Limosilac to bacillus reuteri QS01 is potential probiotic isolated from the intestinal microbiota of healthy women in early pregnancy.In the current study,we examined whether QS01 can prevent gestational diabetes mell...Limosilac to bacillus reuteri QS01 is potential probiotic isolated from the intestinal microbiota of healthy women in early pregnancy.In the current study,we examined whether QS01 can prevent gestational diabetes mellitus(GDM) in an enhanced mouse model of the condition.Female C57BL/6J mouse offspring(F1 generation) born to dams fed a control(CON) or low-protein diet(GDM group) during gestation and lactation were used.Pregnant F1 mice fed a standard diet were randomly assigned to 5 groups:CON,GDM,and GDM mice treated with metformin,QS01 or Lacticaseibacillus rhamnosus HN001.An oral glucose tolerance test was performed before sacrifice at gestational day 17.Glucose tolerance was significantly ameliorated by all 3 treatments.QS01 supplementation fortified the intestinal mucosal barrier and inhibited the escalation of plasma inflammatory cytokines.QS01 treatment altered the cecal microbiota composition and function.Plasma and cecal metabolite profiles were modulated by QS01,prominently demonstrating significant upregulation of indole lactate and L-tryptophan in plasma and 5-hydroxy-tryptophan in the cecum,positively correlated with gut Lactobacillus abundance.In summary,QS01 plays a role in preventing GDM by remodeling the intestinal microbiota,reinforcing the intestinal mucosal barrier and alleviating chronic inflammation.展开更多
AIM To demonstrate that specific bacteria might release bacterial extracellular DNA(e DNA) to exert immunomodulatory functions in the mouse small intestine.METHODS Extracellular DNA was extracted using phosphate buffe...AIM To demonstrate that specific bacteria might release bacterial extracellular DNA(e DNA) to exert immunomodulatory functions in the mouse small intestine.METHODS Extracellular DNA was extracted using phosphate buffered saline with 0.5 mmol/L dithiothreitol combined with two phenol extractions. TOTO-1 iodide, a cell-impermeant and high-affinity nucleic acid stain, was used to confirm the existence of e DNA in the mucus layers of the small intestineand colon in healthy Male C57 BL/6 mice. Composition difference of e DNA and intracellular DNA(i DNA) of the small intestinal mucus was studied by Illumina sequencing and terminal restriction fragment length polymorphism(T-RFLP). Stimulation of cytokine production by e DNA was studied in RAW264.7 cells in vitro.RESULTS TOTO-1 iodide staining confirmed existence of e DNA in loose mucus layer of the mouse colon and thin surface mucus layer of the small intestine. Illumina sequencing analysis and T-RFLP revealed that the composition of the e DNA in the small intestinal mucus was significantly different from that of the i DNA of the small intestinal mucus bacteria. Illumina Miseq sequencing showed that the e DNA sequences came mainly from Gram-negative bacteria of Bacteroidales S24-7. By contrast, predominant bacteria of the small intestinal flora comprised Grampositive bacteria. Both e DNA and i DNA were added to native or lipopolysaccharide-stimulated Raw267.4 macrophages, respectively. The e DNA induced significantly lower tumor necrosis factor-α/interleukin-10(IL-10) and IL-6/IL-10 ratios than i DNA, suggesting the predominance for maintaining immune homeostasis of the gut.CONCLUSION Our results indicated that degraded bacterial genomic DNA was mainly released by Gram-negative bacteria, especially Bacteroidales-S24-7 and Stenotrophomonas genus in gut mucus of mice. They decreased pro-inflammatory activity compared to total gut flora genomic DNA.展开更多
Food allergy is an emerging global health concern with limited treatment options.This study evaluated the efficacy of Limosilactobacillus reuteri(L.reuteri)FN041 in a cow’s milkβ-lactoglobulin-induced murine model o...Food allergy is an emerging global health concern with limited treatment options.This study evaluated the efficacy of Limosilactobacillus reuteri(L.reuteri)FN041 in a cow’s milkβ-lactoglobulin-induced murine model of food allergy.Daily oral administration of L.reuteri FN041 alleviated allergic symptoms,normalized body temperature,and reduced lung inflammation.L.reuteri FN041 lowered serum IgE levels,rebalanced Th1/Th2 cytokines,and expanded splenic regulatory T cells.Intestinal barrier integrity was improved,as evidenced by restored tight junction proteins and enhanced antioxidant capacity.Although the overall gut microbialα-andβ-diversity remained unchanged,L.reuteri FN041 selectively enriched Duncaniella muris and Muribaculum gor-doncarteri,while suppressing Waltera intestinalis and Lacrimispora xylanisolvens.Metabolomic profiling revealed an upregulation of anti-inflammatory flavonoids,particularly naringenin-7-O-glucoside.Mechanistically,L.reuteri FN041 inhibited AKT/mTOR and NF-κB signaling.These findings suggest that L.reuteri FN041 is a promising biotherapeutic for food allergy,acting through immune modulation,gut barrier protection,microbiota remodeling,and oxidative stress mitigation.展开更多
