ABSTRACT
The neutral result of the PROMINENT trial has led to questions about the future for pemafibrate. This commentary discusses possible reasons for the lack of benefit observed in the trial. There were, however, indicators suggesting therapeutic potential in microvascular ischaemic complications associated with peripheral artery disease, with subsequent analysis showing reduction in the incidence of lower extremity ischaemic ulceration or gangrene. Reassurance about the safety of pemafibrate, together with emerging data from PROMINENT and experimental studies, also suggest benefit with pemafibrate in non-alcoholic fatty liver disease (alternatively referred to as metabolic dysfunction-associated steatotic liver disease) and microangiopathy associated with diabetes, which merit further study.
Subject(s)
Benzoxazoles , Butyrates , Animals , Humans , Benzoxazoles/therapeutic use , Benzoxazoles/adverse effects , Butyrates/therapeutic use , Butyrates/adverse effects , Hypolipidemic Agents/therapeutic use , Hypolipidemic Agents/adverse effects , Ischemia/drug therapy , Ischemia/physiopathology , Non-alcoholic Fatty Liver Disease/drug therapy , Peripheral Arterial Disease/drug therapy , Risk Factors , Treatment OutcomeABSTRACT
Aim: Short-term use of pemafibrate (PEM), a selective modulator of peroxisome proliferator-activated receptor alpha, has been reported to improve abnormal liver function in patients with nonalcoholic fatty liver disease with hypertriglyceridemia (HTG-NAFLD). This study aimed to clarify the effects and predictive factors of long-term 72-week PEM administration on body composition, and laboratory tests in HTG-NAFLD patients. Methods: Fifty-three HTG-NAFLD patients receiving a 72-week PEM regimen were retrospectively enrolled. Routine blood and body composition results were analyzed immediately before and at the end of the study period. Results: PEM treatment significantly improved liver enzyme levels such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, and gamma-glutamyl transferase, along with lipid profiles including triglyceride, total cholesterol, and low-density lipoprotein cholesterol. PEM did not have any detectable impact on body composition parameters. The factors of female, higher AST (≥ 46 U/L) and fat mass (≥ 31.9%), as well as lower soft lean mass (< 61.6%), skeletal muscle mass (< 36%), and skeletal muscle mass index (< 6.9 kg/m2) were significantly associated with the treatment response status of a > 30% decrease in ALT. All patients completed the treatment without any adverse effects. Conclusions: Long-term PEM treatment had a positive impact on liver enzymes and lipid profiles, but it did not result in significant changes in body composition among HTG-NAFLD patients. In predicting the response to PEM treatment, the evaluation of AST and body composition may be useful.
Subject(s)
Body Composition , Hypertriglyceridemia , Non-alcoholic Fatty Liver Disease , Humans , Female , Male , Middle Aged , Hypertriglyceridemia/drug therapy , Hypertriglyceridemia/complications , Hypertriglyceridemia/blood , Retrospective Studies , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/blood , Body Composition/drug effects , Benzoxazoles/therapeutic use , Benzoxazoles/administration & dosage , Adult , Butyrates/therapeutic use , Adipose Tissue/drug effects , Adipose Tissue/metabolism , Adipose Tissue/pathology , Aged , Hypolipidemic Agents/therapeutic use , Hypolipidemic Agents/administration & dosageABSTRACT
Colorectal cancer (CRC) is one of the leading causes of cancer-related death. Currently, dietary factors are being emphasized in the pathogenesis of CRC. There is strong evidence that fatty acids (FAs) and free FA receptors (FFARs) are involved in CRC. This comprehensive review discusses the role of FAs and their receptors in CRC pathophysiology, development, and treatment. In particular, butyrate and n-3 polyunsaturated fatty acids have been found to exert anticancer properties by, among others, inhibiting proliferation and metastasis and inducing apoptosis in tumor cells. Consequently, they are used in conjunction with conventional therapies. Furthermore, FFAR gene expression is down-regulated in CRC, suggesting their suppressive character. Recent studies showed that the FFAR4 agonist, GW9508, can inhibit tumor growth. In conclusion, natural as well as synthetic FFAR ligands are considered promising candidates for CRC therapy.
