2’-Fucosyllactose alleviate immune checkpoint blockade-associated colitis by reshaping gut microbiota and activating AHR pathway

Immune checkpoint blockade(ICB)therapeutics are highly effective in cancer immunotherapy,but gastrointestinal toxicity limited the application.Intestinal microbiota plays a crucial role in ICB-associated colitis.2’-Fucosyllactose(2’FL)is most abundance prebiotic in human milk that can reshape gut microbiota and exert immune regulatory effect.The study aimed to determine the effects of 2’FL on ICB-associated colitis and to uncover the mediating mechanism.ICB-associated colitis was induced by the ipilimumab and dextran sulfate sodium.Oral administration of 2’FL(0.6 g/(kg∙day))ameliorated ICB-induced colitis by enhancing regulatory T cells(Treg)and the M2/M1 ratio of macrophages in colon.2’FL treatment also increased the expression of tight junction proteins(zonula occludens-1(ZO-1)and mucin 2(MUC2))and antioxidant stress indicators(superoxide dismutase(SOD)and catalase(CAT)).In addition,administration of 2’FL increased the abundance of Bifidobacterium and Lactobacillus,and elevated the levels of microbial metabolites,such as indole-3-lactic acid(ILA),which activated the aryl hydrocarbon receptor ligands(AHR)pathway.The protective effect of 2’FL was abolished upon depletion of gut microbiota,and ILA treatment partially simulated the protective effect of 2’FL.Notably,2’FL did not exhibit inhibition of antitumor immunity.These findings suggest that 2’FL could serve as a potential protective strategy for ICB-associated colitis by modulating the intestinal microbiota and bacterial metabolites.

Differences in the effects and action modes of gut commensals against dextran sulfate sodium-induced intestinal inflammation

Inflammatory bowel disease(IBD)is a complex relapsing inflammatory disease in the gut and is driven by complicated host-gut microbiome interactions.Gut commensals have shown different functions in IBD prevention and treatment.To gain a mechanistic understanding of how different commensals affect intestinal inflammation,we compared the protective effects of 6 probiotics(belonging to the genera Akkermansia,Bifidobacterium,Clostridium,and Enterococcus)on dextran sulfate sodium(DSS)-induced colitis in mice with or without gut microbiota.Anti-inflammatory properties(ratio of interleukin(IL)-10 and IL-12)of these strains were also evaluated in an in vitro mesenteric lymph nodes(MLN)co-culture system.Results showed that 4 probiotics(belonging to the species Bifidobacterium breve,Bifidobacterium bifidum,and Enterococcus faecalis)can alleviate colitis in normal mice.The probiotic strains differed in regulating the intestinal microbiota,cytokines(IL-10,IL-1βand interferon(IFN)-γ),and tight junction function(Zonulin-1 and Occludin).By constrast,Akkermansia muciniphila AH39 and Clostridium butyricum FHuNHHMY49T1 were not protective.Interestingly,B.breve JSNJJNM2 with high anti-inflammatory potential in the MLN model could relieve colitis symptoms in antibiotic cocktail(Abx)-treated mice.Meanwhile,E.faecalis FJSWX25M1induced low levels of cytokines in vitro and showed no beneficial effects.Therefore,we provided insight into the clinical application of probiotics in IBD treatment.

Akkermansia muciniphila-directed polyphenol chlorogenic acid intervention for obesity in mice

Akkermansia muciniphila play an important in ameliorating obesity but is not allowed for direct consumption in most countries.To date,microbiota-directed foods selectively promote the targeted human gut microbes,providing a strategy for A.muciniphila enhancement.Multiple studies have indicated the potential regulation of the polyphenol on A.muciniphila.Therefore,a polyphenol screening based on A.muciniphila upregulation was performed in mice.Chlorogenic acid(CGA)exhibited a greater response to A.muciniphila upregulation.Furthermore,we found that CGA did not directly promote A.muciniphila growth or mucin secretion.Microbiome and metabolomics revealed that the increased abundance of A.muciniphila resulted from the inhibition of CGA on Desulfovibrio and Alistipes and the influence of docosahexaenoic acid,β-hydroxybutyrate,and N-acetyl-lactosamine.Finally,to confirm the regulation of CGA on A.muciniphila under disease conditions,high-fat diet-fed mice were established.The results showed CGA promoted A.muciniphila growth,and we expectedly found that CGA suppressed the augment in body weight of mice,significantly attenuated adipose tissue abnormality,provided liver protection and improved gut barrier integrity.These results suggest that CGA inhibits the development of obesity.Overall,our results indicate that microbiota-directed food is a promising approach for the treatment of obesity.

