Study On Temperature Stress Induced Schizophrenia Episode And Intestinal Microbiome Dysregulation

Objective（1）The apparent temperature（AT）and temperature variation indicators were used to clarify the association between temperature stress and the risk of hospitalization for schizophrenia in Hefei by time series model.（2）To clarify the causal relationship between temperature stress and intestinal microbiome disturbance.（3）To analyze the difference of intestinal microbiome between schizophrenia episode and remission stage in Hefei.Methods（1）Daily meteorological data,such as temperature and humidity,and hospitalization data of schizophrenia in Hefei from 2005 to 2014 were collected,and the correlation between AT and temperature variation and its lag effect were fitted by the distributed lag nonlinear model.（2）Using a completely random design,four temperature conditions,namely high temperature,low temperature,temperature variation and room temperature,were simulated by climate chamber.The feces of mice were collected and the changes of the intestinal microbiome of mice under different temperature stress conditions were compared and analyzed by high-throughput sequencing technology of 16S r RNA.（3）Based on the case-control study design,patients with schizophrenia were recruited according to strict inclusion and exclusion criteria and were divided into episode stage and remission stage according to the severity of symptoms.The differences in the intestinal microbiome between the two groups were compared.Results（1）The effects of high AT on schizophrenia onset reached its maximum when at lag0（RR=1.062,95%CI:1.019-1.106）,and effects gradually deceased until lag6;The effects of low AT first appeared at lag3 and peaked at lag7（RR=1.018,95%CI:1.009-1.027）.TV_0-t significantly increased the risk of schizophrenia onset,and the effect showed a slight upward trend and peaked at TV_0-7（RR=1.023,95%CI:1.008-1.039）.Both high and low ATs and temperature stress can significantly increase the risk of schizophrenia,among which male patients,married patients,and patients>41 years are susceptible to temperature stress.（2）Animal experiments showed that the intestinal microbiome of mice changed significantly under different temperature stress.Heat and cold stress increased the Alpha diversity of intestinal microbiome in mice,and the composition of intestinal microbiome in the four groups was significantly different under temperature stress.Both cold and heat stress increased the relative abundance of Bacteroidetes,Ruminococcaceae and Prevotellaceae.Cold stress reduced the abundance of Firmicutes.Temperature variation stress significantly increased the relative abundance of Actinobacteria and Verrucomicrobia.（3）Alpha diversity of intestinal microbiome in schizophrenic episode was significantly higher than that in remission stage,and there were significant differences in intestinal microbiome composition.Compared with schizophrenia patients in remission stage,the relative abundance of Bacteroidetes and Ruminococcaceae increased significantly in schizophrenia in episode stage,while the relative abundance of Firmicutes and Actinomycetes decreased significantly.These temperature stress-induced changes in animal intestinal microbiome were also found in patients with schizophrenia in episode stage.Conclusions Temperature stress can significantly increase the risk of schizophrenia and alter the diversity of intestinal microbiome in normal mice.Similar changes in intestinal microbiome have been observed in schizophrenia in episode stage.Temperature stress causes the onset of schizophrenia by affecting the changes in intestinal microbiome.