Milk fat globule membrane supplementation protects againstβ-lactoglobul-ininduced food allergy in mice via upregulation of regulatory T cells and enhancement of intestinal barrier in a microbiota-derived short-chain fatty acids manner

Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects and possible underlying mechanisms of MFGM on cow’s milk allergy(CMA)in aβ-lactoglobulin(BLG)-induced allergic mice model.MFGM was supplemented to allergic mice induced by BLG at a dose of 400 mg/kg body weight.Results demonstrated that MFGM alleviated food allergy symptoms,decreased serum levels of lipopolysaccharide,pro-inflammatory cytokines,immunoglobulin(Ig)E,Ig G1,and Th2 cytokines including interleukin(IL)-4,while increased serum levels of Th1 cytokines including interferon-γand regulatory T cells(Tregs)cytokines including IL-10 and transforming growth factor-β.MFGM modulated gut microbiota and enhanced intestinal barrier of BLG-allergic mice,as evidenced by decreased relative abundance of Desulfobacterota,Rikenellaceae,Lachnospiraceae,and Desulfovibrionaceae,while increased relative abundance of Bacteroidetes,Lactobacillaceae and Muribaculaceae,and enhanced expressions of tight junction proteins including Occludin,Claudin-1 and zonula occludens-1.Furthermore,MFGM increased fecal short-chain fatty acids(SCFAs)levels,which elevated G protein-coupled receptor(GPR)43 and GPR109A expressions.The increased expressions of GPR43 and GPR109A induced CD103+dendritic cells accumulation and promoted Tregs differentiation in mesenteric lymph node to a certain extent.In summary,MFGM alleviated CMA in a BLG-induced allergic mice model through enhancing intestinal barrier and promoting Tregs differentiation,which may be correlated with SCFAs-mediated activation of GPRs.These findings suggest that MFGM may be useful as a promising functional ingredient against CMA.

Effects of forsythin extract in Forsythia leaves on intestinal microbiota and short-chain fatty acids in rats fed a high-fat diet

Forsythia suspensa,belonging to the deciduous shrubs of the Luteaceae family,a traditional Chinese medicine,has effects of alleviating swelling,clearing heat,detoxification and promoting blood circulation.The leaves of F.suspensa contain multiple chemical components and have a long history of use in folk medicines and health foods.The purpose of this study was to explore the effects of forsythin extract from F.suspensa leaves on intestinal microbiota and short-chain fatty acid(SCFA)content in rats with obesity induced by a high-fat diet.Forsythin extract in F.suspensa leaves increased the abundance of the intestinal microbiota,ameliorated intestinal microbiota disorders and inhibited the increase in total SCFA content in the intestinal tract in rats with obesity induced by a high-fat diet.These results suggested that forsythin extract in F.suspensa leaves may slow the development of obesity induced by a high-fat diet;thus,its active components and efficacy are worthy of further study.

Expression and clinical significance of short-chain fatty acids in patients with intrahepatic cholestasis of pregnancy

BACKGROUND Intrahepatic cholestasis of pregnancy(ICP)is a pregnancy-specific liver condition that typically arises in the middle and late stages of pregnancy.Short-chain fatty acids(SCFAs),prominent metabolites of the gut microbiota,have significant connections with various pregnancy complications,and some SCFAs hold potential for treating such complications.However,the metabolic profile of SCFAs in patients with ICP remains unclear.AIM To investigate the metabolic profiles and differences in SCFAs present in the maternal and cord blood of patients with ICP and determine the clinical significance of these findings.METHODS Maternal serum and cord blood samples were collected from both patients with ICP(ICP group)and normal pregnant women(NP group).Targeted metabolomics was used to assess the SCFA levels in these samples.RESULTS Significant differences in maternal SCFAs were observed between the ICP and NP groups.Most SCFAs exhibited a consistent declining trend in cord blood samples from the ICP group,mirroring the pattern seen in maternal serum.Correlation analysis revealed a positive correlation between maternal serum SCFAs and cord blood SCFAs[r(Pearson)=0.88,P=7.93e-95].In both maternal serum and cord blood,acetic and caproic acids were identified as key metabolites contributing to the differences in SCFAs between the two groups(variable importance for the projection>1).Receiver operating characteristic analysis demonstrated that multiple SCFAs in maternal blood have excellent diagnostic capabilities for ICP,with caproic acid exhibiting the highest diagnostic efficacy(area under the curve=0.97).CONCLUSION Compared with the NP group,significant alterations were observed in the SCFAs of maternal serum and cord blood in the ICP group,although they displayed distinct patterns of change.Furthermore,the SCFA levels in maternal serum and cord blood were significantly positively correlated.Notably,certain maternal serum SCFAs,specifically caproic and acetic acids,demonstrated excellent diagnostic efficiency for ICP.

