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.

Alleviative effects of Bacillus coagulans strains on irritable bowel syndrome-unraveling strain specificity through physiological and genomic analysis

The high intraspecies heterogeneity of Baciillus coagulans leads to significant phenotypic differences among different strains.Thus,6 B.coagulans strains were tested in the present study using an irritable bowel syndrome(IBS)animal model to determine whether the IBS-alleviating effects of B.coagulans strains are strain-specific.The results of this study showed that the ingestion of B.coagulans GBI-30,6086,and B.coagulans CCFM1041 significantly alleviated IBS symptoms in mice.In contrast,other B.coagulans strains showed no or limited alleviating effects on IBS symptoms.According to our experimental results,the two main common features of these strains were as follows:1)The resistance of vegetative cells to bile salts,and 2)ability to synthesize specific lipids and secondary metabolites.Screening strains based on these two indicators may greatly reduce costs and provide a basis for mining new functional B.coagulans strains.Our results also suggest that administration of B.coagulans could significantly regulate microbiota dysbiosis in animal models.Moreover,the close relationships between the gut microbiota,gut microbiota metabolites,and IBS were further confirmed in this study.

Ameliorative effects of Lactobacillus fermentum isolated from individuals following vegan, omnivorous and high-meat diets on ulcerative colitis in mice

Lactobacillus spp.can be beneficial for the prevention or treatment of ulcerative colitis(UC).In this study,153 participants who followed vegan,omnivorous,or high-meat diet were recruited.Compositional analysis of the Lactobacillus community in feces revealed that Lactobacillus fermentum strains were significantly affected by diet.Administration of mixed L.fermentum strains from vegans significantly improved inflammation compared to that from omnivores and high-meat consumers,as evidenced by a significant reduction in colonic tissue damage,improvement in inflammatory cytokines,enhanced expression of ZO-1,occludin,and claudin-3,and a significant increase in short chain fatty acids concentration.The effect of a single strain of L.fermentum was similar to that of a mixed strains of L.fermentum group.Genomic analysis suggested that L.fermentum strains from the guts of vegans possessed a higher prevalence of genes involved in carbohydrate catabolism than those from the guts of omnivores and high-meat eaters.In particular,the ME2 gene is involved in the biosynthesis of acetate,a compound considered to possess anti-inflammatory properties.In conclusion,this study indicates strain-specific differences in the ability of L.fermentum strains to alleviate UC in mice,influenced by habitual diets。

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.

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.

Strain-specific effects of Akkermansia muciniphila on the regulation of intestinal barrier

Akkermansia muciniphila, one of the most promising next-generation probiotics, was reported to exhibit beneficial modulatory effects on the gut barrier. However, the strain-specific and underlying regulatory mechanisms of this species on gut barrier function were not well studied. Therefore, this study evaluated the protective effect of A. muciniphila strains on the intestinal barrier and investigated the mode of action and material basis of this modulatory effect. We first confirmed the strain-specific effects of A. muciniphila on intestinal barrier regulation and found that this phenomenon may be explained by the different abilities of strains to affect tight junction protein expression in enterocytes. Comparative genomic analysis proved that the ability of A. muciniphila to regulate the intestinal barrier was exerted in part by the functional genes(such as COG0438, COG0463, and COG2244)related to the synthesis of cellular surface proteins. The role of these surface proteins in intestinal barrier regulation was further verified by strain-comparative experiments in animal and cell models and surface protein removal trials. This study confirmed the different effects of A. muciniphila strains on gut barrier modulation and provided molecular and genetic targets for the screening of A. muciniphila strains with superior protection against gut barrier dysfunction.

Targeting Gut Microbiota Dysbiosis: Potential Intervention Strategies for Neurological Disorders

It is well known that the gut microbiota plays an extremely important role in modulating host physiological functions such as immunity and metabolic homeostasis.In recent years,accumulated evidence has revealed that the gut microbiota can regulate the functions of the central nervous system(CNS)through the gut-brain axis,which provides a novel insight into the interactions between the gut and brain.This review focuses on the molecular mechanism of the crosstalk between the gut microbiota and the brain via the gut-brain axis,and on the onset and development of neurological disorders triggered by gut microbiota dysbiosis.These topics are followed by a critical analysis of potential intervention strategies targeting gut microbiota dysbiosis,including the use of probiotics,prebiotics,synbiotics,and diets.While research on the microbiota-gut-brain axis is still in its relative infancy,clarifying the molecular mechanism that underlies how the gut microbiota regulates neurological functions not only holds the promise of revealing potentially novel pathogeneses of neurological disorders,but also may lead to the development of potential diagnosis biomarkers and intervention strategies targeting microbiota dysbiosis for neurological disorders.

