Inflammatory bowel diseases (IBD) are complex multifactorial disorders that include Crohn’s disease (CD) and ulcerative colitis (UC). Considering that IBD is a genetic and multifactorial disease, we screened for the ...Inflammatory bowel diseases (IBD) are complex multifactorial disorders that include Crohn’s disease (CD) and ulcerative colitis (UC). Considering that IBD is a genetic and multifactorial disease, we screened for the distribution dynamism of IBD pathogenic genetic variants (single nucleotide polymorphisms;SNPs) and risk factors in four (4) IBD pediatric patients, by integrating both clinical exome sequencing and computational statistical approaches, aiming to categorize IBD patients in CD and UC phenotype. To this end, we first aligned genomic read sequences of these IBD patients to hg19 human genome by using bowtie 2 package. Next, we performed genetic variant calling analysis in terms of single nucleotide polymorphism (SNP) for genes covered by at least 20 read genomic sequences. Finally, we checked for biological and genomic functions of genes exhibiting statistically significant genetic variant (SNPs) by introducing Fitcon genomic parameter. Findings showed Fitcon parameter as normalizing IBD patient’s population variability, as well as inducing a relative good clustering between IBD patients in terms of CD and UC phenotypes. Genomic analysis revealed a random distribution of risk factors and as well pathogenic SNPs genetic variants in the four IBD patient’s genome, claiming to be involved in: i) Metabolic disorders, ii) Autoimmune deficiencies;iii) Crohn’s disease pathways. Integration of genomic and computational statistical analysis supported a relative genetic variability regarding IBD patient population by processing IBD pathogenic SNP genetic variants as opposite to IBD risk factor variants. Interestingly, findings clearly allowed categorizing IBD patients in CD and UC phenotypes by applying Fitcon parameter in selecting IBD pathogenic genetic variants. Considering as a whole, the study suggested the efficiency of integrating clinical exome sequencing and computational statistical tools as a right approach in discriminating IBD phenotypes as well as improving inflammatory bowel disease (IBD) molecular diagnostic process.展开更多
Many studies have demonstrated the linkage between the IBD3 region (6p21.1-23), an area which encompasses the famous human leukocyte antigen (HLA) complex, and Crohn’s disease (CD) or ulcerative colitis (U...Many studies have demonstrated the linkage between the IBD3 region (6p21.1-23), an area which encompasses the famous human leukocyte antigen (HLA) complex, and Crohn’s disease (CD) or ulcerative colitis (UC). IBD3 is the only region that meets genome-wide significance, and provides stronger evidence of the linkage than 16p13.1-16q12.2 (IBD1), the locus that contains the susceptibility gene CARD15. However, despite these findings, IBD3 susceptibility genes remain elusive and unclear due to the strong linkage disequilibrium, extensive polymorphism, and high gene density that characterize this area and also due to varying allele frequencies in populations around the world. This area presents an extremely high abundance of genes, including the classical and non-classical major histocompatibility complex (MHC) class I and II genes, and other genes, namely MHC class III genes tumor necrosis factor (TNF)-α and -β, and Hsp, whose proteins play key functions in immunological processes. To date, it is not clear which genes within the MHC family contribute to the IBD pathogenesis, although certain HLA alleles have been associated with IBD. Recent insights into the biological function of other genes encoded within the IBD3 region, such as the MHC class I chain-related (MIC) genes, have led investigators to a more comprehensive exploration of this region. MHC class I chain-related molecule A (MICA) is highly polymorphic and interacts with NKG2D, its receptor on the surface of NK, Tγδ and T CD8<sup>+</sup> cells. Increased expression of MICA in intestinal epithelial cells and increased expression of NKG2D in CD4<sup>+</sup> T cells (lamina propria) in patients with CD have also been reported. MICA alleles have also been associated with IBD, and a variation at amino acid position 129 of the α2-heavy chain domain seems to categorize MICA alleles into strong and weak binders of NKG2D receptor, thereby influencing the effector cells’ function. In this regard, a relevant role of MICA-129-Val/Met single nucleotide polymorphism has recently been implicated in the pathogenesis of IBD. TNF-α and -β also play an important role in inflammatory response. In fact, IBD is commonly treated with TNF-α inhibitors. Additionally, polymorphisms of TNF-α gene are known to affect the gene expression level and particular TNF-α genotypes may influence the response of IBD patients treated with TNF-α inhibitors.展开更多