Probiotics supplementation for management of type Ⅱ diabetes risk factors in adults with polycystic ovarian syndrome: a meta-analysis of randomized clinical trial

This meta-analysis of randomized controlled trials aimed to evaluate the effects of probiotic supplementation on glucose homeostasis in patients with polycystic ovary syndrome(PCOS).The meta-analysis was performed in accordance with the Cochrane Handbook guidelines and relevant the preferred reporting items for systematic reviews and meta-analyses(PRISMA)statement criteria.Of 825 identified reports,11 randomized clinical trials were included in the meta-analysis.An analysis of pooled extracted data revealed that supplementation with probiotics significantly decreased fasting blood glucose(FBG,n=7;standardized mean difference(SMD)=−0.40;95%confidence interval(CI):−2.02,−0.02;P=0.04)and insulin levels(n=6;SMD=−0.57;95%CI:−0.89,−0.25;P=0.0004)and the homeostatic model assessment of insulin resistance(n=7;SMD=−0.64;95%CI:−0.96,−0.31;P=0.0001)while increasing the quantitative insulin sensitivity check index(QUICKI,n=5;SMD=0.58;95%CI:0.08,1.09;P=0.02)in patients with PCOS.The FBG-reducing effect decreased as the baseline body mass index(BMI)and mean age of the participants increased.Indeed,a greater number of bacterial species and a higher bacterial dose were shown to reduce QUICKI effectively.The systematic review indicated that probiotic supplementation may help to control glucose homeostasis in adults with polycystic ovarian syndrome.

Stachyose modulates gut microbiota and alleviates DSS-induced ulcerative colitis in mice

Stachyose is a prebiotic that traditionally extracted from plants,such as vegetable.It has been demonstrated to alleviate intestinal inflammation by regulating gut microbiota,but the mechanism has been unclear.This research aims to detect the potential mechanism of stachyose in alleviating the severity of ulcerative colitis(UC).The results indicated that the administration of stachyose could recover the body weight,protect against the colonic tissue damage,reduce the pro-inflammatory cytokines levels,and reverse the histological abnormalities in UC mice.Oral stachyose could restore dextran sulfate sodium(DSS)-induced disturbance in intestinal bacteria.Besides,the metabolome result of serum samples showed that stachyose treatment significantly altered serum metabolites against inflammatory responses in colitis mice.Also,a significant correlation can be found between 23 metabolite biomarkers and 18 differential genera.Our results provided a strong foundation for the future study of the protective role of stachyose in maintaining intestinal homeostasis.

一种基于Caco-2细胞单层膜的筛选抵抗特定代谢性疾病益生菌的模型

最近的研究揭示了益生菌在缓解与肠道屏障功能障碍相关的代谢疾病方面的潜力。然而,目前还没有一种能高效筛选抵抗特定代谢疾病益生菌菌株的模型。本研究采用肿瘤坏死因子(TNF-α)和酒精处理的Caco-2细胞单层膜模型,评价了139株乳杆菌在体外对肠道屏障功能的影响。然后,我们选择了11株对肠道屏障具有不同调节能力的乳杆菌菌株,进一步在体内评价了它们对卵巢切除引起的骨质疏松症或慢性酒精性肝损伤的作用效果。体外细胞模型和体内动物模型数据的关联性分析显示,两种疾病模型下的Pearson系数分别为0.82和-0.97,表明使用体外细胞模型模拟益生菌在体内的保护作用是可靠的。本研究建立了一种基于Caco-2细胞单层膜模型的体外方法,用于高效筛选可以抵抗特定代谢疾病(如骨质疏松症和慢性酒精性肝病)的益生菌。

Bifidobacterium longum CCFM1077 Attenuates Hyperlipidemia by Modulating the Gut Microbiota Composition and Fecal Metabolites:A Randomized,Double-Blind,Placebo-Controlled Clinical Trial

