Role Of Butyrate Research Articles

Mitigating lead-induced osteoporosis: The role of butyrate in gut-bone axis restoration

Lead (Pb) is an environmentally widespread bone toxic pollutant, contributes to the development of osteoporosis. Butyric acid, mainly produced by the fermentation of indigestible dietary fiber by gut microbiota, plays a pivotal role in the maintenance of bone homeostasis. However, the effects of butyric acids on the Pb induced osteoporosis have not yet been elucidated. In this study, our results showed that Pb exposure was negatively related to the abundance of butyric acid, in the Pb-exposed population and Pb-exposed mice. Pb exposure caused gut microbiota disorders, resulting in the decline of butyric acid-producing bacteria, such as Butyrivibrio_crossotus, Clostridium_sp._JN9, and the butyrate-producing enzymes through the acetyl-CoA pathway. Moreover, results from the NHANES data suggested that dietary intake of butyrate was associated with a reduced risk of osteoporosis in lead-burdened populations, particularly among men or participants aged 18–60 years. In addition, butyrate supplementation in mice with chronic Pb exposure improved the bone microarchitectures, repaired intestinal damage, upregulated the proportion of Treg cells. Taken together, these results demonstrated that chronic Pb exposure disturbs the gut-bone axis, which can be restored by butyric acid supplement. Our results suggest that butyrate supplementation is a possible therapeutic strategy for lead-induced bone toxicity.

Butyrate attenuates cold-induced hypertension via gut microbiota and activation of brown adipose tissue

ObjectiveChronic exposure to cold temperature is known to elevate blood pressure, leading to a condition known as cold-induced hypertension (CIH). Our previous research suggested correlations between alterations in gut microbiota, decrease in butyrate level, and the onset and progression of CIH. However, the role of butyrate in CIH and the underlying mechanisms need further investigation. MethodsWe exposed Specific Pathogen Free (SPF) rats to continuous cold temperature (4 ± 1 °C) for 6 weeks to establish a CIH rat model. Rats were divided into different groups by dose and duration, and the rats under cold were administered with butyrate (0.5 or 1 g/kg/day) daily. We assessed hypertension-associated phenotypes, pathological morphological changes, and endocrine-related phenotypes of brown adipose tissue (BAT). The effects of butyrate on gut microbiota and intestinal content metabolism were evaluated by 16s RNA sequencing and non-targeted metabolomics, respectively. ResultsThe systolic blood pressure (SBP) of rats exposed to cold after supplemented with butyrate were significantly lower than that of the Cold group. Butyrate may increase the species, abundance, and diversity of gut microbiota in rats. Specifically, butyrate intervention enriched beneficial bacterial genera, such as Lactobacillaceae, and decreased the levels of harmful bacteria genera, such as Actinobacteriota and Erysipeiotrichaceae. Cold exposure significantly increased BAT cells and the number of mitochondria. After butyrate supplementation, the levels of peroxisome proliferator-activated receptor gamma coactivator 1a and fibroblast growth factor 21 in BAT were significantly elevated (P < 0.05), and the volume and number of lipid droplets increased. The levels of ANG II and high-density lipoprotein were elevated in the Cold group but decreased after butyrate supplementation. ConclusionButyrate may attenuate blood pressure in CIH by promoting the growth of beneficial bacteria and the secretion of beneficial derived factors produced by BAT, thus alleviating the elevation of blood pressure induced by cold. This study demonstrates the anti-hypertensive effects of butyrate and its potential therapeutic mechanisms, offering novel insights to the prevention and treatment of CIH in populations living or working in cold environments.

Analysis of microbiota-host communication mediated by butyrate in Atlantic salmon

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

Bacterial metabolite butyrate in modulating sorafenib-targeted microRNAs to curtail its resistance in hepatocellular carcinoma.

