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Autism spectrum disorder is a set of neurodevelopmental disorders with unclear etiology and pathogenesis and no cure. Studies have found that the gut microbiota plays a vital role in the occurrence and development of autism spectrum disorder. By supplementing with probiotics, diet management or fecal microbial transplantation, the balance of gut microbiota can be adjusted to improve the behaviors and symptoms of patients with autism spectrum disorder. This article reviews from the perspective of regulating the balance of gut microbiota to treat autism spectrum disorder, and aims to provide assistance for the research and treatment of autism spectrum disorder.
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Live biotherapeutic products (LBPs) refer to the living bacteria derived from human body intestinal gut or in nature that can be used to treat the human disease. However, the naturally screened living bacteria have some disadvantages, such as deficient therapeutic effect and great divergence, which fall short of the personalized diagnosis and treatment needs. In recent years, with the development of synthetic biology, researchers have designed and constructed several engineered strains that can respond to external complex environmental signals, which speeded up the process of development and application of LBPs. Recombinant LBPs modified by gene editing can have therapeutic effect on specific diseases. Inherited metabolic disease is a type of disease that causes a series of clinical symptoms due to the genetic defect of some enzymes in the body, which may cause abnormal metabolism the corresponding metabolites. Therefore, the use of synthetic biology to design LBPs targeting specific defective enzymes will be promising for the treatment of inherited metabolic defects in the future. This review summarizes the clinic applications of LBPs and its potential for the treatment of inherited metabolic defects.
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Humans , Bacteria/genetics , Gene Editing , Metabolic Diseases/therapyABSTRACT
Objective:To summarize and compare the characteristics of oral microbiota in women during the preconception period and the third trimester.Methods:This retrospective cohort study involved 55 women who were recruited in the Preconceptional Offspring Trajectory Study (PLOTS) conducted by Fudan University and followed up to the third trimester in the Maternal and Child Health Care Hospital of Jiading District of Shanghai from September 2016 to December 2019. A total of 110 unstimulated saliva samples were collected in the preconception period ( n=55) and the third trimester ( n=55). Features of oral microbiota in the samples were analyzed by 16S rRNA gene-based sequencing. Moreover, the related factors were also analyzed. Paired t test or Wilcoxon matched-pairs signed-ranks test were used to analyze the differences in α-diversity during preconception and the third trimester; t test, analysis of variance (ANOVA), Kruskal-Wallis test and Mann-Whitney U test for comparison between groups with different characteristics and permutational multivariate analysis of variance (PerMANOVA) for β-diversity were used; Linear discriminant analysis (LDA) effect size (LEfSe 1.0) was used to identify the iconic oral flora. Results:(1) The Ace index of oral microbiota was significantly lower in the third trimester than that in the preconception period [661.14(578.15-752.85) vs 730.64 (632.40-911.00), T=1 077.00, P=0.010]. There was also a significance difference in β-diversity ( F=12.539, R2=0.104, P=0.001). Some species such as Saccharibacteria_TM7_G3, Prevotella_7, Absconditabacteria_SR1_G1, Porphyromonas, Ruminococcaceae_UCG_014, Prevotella, Peptostreptococcus, Prevotella_2, Alloprevotella, Parvimonas, Solobacterium and Eubacterium_nodatum_group in saliva were statistically more abundant in the third trimester than those in the preconception period (all P<0.05). (2) The third-trimester Shannon index was lower among those with lower income [5.44 (5.08-5.77) vs 5.75 (5.44-6.12), U=219.00, P=0.029] and those with gargle habit after meal or dessert [5.36 (4.91-5.48) vs 5.72 (5.44-6.05), U=374.00, P=0.046]. Conclusions:The features of oral microbiota vary in women during the preconception period and the third trimester. There is a significant increase in the abundance of oral pathogenic and opportunistic bacteria in the third trimester.
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Background: Colorectal adenoma is the precursor lesion of colorectal cancer, and diabetes mellitus is associated with an increased risk for colorectal cancer. Aims: To investigate the clinicopathological characteristics of colorectal adenoma in patients with type 2 diabetes mellitus (T2DM) and the risk factors for advanced adenoma. Methods: Seven hundred and eighty T2DM patients who underwent initial colonoscopy from January 2018 to December 2020 at the Second Affiliated Hospital of Zhejiang Chinese Medical University were enrolled retrospectively, including 227 patients with colorectal adenoma and 553 patients without colorectal polyps. Furthermore, 227 non-diabetic patients with colorectal adenoma who were 1:1 matched to T2DM-adenoma group for gender, age, body mass index (BMI) and smoking history were collected for a comparison study. The clinical and pathological characteristics of T2DM patients with colorectal adenoma were analyzed, and the risk factors for advanced adenoma were identified by univariate and multivariate analyses. Results: T2DM patients with colorectal adenoma were older than those without colorectal polyps, and male gender, tobacco smoking, and cholelithiasis/cholecystectomy were more frequently seen in T2DM-adenoma group (all P<0.05). The proportions of multiple adenomas and advanced adenoma in T2DM-adenoma group were greater than those in patients without T2DM (16.7% vs. 10.1%, and 21.6% vs. 14.1%, all P<0.05). Multivariate Logistic regression analysis identified that male gender (OR=1.299, 95% CI: 1.041-1.831, P=0.008), age (OR=1.129, 95% CI: 1.001-1.421, P=0.025), BMI (OR=1.118, 95% CI: 1.022-1.715, P=0.038) and T2DM (OR=1.408, 95% CI: 1.141-1.721, P=0.010) were the independent risk factors for advanced adenoma. Conclusions: Multiple colorectal adenomas and advanced adenoma are more likely to be detected in patients with T2DM. Male gender, age, BMI and T2DM are associated with the risk of advanced adenoma.
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This study was aimed to investigate the effect of sinomenine on the expression of tumor suppressor gene P 16 and P53 in rats with lung cancer.A total of 40 male SD rats were treated by left-lung vein injection of WALKER-256 cell suspension to establish transplanted lung cancer model.After 3 weeks,30 rats screened of tumor were randomly divided into the model group,cyclophosphamide (CP) group and the sinomenine treatment group.Another 10 healthy SD rats were set as the normal control group.Sinomenine treatment group was treated with the subcutaneous injection of 10％ sinomenine hydrochloride for 10 weeks.CP was injected in the CP group as positive control.The same amount of normal saline was injected in the normal control group and the model control group.After 10 weeks of treatments,lung tumors of each group were removed to measure the tumor volume and weight.And the tumor inhibition rate was calculated.Then,flow cytometry was used to detect the proportion of WALKER-256 cells in tumor tissues in G1,G2,M and S around four cycles.Immunohistochemistry was adopted to detect positive expression rates of P16 and P53 protein.Reverse transcription polymerase chain reaction (RT-PCR) were used to detect expression of P16mRNA and P53mRNA.The results showed that compared with the model control group,the inhibition rate of sinomenine group was 30.15％;the positive expression rate of P16mRNA and P53mRNA protein were significantly decreased;expressions of P 16mRNA and P53mRNA were lower;tumor volume and tumor weight in S period got down significantly.The rates of cells in G1 and G2 periods got higher (P＜0.05).It was concluded that sinomenine may inhibit the differentiation and proliferation of WALKER-256 transplanted lung cancer cells in rats by regulating the expression of tumor suppressor gene P 16 and P53,regulating the ratio of cells in G1,G2 and S periods.