The role of gut microbiota and its metabolites short-chain fatty acids in food allergy

Emerging evidence indicated that the increase in food allergy(FA)over the past few decades was associated with the abnormal compositional and metabolic changes of gut microbiota.Gut microbiota played a vital role in maintaining the homeostasis of the immune system and the dysbiosis of gut microbiota promoted the occurrence of FA.Recent research suggested that short-chain fatty acids(SCFAs),the main metabolites derived from gut microbiota,contributed to FA protection.Herein,we provided a comprehensive review on the relationship between gut microbiota and FA.The multifaceted mechanisms underlymg beneficial effects of gut microbiota composition/metabolites on the regulation of diverse cellular pathways in intestinal epithelial cells,dendritic cells,innate lymphoid cells,T cells,B cells and mast cells in the immune system were discussed systematically.These findings emphasized the positive function of gut microbiota in FA and provided novel ideas for the treatment or prevention of FA in the future.

Saikosaponin D improves nonalcoholic fatty liver disease via gut microbiota-bile acid metabolism pathway

Non-alcoholic fatty liver disease(NAFLD)is the main cause of chronic liver disease worldwide.Bupleurum is widely used in the treatment of non-alcoholic fatty liver,and saikosaponin D(SSD)is one of the main active components of Bupleurum.The purpose of this study was to investigate the efficacy of SSD in the treatment of NAFLD and to explore the mechanism of SSD in the improvement of NAFLD based on“gut-liver axis”.Our results showed that SSD dose-dependently alleviated high fat diet-induced weight gain in mice,improved insulin sensitivity,and also reduced liver lipid accumulation and injury-related biomarkers aspartate aminotransferase(AST)and alanine aminotransferase(ALT).Further exploration found that SSD inhibited the mRNA expression levels of farnesoid X receptor(Fxr),small heterodimer partner(Shp),recombinant fibroblast growth factor 15(Fgf15)and apical sodium dependent bile acid transporter(Asbt)in the intestine,suggesting that SSD improved liver lipid metabolism by inhibiting intestinal FXR signaling.SSD can significantly reduce the gut microbiota associated with bile salt hydrolase(BSH)expression,such as Clostridium.Decreased BSH expression reduced the ratio of unconjugated to conjugated bile acids,thereby inhibiting the intestinal FXR.These data demonstrated that SSD ameliorated NAFLD potentially through the gut microbiota-bile acidintestinal FXR pathway and suggested that SSD is a promising therapeutic agent for the treatment of NAFLD.

Unlocking a novel determinant of athletic performance:The role of the gut microbiota,short-chain fatty acids,and“biotics”in exercise

The gut microbiota refers to the collection of trillions of intestinal microorganisms that modulate central aspects of health and disease through influential effects on host physiology.Recently,a connection has been made between the gut microbiota and exercise.Initial investigations demonstrated the beneficial effects of exercise on the gut microbiota,with cross-sectional studies revealing positive correlations between exerciseassociated states,and healthy gut microbiota and exercise interventions showed post-intervention increases in the abundance of beneficial bacterial taxa.More recent investigations have focused on exploring the reverse relationship:the influence of the gut microbiota on exercise performance.Murine investigations have revealed that certain bacterial taxa may enhance endurance exercise performance by augmenting various aspects of lactate metabolism.Further,short-chain fatty acids—which modulate metabolism at various organ sites,including within skeletal muscle—have been shown to enhance endurance exercise capacity in mice.This review highlights what is currently known about the connection between the gut microbiota and exercise,with a particular focus on the ergogenic potential of the gut microbiota and how it may be leveraged to enhance endurance exercise performance.