An increasing number of studies have indicated that gut microbiota and its metabolites are crucial in the development of hyperlipidemia.Bifidobacterium longum(B.longum)CCFM1077 has been shown to have lipid-lowering effects in animals.This study aimed to evaluate the potential of B.longum CCFM1077 in lowering the lipid levels in patients with hyperlipidemia and investigate the effect of this bacterium on serum lipid abnormalities,gut microbiota,and fecal metabolites in these patients.This study was a six-week,randomized,double-blind,and placebo-controlled pilot clinical trial.Subjects with hyperlipidemia(N=62)were randomly assigned to receive placebo(N=31)or B.longum CCFM1077(1×1010colony-forming units(CFUs)per day;N=31).Serum lipid levels including total cholesterol(TC),lowdensity lipoprotein cholesterol(LDL-C),total triglyceride(TG),and high-density lipoprotein cholesterol(HDL-C)were examined at the baseline and interventio nal endpoints.Changes in the gut microbiota composition and diversity were measured based on 16S ribosomal RNA(rRNA)sequencing of the V3-V4region at the end of the intervention period.Non-targeted metabolomics of the feces was performed using ultra-performance liquid chromatography(UPLC)-Q-Exactive Orbitrap/mass spectrometer.Oral administration of B.longum CCFM1077 for six weeks significantly decreased the serum levels of TC(p<0.01)and LDL-C(p<0.01)in patients with hyperlipidemia.B.longum CCFM1077 treatment markedly increased gut microbiota diversity and the relative abundance of anti-obesity-related genera,including Lactobacillus,Butyricicoccus,Bifidobacterium,and Blautia,whereas it decreased the relative abundance of obesity-related genera,including Alistipes,Megamonas,and Catenibacterium.Additionally,some key metabolites(bile acids(BAs),biotin,and caffeine)and their corresponding metabolic pathways(primary BA biosynthesis,and taurine and hypotaurine,biotin,purine,and caffeine metabolisms)were enriched by B.longum CCFM1077,and thus it may lower lipid levels.B.longum CCFM1077 is a probiotic strain with the potential to lower serum TC and LDL-C levels patients with hyperlipidemia.The underlying mechanism may be related to the increased abundance of anti-obesity-related genera and fecal metabolites.These findings provide a foundation for future clinical applications of lipid-lowering probiotics in managing individuals with hyperlipidemia.

Lactobacillus plantarum CCFM8610 Alleviates Irritable Bowel Syndrome and Prevents Gut Microbiota Dysbiosis:A Randomized,Double-Blind,Placebo-Controlled,Pilot Clinical Trial

Irritable bowel syndrome with diarrhea(IBS-D)is chronic intestinal dysfunction with diarrhea and othercomplicated clinical symptoms,and it has a great impact on the daily life and mental state of patients.Some studies have reported that ingestion of probiotics can significantly alleviate a variety of intestinaldiseases.The pupose of this study was to investigate the IBS-D-alleviating effects of a probiotic strain,lactobacillus plantarum(L.plantarum)CCFM8610,with multiple health-promoting effects.The studywas a 12-week,randomized,double-blind,placebo-controlled,pilot clinical trial.Seventy-five patientswere randomly assigned to receive the placebo,oligosaccharides,or L.plantarum CCFM8610(1×10^(10) colony-forming units(CFU)per day),with a 2-week run-in period,an 8-week intervention period,anda 2-week follow-up observation period.The patients'clinical symptoms and quality of life were exam-ined by the IBS symptom severity scale(IBS-SsS)and the IlBS quality of life scale(IBS-QOL).Changes ingut microbiota composition and diversity were measured at the end of the intervention period.The oraladministration of L.plantarum CCFM8610 significantly decreased the IBS-SSS and IBS-QOL scores,reduced IBS-D symptom severity,recovered gut microbiota diversity,decreased the relative abundanceof bloating-related genus Methanobrevibacter,and increased the relative abundance of butyric acid-producing genera,including Anaerostipes,Anaerotruncus,Bifidobacterium,Butyricimonas,andOdoribacter.These findings suggest that ingestion of L.plantarum CCFM8610 can significantly alleviate clinical symptoms and gut microbiota dysbiosis in IBS-D patients.The IBS-D-alleviating effect of L.plan-tarum CCFM8610 may be related to theincrease in the relative abundance of butyric acid-producing genera in the intestine.