This paper reviews the advances in research of co-pathogenesis and clinical treatment of ankylosing spondylitis(AS)and inflammatory bowel disease(IBD),in order to offer ideal therapeutic effects for comorbid patients ...This paper reviews the advances in research of co-pathogenesis and clinical treatment of ankylosing spondylitis(AS)and inflammatory bowel disease(IBD),in order to offer ideal therapeutic effects for comorbid patients and to provide new ideas for clinical practice.展开更多
AIM:To investigate the interaction of interleukin-23 receptor(IL23R)(rs1004819 and rs2201841),autophagy-related 16-like 1(ATG16L1)(rs2241880), caspase recruitment domain-containing protein 15 (CARD15)genes,and IBD5 lo...AIM:To investigate the interaction of interleukin-23 receptor(IL23R)(rs1004819 and rs2201841),autophagy-related 16-like 1(ATG16L1)(rs2241880), caspase recruitment domain-containing protein 15 (CARD15)genes,and IBD5 locus in Crohn's disease(CD) patients. METHODS:A total of 315 unrelated subjects with CD and 314 healthy controls were genotyped.Interactions and specific genotype combinations of a total of eight variants were tested.The variants of IBD5locus(IGR2198a_1 rs11739135 and IGR2096a_1 rs12521868),CARD15(R702W rs2066845 and L1007fs rs2066847),ATG16L1(rs2241880)and IL23R (rs1004819,rs2201841)genes were genotyped by PCR-RFLP,the G908R(rs2066844)in CARD15 was determined by direct sequencing. RESULTS:The association of ATG16L1 T300A with CD was confirmed[P=0.004,odds ratio(OR)=1.69, 95%CI:1.19-2.41],and both IL23R variants were found to represent significant risk for the disease(P= 0.008,OR=2.05,95%CI:1.20-3.50 for rs1004819 AA;P<0.001,OR=2.97,95%CI:1.65-5.33 for rs2201841 CC).Logistic regression analysis of pairwise interaction of the inflammatory bowel disease (IBD)loci indicated that IL23R,ATG16L1,CARD15 and IBD5(IGR2198a_1)contribute independently to disease risk.We also analysed the specific combina- tions by pair of individual ATG16L1,IL23R rs1004819, rs2201841,IGR2198a_1,IGR2096a_1 and CARD15 genotypes for disease risk influence.In almost all cases,the combined risk of susceptibility pairs was higher in patients carrying two different risk-associated gene variants together than individuals with just one polymorphism.The highest OR was found for IL23R rs2201841 homozygous genotype with combination of positive CARD15 status(P<0.001,OR=9.15,95% CI:2.05-40.74). CONCLUSION:The present study suggests a cumulative effect of individual IBD susceptibility loci.展开更多
Inflammatory bowel disease (IBD) is a chronic, sometimes debilitating condition that affects mainly the young population. The effect of IBD on pregnancy is therefore an important clinical issue. Many Obstetricians are...Inflammatory bowel disease (IBD) is a chronic, sometimes debilitating condition that affects mainly the young population. The effect of IBD on pregnancy is therefore an important clinical issue. Many Obstetricians are likely to come across the occasional patient with this chronic condition. The following article discusses the salient factors which need to be considered in pregnant women with IBD and serves as a quick, practical but nevertheless comprehensive guide for the practicing Obstetrician.展开更多