Supplementation with yak (Bos grunniens) bone collagen hydrolysate altered the structure of gut microbiota and elevated short-chain fatty acid production in mice

In this study, yak bone collagen hydrolysate(YBCH)was produced by mixed proteases and provided to standard-diet mice at a different dose(low dose(LD), medium dose(MD), and high dose(HD))to investigate its effects on the composition of gut microbiota and short-chain fatty acids(SCFA)production. It was found that YBCH was mainly composed of small molecular peptides whose molecular weight below 2 000 Da. Notably, supplementation with different doses of YBCH could significantly downregulate the ratio of Firmicutes to Bacteroidetes in the fecal microbiota. At the family level, the Lachnospiraceae abundance was significantly reduced in the YBCH gavage groups(mean reduction ratio 41.7 %, 35.2%, and 36.4% for LD, MD, and HD group, respectively). The predicted functions of gut microbes in the MD group were significantly increased at “lipid metabolism” and “glycan biosynthesis and metabolism”. Moreover, the SCFA production in the YBCH groups was elevated. Especially, the concentration of acetic acid, propionic acid, and butyric acid in the MD group was separately increased 79.7%, 89.2%, and 78.8% than that in the NC group. These results indicated that YBCH might be applied in the development of functional food for intestinal microecological regulation.

Supplementing the early diet of broilers with soy protein concentrate can improve intestinal development and enhance short-chain fatty acid-producing microbes and short-chain fatty acids,especially butyric acid

Background:Research on nutrition in early-life commonly focuses on the maturation of the intestine because the intestinal system is crucial for ensuring continued growth.To explore the importance of early nutrition regulation in animals,soy protein concentrate(SPC)was added to the early diet of broilers to investigate its effects on amino acid digestibility,intestinal development,especially intestinal microorganisms,and broiler metabolites.A total of 192 oneday-old Arbor Acres(AA)male broilers were randomly assigned to two experimental treatments with 8 replicates of 12 birds.The control group was fed a basal diet(control),and the treatment group was fed a basal diet supplemented with 12%SPC(SPC12)during the first 10 d(starter phase).From d 11 to 21(grower phase)and d 22 to 42(finisher phase),a basal diet was fed to both treatment groups.Results:SPC reduced the pH value and acid-binding capacity of the starter diet(P<0.05,d 10);SPC in the early diet enhanced the gizzard weight(P<0.05,d 10 and d 42)and the ileum weight(P<0.05,d 10)and decreased the weight and length of the jejunum(P<0.05,d 10)and the relative length of the duodenum and jejunum(P<0.05,d 10).At the same time,SPC enhanced villus height(P<0.05,d 10)and muscle thickness in the jejunum and ileum(P<0.05,d 10)and increased the number of goblet cells in the duodenum(P<0.05,d 10).Meanwhile,SPC increased the Chao1 index and the ACE index(P<0.05,d 10)and altered the composition of caecal microflora at d 10.SPC also increased the relative abundance of Alistipes,Anaerotruncus,Erysipelatoclostridium,Intestinimonas and Flavonifractor bacteria(P<0.05,d 10).At the same time,the concentrations of caecal butyric acid and total short-chain fatty acids(SCFAs)were also increased in the SPC12 group(P<0.05,d 10).Conclusions:In summary,the results showed that supplementing the starter diet of broilers with SPC has a significant effect on the early development of the intestine and the microflora.

Cinnamic acid regulates the intestinal microbiome and short-chain fatty acids to treat slow transit constipation

BACKGROUND Slow transit constipation(STC)is a disorder with delayed colonic transit.Cinnamic acid(CA)is an organic acid in natural plants,such as Radix Scrophulariae(Xuan Shen),with low toxicity and biological activities to modulate the intestinal microbiome.AIM To explore the potential effects of CA on the intestinal microbiome and the primary endogenous metabolites-short-chain fatty acids(SCFAs)and evaluate the therapeutic effects of CA in STC.METHODS Loperamide was applied to induce STC in mice.The treatment effects of CA on STC mice were assessed from the 24 h defecations,fecal moisture and intestinal transit rate.The enteric neurotransmitters:5-hydroxytryptamine(5-HT)and vasoactive intestinal peptide(VIP)were determined by the enzyme-linked immunosorbent assay.Hematoxylin-eosin and Alcian blue and Periodic acid Schiff staining were used to evaluate intestinal mucosa's histopathological performance and secretory function.16S rDNA was employed to analyze the composition and abundance of the intestinal microbiome.The SCFAs in stool samples were quantitatively detected by gas chromatography-mass spectrometry.RESULTS CA ameliorated the symptoms of STC and treated STC effectively.CA ameliorated the infiltration of neutrophils and lymphocytes,increased the number of goblet cells and acidic mucus secretion of the mucosa.In addition,CA significantly increased the concentration of 5-HT and reduced VIP.CA significantly improved the diversity and abundance of the beneficial microbiome.Furthermore,the production of SCFAs[including acetic acid(AA),butyric acid(BA),propionic acid(PA)and valeric acid(VA)]was significantly promoted by CA.The changed abundance of Firmicutes,Akkermansia,Lachnoclostridium,Monoglobus,UCG.005,Paenalcaligenes,Psychrobacter and Acinetobacter were involved in the production of AA,BA,PA and VA.CONCLUSION CA could treat STC effectively by ameliorating the composition and abundance of the intestinal microbiome to regulate the production of SCFAs.