Subject(s)
Colorectal Neoplasms , Fatty Acids, Nonesterified , Fatty Acids, Omega-3 , Receptors, G-Protein-Coupled , Humans , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/metabolism , Receptors, G-Protein-Coupled/metabolism , Fatty Acids, Nonesterified/metabolism , Fatty Acids, Omega-3/therapeutic use , Fatty Acids, Omega-3/pharmacology , Butyrates/therapeutic use , Butyrates/pharmacology , Animals , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/pharmacology , Methylamines/metabolism , Apoptosis/drug effects , Cell Proliferation/drug effects , PropionatesABSTRACT
BACKGROUND: Radiation proctitis (RP) is a significant complication of pelvic radiation. Effective treatments for chronic RP are currently lacking. We report a case where chronic RP was successfully managed by metformin and butyrate (M-B) enema and suppository therapy. CASE PRESENTATION: A 70-year-old Asian male was diagnosed with prostate cancer of bilateral lobes, underwent definitive radiotherapy to the prostate of 76 Gy in 38 fractions and six months of androgen deprivation therapy. Despite a stable PSA nadir of 0.2 ng/mL for 10 months post-radiotherapy, he developed intermittent rectal bleeding, and was diagnosed as chronic RP. Symptoms persisted despite two months of oral mesalamine, mesalamine enema and hydrocortisone enema treatment. Transition to daily 2% metformin and butyrate (M-B) enema for one week led to significant improvement, followed by maintenance therapy with daily 2.0% M-B suppository for three weeks, resulting in continued reduction of rectal bleeding. Endoscopic examination and biopsy demonstrated a good therapeutic effect. CONCLUSIONS: M-B enema and suppository may be an effective treatment for chronic RP.
Subject(s)
Enema , Metformin , Proctitis , Prostatic Neoplasms , Radiation Injuries , Humans , Male , Proctitis/drug therapy , Proctitis/etiology , Aged , Metformin/therapeutic use , Metformin/administration & dosage , Prostatic Neoplasms/radiotherapy , Prostatic Neoplasms/drug therapy , Radiation Injuries/drug therapy , Chronic Disease , Treatment Outcome , Butyrates/therapeutic use , Gastrointestinal Hemorrhage/drug therapy , Gastrointestinal Hemorrhage/therapy , Gastrointestinal Hemorrhage/etiology , SuppositoriesABSTRACT
Butyrate-a metabolite produced by commensal bacteria-has been extensively studied for its immunomodulatory effects on immune cells, including regulatory T cells, macrophages and dendritic cells. However, the development of butyrate as a drug has been hindered by butyrate's poor oral bioavailability, owing to its rapid metabolism in the gut, its low potency (hence, necessitating high dosing), and its foul smell and taste. Here we report that the oral bioavailability of butyrate can be increased by esterifying it to serine, an amino acid transporter that aids the escape of the resulting odourless and tasteless prodrug (O-butyryl-L-serine, which we named SerBut) from the gut, enhancing its systemic uptake. In mice with collagen-antibody-induced arthritis (a model of rheumatoid arthritis) and with experimental autoimmune encephalomyelitis (a model of multiple sclerosis), we show that SerBut substantially ameliorated disease severity, modulated key immune cell populations systemically and in disease-associated tissues, and reduced inflammatory responses without compromising the global immune response to vaccination. SerBut may become a promising therapeutic for autoimmune and inflammatory diseases.
