| Objective: Schizophrenia is a group of mental disorders with unknown etiology,whose clinical characteristics mainly include positive symptoms,negative symptoms and cognitive impairment.Changes will be taken place in not only the brain structure and volume but also in some brain regions function of patients with schizophrenia.With the development of functional magnetic resonance imaging(fMRI),researchers have found that regional consistency and abnormal low-frequency amplitudes will exhibit in multiple brain regions of patients with schizophrenia.In addition,some researches have suggested that changes have also taken place to a certain extent in the intestinal flora of patients with schizophrenia when changes have taken place in brain regions function.It has been proved that the difference of dominant flora in human gut can affect the brain development of host,whose cognitive level will be influenced by the abundance of lactic acid bacteria.However,studies on the correlation between intestinal flora changes and brain function in patients with schizophrenia have not been reported yet.Hence,it is urgent to explore the correlation between intestinal flora changes and brain function in patients with schizophrenia.Methods: This study is a cross-sectional study.A total of 21 outpatient or inpatient patients in Beijing Huilongguan hospital who met the inclusion and exclusion criteria were enrolled in this study,and 30 healthy subjects were enrolled in Beijing Huilongguan hospital during the same period.The inclusion criteria of PG were as follows:(1)definite diagnosis of schizophrenia according to ICD-10 criteria;(2)20-55 years old;(3)regular defecation(1-3 times /1-3 days).The inclusion criteria of HC were as follows:(1)age 20-55 years;(2)regular defecation(1-3 times /1-3 days);(3)without the disease may affect the internal movement.Exclusion criteria were as follows:(1)patients with any contraindications to MRI were excluded;(2)exclude patients with other mental disorders explicitly diagnosed by clinicians;(3)exclude patients suffering from serious physical disease,and patients having done surgery except appendicitis surgery;(4)antibiotics,contraceptive or non-steroidal anti-inflammatory were used in the first four weeks;(5)pregnant or nursing women;(6)patients who changed their eating habits within the past four weeks.The severity of each patient with schizophrenia was assessed by using the Positive and Negative Symptom Scale.Resting magnetic resonance imaging(rest-MRI)images were collected from PG.Fecal samples of every volunteers were collected and 16 S rRNA high-throughput sequencing was performed to explore the differences in flora between PG and HC.To explore the correlation between gut flora and brain function in patients with schizophrenia,the correlation between different brain regions and different microflora was analyzed.Results: First of all,there was no significant difference in age,height,weight and gender between two groups.Secondly,based on high-throughput sequencing,we found significant differences in the structure of gut flora between schizophrenia patients and healthy people.Dominant bacteria of patients with Schizophrenia and healthy people were Firmicutes,Bacteroidetes and Proteobacteria.Compared with healthy people,the abundance of the Actinomycetes and its subordinate flora such as Coriobacteriia(p=0.014),Coriobacteriales(p=0.018),Collinsella(p=0.033)of the Schizophrenic significantly increased.Although there was no significant difference in Proteobacteria abundance between the two groups,a significant increase has taken place in the abundance of Oceanospirillales(p=0.001),Rhizobiales(p=0.001),Pseudomonadales(p=0.001)which were subordinate bacteria of proteobacteria.In addition,based on the LEfSe analysis,we found that there were 23 bacterial species whose abundance was different between two groups.According to LEfSe analysis,8 species of bacteria(Actinomycetes,Coriobacteriia,Gamma-proteobacteria,Coriobacteriales,Coriobacteriaceae,Megasphaera and Collinsella)with significantly increased abundance in patients with schizophrenia were selected for correlation analysis with amplitude of low frequency fluctuations(ALFF)and Regional Homogeneity(ReHo)in the brain of patients.First of all,based on the correlation analysis of ALFF and flora,the brain regions with significant positive correlation with Actinomycetes were prefrontal lobe and right medial frontal gyrus;the brain region with significant positive correlation with Acidminococcaceae was the occipital lobe,and the one with significant negative correlation was the temporal lobe.Secondly,in this study,we have found that the ALFF correlations of Coriobacteriia,Coriobacteriales and Coriobacteriaceae were basically consistent.The brain regions with significant positive correlation were dorsolateral prefrontal cortex(DLPFC),sensorimotor and left superior occipital gyrus(LSOG),while those with significant negative correlation were medial superior frontal gyrus and TL.And the brain regions with significant positive correlation with Collonsella were left medial frontal gyrus(LMFG),sensorimotor and right intraorbital superior frontal gyrus.In addition,the brain regions with significant positive correlation with Gamma-proteobacteria were sensorimotor and SOG,and those with significant negative correlation includes right orbital medial frontal gyrus(ROMFG).The brain regions with significant positive correlation with Megasphaera were LSOG and LMFG,while the one with significant negative correlation was ROMFG.According to the correlation analysis between ReHo and intestinal flora,first of all,the brain regions with significant positive correlation with Actinomycetes in patients with schizophrenia were sensorimotor and DLPFC,while those with significant negative correlation were inferior temporal gyrus and middle temporal lobe.Secondly,the sensorimotor and DLPFC were the brain regions significantly positively correlated with Coriobacteriia in patients with schizophrenia,and left inferior temporal gyrus and right middle temporal gyrus were the brain regions significantly negatively correlated with it.The brain regions with significant positive correlation with Proteobacteria were right inferior temporal gyrus and right middle frontal gyrus,while those with significant negative correlation were left superior occipital gyrus and left medial superior frontal gyrus.Conclusion: First of all,this study has found that the intestinal microflora structure of patients with schizophrenia was significantly different from that of healthy people.The abundance of Coriobacteriia,Oceanospirillales increased significantly,while that of Lachnospiraceae and Bacteroides decreased significantly.Secondly,this study has found that the significantly increased intestinal flora in patients with schizophrenia was associated with the activation of brain regions such as DLPFC and sensorimotor.The correlation between Coriobacteriia and DLPFC suggests that the increased abundance of Coriobacteriia may be one of the causes of negative symptoms and cognitive impairment in patients with schizophrenia. |
PDF Full Text Request