The host dietary fibre is fermented into short-chain fatty acids (SCFA) by intestinal microbiota as bacterial metabolites like propionate, acetate and butyrate. Among these metabolites, the role of butyrate is well documented to provide energy to intestinal epithelial cells. Also, butyrate has anti-inflammatory and anti-tumour properties and decrease in its level by unbalanced diet can develops cancer. Lately, some research has suggested that sodium butyrate as an inhibitor of histone deacetylase (HDAC) may have anticancer potential for hepatocellular carcinoma (HCC), the most common type of liver cancer. Since, HCC is asymptomatic it is usually diagnosed at its advanced stage. Sorafenib with antiproliferative and antiangiogenic effects is the first line of treatment in advanced HCC. However, prolonged drug treatment to HCC patients develops adaptive resistance towards the sorafenib. Sorafenib resistance can also be enhanced by differentially expressed microRNAs. However, the significance of butyrate in HCC sorafenib resistance and its association with sorafenib-targeted microRNAs is yet to be unfurled. Here, an attempt has been made to explore the role of bacterial metabolite butyrate on sorafenib resistant HCC as well as on sorafenib-targeted microRNAs (miR-7641 and miR-199) to curtail sorafenib resistance in HCC. Initially, in-silico analysis was performed using Human Metabolome Database (HMDB) so to identify specific butyrate producing faecal bacteria. Then, their specific 16s rRNA expression was compared between HCC patients and healthy individuals using qRT-PCR. Additionally, the cell viability (MTT) and apoptosis assays were performed in both parental and sorafenib resistant HepG2 cells to evaluate the role of sodium butyrate in sorafenib resistant HCC. Moreover, the association of sodium butyrate with sorafenib-targeted miR-7641 and miR-199 was also assessed using real time PCR, cell viability, cell apoptosis and transfection assays. In silico analysis demonstrated Roseburia cecical, Roseburia intestinalis, Eubacterium rectal, Faecalibacterium prausnitzii as specific butyrate producing faecal bacteria and their 16s rRNA expression was downregulated in HCC patients. In vitro study revealed the presence of sodium butyrate also decreased the cell viability as well as enhanced cell apoptosis of both parental and resistant HepG2 cells. Interestingly, sodium butyrate also decreased the expression of both sorafenib-targeted miR-7641 and miR-199. Further, combination of both sodium butyrate and antimiR-7641 or antimiR-199 also increased apoptosis and decreased viability of resistant cells. This is first study to unravel the association of butyrate producing bacteria with HCC patients and the significance of bacterial metabolite butyrate as anti-tumour in sorafenib resistant hepatocellular carcinoma. The study also demonstrated the plausible new aspects of bacterial metabolite butyrate association with sorafenib-targeted miRNAs (miR-7641 and miR-199). Hence, the study highlighted the therapeutic potential of bacterial metabolite butyrate that might improve the clinical management of hepatocellular carcinoma.

Sodium butyrate reduces overnutrition-induced microglial activation and hypothalamic inflammation

Overnutrition-induced hypothalamic inflammation greatly disturbs feeding behavior and energy homeostasis as well as the pathogenesis of obesity. Butyrate, a short-chain fatty acid, reportedly participates in the regulation of the immune response and energy metabolism in the body. However, the role of butyrate in overnutrition-induced microglial activation and hypothalamic inflammation remains unclear. In the present study, we established a high-fat diet (HFD)-induced hypothalamic inflammation model in mice. Oral supplementation with sodium butyrate (NaB) significantly reduced HFD-induced microgliosis, inflammatory cytokine expression, endoplasmic reticulum (ER) stress, neuronal apoptosis, and neuropeptide Y (NPY) expression in the mouse hypothalamus. Utilizing a high-glucose (HG)-stimulated microglial activation model in vitro, we found that NaB inhibited the HG-induced expression of the inflammatory factor IL-1β. Moreover, NaB exerted an antioxidant effect by balancing HO-1 and NOX4 expression, thus preventing reactive oxygen species (ROS) production in HG-treated microglia. Interestingly, NaB treatment promoted microglial process formation and extension via the Akt/Cdc42 pathway under both normal and HG-stimulated conditions, indicating a resting morphology of microglia. Taken together, our study revealed for the first time the anti-inflammatory and antioxidant effects of NaB in overnutrition-induced microglial activation and hypothalamic inflammation, which might become a potential therapeutic option for obesity prevention and treatment.