Subject(s)
Arthritis, Experimental , Biological Availability , Butyrates , Prodrugs , Serine , Animals , Prodrugs/pharmacology , Prodrugs/therapeutic use , Prodrugs/pharmacokinetics , Prodrugs/chemistry , Mice , Serine/metabolism , Butyrates/pharmacology , Butyrates/therapeutic use , Butyrates/chemistry , Butyrates/administration & dosage , Administration, Oral , Arthritis, Experimental/drug therapy , Arthritis, Experimental/immunology , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/immunology , Encephalomyelitis, Autoimmune, Experimental/drug therapy , Encephalomyelitis, Autoimmune, Experimental/immunology , Mice, Inbred C57BL , Neuroinflammatory Diseases/drug therapy , FemaleABSTRACT
Maintaining an optimum microbial community within the gastrointestinal tract is intricately linked to human metabolic, immune and brain health. Disturbance to these microbial populations perturbs the production of vital bioactive compounds synthesised by the gut microbiome, such as short-chain fatty acids (SCFAs). Of the SCFAs, butyrate is known to be a major source of energy for colonocytes and has valuable effects on the maintenance of intestinal epithelium and blood brain barrier integrity, gut motility and transit, anti-inflammatory effects, and autophagy induction. Inducing endogenous butyrate production is likely to be beneficial for gut-brain homeostasis and for optimal neuronal function. For these reasons, butyrate has gained interest as a potential therapy for not only metabolic and immunological disorders, but also conditions related to the brain, including neurodegenerative diseases. While direct and indirect sources of butyrate, including prebiotics, probiotics, butyrate pro-drugs and glucosidase inhibitors, offer a promising therapeutic avenue, their efficacy and dosage in neurodegenerative conditions remain largely unknown. Here, we review current literature on effects of butyrate relevant to neuronal function, the impact of butyrate in a range of neurodegenerative diseases and related treatments that may have potential for the treatment of neurodegenerative diseases.
Subject(s)
Butyrates , Gastrointestinal Microbiome , Neurodegenerative Diseases , Humans , Butyrates/therapeutic use , Butyrates/pharmacology , Butyrates/metabolism , Gastrointestinal Microbiome/drug effects , Gastrointestinal Microbiome/physiology , Neurodegenerative Diseases/drug therapy , Neurodegenerative Diseases/metabolism , Probiotics/therapeutic useABSTRACT
Cancer is one of the leading causes of mortality worldwide. The etiology of cancer has not been fully elucidated yet, and further enhancements are necessary to optimize therapeutic efficacy. Butyrate, a shortchain fatty acid, is generated through gut microbial fermentation of dietary fiber. Studies have unveiled the relevance of butyrate in malignant neoplasms, and a comprehensive understanding of its role in cancer is imperative for realizing its full potential in oncological treatment. Its full antineoplastic effects via the activation of G proteincoupled receptors and the inhibition of histone deacetylases have been also confirmed. However, the underlying mechanistic details remain unclear. The present study aimed to review the involvement of butyrate in carcinogenesis and its molecular mechanisms, with a particular emphasis on its association with the efficacy of tumor immunotherapy, as well as discussing relevant clinical studies on butyrate as a therapeutic target for neoplastic diseases to provide new insights into cancer treatment.