This study explored how breast milk-derived Limosilactobacillus reuteri FN041 regulates lipid metabolism.C57BL/6N mice on a high-fat diet were treated with FN041,Lacticaseibacillus rhamnosus GG,indole-3-carboxaldehyde...This study explored how breast milk-derived Limosilactobacillus reuteri FN041 regulates lipid metabolism.C57BL/6N mice on a high-fat diet were treated with FN041,Lacticaseibacillus rhamnosus GG,indole-3-carboxaldehyde,or lovastatin(Lova).Low-fat diet-fed mice and those treated with FN041 served as controls.An oral glucose tolerance test was conducted at week 7,with the experiment concluding at week 8.Results showed that all treatments significantly reduced weight gain rate(p<0.01)and inhibited increases in plasma total cholesterol,low-density lipoprotein cholesterol,hepatic lipid droplet area,and white adipose tissue area(p<0.05).Only FN041 significantly decreased body fat percentage(p<0.05).Mechanistically,treatments attenuated high-fatinduced increases in intestinal permeability and plasma levels of lipopolysaccharide,IL-6,and TNF-α(p<0.01)while enhancing expression of intestinal Claudin-1 and Occludin.FN041 and Lova increased cecal microbiota richness(Chao1 and ACE indices)and alteredβ-diversity(PERMANOVA).FN041 specifically upregulated lipid metabolism-regulating bacteria(e.g.,Marvinbryantia formatexigens,Bacteroides acidifaciens)and reduced the abundance of Lactobacillus johnsonii and Ligilactobacillus murinus.It also altered cecal and plasma metabolite profiles,increasing levels of cecal indole-3-carboxaldehyde,plsama indole-3-butyric acid,and plsama 5,6-dihydroxyindole-2-carboxylic acid.In summary,FN041 mitigated high-fat-induced weight gain and lipid disorders by enriching beneficial gut bacteria and producing indole derivatives.展开更多
Limosilactobacillus reuteri(L.reuteri)FN041,a probiotic isolated from breast milk,exhibits immunomodulatory effects against allergic and immune-related diseases.However,the preventive and therapeutic potential of L.re...Limosilactobacillus reuteri(L.reuteri)FN041,a probiotic isolated from breast milk,exhibits immunomodulatory effects against allergic and immune-related diseases.However,the preventive and therapeutic potential of L.reuteri FN041 in ulcerative colitis(UC)remains unreported.This study investigates the protective effects of L.reuteri FN041 in a mouse model of colitis induced by dextran sodium sulfate(DSS).Significant alleviation of colitis symptoms was observed with L.reuteri FN041 treatment,demonstrated by decreased weight loss,reduced colon shortening,and lower Disease Activity Index and Histological Index scores.Inflammation and oxidative stress levels were reduced,as shown by lower local and systemic IL-6,elevated IL-10 and increased colonic malondialdehyde levels.The expression of tight junction proteins,indicators of intestinal mucosal permeability,increased,while serum lipopolysaccharide and D-lactate levels decreased.Fecal metagenomic analysis indicated that therapeutic effects of L.reuteri FN041 may be microbiota-dependent,demonstrated by increased beneficial gut bacteria and decreased bacteria associated with inflammation and tissue damage.Metabolomic analysis of cecal contents revealed that 1-myristoyl-sn-glycero-3-phosphocholine,4-androsten-17-beta-ol-3-one glucosiduronate,gamma-L-glutamylputrescine,fosfomycin and alpha-cyperone were metabolite markers significantly disrupted by DSS and partially restored by probiotics.Correlation analysis among clinical colitis parameters,metagenomics,and metabolomics confirmed the interdependence of these factors.Thus,L.reuteri FN041 may alleviate colitis by reshaping the intestinal microbial flora and metabolites.In summary,L.reuteri FN041 represents a promising probiotic for UC prevention and treatment.展开更多
基金supported by the grants from the Nutrition and care of Maternal and Child Research Funding program (2020BINCMCF056)。
文摘Limosilac to bacillus reuteri QS01 is potential probiotic isolated from the intestinal microbiota of healthy women in early pregnancy.In the current study,we examined whether QS01 can prevent gestational diabetes mellitus(GDM) in an enhanced mouse model of the condition.Female C57BL/6J mouse offspring(F1 generation) born to dams fed a control(CON) or low-protein diet(GDM group) during gestation and lactation were used.Pregnant F1 mice fed a standard diet were randomly assigned to 5 groups:CON,GDM,and GDM mice treated with metformin,QS01 or Lacticaseibacillus rhamnosus HN001.An oral glucose tolerance test was performed before sacrifice at gestational day 17.Glucose tolerance was significantly ameliorated by all 3 treatments.QS01 supplementation fortified the intestinal mucosal barrier and inhibited the escalation of plasma inflammatory cytokines.QS01 treatment altered the cecal microbiota composition and function.Plasma and cecal metabolite profiles were modulated by QS01,prominently demonstrating significant upregulation of indole lactate and L-tryptophan in plasma and 5-hydroxy-tryptophan in the cecum,positively correlated with gut Lactobacillus abundance.In summary,QS01 plays a role in preventing GDM by remodeling the intestinal microbiota,reinforcing the intestinal mucosal barrier and alleviating chronic inflammation.