The Role of Butyrate in Paclitaxel and Morphine Induced Peripheral Hypersensitivity

Recent evidence implicates the gut microbiome in peripheral hypersensitivity in chronic opioid use models, and in chemotherapeutic‐induced hypersensitivity in mice. An important constituent of the commensal microbiome are bacterial species that ferment fibers through complex enzymatic pathways and produce short chain fatty acids, acetate, propionate, and butyrate. Butyrate is known to improve the integrity of the epithelium and enhance antimicrobial peptides thus preventing colonization by pathogenic bacteria, as well as having an established role in reducing inflammation through the inhibition of histone deacetylase. Based on this, we hypothesized that sodium butyrate can relieve peripheral hypersensitivity as well as reduce primary nociceptor hyperexcitability in experimental models of peripheral hypersensitivity. We used both paclitaxel (PAC) and morphine (MOR) animal models, which were organized into the following treatment groups: PAC (8mg/kg i.p q.d, total 4 injections) ± Sodium Butyrate (10mg/kg i.p b.i.d), MOR (escalating from 20mg/kg i.p b.i.d on day 1 to 80mg/kg i.p b.i.d on day 4) ± Sodium Butyrate (10mg/kg i.p b.i.d). PAC animals were assessed for peripheral cold hypersensitivity using an acetone evaporation assay. MOR‐treated animals were assayed using a hot‐plate test for opioid‐induced hyperalgesia. Primary nociceptors from L4‐S1 dorsal root ganglia were collected from these mice for whole‐cell patch clamp electrophysiological recordings to assess for enhanced excitability. PAC‐treated mice developed significant cold hypersensitivity 7 days post PAC, when compared with vehicle (average time engaging stimulated paw 2.0s vs 8.6s respectively). Butyrate ameliorated this paclitaxel‐induced hypersensitivity (average time reduced to 2.5s). Similarly, MOR induced thermal hypersensitivity (Hot‐plate latency of 14.8s vs 28.16s saline), which was also reversed by sodium butyrate (Hot‐plate latency of 24.84s). Whole‐cell patch clamp recordings revealed that PAC and MOR‐treated neurons fired a greater number of regenerating action potentials compared to respective controls (PAC: 4 vs 2; MOR: 3.8 vs 2.1), indicating enhanced excitability. In‐vivo butyrate treatment attenuated this enhanced excitability. Hysteresis plots of hyperexcitable cells revealed a depolarizing shift in the membrane potential of regenerating action potentials. Sodium butyrate treatment recovered this shift in membrane potential within the repetitive action potentials. Therefore, similar to the in‐vivo peripheral hypersensitivity, butyrate reversed enhanced excitability of PAC and MOR‐treated DRG neurons. These findings demonstrate that the short chain fatty acid, butyrate, a major metabolite of the gut microbiome plays an important role in preventing the development of drug‐induced peripheral hypersensitivity.

Putative probiotics decrease cell viability and enhance chemotherapy effectiveness in human cancer cells: role of butyrate and secreted proteins

Recent advances have highlighted probiotic role in preventing colorectal cancer, by promoting differentiation, inhibiting proliferation, and inducing apoptosis in colonocytes. Here, three ascertained probiotics (L. rhamnosus GG ATCC 53103, L. reuterii DSM 17938 and L. johnsonii LC1) and four food-isolated putative probiotics (L. plantarum S2, L. plantarum O2, L. pentosus S3, L. rhamnosus 14E4) were investigated for their ability to adhere to HT29 cancer cells and to inhibit their and the chemoresistant counterpart (HT29-dx cells) proliferation. Three putative probiotics (S2, S3 and 14E4) were able to decrease viability of both sensitive and chemo-resistant HT-29 cells. Supposing this effect related to secreted metabolites (namely short chain fatty acids (SCFA), exopolysaccharides (EPS) and extracellular proteins) we tested the efficacy of extracellular extracts and butyrate with or without the chemotherapeutic agent doxorubicin (DOXO) (10 µM, 4 h). Increased production of mitochondrial reactive oxygen species (ROS) in HT29 and HT29-dx cells was observed. Moreover, cell exposure to DOXO (10 µM, 24 h) and extracellular extracts (48 h) reduced cell viability. Comparative phenotypic and secretome analyses on the effective/non effective strains, revealed quantitative/qualitative differences in EPS content and protein profiles, suggesting that P40, phage-tail-like and capsid-like proteins may be also involved. These results suggest that food-isolated bacteria releasing bioactive compounds (butyrate, EPS and peculiar proteins) may control cancer cell proliferation and improve their response to chemotherapy.

Role of Butyrate, a Gut Microbiota Derived Metabolite, in Cardiovascular Diseases: A comprehensive narrative review.