Gut microbiota as a target in the bone health of livestock and poultry: roles of short-chain fatty acids

The regulation and maintenance of bone metabolic homeostasis are crucial for animal skeletal health.It has been established that structural alterations in the gut microbiota and ecological dysbiosis are closely associated with bone metabolic homeostasis.The gut microbiota and its metabolites,especially short-chain fatty acids(SCFAs),affect almost all organs,including the bone.n this process,SCFAs positively affect bone healing by acting directly on cells involved in bone repair after or by shaping appropriate anti-inflammatory and immunomodulatory responses:Addi-tionally,SCFAs have the potential to maintain bone health in livestock and poultry because of their various biological functions in regulating bone metabolism,including immune function,calcium absorption,osteogenesis and oste-olysis.This review primarily focuses on the role of sCFAs in the regulation of bone metabolism by gut microbiota and provides insight into studies related to bone health in livestock and poultry.

Anti-inflammatory properties of the short-chain fatty acids acetate and propionate:A study with relevance to inflammatory bowel disease

AIM： To compare the anti-inflammatory properties of butyrate with two other SCFAs, namely acetate and propionate, which have less well-documented effects on inflammation. METHODS： The effect of SCFAs on cytokine release from human neutrophils was studied with EHSA. SCFA- dependent modulation of NF-κB reporter activity was assessed in the human colon adenocarcinoma cell line, Colo320DM. Finally, the effect of SCFAs on gene expression and cytokine release, measured with RT-PCR and ELISA, respectively, was studied in mouse colon organ cultures established from colitic mice. RESULTS： Acetate, propionate and butyrate at 30 mmol/L decreased LPS-stimulated TNFα release from neutrophils, without affecting IL-8 protein release. All SCFAs dose dependently inhibited NF-κB reporter activity in Colo320DM cells. Propionate dose-dependently suppressed IL-6 mRNA and protein release from colon organ cultures and comparative studies revealed that propionate and butyrate at 30 mmol/L caused a strong inhibition of immune-related gene expression, whereas acetate was less effective. A similar inhibition was achieved with the proteasome inhibitor MG-132, but not the p38 MAPK inhibitor SB203580. All SCFAs decreased IL-6 protein release from organ cultures. CONCLUSION： In the present study propionate and butyrate were equipotent, whereas acetate was less effective, at suppressing NF-κB reporter activity, immune-related gene expression and cytokine release in vitro. Our findings suggest that propionate and acetate, in addition to butyrate, could be useful in the treatment of inflammatory disorders, including IBD.

Bile acid receptors and nonalcoholic fatty liver disease

With the high prevalence of obesity, diabetes, and otherfeatures of the metabolic syndrome in United States, nonalcoholic fatty liver disease(NAFLD) has inevitably become a very prevalent chronic liver disease and is now emerging as one of the leading indications for liver transplantation. Insulin resistance and derangement of lipid metabolism, accompanied by activation of the pro-inflammatory response and fibrogenesis, are essential pathways in the development of the more clinically significant form of NAFLD, known as nonalcoholic steatohepatitis(NASH). Recent advances in the functional characterization of bile acid receptors, such as farnesoid X receptor(FXR) and transmembrane G protein-coupled receptor(TGR) 5, have provided further insight in the pathophysiology of NASH and have led to the development of potential therapeutic targets for NAFLD and NASH. Beyond maintaining bile acid metabolism, FXR and TGR5 also regulate lipid metabolism, maintain glucose homeostasis, increase energy expenditure, and ameliorate hepatic inflammation. These intriguing features have been exploited to develop bile acid analogues to target pathways in NAFLD and NASH pathogenesis. This review provides a brief overview of the pathogenesis of NAFLD and NASH, and then delves into the biological functions of bile acid receptors, particularly with respect to NASH pathogenesis, with a description of the associated experimental data, and, finally, we discuss the prospects of bile acid analogues in the treatment of NAFLD and NASH.