<strong>Objective:</strong> The study was conducted to understand the situation of patients with inflammatory bowel disease (IBD) to participant clinical trials and to analyze the factors affecting the cli...<strong>Objective:</strong> The study was conducted to understand the situation of patients with inflammatory bowel disease (IBD) to participant clinical trials and to analyze the factors affecting the clinical trial participation of patients with IBD. A clinical experiment guidance will be proved by this study to maximized the benefits to patients and to help the clinical trial to conduct successfully. <strong>Method: </strong>An anonymous questionnaire was designed and was administrated to the patients with IBD who were randomly delivered in the inpatient or outpatient departments. The survey result was analyzed. <strong>Result:</strong> Total 372 available questionnaires were returned. Among these patients, 26.3% patients with IBD indicated willingness to participate, 57.3% indicated a situation dependence, and 41.04% indicated unwillingness. Among the potential factors that may influence the patient’s willingness to participate the clinical, trusted physician’s recommendation, no proved drugs to use and accessing to free medication to release financial burden were statistically significant. <strong>Conclusion:</strong> The overall willingness of IBD patients to participate in drug clinical trials is not high. Among the patients who are willing to participate in clinical trials, the main reasons for their participation are that they trust doctors’ recommendation, can get free medication and examination, and can reduce the economic burden. Efficacy and safety were the main influencing factors in patients who were case-dependent and unwilling to participate in clinical trials.展开更多
Purpose: The objective of this study was to examine the correlation between the sexuality of patients with Inflammatory Bowel Disease and family functioning. Methods: The study took the form of a self-administered que...Purpose: The objective of this study was to examine the correlation between the sexuality of patients with Inflammatory Bowel Disease and family functioning. Methods: The study took the form of a self-administered questionnaire survey, utilizing the Sexuality Satisfaction Index for IBD (SEXSI-IBD) for measuring sexuality and the Survey of Family Environment Survey of Family Environment (SFE) for measuring family functioning. SEXSI-IBD consists of 28 items and five domains, and SFE consists of 30 items and five domains. The participants were recruited at 15 self-help groups and 14 hospitals. Results: Of 146 participants, 48.6% were male and 52.4% female, with an average age of 41.1 years. A significant correlation was observed between the item average score of SEXSI-IBD and Overall Satisfaction Score (OSS) of SFE. Significant correlations were observed in two domains of the SEXSI-IBD, “Daily interaction” and “Sexual communication,” and in all five domains of the SFE. In particular, for “Daily interaction,” the strongest correlation was observed in the SFE’s “Macro system” and “Family internal environment system.” A correlation was observed between the “Physical contact importance” in SEXSI-IBD and the “Macro system” in the OSS of the SFE. Conclusions: Sexuality correlates with family functioning not only in the family internal environment system but also in the family external environment system. Through an approach aimed at elevating the degree of satisfaction for sexuality, it becomes possible to improve family functioning and realize a sense of family well-being.展开更多
据估计,全球约有700万人受炎症性肠病(inflammatory bowel disease,IBD)的影响,对医疗系统和社会造成了极大负担。在IBD的发生、进展及治疗过程中,肠道菌群及其关键代谢产物——胆汁酸扮演着至关重要的角色。肠道菌群不仅参与胆汁酸的...据估计,全球约有700万人受炎症性肠病(inflammatory bowel disease,IBD)的影响,对医疗系统和社会造成了极大负担。在IBD的发生、进展及治疗过程中,肠道菌群及其关键代谢产物——胆汁酸扮演着至关重要的角色。肠道菌群不仅参与胆汁酸的生物转化,丰富胆汁酸的多样性,还通过法尼酯X受体(farnesoid X receptor,FXR)调控其合成与转运过程。同时,胆汁酸亦通过对微生物多样性的支持、直接毒性、间接抗微生物途径和对微生物代谢能力的影响,参与调整肠道菌群的结构和功能。此外,在正常生理条件下,经肠道菌群修饰后的胆汁酸能够促进肠上皮屏障的损伤修复过程,并且通过调节辅助性T细胞(helper T cell,Th细胞)17、调节性T细胞(regulatory T cell,Treg细胞)、CD8^(+)T细胞和自然杀伤T细胞(natural killer T cell,NKT细胞)等多种免疫细胞功能,促进免疫系统的平衡,减缓IBD的发展。该文重点探讨了肠道菌群通过介导胆汁酸在IBD的发生和发展中发挥的作用,并探索以肠道菌群和胆汁酸为靶点的新型有效治疗策略,如胆汁酸受体调节剂、益生菌和益生元干预、粪便菌群移植(fecal microbiota transplantation,FMT)以及噬菌体疗法等。展开更多