Subject(s)
Antineoplastic Agents , Butyrates , Neoplasms , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Butyrates/pharmacology , Butyrates/therapeutic use , Dietary Fiber , Receptors, G-Protein-Coupled , Neoplasms/drug therapyABSTRACT
BACKGROUND/AIMS: Pemafibrate is a selective peroxisome proliferator-activated receptor α modulator that improves serum alanine aminotransferase (ALT) in dyslipidemia patients. We previously reported that pemafibrate significantly improves liver function, serum triglyceride (TG) levels and liver stiffness in non-alcoholic fatty liver disease patients, however the influence of alcohol consumption was not considered. Therefore, we explored pemafibrate efficacy in patients with steatotic liver disease (SLD) and alcohol-associated liver disease (ALD). METHODS: We retrospectively evaluated pemafibrate efficacy on liver enzymes and lipids in metabolic dysfunction-associated SLD (MASLD) (nâ =â 93), MASLD plus increased alcohol intake (MetALD; nâ =â 23) and ALD (nâ =â 22) patients who had taken pemafibrate for at least 48 weeks. Liver shear wave velocity (SWV, nâ =â 75) was also evaluated. RESULTS: In MASLD group, ALT, aspartate aminotransferase (AST), γ-glutamyl transpeptidase (γ-GTP) and TG values were significantly decreased from baseline to week 24 and week 48 ( P â <â 0.0001). ALT and TG values in MetALD group and ALT and AST values in ALD group were also significantly decreased from baseline to week 24 and week 48. Study participant SWV values decreased from baseline to week 48. We observed no significant difference in changes to ALT, AST, γ-GTP and TG (value at week 24 or week 48 minus value at baseline) among the three groups. CONCLUSION: Pemafibrate improves liver function and liver stiffness thus making it a promising therapeutic agent for SLD, even in patients with excess alcohol consumption (MetALD and ALD groups).
Subject(s)
Alanine Transaminase , Alcohol Drinking , Aspartate Aminotransferases , Benzoxazoles , Butyrates , Liver , Triglycerides , gamma-Glutamyltransferase , Humans , Male , Female , Middle Aged , Retrospective Studies , gamma-Glutamyltransferase/blood , Alcohol Drinking/adverse effects , Treatment Outcome , Butyrates/therapeutic use , Benzoxazoles/therapeutic use , Alanine Transaminase/blood , Triglycerides/blood , Aspartate Aminotransferases/blood , Aged , Liver/drug effects , Liver/pathology , Elasticity Imaging Techniques , Adult , Non-alcoholic Fatty Liver Disease/drug therapy , Time Factors , Biomarkers/blood , Fatty Liver/drug therapy , Fatty Liver, Alcoholic/drug therapyABSTRACT
PURPOSE OF REVIEW: Although high triglycerides are consistently associated with elevated risk of cardiovascular disease (CVD), therapies that reduce triglyceride levels have inconsistently translated into reduced CVD risk. RECENT FINDINGS: To date, three clinical trials have tested triglyceride-lowering therapies in patients with hypertriglyceridemia (HTG) and elevated risk of incident/recurrent CVD. In REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial), assignment to IPE, a highly purified eicosapentanoic acid (EPA), resulted in a 25% reduction in nonfatal myocardial infarction), nonfatal stroke, cardiovascular death, coronary revascularization and hospitalization for unstable angina. By contrast, the combination of EPA and docosahexanoic acid (DHA) carboxylic fatty acids used in the STRENGTH trial (Statin Residual Risk With Epanova in High Cardiovascular Risk Patients With Hypertriglyceridemia) failed to reduce CVD risk. Most recently, PROMINENT (Pemafibrate to Reduce Cardiovascular Outcomes by Reducing Triglycerides in Patients with Diabetes) also failed to demonstrate reduction in CVD events despite use of a potent triglyceride-lowering, fibric-acid derivative. However, improvement in HTG-associated metabolic complications (e.g. nonalcoholic fatty liver disease) was observed with pemafibrate as well as with another potent triglyceride-lowering therapy (i.e. pegozafermin). Moreover, trials are underway evaluating whether the most fatal metabolic complication of HTG, pancreatitis, may be reduced with highly potent triglyceride-lowering therapies (e.g. apolipoprotein C3 inhibitors). SUMMARY: Taken together, HTG is associated with increased risk of CVD and attendant adverse metabolic sequalae. To this end, a potentially promising and evidence-based landscape is emerging for treating a clinical phenotype that in the past has been insufficiently addressed.