Effects of Saccharomycesboulardiion fecal short-chain fatty acids and microflora in patients on long-term total enteral nutrition

AIM： To assess the effects of Sb on fecal flora and shortchain fatty acids （SCFA） in patients on long-term TEN. METHODS： Ten patients （3 females, 7 males, 59±5.5 years）, on TEN for a median of 13 mo （1-125）, and 15 healthy volunteers （4 females, 11 males, 32±2.0 years） received Sb （0.5 g bid PO） for 6 d. Two stool samples were taken before, on the last 2 d and 9-10 d after treatment, for SCFA measurement and for culture and bacterial identification. Values （mean4-SE） were compared using sign tests and ANOVA. RESULTS： Fecal butyrate levels were lower in patients （10.1±2.9 mmol/kg） than in controls （19.2±3.9, P= 0.02）. Treatment with Sb increased total fecal SCFA levels in patients （150.2＋27.2 vs 107.5±18.2 mmol/kg, P= 0.02） but not in controls （129.0±28.6 vs 113.0±15.2 mmol/kg, NS）. At the end of treatment with Sb, patients had higher fecal butyrate（16.0±4.4 vs 10.1 [2.9] mmol/kg, P= 0.004）. Total SCFAs remained high 9 d after treatment was discontinued. Before the treatment, the anaerobe to aerobe ratio was lower in patients compared to controls （2.4±2.3 vs 69.8±1.8, P= 0.003）. There were no significant changes in the fecal flora of TEN patients. CONCLUSION： Sb-induced increase of fecal SCFA concentrations （especially butyrate） may explain the preventive effects of this yeast on TEN-induced diarrhea.

Short-chain fatty acids act as antiinflammatory mediators by regulating prostaglandin E_2 and cytokines

AIM： To investigate the effect of short-chain fatty acids （SCFAs） on production of prostaglandin E2 （PGE2）, cytokines and chemokines in human monocytes. METHODS： Human neutrophils and monocytes were isolated from human whole blood by using 1-Step Polymorph and RosetteSep Human Monocyte Enrichment Cocktail, respectively. Human GPR41 and GPR43 mRNA expression was examined by quantitative realtime polymerase chain reaction, The calcium flux assay was used to examine the biological activities of SCFAs in human neutrophils and monocytes. The effect of SCFAs on human monocytes and peripheral blood mononuclear cells （PBMC） was studied by measuring PGE2, cytokines and chemokines in the supernatant. The effect of SCFAs in vivo was examined by intraplantar injection into rat paws. RESULTS： Human GPR43 is highly expressed in human neutrophils and monocytes. SCFAs induce robust calcium flux in human neutrophils, but not in human monocytes. In this study, we show that SCFAs can induce human monocyte release of PGE2 and that this effect can be enhanced in the presence of lipopolysaccharide （LPS）. In addition, we demonstrate that PGE2 production induced by SCFA was inhibited by pertussis toxin, suggesting the involvement of a receptor-mediated mechanism. Furthermore, SCFAs can specifically inhibit constitutive monocyte chemotactic protein-1 （MCP-1） production and LPS-induced interleukin-10 （IL-10） production in human monocytes without affecting the secretion of other cytokines and chemokines examined. Similar activities were observed in human PBMC for the release of PGE2, MCP-1 and IL-10 after 5CFA treatment. In addition, SCFAs inhibit LPS-induced production of tumor necrosis factor-α and interferon-7 in human PBIVlC. Finally, we show that SCFAs and LPS can induce PGE2 production in vivo by intraplantar injection into rat paws （P 〈 0.01）. CONCLUSION： SCFAs can have distinct antiinflammatory activities due to their regulation of PGE2, cytokine and chemokine release from human immune cells.