基金Supported by China Postdoctoral Science Foundation,No.172774Fund of Key Laboratory of Carbohydrate Chemistry and Biotechnology,Ministry of Education,Jiangnan University,No.KLCCB-KF201603National Natural Science Foundation of China,No.31201805
文摘AIM To demonstrate that specific bacteria might release bacterial extracellular DNA(e DNA) to exert immunomodulatory functions in the mouse small intestine.METHODS Extracellular DNA was extracted using phosphate buffered saline with 0.5 mmol/L dithiothreitol combined with two phenol extractions. TOTO-1 iodide, a cell-impermeant and high-affinity nucleic acid stain, was used to confirm the existence of e DNA in the mucus layers of the small intestineand colon in healthy Male C57 BL/6 mice. Composition difference of e DNA and intracellular DNA(i DNA) of the small intestinal mucus was studied by Illumina sequencing and terminal restriction fragment length polymorphism(T-RFLP). Stimulation of cytokine production by e DNA was studied in RAW264.7 cells in vitro.RESULTS TOTO-1 iodide staining confirmed existence of e DNA in loose mucus layer of the mouse colon and thin surface mucus layer of the small intestine. Illumina sequencing analysis and T-RFLP revealed that the composition of the e DNA in the small intestinal mucus was significantly different from that of the i DNA of the small intestinal mucus bacteria. Illumina Miseq sequencing showed that the e DNA sequences came mainly from Gram-negative bacteria of Bacteroidales S24-7. By contrast, predominant bacteria of the small intestinal flora comprised Grampositive bacteria. Both e DNA and i DNA were added to native or lipopolysaccharide-stimulated Raw267.4 macrophages, respectively. The e DNA induced significantly lower tumor necrosis factor-α/interleukin-10(IL-10) and IL-6/IL-10 ratios than i DNA, suggesting the predominance for maintaining immune homeostasis of the gut.CONCLUSION Our results indicated that degraded bacterial genomic DNA was mainly released by Gram-negative bacteria, especially Bacteroidales-S24-7 and Stenotrophomonas genus in gut mucus of mice. They decreased pro-inflammatory activity compared to total gut flora genomic DNA.
基金supported by the Jiangsu Provincial Department of Science and Technology(No.BE2022698)the Wuxi Municipal Science and Technology Bureau(No.Y20222003)+2 种基金the Medical Key Discipline Program of Wuxi Health Commission(No.CXTD202113)the Top Talent Support Program for young and middle-aged people of Wuxi Health Commission(No.BJ2023077)the Biobank Program of Wuxi Health Commission(No.SW202201).
文摘Food allergy is an emerging global health concern with limited treatment options.This study evaluated the efficacy of Limosilactobacillus reuteri(L.reuteri)FN041 in a cow’s milkβ-lactoglobulin-induced murine model of food allergy.Daily oral administration of L.reuteri FN041 alleviated allergic symptoms,normalized body temperature,and reduced lung inflammation.L.reuteri FN041 lowered serum IgE levels,rebalanced Th1/Th2 cytokines,and expanded splenic regulatory T cells.Intestinal barrier integrity was improved,as evidenced by restored tight junction proteins and enhanced antioxidant capacity.Although the overall gut microbialα-andβ-diversity remained unchanged,L.reuteri FN041 selectively enriched Duncaniella muris and Muribaculum gor-doncarteri,while suppressing Waltera intestinalis and Lacrimispora xylanisolvens.Metabolomic profiling revealed an upregulation of anti-inflammatory flavonoids,particularly naringenin-7-O-glucoside.Mechanistically,L.reuteri FN041 inhibited AKT/mTOR and NF-κB signaling.These findings suggest that L.reuteri FN041 is a promising biotherapeutic for food allergy,acting through immune modulation,gut barrier protection,microbiota remodeling,and oxidative stress mitigation.