The destruction of the intestinal barrier is likely to cause an increase in intestinal permeability and cause pathological damage.Numerous studies have demonstrated that intestinal barrier function plays an important ...The destruction of the intestinal barrier is likely to cause an increase in intestinal permeability and cause pathological damage.Numerous studies have demonstrated that intestinal barrier function plays an important role in the occurrence and development of inflammatory bowel disease(IBD).Oral administration is the most common route for intestinal diseases.In this study,a synergistic strategy is proposed for IBD management through active barrier repair combined with anti-inflammatory treatment,which can interrupt the pathological process of IBD,resulting in the significantly improved efficacy of existing treatments.Based on the specific pH values and high reactive oxygen species(ROS)levels in inflammatory sites of IBD,an orally administrated ROS-responsive drug delivery system targeting inflamed colon has been designed,and confirmed in vitro and in vivo.The anti-inflammatory drug dexamethasone acetate(Dex)and the barrier function regulator LY294002 are delivered by the synthesized nanocarrier to treat IBD synergistically by inhibiting inflammation and actively repairing the intestinal barrier through tight junctions(TJs).The accumulation of nanocarriers in the inflamed colon and synergistic efficacy has been validated in mice with colitis.In brief,a drug delivery system and a therapeutic strategy for IBD are successfully developed.展开更多
Anti-inflammatory compounds,delivered as a payload to the gastrointestinal tract(GIT)by carriers,still cannot treat inflammatory bowel diseases without avoid-ing side effects.Here,we developed payload-free protein nanop...Anti-inflammatory compounds,delivered as a payload to the gastrointestinal tract(GIT)by carriers,still cannot treat inflammatory bowel diseases without avoid-ing side effects.Here,we developed payload-free protein nanoparticles(PNPs)that crossed GIT to retain in the colon and treat colitis by restoring intestinal bar-rier integrity by modulating gut microbiome and metabolome.Specifically,PNPs,orally administered to mice with acute colitis,reached the colon within three hours.Consequently,PNPs improve gut microbiota dysbiosis to reverse metabolism bal-ance,suppressing the expression of tumor-necrosis factorαand toll-like receptor 4 that restores the intestinal barrier integrity.PNPs then ameliorated colon inflam-mation and attenuated gut microbiota dysbiosis by exerting probiotic effects on gut microbiota,treating colitis in a week more effectively than the clinically often used 5-aminosalicylic acid without causing undesired side effects.Such PNPs repre-sent safe,sustainable,and cost-effective therapeutics for treating inflammatory and metabolic diseases by eliminating microbial and metabolomic imbalance.展开更多
文摘Inflammatory bowel diseases (IBD) are complex multifactorial disorders that include Crohn’s disease (CD) and ulcerative colitis (UC). Considering that IBD is a genetic and multifactorial disease, we screened for the distribution dynamism of IBD pathogenic genetic variants (single nucleotide polymorphisms;SNPs) and risk factors in four (4) IBD pediatric patients, by integrating both clinical exome sequencing and computational statistical approaches, aiming to categorize IBD patients in CD and UC phenotype. To this end, we first aligned genomic read sequences of these IBD patients to hg19 human genome by using bowtie 2 package. Next, we performed genetic variant calling analysis in terms of single nucleotide polymorphism (SNP) for genes covered by at least 20 read genomic sequences. Finally, we checked for biological and genomic functions of genes exhibiting statistically significant genetic variant (SNPs) by introducing Fitcon genomic parameter. Findings showed Fitcon parameter as normalizing IBD patient’s population variability, as well as inducing a relative good clustering between IBD patients in terms of CD and UC phenotypes. Genomic analysis revealed a random distribution of risk factors and as well pathogenic SNPs genetic variants in the four IBD patient’s genome, claiming to be involved in: i) Metabolic disorders, ii) Autoimmune deficiencies;iii) Crohn’s disease pathways. Integration of genomic and computational statistical analysis supported a relative genetic variability regarding IBD patient population by processing IBD pathogenic SNP genetic variants as opposite to IBD risk factor variants. Interestingly, findings clearly allowed categorizing IBD patients in CD and UC phenotypes by applying Fitcon parameter in selecting IBD pathogenic genetic variants. Considering as a whole, the study suggested the efficiency of integrating clinical exome sequencing and computational statistical tools as a right approach in discriminating IBD phenotypes as well as improving inflammatory bowel disease (IBD) molecular diagnostic process.