Cardiovascular diseases (CVD) are major causes of death worldwide. Recently, new roles for intestinal microbiota in pathology and treatment of CVD have been proposed. Butyrate, a bacterial metabolite, is synthesized in the gut and performs most of its functions in there. However, researchers have discovered that butyrate could enter to portal vein and interact with various organs. Butyrate exhibits a broad range of pharmacological activities, including microbiome modulator, anti-inflammatory, anti-obesity, metabolic pathways regulator, anti-angiogenesis, and antioxidant. In this article we review evidence supporting a potentially therapeutic role for butyrate in CVD and the mechanisms and pathways involved in the cardio-protective effects of butyrate from the gut and circulation to the nervous system. In summary, although butyrate exhibits a wide variety of biological activities in different pathways including energy homeostasis, glucose and lipid metabolism, inflammation, oxidative stress, neural signaling, and epigenetic modulation in experimental settings, it remains unclear whether these findings are clinically relevant and whether the molecular pathways are activated by butyrate in humans.

Butyrate and the Intestinal Epithelium: Modulation of Proliferation and Inflammation in Homeostasis and Disease.

The microbial metabolite butyrate serves as a link between the intestinal microbiome and epithelium. The monocarboxylate transporters MCT1 and SMCT1 are the predominant means of butyrate transport from the intestinal lumen to epithelial cytoplasm, where the molecule undergoes rapid β-oxidation to generate cellular fuel. However, not all epithelial cells metabolize butyrate equally. Undifferentiated colonocytes, including neoplastic cells and intestinal stem cells at the epithelial crypt base preferentially utilize glucose over butyrate for cellular fuel. This divergent metabolic conditioning is central to the phenomenon known as “butyrate paradox”, in which butyrate induces contradictory effects on epithelial proliferation in undifferentiated and differentiated colonocytes. There is evidence that accumulation of butyrate in epithelial cells results in histone modification and altered transcriptional activation that halts cell cycle progression. This manifests in the apparent protective effect of butyrate against colonic neoplasia. A corollary to this process is butyrate-induced inhibition of intestinal stem cells. Yet, emerging research has illustrated that the evolution of the crypt, along with butyrate-producing bacteria in the intestine, serve to protect crypt base stem cells from butyrate’s anti-proliferative effects. Butyrate also regulates epithelial inflammation and tolerance to antigens, through production of anti-inflammatory cytokines and induction of tolerogenic dendritic cells. The role of butyrate in the pathogenesis and treatment of intestinal neoplasia, inflammatory bowel disease and malabsorptive states is evolving, and holds promise for the potential translation of butyrate’s cellular function into clinical therapies.

Could the use of butyric acid have a positive effect on microbiota and treatment of type 2 diabetes?

This review focuses on the role of butyrate as one of the key metabolites of gut microbiota. Butyrate along with other short-chain fatty acids, acetate and propionate, is one of the most important regulators of human metabolism. In this review, we discuss how changes in gut microbiota triggered by type 2 diabetes mellitus and its treatment (e.g., metformin) affect butyrate synthesis, how to increase butyrate production and whether there is robust evidence for the positive effects of sodium butyrate in the treatment of diabetes mellitus. Literature review was conducted by all authors. Studies published until 27/03/2020 were included. Search words were: ("butyric acid" OR "butyrate") AND ("type 2 diabetes "OR "T2DM"). The articles selected for the study were not chosen in a systematic manner, so the evidence may not be comprehensive. Butyrate was found to effectively reduce inflammation and plays a prominent role in the function of the intestinal barrier. To date the use of sodium butyrate in the treatment of patients with T2DM is not very popular. Meanwhile, butyric acid can beneficially modulate intestinal functions, counteracting the negative effects of the disease as well as the drugs used to treat diabetes. T2DM is a widespread chronic disease. Understanding role of microbiota in type 2 diabetes and the mechanisms connecting T2DM and alterations in gut microbiota could be the key to improved treatment of T2DM.