Subject(s)
Benzoxazoles , Butyrates , Cardiovascular Diseases , Hypertriglyceridemia , Hypolipidemic Agents , Humans , Cardiovascular Diseases/prevention & control , Hypertriglyceridemia/drug therapy , Hypertriglyceridemia/complications , Hypolipidemic Agents/therapeutic use , Benzoxazoles/therapeutic use , Butyrates/therapeutic use , Butyrates/pharmacology , Triglycerides/blood , Metabolic Diseases/prevention & controlABSTRACT
Many clinical studies have now highlighted how the composition of the intestinal microbiota can regulate the effects of many oncological therapies. In particular, the modulation of microbial composition has been shown to enhance their efficacy and reduce potential side effects. Numerous adverse events induced by chemotherapy and radiotherapy appear to be strongly associated with an alteration in the intestinal microbiota caused by these treatments. This supports the hypothesis that the modulation or correction of the microbiota may decrease the toxic impact of therapies, improving patient compliance and quality of life. Among the most debilitating disorders related to oncological treatments is certainly mucositis, and recent clinical data highlight how the deficiency of short-chain fatty acids, especially butyrate, and specifically the lack of certain bacterial groups responsible for its production (butyrate producers), is strongly associated with this disorder. It is hypothesized that restoring these elements may influence the onset and severity of adverse events. Therefore, the intake of probiotics, especially butyrate producers, and specifically Clostridium butyricum (CBM588), currently the only cultivable and usable strain with a history of data proving its safety, could be a valuable ally in oncological therapies, reducing the associated discomfort and improving compliance, efficacy, and quality of life for patients.
Subject(s)
Mucositis , Probiotics , Humans , Butyrates/therapeutic use , Mucositis/chemically induced , Mucositis/therapy , Quality of Life , Probiotics/pharmacology , Chemoradiotherapy/adverse effectsABSTRACT
This study examined the effects of pemafibrate, a selective peroxisome proliferator-activated receptor α agonist, on the serum biochemical parameters of male patients with coronary artery disease and metabolic syndrome (MetS). This was a post hoc analysis of a randomized, crossover study that treated hypertriglyceridemia with pemafibrate or bezafibrate for 24 weeks, followed by a crossover of another 24 weeks. Of the 60 patients enrolled in the study, 55 were male. Forty-one of 55 male patients were found to have MetS. In this sub-analysis, male patients with MetS (MetS group, n = 41) and those without MetS (non-MetS group, n = 14) were compared. The primary endpoint was a change in fasting serum triglyceride (TG) levels during pemafibrate therapy, and the secondary endpoints were changes in insulin resistance-related markers and liver function parameters. Serum TG levels significantly decreased (MetS group, from 266.6 to 148.0 mg/dL, p < 0.001; non-MetS group, from 203.9 to 97.6 mg/dL, p < 0.001); however, a percent change (%Change) was not significantly different between the groups (- 44.1% vs. - 51.6%, p = 0.084). Serum insulin levels and homeostasis model assessment of insulin resistance significantly decreased in the MetS group but not in the non-MetS group. %Change in liver enzyme levels was markedly decreased in the MetS group compared with that in the non-MetS group (alanine aminotransferase, - 25.1% vs. - 11.3%, p = 0.027; gamma-glutamyl transferase, - 45.8% vs. - 36.2%, p = 0.020). In conclusion, pemafibrate can effectively decrease TG levels in patients with MetS, and it may be a more efficient drug for improving insulin resistance and liver function in such patients.