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.

MLST analysis of genetic diversity of Bacillus coagulans strains to evaluate effects on constipation model

Bacillus coagulans can help ameliorate or prevent gastrointestinal diseases, but the genetic relationships among B. coagulans isolates are not well studied. Multilocus sequence typing analysis was conducted on 57 isolates of B. coagulans from 22 provinces or autonomous regions in China. B. coagulans isolates were highly diverse and a total of 33(sequence typings) STs were found. These isolates had a weak clonal population structure and strong indications of intraspecies recombination. The evolution direction of B. coagulans was not correlated with geography or isolation source. Fifteen strains were selected for further analysis based on proximity relationships from the phylogenetic tree. Five isolates(B. coagulans-1, B. coagulans-10, B. coagulans-39, B. coagulans-70 and B. coagulans-71) with good spore-forming ability relative to the rest of the isolates were evaluated for constipation relief. B. coagulans-39 significantly relieved constipation symptoms in mice by regulating intestinal flora, increasing the production of short-chain fatty acids and restoring the level of gastrointestinal regulatory peptides. Comparative genomic analysis showed the beneficial effects of B. coagulans-39 might be associated with specific functional genes that are involved in the utilization of various carbohydrates as primary substrates and short-chain fatty acid production.

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.

具有硒吸附能力乳酸菌的筛选及安全性评价

乳酸菌具有将无机硒转化为有机硒的潜在能力和多种益生特性,故将其作为安全高效的硒载体进行补硒已日益成为研究热点.本研究通过测定来源于8个种水平的43株乳杆菌的硒吸附能力,最终筛选出一株具有硒吸附能力较高的乳杆菌菌株植物乳杆菌(Lactobacillusplantarum)RS7-1,其对硒的吸附率可达40.79%.同时,通过测定不同初始p H、初始菌体浓度、初始硒浓度和不同吸附时间研究该菌株的吸附特性.此外,测定该菌株的耐酸和耐胆盐特性以研究其在胃肠道中是否仍可保持较高活性,并通过体外抗生素耐受性实验以及体内急性毒性实验和30d喂养实验对其安全性进行评价.结果表明,植物乳杆菌RS7-1硒吸附的最适p H为5.0,最适初始菌体浓度为2g/L,在初始硒浓度为20mg/L时达到最大吸附量,在吸附时间为60min即达到平衡.同时,该菌株具有较强的耐酸和耐胆盐能力,不存在非种属特有的抗生素耐受性.动物实验结果表明,饲喂植物乳杆菌RS7-1菌悬液的实验组小鼠的摄食量、体重、血常规指标和血生化指标与空白组无显著差异,且组织器官无病变.因此,综合评价植物乳杆菌RS7-1是一株硒吸附能力强、耐酸和耐胆盐、安全性好的乳酸菌,具有良好的应用价值.

Effects of subchronic oral toxic metal exposure on the intestinal microbiota of mice

Oral exposure to toxic metals such as cadmium （Cd）, lead （Pb）, copper （Cu） and aluminum （AI） can induce various adverse health effects in humans and animals. However, the effects of these metals on the gut microbiota have received limited attention. The present study demonstrated that long-term toxic metal exposure altered the intestinal microbiota of mice in a metal-specific and time-dependent manner. Subchronic oral Cu exposure for eight weeks caused a profound decline in gut microbial diversity in mice, whereas no significant changes were observed in groups treated with other metals. Cd exposure signif- icantly increased the relative abundances of organisms from the genera Alistipes and Odoribacter and caused marked decreases in Mollicutes and unclassified Ruminococcaceae. Pb exposure significantly decreased the abundances of eight genera： unclassified and uncultured Ruminococcaceae, unclassified Lachnospiraceae, Ruminiclostridium_9, Rikenellaceae_RCg_gut group, Oscillibacter, Anaerotruncus and Lachnoclostridium. Cu exposure affected abundances of the genera Alistipes, Bacteroides, Ruminococcaceae_UCG-014, AUobaculum, Mollicutes_RF9_norank, Rikenellaceae_RCg gut_group, Ruminococcaceae_unclassified and Turicibacter. A1 exposure increased the abundance of Odoribacter and decreased that of Anaerotruncus. Exposure to any metal for eight weeks significantly decreased the abun- dance of Akkermansia. These results provide a new understanding regarding the role of toxic metals in the pathogenesis of intestinal and systemic disorders in the host within the gut microbiota framework.