基金supported by the National Natural Science Foun-dation of China(No.31201805)the China Postdoctoral Science Foun-dation(No.172774).
文摘This study explored how breast milk-derived Limosilactobacillus reuteri FN041 regulates lipid metabolism.C57BL/6N mice on a high-fat diet were treated with FN041,Lacticaseibacillus rhamnosus GG,indole-3-carboxaldehyde,or lovastatin(Lova).Low-fat diet-fed mice and those treated with FN041 served as controls.An oral glucose tolerance test was conducted at week 7,with the experiment concluding at week 8.Results showed that all treatments significantly reduced weight gain rate(p<0.01)and inhibited increases in plasma total cholesterol,low-density lipoprotein cholesterol,hepatic lipid droplet area,and white adipose tissue area(p<0.05).Only FN041 significantly decreased body fat percentage(p<0.05).Mechanistically,treatments attenuated high-fatinduced increases in intestinal permeability and plasma levels of lipopolysaccharide,IL-6,and TNF-α(p<0.01)while enhancing expression of intestinal Claudin-1 and Occludin.FN041 and Lova increased cecal microbiota richness(Chao1 and ACE indices)and alteredβ-diversity(PERMANOVA).FN041 specifically upregulated lipid metabolism-regulating bacteria(e.g.,Marvinbryantia formatexigens,Bacteroides acidifaciens)and reduced the abundance of Lactobacillus johnsonii and Ligilactobacillus murinus.It also altered cecal and plasma metabolite profiles,increasing levels of cecal indole-3-carboxaldehyde,plsama indole-3-butyric acid,and plsama 5,6-dihydroxyindole-2-carboxylic acid.In summary,FN041 mitigated high-fat-induced weight gain and lipid disorders by enriching beneficial gut bacteria and producing indole derivatives.
基金supported by the Jiangsu Provincial Department of Science and Technology(No.BE2022698)the Wuxi Municipal Science and Technology Bureau(No.Y20222003)+2 种基金Medical Key Discipline Program of Wuxi Health Commission(No.CXTD202113)the Top Talent Support Program for young and middle-aged people of Wuxi Health Commission(No.BJ2023077)the Biobank Program of Wuxi Health Commission(No.SW202201).
文摘Limosilactobacillus reuteri(L.reuteri)FN041,a probiotic isolated from breast milk,exhibits immunomodulatory effects against allergic and immune-related diseases.However,the preventive and therapeutic potential of L.reuteri FN041 in ulcerative colitis(UC)remains unreported.This study investigates the protective effects of L.reuteri FN041 in a mouse model of colitis induced by dextran sodium sulfate(DSS).Significant alleviation of colitis symptoms was observed with L.reuteri FN041 treatment,demonstrated by decreased weight loss,reduced colon shortening,and lower Disease Activity Index and Histological Index scores.Inflammation and oxidative stress levels were reduced,as shown by lower local and systemic IL-6,elevated IL-10 and increased colonic malondialdehyde levels.The expression of tight junction proteins,indicators of intestinal mucosal permeability,increased,while serum lipopolysaccharide and D-lactate levels decreased.Fecal metagenomic analysis indicated that therapeutic effects of L.reuteri FN041 may be microbiota-dependent,demonstrated by increased beneficial gut bacteria and decreased bacteria associated with inflammation and tissue damage.Metabolomic analysis of cecal contents revealed that 1-myristoyl-sn-glycero-3-phosphocholine,4-androsten-17-beta-ol-3-one glucosiduronate,gamma-L-glutamylputrescine,fosfomycin and alpha-cyperone were metabolite markers significantly disrupted by DSS and partially restored by probiotics.Correlation analysis among clinical colitis parameters,metagenomics,and metabolomics confirmed the interdependence of these factors.Thus,L.reuteri FN041 may alleviate colitis by reshaping the intestinal microbial flora and metabolites.In summary,L.reuteri FN041 represents a promising probiotic for UC prevention and treatment.