Subject(s)
Benzoxazoles , Butyrates , Coronary Artery Disease , Cross-Over Studies , Hypertriglyceridemia , Insulin Resistance , Metabolic Syndrome , Humans , Male , Metabolic Syndrome/blood , Metabolic Syndrome/drug therapy , Metabolic Syndrome/complications , Metabolic Syndrome/diagnosis , Hypertriglyceridemia/blood , Hypertriglyceridemia/drug therapy , Hypertriglyceridemia/complications , Hypertriglyceridemia/diagnosis , Middle Aged , Coronary Artery Disease/blood , Coronary Artery Disease/drug therapy , Benzoxazoles/therapeutic use , Benzoxazoles/pharmacology , Butyrates/therapeutic use , Butyrates/pharmacology , Treatment Outcome , Aged , Triglycerides/blood , Hypolipidemic Agents/therapeutic use , Hypolipidemic Agents/pharmacology , Biomarkers/blood , PPAR alpha/agonists , Bezafibrate/therapeutic use , Bezafibrate/pharmacologyABSTRACT
BACKGRUOUND: Fibrates have renal toxicity limiting their use in subjects with chronic kidney disease (CKD). However, pemafibrate has fewer toxic effects on renal function. In the present analysis, we evaluated the effects of pemafibrate on the renal function of diabetic subjects with or without CKD in a real-world clinical setting. METHODS: We performed a sub-analysis of data collected during a multi-center, prospective, observational study of the effects of pemafibrate on lipid metabolism in subjects with type 2 diabetes mellitus complicated by hypertriglyceridemia (the PARM-T2D study). The participants were allocated to add pemafibrate to their existing regimen (ADD-ON), switch from their existing fibrate to pemafibrate (SWITCH), or continue conventional therapy (CTRL). The changes in estimated glomerular filtration rate (eGFR) over 52 weeks were compared among these groups as well as among subgroups created according to CKD status. RESULTS: Data for 520 participants (ADD-ON, n=166; SWITCH, n=96; CTRL, n=258) were analyzed. Of them, 56.7% had CKD. The eGFR increased only in the SWITCH group, and this trend was also present in the CKD subgroup (P<0.001). On the other hand, eGFR was not affected by switching in participants with severe renal dysfunction (G3b or G4) and/or macroalbuminuria. Multivariate analysis showed that being older and a switch from fenofibrate were associated with elevation in eGFR (both P<0.05). CONCLUSION: A switch to pemafibrate may be associated with an elevation in eGFR, but to a lesser extent in patients with poor renal function.
Subject(s)
Butyrates , Diabetes Mellitus, Type 2 , Glomerular Filtration Rate , Hypolipidemic Agents , Renal Insufficiency, Chronic , Humans , Male , Female , Middle Aged , Renal Insufficiency, Chronic/drug therapy , Renal Insufficiency, Chronic/complications , Glomerular Filtration Rate/drug effects , Aged , Prospective Studies , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/complications , Hypolipidemic Agents/therapeutic use , Butyrates/therapeutic use , Butyrates/pharmacology , Benzoxazoles/therapeutic use , Benzoxazoles/pharmacology , Hypertriglyceridemia/drug therapy , Hypertriglyceridemia/complications , Diabetic Nephropathies/drug therapy , Kidney/drug effects , Kidney/physiopathologyABSTRACT
OBJECTIVE: Oxidative damage is observed in the ischemic limbs of patients with arteriosclerosis obliterans. We investigated whether pemafibrate, a selective peroxisome proliferator-activated receptor alpha modulator, reduced oxidative stress in ischemic limbs and consequently rescued limb damage in model mice. MATERIALS AND METHODS: We surgically induced hind-limb ischemia in mice and orally administered pemafibrate solution (P-05 group, 0.5 mg/kg/day; P-10 group, 1.0 mg/kg/day) or control solution (control group). Seven days after the surgery, differences in reactive oxygen species (ROS) contents, antioxidative enzyme and transcription factor expression, blood flow, and capillary density in ischemic limbs were assessed. RESULTS: Tissue ROS levels were lower in the P-05 and P-10 groups compared with those in the control group. Although the tissue expression levels of nuclear factor-erythroid 2-related factor 2 increased in the P-10 group compared with that in the control group, no corresponding changes were observed in the tissue expression of four antioxidative enzymes. The limb salvage rates and capillary densities in ischemic limbs were higher in the P-05 and P-10 groups than that in the control group. CONCLUSION: Pemafibrate treatment reduced oxidative stress and augmented angiogenesis in ischemic limbs, contributing to prevention of limb damage in mice.