基金Supported by The Projects from Foundation Seneca,No.05748/PI/07 and No.04487/GERM/06the Fondo de Investigación Sanitaria(FIS)projects CIBERehd,No.PI11/02644 and No.PI11/02686(in part)the ISCⅡ and Fundación para la Formación e Investigación Sanitarias de la Región de Murcia(FFIS),No.CA11/00034(to López-Hernández R)
文摘Many studies have demonstrated the linkage between the IBD3 region (6p21.1-23), an area which encompasses the famous human leukocyte antigen (HLA) complex, and Crohn’s disease (CD) or ulcerative colitis (UC). IBD3 is the only region that meets genome-wide significance, and provides stronger evidence of the linkage than 16p13.1-16q12.2 (IBD1), the locus that contains the susceptibility gene CARD15. However, despite these findings, IBD3 susceptibility genes remain elusive and unclear due to the strong linkage disequilibrium, extensive polymorphism, and high gene density that characterize this area and also due to varying allele frequencies in populations around the world. This area presents an extremely high abundance of genes, including the classical and non-classical major histocompatibility complex (MHC) class I and II genes, and other genes, namely MHC class III genes tumor necrosis factor (TNF)-α and -β, and Hsp, whose proteins play key functions in immunological processes. To date, it is not clear which genes within the MHC family contribute to the IBD pathogenesis, although certain HLA alleles have been associated with IBD. Recent insights into the biological function of other genes encoded within the IBD3 region, such as the MHC class I chain-related (MIC) genes, have led investigators to a more comprehensive exploration of this region. MHC class I chain-related molecule A (MICA) is highly polymorphic and interacts with NKG2D, its receptor on the surface of NK, Tγδ and T CD8<sup>+</sup> cells. Increased expression of MICA in intestinal epithelial cells and increased expression of NKG2D in CD4<sup>+</sup> T cells (lamina propria) in patients with CD have also been reported. MICA alleles have also been associated with IBD, and a variation at amino acid position 129 of the α2-heavy chain domain seems to categorize MICA alleles into strong and weak binders of NKG2D receptor, thereby influencing the effector cells’ function. In this regard, a relevant role of MICA-129-Val/Met single nucleotide polymorphism has recently been implicated in the pathogenesis of IBD. TNF-α and -β also play an important role in inflammatory response. In fact, IBD is commonly treated with TNF-α inhibitors. Additionally, polymorphisms of TNF-α gene are known to affect the gene expression level and particular TNF-α genotypes may influence the response of IBD patients treated with TNF-α inhibitors.
文摘This paper reviews the advances in research of co-pathogenesis and clinical treatment of ankylosing spondylitis(AS)and inflammatory bowel disease(IBD),in order to offer ideal therapeutic effects for comorbid patients and to provide new ideas for clinical practice.
基金Supported by Grant of Hungarian Scientific Research Foundation,No.OTKA T 73430
文摘AIM:To investigate the interaction of interleukin-23 receptor(IL23R)(rs1004819 and rs2201841),autophagy-related 16-like 1(ATG16L1)(rs2241880), caspase recruitment domain-containing protein 15 (CARD15)genes,and IBD5 locus in Crohn's disease(CD) patients. METHODS:A total of 315 unrelated subjects with CD and 314 healthy controls were genotyped.Interactions and specific genotype combinations of a total of eight variants were tested.The variants of IBD5locus(IGR2198a_1 rs11739135 and IGR2096a_1 rs12521868),CARD15(R702W rs2066845 and L1007fs rs2066847),ATG16L1(rs2241880)and IL23R (rs1004819,rs2201841)genes were genotyped by PCR-RFLP,the G908R(rs2066844)in CARD15 was determined by direct sequencing. RESULTS:The association of ATG16L1 T300A with CD was confirmed[P=0.004,odds ratio(OR)=1.69, 95%CI:1.19-2.41],and both IL23R variants were found to represent significant risk for the disease(P= 0.008,OR=2.05,95%CI:1.20-3.50 for rs1004819 AA;P<0.001,OR=2.97,95%CI:1.65-5.33 for rs2201841 CC).Logistic regression analysis of pairwise interaction of the inflammatory bowel disease (IBD)loci indicated that IL23R,ATG16L1,CARD15 and IBD5(IGR2198a_1)contribute independently to disease risk.We also analysed the specific combina- tions by pair of individual ATG16L1,IL23R rs1004819, rs2201841,IGR2198a_1,IGR2096a_1 and CARD15 genotypes for disease risk influence.In almost all cases,the combined risk of susceptibility pairs was higher in patients carrying two different risk-associated gene variants together than individuals with just one polymorphism.The highest OR was found for IL23R rs2201841 homozygous genotype with combination of positive CARD15 status(P<0.001,OR=9.15,95% CI:2.05-40.74). CONCLUSION:The present study suggests a cumulative effect of individual IBD susceptibility loci.