Effect of bacteriocin-producing Pediococcus acidilactici strains on the immune system and intestinal flora of normal mice

This study was performed to determine the effects of bacteriocin-producing and non-bacteriocin-producing Pediococcus acidilactici strains on the immune system and intestinal flora of normal mice.Two P.acidilactici strains with antibacterial activity(P.acidilactici CCFM28 and CCFM18)were obtained based on the inhibition-zone assay.The produced components were identified as bacteriocins through protease treatment,pH adjustment and hydrogen peroxide treatment.Bacteriocin-producing and non-bacteriocin-producing P.acidilactici strains(P.acidilactici CCFM28,CCFM18 and NT17-3)caused significant changes in serum immune factors and intestinal flora of normal mice.After 14 days of intervention,the relative abundance of Firmicutes was significantly decreased,but that of Proteobacteria was significantly increased at the phylum level.At the genus level,the administration of three P.acidilactici strains resulted in the downregulation of Blautia and the upregulation of Ruminococcus and Lactobacillus.Furthermore,there were also different regulations on some probiotic strains,such as Bifidobacterium,Coprococcus and Akkermansia,which were closely related to the antibacterial ability of the bacteriocin and the type of strain.The results indicated that the intervention of different P.acidilactici strains could differently change the structure of intestinal flora in normal mice,which provided theoretical guidance for the selective use of bacteriocin-producing strains for health regulation in the future.

Effects of vegetarian diet-associated nutrients on gut microbiota and intestinal physiology

People are increasingly aware of the role of vegetarian diets in modulating human gut microbial abundance and intestinal physiology.A plant-based diet is thought to benefit host health by contributing to establish a diverse and stable microbiome.In addition,microbe-derived metabolites of specific nutrients known to be abundant in vegetarian diets(such as indigestible carbohydrates,arginine,and others) are important to promote effective intestinal immune responses,maintain intestinal barrier function,and protect against pathogens.This review explores the characteristics of the gut microbiome formed by vegetarian diets and the effects of diet-associated nutrients on intestinal microbial abundance.The interactions between the microbe-derived metabolites of vegetarian diet-associated nutrients and intestinal physiology are also discussed.

Capsular polysaccarides of probiotics and their immunomodulatory roles

Studies have determined the immunomodulatory activities of cell-surface polysaccharides of lactic acid bacteria(LAB)and Bacteroides;however,the mechanisms,synthesis,regulation,structure,and functional links have not been systematically discussed.We first introduce the structure of the capsular poly saccharides(CPS s)of commonly studied probiotics and Bacteroides.Wzx-Wzy dependent and ATP-binding cassette(ABC)transporter-dependent pathways are the two main biosynthesis and secretion of CPS pathways.The genes known to be associated with these two pathways are mainly those associated with priming glycosyltransferase(pGT);a variable number of genes encoding for different glycosyl transferases(GTs);Wzx/Wzy-encoding enzymes related to flippases and polymerases;and ABC-transporter genes.In addition,the effects of CPSs on host immunity as well as their related underlying mechanisms are described.Surface polysaccharides on probiotics can serve as a mask to aid in their escape from attacks from the host’s immune system.In turn,they also exhibit immunomodulatory activities,such as strengthening the functions of macrophages,promoting the maturation of antigen-presenting cells,and inducing regulatory T cells.All of these effects of cell-surface polysaccharides exhibit their significant protective properties in immunocompromised diseases,such as colitis,arthritis,and dermatitis.Finally,we focused on their structure and functional links.

Phylogenetic and Comparative Genomic Analysis of Lactobacillus fermentum Strains and the Key Genes Related to their Intestinal Anti-Inflammatory Effects

Emerging evidence shows that some Lactobacillus fermentum(L.fermentum)strains can contribute to the prevention and treatment of ulcerative colitis(UC).In this study,105 isolates of L.fermentum strains were separated from fecal samples of populations in different regions in China and their draft genomes were sequenced.Pan-genomic and phylogenetic characterizations of these strains and four model strains(L.fermentum 3872,CECT5716,IF03956,and VRI003)were performed.Phylogenetic analysis ind icated that there was no significant adaptive evolution between the genomes of L.fermentum strains and the geographical location,sex,ethnicity,and age of the hosts.Three L.fermentum strains(FWXBH115,FGDLZR121,and FXJCJ61)from different branches of the phylogenetic tree and strain type L.fermentum CECT5716 were selected and their anti-inflammatory and immune modulatory activities in a dextran sulphate sodium(DSS)-induced colitis mouse model were further investigated.Both L.fermentum FXJCJ61 and CECT5716 significantly alleviated UC by reducing all colitis-associated histological indices,maintaining mucosal integrity,and stimulating replenishment of short-chain fatty acids(SCFAs),while the other two strains failed to offer similar protection.The anti-inflammato ry mechanisms of L.fermentum FXJCJ61 and CECT5716 were related to the inhibition of nuclear factor kappa-B(NF-κB)signaling pathway activation and enhancement of interleukin 10(IL-10)production.Comparative genomic analysis of these strains identified candidate genes that may contribute to the anti-inflammatory effects of specific L.fermentum strains.