Butyrate mediates the amelioration of Staphylococcal Enterotoxin B-induced Acute Respiratory Distress Syndrome by downregulating the expression of Histone Deacetylases

Abstract Despite rigorous global containment and quarantine efforts that have been applied globally to control SARS-CoV-2, the spreading of this contagious disease has accelerated all over the world. In our study, we used staphylococcal enterotoxin B (SEB), which is a superantigen can lead to toxic shock syndrome in C57BL/6 murine model and thus, mimics COVID19. In the current study, we investigated the suppressive effect of sodium butyrate (BUT) on a murine model of SEB-induced Acute Respiratory Distress Syndrome (ARDS). The data shows that supplementation with BUT at a dose of 200 mg/kg orally reduced overall ARDS severity. Plethysmography analysis data indicated that sodium butyrate improves the clinical functions of the lungs. In addition, our flow cytometry data indicated that BUT mediated the suppression of lung mononuclear cells such as CD4+ T cells, CD8+ T cells, VB8+ T cells and NK-T cells while at the same time increasing T regulatory cells. Cytokine storm is one of the most important challenge in COVID19 cases, in our study, we have found that the proinflammatory cytokines such as IL-2, TNFα and IFNγ in broncho-alveolar lavage fluid (BALF) significantly decreased in SEB+BUT compared to SEB+VEH as detected by ELISA. Additionally, histopathological analysis of H &amp; E stained lungs indicated that BUT decreased the level of infiltration of inflammatory cells in the lungs of SEB+BUT compared to SEB+VEH mice. Additionally, we investigated the role of BUT on the expression of histone deacetylases (HDACs). Collectively, our data suggested that BUT ameliorated SEB-induced ARDS by downregulating the expression of class I and Class II HDACs which mediate the increase in T regulatory cells that suppress the inflammatory response in SEB-induced ARDS.

The role of butyrate in surgical and oncological outcomes in colorectal cancer.

Butyrate is a short-chain fatty acid produced by colonic gut bacteria as a result of fermentation of dietary fibers. In the colon, butyrate is a major energy substrate and contributes to the nutritional support and proliferation of a healthy mucosa. It also promotes the intestinal barrier function by enhancing mucus production and tight junctions. In addition to its pro-proliferative effect in healthy colonocytes, butyrate inhibits the proliferation of cancer cells. The antineoplastic effect of butyrate is associated with the inhibitory effect of butyrate on histone deacetylase (HDAC) enzymes, which promote carcinogenesis. Due to the metabolic shift of cancer cells toward glycolysis, unused butyrate accumulates and inhibits procarcinogenic HDACs. In addition, recent studies suggest that butyrate may improve the healing of colonic tissue after surgery in animal models, specifically at the site of reconnection of colonic ends, anastomosis, after surgical resection. Here, we review current evidence on the impact of butyrate on epithelial integrity and colorectal cancer and present current knowledge on data that support its potential applications in surgical practice.

Sodium butyrate protects against lipopolysaccharide-induced liver injury partially via the GPR43/ β-arrestin-2/NF-κB network.

BackgroundButyrate acts as a regulator in multiple inflammatory organ injuries. However, the role of butyrate in acute liver injury has not yet been fully explored. In the present study, we aimed to investigate the association between butyrate and lipopolysaccharide (LPS)-induced acute liver injury and the signaling pathways involved.MethodsLPS-induced acute liver injury was induced by intraperitoneal injection of LPS (5 mg/kg) in G-protein-coupled receptor 43 (GPR43)-knockout (KO) and wild-type female C57BL/6 mice. Sodium butyrate (500mg/kg) was administered intraperitoneally 30 min prior to LPS exposure. Liver injury was detected by serum markers, tissue morphology, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). Pro-inflammatory-factor levels were detected by enzyme-linked immunosorbent assay and real-time polymerase chain reaction (RT-PCR). Cell models were first treated with sodium butyrate (4 μmol/mL), followed by LPS (1 μg/mL) half an hour later in GPR43 small interfering RNA (siRNA)-transfected or control RAW264.7 cells. Cell-inflammation status was evaluated through detecting pro-inflammatory-factor expression by RT-PCR and also through checking toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB)-element levels including TLR4, TRAF6, IKKβ, IкBα, phospho-IкBα, p65, and phospho-p65 by Western blot. The interaction between GPR43 and β-arrestin-2 was tested by co-immunoprecipitation.ResultsSodium butyrate reversed the LPS-induced tissue-morphology changes and high levels of serum alanine aminotransferase, aspartate transaminase, myeloperoxidase, TUNEL, and pro-inflammatory cytokines such as tumor necrosis factor-α and interleukin-6. The ameliorating effect of sodium butyrate was weakened in GPR43-KO mice and GPR43 siRNA RAW264.7 cells, compared with those of GPR43-positive controls. Sodium butyrate downregulated some elements of the TLR4/NF-κB pathway, including phospho-IκBα and phospho-p65, in RAW264.7 cells. Increased interactions between GPR43 and β-arrestin-2, and between β-arrestin-2 and IкBα were observed.ConclusionSodium butyrate significantly attenuated LPS-induced liver injury by reducing the inflammatory response partially via the GPR43/β-arrestin-2/NF-κB signaling pathway.

