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Wang Wei (first from left) and Kang Wei (second from left) and other team members are discussing communication.
scientists have been exploring the link between the pathogenesis of autism and the presence of gut microbiotics. The reason is that most children with autism have digestive tract disease, and many studies have also found that autistic children have intestinal bacteria disorders, such as lower Bifidobacteria abundance and an increase in Thyrobacter acuity. However, it has not been clarified how intestinal bacteria are involved in the pathogenesis of autism.
recently, the Wang Wei team from Peking University's School of Basic Medicine, in cooperation with the Kang Wei team from the Beijing Genomics Research Institute of the Chinese Academy of Sciences, gave the answer. Their study found that microbial detoxification is impaired due to imbalances in the microbiome of autistic children, which in turn leads to toxin accumulation and mitochondrial function in autistic individuals, which may be an important new mechanism for microbial involvement in the onset of autism. The findings were published in Science Advances with the title "Class pairing analysis strategies reveal impaired detoxification of intestinal bacteria in autistic children."
" findings could help explain why autistic children are more sensitive to environmental toxin exposure, explore strategies for developing medical treatments for autism, and potentially produce more targeted products or methods. Wang said in an interview with China Science Daily.autism spectrum disorder (ASD) is a complex set of neurodevelopmental disorders characterized by impaired social function, repeated stereotyped behavior, and narrow interests. Especially in recent years, the incidence of autism has gradually increased, it has become the most serious and common neurodevelopmental disorders, far more than other types of developmental disorders.
2020, the prevalence of autism among eight-year-olds in the United States will be 1/54, up from 1/59 previously reported, according to a team released by the Centers for Disease Control and Prevention. Although there is no large-scale data on autism in China, some scholars reported this year that the incidence of autism in some parts of the country is 0.7%.
" incidence of autism has a significant gender difference, with a ratio of about 4.5 to 1 men, meaning that men make up the majority of the patient population. Jia Meixiang, chief physician at Peking University's Sixth Hospital, said there was no significant regional difference in the incidence of autism.
currently, the internationally recognized standard for the diagnosis of autism is the combination of ADOS assessment and ADIR questionnaires, which can be diagnosed as autism spectrum disorder when a patient's assessment score reaches the diagnostic threshold. However, due to the time-and-effort of ADOS-ADIR, the more commonly used method in clinical practice is to use DSM-V as the diagnostic standard, combined with the ABC scale, etc.
in the treatment of autism, although the United States has approved two drugs, lipesterone and alepende, but mainly for impulse behavior control, and not for the cause of treatment. In addition, there are co-disease treatment, behavioral intervention, sensory unity intervention and other methods used in autistic patients.treatment for autism is "overstretched" more because it is a typically complex disease whose pathogenesies include genetic and environmental factors and their interactions.
Wang is more supportive of the view expressed by Trent Gaugle of Carnegie Mellon University and others in a 2014 article in Nature that about 50 percent of the causes of autism are related to common genetic mutations, 3 percent are new mutations, and about 40 percent may be environmental factors.
"Since science has confirmed that autism is not a purely genetic disease, but a complex disease in which genetic factors and environmental factors work together, individuals vary widely. So if we start with environmental factors to explore the pathogenesic mechanism of autism, autism can be treated, preventable, rather than a medical powerlessness, can only rely on behavioral intervention of the disease. Wang said.
, Wang's team did find differences in the composition of intestinal bacteria between autistic and healthy control children in early work using 16S RNA sequencing. However, even in healthy populations, the microbiome is extremely heterogeneic, and the microbial group is affected by complex metabolic relationships, but also in complex metabolic networks.
Based on these factors, Wang and Kang's team team applied a new macro-genome analysis strategy, class pairing analysis, in which they paired autistic groups with similar metabolic backgrounds with control group individuals to convert the original groups into pairing groups.
researchers recruited 39 autistic children and 40 control group children aged 3 to 8 years to collect their feces and morning urine for macrogenomic sequencing and urine metabolite testing, respectively. The microbial characteristics of the two groups were analyzed by boundary pairing. Urine markers and clinical assessment scores are used to verify the role of autism-related microbial characteristics.
, we found that five paths associated with intestinal detoxification in autistic children were damaged, and that all the detoxases in the path paths were reduced in the autistic group. Impaired microbial detoxification in autistic children is significantly associated with mitochondrial dysfunction and the severity of autism. The analysis of the detoxase used to build a diagnostic model of autism, can be a good distinction between autism group and health control group. Compared with healthy individuals, children with autism may experience toxin accumulation, glutathione depletion, which in turn can lead to impaired mitochondrial function and physical dysfunction due to the imbalance in the composition of the intestinal bacteria and detoxifying dysfunction, Wang said.article, industry experts generally believe the study could provide a new direction for the clinical treatment of autism. And parents are more concerned about when the results of the study will be used for treatment.
interview, Wang wei told reporters that the biggest difficulty they encountered is that autistic children are very different individuals, in the early work of the analysis of a number of inter-group differences, with the increase in the sample size, there is no longer a significant difference. "So we need to look for ways to analyze high-quality, multi-dimensional data that is suitable for the autistic microbiome."
pairing analysis developed by the Kangxuan team solved Wang's "urgent need". Kang told china Science Daily that the method can pair samples with similar metabolic background but different ideosis, exclude the common metabolic background, excavate the functional characteristics of the bacteria between the two groups of samples, and basically solve the problem of large differences in data within the group and mask differences between groups.
During the review process, the reviewers first focused on the use of class pairing analysis methods, which were used for the first time in the analysis of the gut microbiome microbiome, so the team conducted a long-term methodological certification.
for mitochondrial dysfunction, the reviewer recommended that blood samples be used for further examination. "But the relationship between impaired intestinal microbial detoxification and mitochondrial dysfunction, which we found after analyzing all the data, was not designed at the beginning of the study to specifically target mitochondrial function." Mr Wang said follow-up studies would continue to validate the results of the analysis in separate samples and analyse how damaged detox pathways might be remedied. In addition, clinical trials will be conducted in collaboration with clinicians to identify and identify possible interventions. (Source: Zhang Siwei, China Science Journal)
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