (SCFA), propionate and acetate concentrations were increased by SB (P < 0.05). 16S rRNA gene amplicon sequencing showed cecal abundance of butyrate producers Butyrivibrio and Shuttleworthia were decreased by SB (P < 0.05), while that of the propionate producer Phascolarctobacterium was higher (P < 0.05). Mogibacterium is associated with impaired gut health and was reduced in the cecum of SB calves (P < 0.05). These data show that the beneficial effects of SB on growth and performance occur in tandem with changes in the abundance of important SCFA producing and health-associated bacteria in the hindgut in milk-fed calves.

Effects of butyrate supplementation in antibiotic-free milk replacer and starter on growth performance in suckling calves.

The aim of this study was to evaluate butyrate supplementation of antibiotic-free milk replacer and starter on growth performance in male Holstein calves. Twenty-nine calves were divided into two groups. Group C (n=13) was fed antibiotic-free milk replacer without supplementation, and Group B (n=16) was fed antibiotic-free milk replacer supplemented with butyrate (1.6 % DM of Gustor BP70® ). Starter in Group B contained 0.3 % DM of Gustor BP70® . The intake of milk replacer was lower in group B than in C (p=0.07 for the treatment x week interaction). Body weight (BW) and heart girth (HG) in group B was higher than in C during the experimental period (p=0.07 and 0.01 for the treatment×week interaction, respectively). The duration of the weaning period in group B was shorter than in group C (p=0.02). β-hydroxybutyrate (BHBA) was higher in group B than in C (p=0.04). Insulin like growth factor-1 (IGF-1) concentrations tended to be higher in group B than in C (p=0.07 for treatment × week interaction). Our results show that butyrate supplementation in antibiotic-free milk replacer and starter exerted positive effects on growth performance in suckling calves.

Sodium butyrate supplementation ameliorates diabetic inflammation in db/db mice.

Endotoxemia has been recognized to be closely accompanied with type 2 diabetes mellitus (T2DM) and is responsible for many diabetic complications. Recent study suggests the potential role of butyrate, a short-chain fatty acid (SCFA) from microbiota metabolite, on T2DM. Gut-leak is a key event in diabetic-endotoxemia. To investigate if butyrate could ameliorate diabetic-endotoxemia, both in vivo and in vitro experiments were carried out in the present study. The effect of butyrate supplementation on blood HbA1c and inflammatory cytokines were determined in db/db mice; gut barrier integrity and expression of tight junction proteins were investigated both in vivo and in vitro Oral butyrate administration significantly decreased blood HbA1c, inflammatory cytokines and LPS in db/db mice; inflammatory cell infiltration was reduced, and gut integrity and intercellular adhesion molecules were increased as detected by HE staining, immunohistochemistry and Western blot. By gut microbiota assay, ratio of Firmicutes:Bacteroidetes for gut microbiota was reduced by butyrate. In Caco-2 cells, butyrate significantly promoted cell proliferation, decreased inflammatory cytokines' secretion, enhanced cell anti-oxidative stress ability and preserved the epithelial monocellular integrity, which was damaged by LPS. The present findings demonstrated that butyrate supplementation could ameliorate diabetic-endotoxemia in db/db mice via restoring composition of gut microbiota and preserving gut epithelial barrier integrity.

Effects of supplementing a milk replacer with sodium butyrate or tributyrin on performance and metabolism of Holstein calves

The effects of butyrate supplementation in diets of calves are inconsistent in the literature. Fifty-one Holstein calves (45.7 ± 5.8 kg of bodyweight and 11.8 ± 3.1 days of age; mean ± s.d.) were randomly allocated to three treatments to assess the effects of supplementing the milk replacer at 0.3% dry matter with butyrate in the form of sodium butyrate or tributyrin compared with no supplementation (CTR). Calves were fed 4 L/day of milk replacer (25% crude protein and 19.2% ether extract) and starter feed (20% crude protein and 3.8% ether extract) ad libitum over a period of 6 weeks. Individual intake was measured daily and bodyweight and blood β-hydroxybutyrate, glucose-like peptide-1, glucose and insulin were measured fortnightly. A glucose tolerance test was performed on Days 0 and 35 of the study. No effects of butyrate supplementation were found on starter and total dry matter intake. CTR calves had greater average daily gain than tributyrin calves. CTR calves tended to have greater final bodyweight than tributyrin and sodium butyrate calves. Gain : feed ratio tended to be greater for CTR calves. There were no differences in plasma glucose, insulin, β-hydroxybutyrate and glucose-like peptide-1 concentrations throughout among treatments the study. During the glucose tolerance test, no differences on insulin sensitivity were found among treatments. In conclusion, no apparent advantages of supplementing milk replacer with sodium butyrate or tributyrin were found on performance and glucose metabolism in calves.

Abstract 244: Sodium Butyrate Improves In Vivo and In Vitro Inflammation and Increases Plaque Stability in Apoe-Deficient Mice

Butyrate is a short chain fatty acid, formed by fermentation in the large intestine, with a well-known anti-inflammatory property. As inflammation plays a key role in atherogenesis and insulin resistance, we studied the effects of butyrate supplementation on atherosclerosis and glucose homeostasis. ApoE-deficient mice received control diet (CT, n=8) or 1% butyrate supplemented diet (BUT, n=8) for 10 weeks. Oral glucose tolerance test (OGTT), insulin sensitivity test (IST), lipid profile and fasting glucose were evaluated. Atherosclerosis lesion area was studied in two sites, aorta and aortic root. In the latter, CCL2, VCAM-1, collagen, and matrix metalloproteinase-2 (MMP-2) were also assessed. In order to confirm the in vivo data, culture of human endothelial cells (E.A. Hy926) were pre-incubated with butyrate (0.5 or 1.0mM) and stimulated with oxidized LDL (oxLDL) for 4h for CCL2 and VCAM-1 evaluation by immunofluorescence. Lipid profile, fasting glucose and OGTT were similar between groups. Insulin sensitivity was improved in BUT group mice. Butyrate-treated mice showed reduction in the aorta atherosclerosis lesion (CT=4.1%, BUT=1.8%; percentage of the surface area). Despite of similar lesion area in the BUT- treated mice aortic roots presented reduced inflammation-related molecules, CCL2 (CT=0.25FI, BUT=1.2FI) and VCAM-1(CT=0.42FI, BUT=013FI), and improvement on plaque stability with reduced MMP2 (CT=0.51FI, BUT=0.13FI) and increased collagen (CT=0.19FI, BUT=0.44FI). These results suggest that aortic root lesion areas were similar probably due to a more stable and thicker fibrous cap in the BUT group (beneficial factor). The production of VCAM-1 and CCL2 by butyrate pretreated endothelial cells was reduced compared to control cells, suggesting that butyrate reduces leukocyte migration toward lesion reducing atherogenesis. In conclusion our data show that butyrate supplementation ameliorates atherosclerosis due to the anti-inflammatory effect and increased plaque stability.