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.

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.

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.

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.

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.

Possible therapeutic role of short-chain fatty acids from skin commensal bacteria in UVB-induced skin carcinogenesis

Solar ultraviolet B(UVB)radiation is a major skin cancer-causing agent.Initiation,promotion,and progression are the diverse phases of UVB-induced carcinogenesis.Exposure to UVB causes abnormalities in a series of biochemical and molecular pathways:thymine dimer formation,DNA damage,oxidative stress,inflammatory responses,and altered cell signaling,eventually resulting in tumor formation.The increased skin cancer rates urge researchers to develop more efficient drugs,but synthetic chemotherapeutic drugs have more contrary effects and drug resistance issues,which have been reported recently.The current review focuses on the relationship between microbes and cancer.Human skin acts as a barrier against the external environment and serves as a protective shield for its inhabitant microbiota,collectively called skin microbes.The gut microbiome plays a vital role in cancer therapy.Production of short-chain fatty acids(SCFAs)such as butyrate,acetate,and propionate by intestinal microbes has anti-cancer properties against various cancer cell lines.Yet,the knowledge of SCFAs produced by skin microbes remains yet to be elucidated exhaustively.In this review,we strive to summarize the findings of studies performed to date regarding the anti-cancer properties of SCFA against various cancer cell lines and provide insight into future directions in the skin microbiome field.

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.

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.

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.

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.

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.

Effects of common prebiotics on iron status and production of colonic short-chain fatty acids in anemic rats

Prebiotics may enhance iron absorption,and one plausible mechanism involves the production of shortchain fatty acids(SCFA)in the colon by intestinal microflora.The objectives of this study were to determine the effects of common commercially-available prebiotics including fructooligosaccharide(FOS),inulin,FOS-inulin mixture,galactooligosaccharide(GOS),and lactulose on the iron status of anemic rats,and to monitor changes in the production of colonic SCFA.Anemic Sprague-Dawley rats receiving a lowiron diet(12μg Fe/g diet)were supplemented with or without prebiotics(5%m/V in drinking water)for 5 weeks.Hemoglobin concentration in rats supplemented with GOS after 3 weeks(4.3 g/dL)was significantly higher than rats without supplementation(3.7 g/dL),while FOS also significantly increased hemoglobin concentration after 4 weeks(4.1 g/dL vs.3.7 g/dL).All other prebiotics showed no effects.Anemic rats showed lower overall SCFA production in the colon than normal rats,and only FOS signifi cantly increased the production of the three main SCFA(acetic acid,propionic acid and isobutyric acid)identifi ed in anemic rats,with other prebiotics showing no noticeable trends.Our results suggest that GOS and FOS may slightly improve iron status of anemic rats,but the role of SCFA in the colon is not clear.

Short-Chain Fatty Acids-A Healthy Bus between Gut Microbiota and Organs beyond the Gut

The impact of the gut microbiota is not limited to the intestine, but its interaction with the host produces active metabolites, which can be transported by the blood circulation to play important roles in various parts of the body. Among them, short-chain fatty acids (SCFAs), as important active products of gut bacteria, have been shown to exert anti-inflammatory and immunomodulatory effects and can play active roles as signaling molecules in the development of various intestinal and extraintestinal diseases, such as inflammatory bowel disease, colon cancer, multiple sclerosis, hypertension, allergic airway disease, obesity, diabetes, kidney disease, rheumatoid arthritis, etc. In this way, modulation of the intestinal microbiota and metabolism-active substances has gradually become a popular therapeutic method for many diseases of organs beyond the gut. To find new therapeutic targets for major human health problems, this article reviews the research on SCFAs in extraintestinal diseases.

Relationship Between Short-chain Fatty Acids and Parkinson’s Disease:A Review from Pathology to Clinic

Parkinson’s disease(PD)is a complicated neurodegenerative disease,characterized by the accumulation ofα-synuclein(α-syn)in Lewy bodies and neurites,and massive loss of midbrain dopamine neurons.Increasing evidence suggests that gut microbiota and microbial metabolites are involved in the development of PD.Among these,short-chain fatty acids(SCFAs),the most abundant microbial metabolites,have been proven to play a key role in brain-gut communication.In this review,we analyze the role of SCFAs in the pathology of PD from multiple dimensions and summarize the alterations of SCFAs in PD patients as well as their correlation with motor and non-motor symptoms.Future research should focus on further elucidating the role of SCFAs in neuroinflammation,as well as developing novel strategies employing SCFAs and their derivatives to treat PD.

Vitamin A deficiency suppresses CEACAM1 to impair colonic epithelial barrier function via downregulating microbial-derived short-chain fatty acids

Vitamin A (VA) plays an essential role in modulating both the gut microbiota and gut barrier function.Short-chain fatty acids (SCFAs),as metabolites of the gut microbiota,protect the physiological intestinal barrier;however,they are compromised when VA is deficient.Thus,there is an urgent need to understand how and which SCFAs modulate colonic epithelial barrier integrity in VA deficiency (VAD).Herein,compared with normal VA rats (VAN),at the beginning of pregnancy,we confirmed that the colonic desmosome junction was impaired in the VAD group,and the amounts of acetate,propionate,and butyrate declined because of the decreased abundance of SCFA-producing bacteria (Romboutsia ,Collinsella ,and Allobaculum ).The differentially expressed genes correlated with the gut barrier and the histone deacetylase complex between the VAD and VAN groups were enriched by RNA sequencing.In the VAD group,the expression levels of colonic CEA cell adhesion molecule 1 (CEACAM1) were down-regulated,and the levels of histone deacetylase 1 (HDAC1) and HDAC3 were up-regulated.Intriguingly,the above changes in the VAD groups were rescued by VA supplementation in the early postnatal period.Further study indicated that in Caco-2 cells,butyrate treatment significantly repressed the enrichment of HDAC3 on the promoter of the CEACAM1 gene to induce its expression.Our findings support that butyrate intervention can alleviate the impairment of colonic barrier function caused by VAD,and timely postnatal VA intervention may reverse the damage caused by VAD on gut barrier integrity during pregnancy.

Role of short-chain fatty acids in host physiology

Short-chain fatty acids(SCFAs)are major metabolites produced by the gut microbiota through the fermentation of dietary fiber,and they have garnered significant attention due to their close association with host health.As important mediators between the gut microbiota and the host,SCFAs serve as energy substrates for intestinal epithelial cells and maintain homeostasis in host immune and energy metabolism by influencing host epigenetics,activating G protein-coupled receptors,and inhibiting pathogenic microbial infections.This review provides a comprehensive summary of SCFAs synthesis and metabolism and offering an overview of the latest research progress on their roles in protecting gut health,enhancing energy metabolism,mitigating diseases such as cancer,obesity,and diabetes,modulating the gut-brain axis and gut-l ung axis,and promoting bone health.