文摘Inflammatory bowel disease (IBD) is a chronic, sometimes debilitating condition that affects mainly the young population. The effect of IBD on pregnancy is therefore an important clinical issue. Many Obstetricians are likely to come across the occasional patient with this chronic condition. The following article discusses the salient factors which need to be considered in pregnant women with IBD and serves as a quick, practical but nevertheless comprehensive guide for the practicing Obstetrician.
文摘<strong>Objective:</strong> The study was conducted to understand the situation of patients with inflammatory bowel disease (IBD) to participant clinical trials and to analyze the factors affecting the clinical trial participation of patients with IBD. A clinical experiment guidance will be proved by this study to maximized the benefits to patients and to help the clinical trial to conduct successfully. <strong>Method: </strong>An anonymous questionnaire was designed and was administrated to the patients with IBD who were randomly delivered in the inpatient or outpatient departments. The survey result was analyzed. <strong>Result:</strong> Total 372 available questionnaires were returned. Among these patients, 26.3% patients with IBD indicated willingness to participate, 57.3% indicated a situation dependence, and 41.04% indicated unwillingness. Among the potential factors that may influence the patient’s willingness to participate the clinical, trusted physician’s recommendation, no proved drugs to use and accessing to free medication to release financial burden were statistically significant. <strong>Conclusion:</strong> The overall willingness of IBD patients to participate in drug clinical trials is not high. Among the patients who are willing to participate in clinical trials, the main reasons for their participation are that they trust doctors’ recommendation, can get free medication and examination, and can reduce the economic burden. Efficacy and safety were the main influencing factors in patients who were case-dependent and unwilling to participate in clinical trials.
文摘Purpose: The objective of this study was to examine the correlation between the sexuality of patients with Inflammatory Bowel Disease and family functioning. Methods: The study took the form of a self-administered questionnaire survey, utilizing the Sexuality Satisfaction Index for IBD (SEXSI-IBD) for measuring sexuality and the Survey of Family Environment Survey of Family Environment (SFE) for measuring family functioning. SEXSI-IBD consists of 28 items and five domains, and SFE consists of 30 items and five domains. The participants were recruited at 15 self-help groups and 14 hospitals. Results: Of 146 participants, 48.6% were male and 52.4% female, with an average age of 41.1 years. A significant correlation was observed between the item average score of SEXSI-IBD and Overall Satisfaction Score (OSS) of SFE. Significant correlations were observed in two domains of the SEXSI-IBD, “Daily interaction” and “Sexual communication,” and in all five domains of the SFE. In particular, for “Daily interaction,” the strongest correlation was observed in the SFE’s “Macro system” and “Family internal environment system.” A correlation was observed between the “Physical contact importance” in SEXSI-IBD and the “Macro system” in the OSS of the SFE. Conclusions: Sexuality correlates with family functioning not only in the family internal environment system but also in the family external environment system. Through an approach aimed at elevating the degree of satisfaction for sexuality, it becomes possible to improve family functioning and realize a sense of family well-being.