PSO-LSSVM-based Online SOC Estimation for Simulation Substation Battery

As the emergency power supply for a simulation substation,lead-acid batteries have a work pattern featuring noncontinuous operation,which leads to capacity regeneration.However,the accurate estimation of battery state of charge(SOC),a measurement of the amount of energy available in a battery,remains a hard nut to crack because of the non-stationarity and randomness of battery capacity change.This paper has proposed a comprehensive method for lead-acid battery SOC estimation,which may aid in maintaining a reasonable charging schedule in a simulation substation and improving battery’s durability.Based on the battery work pattern,an improved Ampere-hour method is used to calculate the SOC during constant current and constant voltage(CC/CV)charging and discharging.In addition,the combined Particle Swarm Optimization(PSO)and Least Squares Support Vector Machine(LSSVM)model is used to estimate the SOC during non-CC discharging.Experimental results show that this method is workable in online SOC estimation of working batteries in a simulation substaion,with the maximum relative error standing at only 2.1%during the non-training period,indicating a high precision and wide applicability.

肠道菌群的聚糖利用特性主导其交叉喂养网络:聚焦双歧杆菌

The diverse carbon sources in the gut tract provide various nutritional niches for the gut microbiota(GM).Differential glycan utilization influences GM formation in these niches[1].Bifidobacteria are key microorganisms in the human gut,as they maintain a long-term symbiotic relationship with their hosts,which is essential for gut homeostasis and health.The high abundance and colonization of Bifidobacteria in the gut are closely related to their strong ability to degrade human milk oligosaccharides(HMOs)and dietary glycans.

Hyaluronic acid modulates gut microbiota and metabolites relieving inflammation:A molecular weight-dependent study

Hyaluronic acid(HA),a linear glycosaminoglycan polymer,is an inherent carbon source for gut microbiota and is capable of mitigating host inflammation by modulating gut microbiota.The length of hyaluronan can range from an oligomer to an extremely long-form up to millions of Daltons,and its biological functions depend on its molecular mass[1,2].Presently,the precise mechanisms through which HA of varying molecular weights alleviates inflammation by modulating the gut microbiota remain unclear[3].

Species-or genus-dependent immunostimulatory effects of gut-derived potential probiotics

The immune regulatory effects of probiotics have been widely recognized to be strain-specific.However,it is unknown if there is a species-or genus-dependent manner.In this study,we use an in vitro mesenteric lymph node(MLN)model to systematically evaluate the immunostimulatory effects of gut-derived potential probiotics.The results exhibit an obvious species or genus consensus immune response pattern.RNA-seq shows that T cell-dependent B cell activation and antibody responses may be inherent to this model.Of the five tested genera,Akkermansia spp.and Clostridium butyrium directly activate the immune response in vitro,as indicated by the secretion of interleukin-10.Bifidobacterium spp.and Bacteroides spp.activate immune response with the help of stimuli(anti-CD3 and anti-CD28 antibodies).Lactobacillus spp.blunt the immune response with or without stimuli.Further investigations show that the cell surface protein of A.muciniphila AH39,which may serve as a T cell receptor cognate antigen,might evoke an in vitro immune activation.In vivo,oral administration of A.muciniphila AH39 influences the proportion of T regulatory cells(Tregs)in MLNs and the spleen under homeostasis in both specific pathogen-free and germ-free mice.All these findings indicate the distinct effects of different genera or species of potential gut-derived probiotics on intestinal and systemic immunity.