Dietary saturated fatty acid and polyunsaturated fatty acid oppositely affect hepatic NOD-like receptor protein 3 inflammasome through regulating nuclear factor-kappa B activation

AIM: To investigate the effect of different dietary fatty acids on hepatic inflammasome activation.METHODS: Wild-type C57BL/6 mice were fed either a high-fat diet or polyunsaturated fatty acid (PUFA)-enriched diet. Primary hepatocytes were treated with either saturated fatty acids (SFAs) or PUFAs as well as combined with lipopolysaccharide (LPS). The expression of NOD-like receptor protein 3 (NLRP3) inflammasome, peroxisome proliferator-activated receptor-&#x003b3; and nuclear factor-kappa B (NF-&#x003ba;B) was determined by real-time PCR and Western blot. The activity of Caspase-1 and interleukine-1&#x003b2; production were measured.RESULTS: High-fat diet-induced hepatic steatosis was sufficient to induce and activate hepatic NLRP3 inflammasome. SFA palmitic acid (PA) directly activated NLRP3 inflammasome and increased sensitization to LPS-induced inflammasome activation in hepatocytes. In contrast, PUFA docosahexaenoic acid (DHA) had the potential to inhibit NLRP3 inflammasome expression in hepatocytes and partly abolished LPS-induced NLRP3 inflammasome activation. Furthermore, a high-fat diet increased but PUFA-enriched diet decreased sensitization to LPS-induced hepatic NLRP3 inflammasome activation in vivo. Moreover, PA increased but DHA decreased phosphorylated NF-&#x003ba;B p65 protein expression in hepatocytes.CONCLUSION: Hepatic NLRP3 inflammasome activation played an important role in the development of non-alcoholic fatty liver disease. Dietary SFAs and PUFAs oppositely regulated the activity of NLRP3 inflammasome through direct activation or inhibition of NF-&#x003ba;B.

Kinetic analysis of waste activated sludge hydrolysis and short-chain fatty acids production at pH 10

The accumulation of short-chain fatty acids （SCFAs）, a preferred carbon source for enhanced biological phosphorus removal microbes, was significantly improved when waste activated sludge （WAS） was fermented at pH 10. The kinetics of WAS hydrolysis and SCFAs production at pH 10 was investigated. It was observed that during WAS anaerobic fermentation the accumulation of SCFAs was limited by the hydrolysis process, and both the hydrolysis of WAS particulate COD and the accumulation of SCFAs followed first-order kinetics. The hydrolysis and SCFAs accumulation rate constants increased with increasing temperature from 10 to 35℃, which could be described by the Arrhenius equation. The kinetic data further indicated that SCFAs production at pH 10 was a biological process. Compared with the experiment of pH uncontrolled （blank test）, both the rate constants of WAS hydrolysis and SCFAs accumulation at 20℃ were improved significantly when WAS was fermented at pH 10.

Effects of ω-3 fatty acids on toll-like receptor 4 and nuclear factor-κB p56 in lungs of rats with severe acute pancreatitis

AIM To determine the effects of ω-3 fatty acids(ω-3FA) on the toll-like receptor 4(TLR4)/nuclear factor κB p56(NF-κBp56) signal pathway in the lungs of rats with severe acute pancreatitis(SAP).METHODS A total of 56 Sprague-Dawley rats were randomly divided into 4 groups: control group, SAP-saline group, SAP-soybean oil group and SAP-ω-3FA group. SAP was induced by the retrograde infusion of sodium taurocholate into the pancreatic duct. The expression of TLR4 and NF-κBp56 in the lungs was evaluated by immunohistochemistry and Western blot analysis. The levels of inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha in the lungs were measured by enzyme-linked immunosorbent assay. RESULTS The expression of TLR4 and NF-κBp56 in lungs and of inflammatory cytokines in serum significantly increased in the SAP group compared with the control group(P < 0.05), but was significantly decreased in the ω-3FA group compared with the soybean oil group at 12 and 24 h(P < 0.05).CONCLUSION During the initial stage of SAP, ω-3FA can efficiently lower the inflammatory response and reduce lung injury by triggering the TLR4/NF-κBp56 signal pathway.