A double-edged sword: Role of butyrate in the oral cavity and the gut.

Butyrate, a four-carbon short-chain fatty acid (SCFA), is a metabolite of anaerobic bacteria. Butyrate has primarily been described as an energy substance in the studies on the digestive tract. The multiple mechanisms of its protective function in the gut and on underlying diseases (including metabolic diseases, diseases of the nervous system, and osteoporosis) via interaction with intestinal epithelial cells and immune cells have been well documented. There are many butyrogenic bacteria in the oral cavity as well. As essential components of the oral microbiome, periodontal pathogens are also able to generate butyrate when undergoing metabolism. Considerable evidence has indicated that butyrate plays an essential role in the initiation and perpetuation of periodontitis. However, butyrate is considered to participate in the pro-inflammatory activities in periodontal tissue and the reactivation of latent viruses. In this review, we focused on the production and biological impact of butyrate in both intestine and oral cavity and explained the possible pathway of various diseases that were engaged by butyrate. Finally, we suggested two hypotheses, which may give a better understanding of the significantly different functions of butyrate in different organs (i.e., the expanded butyrate paradox).

Sodium Butyrate Ameliorates Gut Microbiota Dysbiosis in Lupus-Like Mice.

Gut microbiota has a strong influence on the onset and development of systemic lupus erythematosus (SLE), and several studies have demonstrated the effectiveness of microbiota-derived butyrate to ameliorate SLE. However, the roles of butyrate on gut microbiota in SLE are not understood. Using MRL/lpr lupus-prone mice, we examined gut microbiota profiles after butyrate treatment by 16S rRNA sequencing. Alterations in intestinal microbiome in mice with lupus-like disease were mainly characterized by a reduction in microbial diversity, with an increased abundance of Bacteroidetes and a decrease of Firmicutes. Treatment of lupus-prone mice with butyrate resulted in increased abundance of Firmicutes (P = 0.003), Clostridia (P = 0.005), Clostridiales (P = 0.005), Lachnospiraceae (P = 0.009), Ruminococcaceae (P = 0.021), Peptostreptococcaceae (P = 0.021), Ruminiclostridium (P = 0.016), Oscillibacter (P = 0.048), Romboutsia (P = 0.025), Lachnoclostridium (P = 0.012), Coprococcus (P = 0.015), Ruminococcus (P = 0.011), Clostridium leptum (P < 0.05), and Dorea_spp. (P = 0.019), and a reduced proportion of Bacteroidetes (P = 0.004), Bacteroidia (P = 0.004), and Bacteroidales (P = 0.004). Further, butyrate supplementation could ameliorate kidney damage. Overall, this study suggests that gut microbiota alterations occur in MRL/lpr lupus-prone mice following treatment with butyrate. Butyrate supplementation ameliorated gut microbiota dysbiosis. These findings support the use of butyrate and butyrate-producing bacteria as potential treatments for SLE.

Gut microbiota orchestrates PTH action in bone: role of butyrate and T cells

Parathyroid hormone (PTH) is an important regulator of bone remodeling. It has the capacity to stimulate both bone formation and bone resorption, 2 apparently opposite actions. Bone loss and increased bone fragility due to predominant bone resorption mainly occur when bone cells are exposed to PTH continuously, as is seen in primary and secondary hyperparathyroidism. In contrast, gain of bone mass and bone strength is observed in response to intermittent PTH release or administration, owing to more bone formation than resorption.

Butyrate improves cardiac function and sympathetic neural remodeling following myocardial infarction in rats.