文摘据估计,全球约有700万人受炎症性肠病(inflammatory bowel disease,IBD)的影响,对医疗系统和社会造成了极大负担。在IBD的发生、进展及治疗过程中,肠道菌群及其关键代谢产物——胆汁酸扮演着至关重要的角色。肠道菌群不仅参与胆汁酸的生物转化,丰富胆汁酸的多样性,还通过法尼酯X受体(farnesoid X receptor,FXR)调控其合成与转运过程。同时,胆汁酸亦通过对微生物多样性的支持、直接毒性、间接抗微生物途径和对微生物代谢能力的影响,参与调整肠道菌群的结构和功能。此外,在正常生理条件下,经肠道菌群修饰后的胆汁酸能够促进肠上皮屏障的损伤修复过程,并且通过调节辅助性T细胞(helper T cell,Th细胞)17、调节性T细胞(regulatory T cell,Treg细胞)、CD8^(+)T细胞和自然杀伤T细胞(natural killer T cell,NKT细胞)等多种免疫细胞功能,促进免疫系统的平衡,减缓IBD的发展。该文重点探讨了肠道菌群通过介导胆汁酸在IBD的发生和发展中发挥的作用,并探索以肠道菌群和胆汁酸为靶点的新型有效治疗策略,如胆汁酸受体调节剂、益生菌和益生元干预、粪便菌群移植(fecal microbiota transplantation,FMT)以及噬菌体疗法等。
基金the National Natural Science Foundation of China(No.81973267)the Zhejiang Provincial Natural Science Foundation of China(No.LZ22H060001).
文摘The destruction of the intestinal barrier is likely to cause an increase in intestinal permeability and cause pathological damage.Numerous studies have demonstrated that intestinal barrier function plays an important role in the occurrence and development of inflammatory bowel disease(IBD).Oral administration is the most common route for intestinal diseases.In this study,a synergistic strategy is proposed for IBD management through active barrier repair combined with anti-inflammatory treatment,which can interrupt the pathological process of IBD,resulting in the significantly improved efficacy of existing treatments.Based on the specific pH values and high reactive oxygen species(ROS)levels in inflammatory sites of IBD,an orally administrated ROS-responsive drug delivery system targeting inflamed colon has been designed,and confirmed in vitro and in vivo.The anti-inflammatory drug dexamethasone acetate(Dex)and the barrier function regulator LY294002 are delivered by the synthesized nanocarrier to treat IBD synergistically by inhibiting inflammation and actively repairing the intestinal barrier through tight junctions(TJs).The accumulation of nanocarriers in the inflamed colon and synergistic efficacy has been validated in mice with colitis.In brief,a drug delivery system and a therapeutic strategy for IBD are successfully developed.
基金Zhejiang Provincial Science and Technology Plan,Grant/Award Number:2021C02072-6National Natural Science Foundation of China,Grant/Award Numbers:81911530223,32101095+4 种基金Provincial Key Laboratory Construction Plans,Grant/Award Number:2020E10025Plan of National and Zhejiang Provincial Youth Science and Technology Innovation Leader,Grant/Award Numbers:[2020]366,2018R52021Zhejiang Province Public Welfare Technology Research Plans,Grant/Award Number:LGF21H060008National Key Research and Development Program of China,Grant/Award Number:2023YFF1103900China Agriculture Research System of MOF and MARA。
文摘Anti-inflammatory compounds,delivered as a payload to the gastrointestinal tract(GIT)by carriers,still cannot treat inflammatory bowel diseases without avoid-ing side effects.Here,we developed payload-free protein nanoparticles(PNPs)that crossed GIT to retain in the colon and treat colitis by restoring intestinal bar-rier integrity by modulating gut microbiome and metabolome.Specifically,PNPs,orally administered to mice with acute colitis,reached the colon within three hours.Consequently,PNPs improve gut microbiota dysbiosis to reverse metabolism bal-ance,suppressing the expression of tumor-necrosis factorαand toll-like receptor 4 that restores the intestinal barrier integrity.PNPs then ameliorated colon inflam-mation and attenuated gut microbiota dysbiosis by exerting probiotic effects on gut microbiota,treating colitis in a week more effectively than the clinically often used 5-aminosalicylic acid without causing undesired side effects.Such PNPs repre-sent safe,sustainable,and cost-effective therapeutics for treating inflammatory and metabolic diseases by eliminating microbial and metabolomic imbalance.