Short-chain fatty acids can improve lipid and glucose metabolism independently of the pig gut microbiota

Background:Previous studies have shown that exogenous short-chain fatty acids(SCFAs)introduction attenuated the body fat deposition in conventional mice and pigs.However,limited studies have evaluated the effects of exogenously introduced SCFAs on the lipid and glucose metabolism independently of the gut microbiota.This study was to investigate the effects of exogenous introduction of SCFAs on the lipid and glucose metabolism in a germ-free(GF)pig model.Methods:Twelve hysterectomy-derived newborn pigs were reared in six sterile isolators.All pigs were hand-fed with sterile milk powder for 21 d,then the sterile feed was introduced to pigs for another 21 d.In the second 21-d period,six pigs were orally administrated with 25 mL/kg sterile saline per day and considered as the GF group,while the other six pigs were orally administrated with 25 mL/kg SCFAs mixture(acetic,propionic,and butyric acids,45,15,and 11 mmol/L,respectively)per day and regarded as FA group.Results:Orally administrated with SCFAs tended to increase the adiponectin concentration in serum,enhance the CPT-1 activity in longissimus dorsi,and upregulate the ANGPTL4 mRNA expression level in colon(P<0.10).Meanwhile,the mRNA abundances of ACC,FAS,and SREBP-1C in liver and CD36 in longissimus dorsi of the FA group were decreased(P<0.05)compared with those in the GF group.Besides,the mRNA expression of PGC-1αin liver and LPL in longissimus dorsi tended to(P<0.10)upregulate and downregulate respectively in the FA group.Moreover,oral administration of SCFAs tended to increase the protein level of GPR43(P<0.10)and decrease the protein level of ACC(P<0.10)in liver.Also,oral administration of SCFAs upregulated the p-AMPK/AMPK ratio and the mRNA expressions of GLUT-2 and GYS2 in liver(P<0.05).In addition,the metabolic pathway associated with the biosynthesis of unsaturated fatty acids was most significantly promoted(P<0.05)by oral administration of SCFAs.Conclusions:Exogenous introduction of SCFAs might attenuate the fat deposition and to some extent improve the glucose control in the pig model,which occurred independently of the gut microbiota.

Gut-brain axis:Focus on gut metabolites short-chain fatty acids

Emerging evidence supports that the gut microbiome,reconsidered as a new organ in the human body,can not only affect the local gut,but also communicate with the brain via multiple pathways related to neuroendocrine,immune,and neural pathways,thereby proposing the new concept of the microbiome-gut-brain(MGB)axis.Recently,the role of short-chain fatty acids(SCFAs),which are the main anaerobic fermented metabolites of the gut microbiota in the MGB axis,has garnered significant attention.SCFAs are involved in a broad range of central neurological diseases,including neurodegenerative diseases,cerebral vascular diseases,epilepsy,neuroimmune inflammatory diseases,and mood disorders.However,the underlying mechanism of SCFA-related distant organ crosstalk is yet to be elucidated.Herein,we summarize current knowledge regarding interactions between SCFAs and the MGB axis,as well as their protective effects against central neurological diseases.

Targeting fatty acid synthase sensitizes human nasopharyngeal carcinoma cells to radiationvia downregulating frizzled class receptor 10

Objective:Our aim was to test the hypothesis that fatty acid synthase(FASN)expression contributes to radioresistance of nasopharyngeal carcinoma(NPC)cells and that inhibiting FASN enhances radiosensitivity.Methods:Targeting FASN using epigallocatechin gallate(EGCG)or RNA interference in NPC cell lines that overexpress endogenous FASN was performed to determine their effects on cellular response to radiationin vitro using MTT and colony formation assays,andin vivo using xenograft animal models.Western blot,immunohistochemistry,real-time PCR arrays,and real-time RT-PCR were used to determine the relationship between FASN and frizzled class receptor 10(FZD10)expression.FZD10 knockdown and overexpression were used to determine its role in mediating FASN function in cellular response to radiation.Immunohistochemical staining was used to determine FASN and FZD10 expressions in human NPC tissues,followed by analysis of their association with the overall survival of patients.Results:FASN knockdown or inhibition significantly enhanced radiosensitivity of NPC cells,bothin vitro andin vivo.There was a positive association between FASN and FZD10 expression in NPC cell lines grown as monolayers or xenografts,as well as human tissues.FASN knockdown reduced FZD10 expression,and rescue of FZD10 expression abolished FASN knockdown-induced enhancement of radiosensitivity.FASN and FZD10 were both negatively associated with overall survival of NPC patients.Conclusions:FASN contributes to radioresistance,possiblyvia FZD10 in NPC cells.Both FZD10 and FASN expressions were associated with poor outcomes of NPC patients.EGCG may sensitize radioresistance by inhibiting FASN and may possibly be developed as a radiosensitizer for better treatment of NPCs.