Increased inflammation is found in cardiac sympathetic neural remodeling with malignant ventricular arrhythmia (VA) following myocardial infarction (MI). Butyrate, as a microbiota-derived short-chain fatty acid, can inhibit inflammation and myocardial hypertrophy. However, the role of butyrate in sympathetic neural remodeling after MI is unknown. This study aimed to investigate whether butyrate could improve cardiac dysfunction and VA following MI by regulating inflammation and sympathetic neural remodeling. MI rats were randomized to administrate the butyrate or vehicle through intraperitoneal injection to undergo the study. Our data demonstrated that butyrate treatment preserved the partial cardiac function at 7 days post-MI. Butyrate downregulated the expression of essential for inflammatory response in the infarct border zone at 3 days post-MI. Particularly, butyrate promoted expression of M2 macrophage markers. Increased expressions of nerve growth factor and norephinephrine at 7 days after MI were inhibited in butyrate-treated rats. Furthermore, butyrate significantly decreased the density of nerve fibers for growth-associated protein-43 and tyrosine hydroxylase and resulted in fewer episodes of inducible VA. In conclusion, butyrate administration ameliorated cardiac function and VA after MI possibly through promoting M2 macrophage polarization to suppress inflammatory responses and inhibit sympathetic neural remodeling and may present an effective pharmacological strategy for the prevention of MI-related remodeling.

The Role of Butyrate on Monocyte Migration and Inflammation Response in Patient with Type 2 Diabetes Mellitus.

Type 2 Diabetes Mellitus (T2DM) is a very serious global problem. In Indonesia, this disease attacks at the most productive age; consequently, it can reduce economic status and life expectancy. The pathogenesis of T2DM is very closely related to inflammation and macrophage accumulation. However, no anti-inflammatory agent has been proven to play a role in the management of T2DM. Butyrate is a short chain fatty acid produced from resistant starch fermentation in the intestinal lumen. It is able to bind to GPR41 and GPR43 receptors on monocytes, so that it can change the pattern of cytokine expression, activation, migration and cell differentiation. Hence, it is interesting to examine the anti-inflammation effect of butyrate and the effect on monocyte migration. A total of 37 subjects were examined in this study. They were divided into two groups, with and without butyrate treatment. We analyzed two pro-inflammatory cytokines (Tumor Necrosis Factor TNF-α and Interleukin IL-6) and one anti-inflammatory cytokine, IL 10. Monocytes were isolated in type 1 collagen gel for migration testing using the µ-slide chemotaxis IBIDI. Image analysis used ImageJ and Chemotaxis tool software. There was a significant difference in the TNFα/IL 10 ratio between healthy groups and T2DM. Butyrate also appears to suppress TNFα cytokine production and increase IL10 production. It also decreases the accumulation distance of monocyte migration in T2DM.

The role of the gut microbiome in chronic liver disease: the clinical evidence revised.

SummaryRecent research has suggested a role for the intestinal microbiota in the pathogenesis and potential treatment of a wide range of liver diseases. The intestinal microbiota and bacterial products may contribute to the development of liver diseases through multiple mechanisms including increased intestinal permeability, chronic systemic inflammation, production of short-chain fatty acids and changes in metabolism. This suggests a potential role for pre-, pro- and synbiotic products in the prevention or treatment of some liver diseases. In addition, there is emerging evidence on the effects of faecal microbial transplant. Herein, we discuss the relationship between the intestinal microbiota and liver diseases, as well as reviewing intestinal microbiota-based treatment options that are currently being investigated.

Identification of the novel role of butyrate as AhR ligand in human intestinal epithelial cells

The ligand activated transcription factor, aryl hydrocarbon receptor (AhR) emerged as a critical regulator of immune and metabolic processes in the gastrointestinal tract. In the gut, a main source of AhR ligands derives from commensal bacteria. However, many of the reported microbiota-derived ligands have been restricted to indolyl metabolites. Here, by screening commensal bacteria supernatants on an AhR reporter system expressed in human intestinal epithelial cell line (IEC), we found that the short chain fatty acid (SCFA) butyrate induced AhR activity and the transcription of AhR-dependent genes in IECs. We showed that AhR ligand antagonists reduced the effects of butyrate on IEC suggesting that butyrate could act as a ligand of AhR, which was supported by the nuclear translocation of AhR induced by butyrate and in silico structural modelling. In conclusion, our findings suggest that (i) butyrate activates AhR pathway and AhR-dependent genes in human intestinal epithelial cell-lines (ii) butyrate is a potential ligand for AhR which is an original mechanism of gene regulation by SCFA.