Therapeutic effect of acupuncture and massage for shoulder-hand syndrome in hemiplegia patients:a clinical two-center randomized controlled trial

OBJECTIVE:To evaluate the therapeutic effects of acupuncture and massage for shoulder-hand syndrome in hemiplegia patients.METHODS:One hundred and twenty hemiplegia patients with stage I shoulder-hand syndrome were randomly divided into a group treated with standardized electric acupuncture and massage,and a group treated with rehabilitation therapy for 6 weeks.The primary indices evaluated were pain on passive movement of the shoulder using the numeric pain rating scale(NPRS),and the number of patients with shoulder-hand syndrome at Steinbrocker stage II or III after treatment.The secondary indices were Fugl-Meyer evaluation of functional movement of the upper limb and hand using the modified rankin scale(MRS).RESULTS:At post-treatment evaluation and a 12-week follow-up visit,NPRS score,number of patients with stage II or III shoulder-hand syndrome,and MRS score were all improved in the acupuncture-massage group compared with the rehabilitation group(P<0.05).On Fugl-Meyer evaluation,functional movement of the upper limb was also improved in the acupuncture-massage group compared with the rehabilitation group(P<0.05).CONCLUSION:Standardized acupuncture-massage therapy may have curative effects on shoulder-hand syndrome in hemiplegia patients.

Clinical curative effect of electric acupuncture on acute cerebral infarction:a randomized controlled multicenter trial

OBJECTIVE: To examine whether electric acupuncture can improve the daily life of patients with ischemic cerebral apoplexy at acute stage.METHODS: A stratified-block randomized controlled multicenter trial was designed for this study.Totally 340 patients with acute ischemic cerebral apoplexy were randomly divided into an electric acupuncture group and a control group. In the electric acupuncture group, 170 patients were treated with electric acupuncture and routine therapy, and170 patients in the control group with routine therapy alone. Major indexes for judging curative effect were Barthel index at 3- and 6- months follow-up visits and number of re-hospitalized patients. Mi-nor indexes for judging curative effect were change in the score for nervous dysfunction at 4and 12 weeks follow-up visits and number of patients persisting in rehabilitation treatment with acupuncture during follow-up visit.RESULTS: Baseline data at the time of case selection between the two groups were similar. The odds ratio(OR) was 0.92, and the 95% confidence interval(CI) was 0.49-1.73 in disabled rate and 0.73 and 0.51-1.05 in the number of re-hospitalized patients in the electric acupuncture group at 6-month follow up visit compared with the control group.There was no difference in the score for nervous dysfunction at the end of 12-week follow-up visit between the two groups. The score for nervous dysfunction at the end of 4-week treatment in the electric acupuncture group was significantly higher than that in the control group(P<0.05). The number of patients discharged from hospital who persisted in rehabilitation treatment with acupuncture in the acupuncture group was significantly higher than that in the control group.CONCLUSION: Using electric acupuncture to treat patients with acute ischemic cerebral apoplexy can effectively improve the nervous dysfunction scores after 4-week treatment and their ability to deal with daily life after 6-month follow-up visit. Systematic treatment with acupuncture may also reduce the number of patients with secondary apoplexy.

Underlying mechanisms of the antagonistic effects of Bifidobacterium adolescentis CCFM1108 on Penicillium expansum:Based on comparative transcriptome analysis

Penicillium expansum is the primary postharvest pathogen that attacks fruits and vegetables and threatens human health.Bifidobacterium adolescentis CCFM1108 has been previously demonstrated to inhibit the growth of Penicillium expansum and patulin production;however,its modes of action remain unclear.RNA-seq analysis was used to investigate the underlying antifungal mechanism of metabolites produced by B .adolescents CCFM1108.The expression of genes in the control group and three treatment groups (1/2 MIC CFS,1/4 MIC CFS,and acid treatment groups) was determined and further compared using GO and KEGG analyses.The inhibitory metabolites were found to participate in the dysfunction of the mitochondrial membrane,affecting energy metabolism,reactive oxidative species production,and patulin biosynthesis.Compared with the mixture of multiple metabolites of Bifidobacterium ,the acid mixture affected gene expression in a more significant manner by inhibiting all critical genes included in the patulin biosynthetic pathway.The changes in the patulin biosynthetic were verified by qRT-PCR in the presence of acids.Collectively,the present study provides a clear perspective on the antifungal mechanism of metabolites produced by a B.adolescents strain through transcriptome analysis and suggests that acid mixtures could be potential candidates for the postharvest control of P .expansum .