Subject(s)
Benzoxazoles , Butyrates , Disease Models, Animal , Hindlimb , Ischemia , Neovascularization, Physiologic , Oxidative Stress , Reactive Oxygen Species , Animals , Oxidative Stress/drug effects , Benzoxazoles/pharmacology , Benzoxazoles/therapeutic use , Ischemia/drug therapy , Ischemia/metabolism , Neovascularization, Physiologic/drug effects , Male , Hindlimb/blood supply , Reactive Oxygen Species/metabolism , Butyrates/pharmacology , Butyrates/therapeutic use , Mice , Antioxidants/pharmacology , NF-E2-Related Factor 2/metabolism , Regional Blood Flow/drug effects , PPAR alpha/metabolism , Limb Salvage , AngiogenesisABSTRACT
Objectives:We aimed to explore the potential role of omega-3 (ω-3) fatty acids on acne vulgaris by modulating gut microbiota.Materials and Methods:We randomly divided the untreated acne patients into two groups with or without ω-3 fatty acids intervention for 12 weeks. The Sprague Dawley (SD) rats with acne model were given isotretinoin, ω-3 fatty acids or their combination respectively. Then the colonic contents samples of the drug intervention SD rats were transferred to the pseudo sterile rats with acne model. The severity of the disease was assessed by the Global Acne Grading System (GAGS) score of the patients, and the swelling rate of auricle and the pathological section of the rat with acne model. The 16S rDNA gene sequencing was performed to detect the alteration of the gut microbiota.Results:ω-3 fatty acids could increase the diversity of the gut microbiota and regulate the flora structure positively both in the patients and rats, increase the abundance of butyric acid producing bacteria and GAGS score in the patients, and alleviate the inflammation and comedones of rats.Conclusion:Supplementation of ω-3 fatty acids could alleviate the inflammation of acne vulgaris by increasing the abundance of butyric acid producing bacteria.
Subject(s)
Acne Vulgaris , Fatty Acids, Omega-3 , Gastrointestinal Microbiome , Animals , Humans , Rats , Acne Vulgaris/microbiology , Adjuvants, Immunologic , Butyrates/therapeutic use , Fatty Acids, Omega-3/pharmacology , Fatty Acids, Omega-3/therapeutic use , Inflammation/drug therapy , Rats, Sprague-DawleyABSTRACT
Short-chain fatty acids (SCFAs), the main metabolites of gut microbiota, have been associated with lower blood glucose and lipid levels in diabetic mice. However, a comprehensive summary and comparison of the effects of different SCFA interventions on blood glucose and lipid levels in diabetic mice is currently unavailable. This study aims to compare and rank the effects of different types of SCFAs on blood glucose and lipid levels by collecting relevant animal research. A systematic search through PubMed, Embase, Cochrane Library, and Web of Science database was conducted to identify relevant studies from inception to March 17, 2023. Both pairwise meta-analysis and Bayesian network meta-analysis were used for statistical analyses. In total, 18 relevant studies involving 5 interventions were included after screening 3793 citations and 53 full-text articles. Notably, butyrate therapy (mean difference [MD] = -4.52, 95% confidence interval [-6.29, -2.75]), acetate therapy (MD = -3.12, 95% confidence interval [-5.79, -0.46]), and propionate therapy (MD = -2.96, 95% confidence interval [-5.66, -0.26]) significantly reduced the fasting blood glucose levels compared to the control group; butyrate therapy was probably the most effective intervention, with a surface under the cumulative ranking curve (SUCRA) value of 85.5%. Additionally, acetate plus propionate therapy was probably the most effective intervention for reducing total cholesterol (SUCRA = 85.8%) or triglyceride levels (SUCRA = 88.1%). These findings underscore the potential therapeutic implications of SCFAs for addressing metabolic disorders, particularly in type 2 diabetes mellitus.