On November 2, 2021, molecular psychiatry, a top international journal in the field of mental illness under nature magazine, published the latest research results of the intestinal-immune-brain axis mechanism of the team of Professor Ma Xiancang and Zhu Feng of the First Affiliated Hospital of Xi'an Jiaotong University in the form of article, entitled "systems biological assessment of altered" cytokine responses to bacteria and fungi reveals impaired immune functionality in schizophrenia》。
Schizophrenia is a mental illness with a high disability rate, with a lifetime prevalence of about 1%, although its pathogenesis has not been fully elucidated, but the role of the peripheral immune system in the occurrence and development of the disease is receiving more and more attention. Immune disorders are thought to be a persistent pathophysiological phenomenon of schizophrenia, not just the result of the development of the disease. Epidemiological studies have also confirmed that early infections in life, as well as autoimmune diseases, lead to an increased risk of schizophrenia. However, although the causal relationship between immune alterations and schizophrenia has been studied for decades, the origin and persistence of immune activation remain unclear, and one of the important reasons is the lack of suitable in vitro models to explore functional changes in immune cell physiology. Peripheral blood mononuclear cells (pbmcs) have been shown to share many common features with brain tissue, making them suitable in vitro models of central nervous system pathology. The study systematically compared the immune responses of schizophrenia patients and healthy peripheral blood mononuclear cells (pbmcs) to ten pathogenic stimulators such as bacteria, fungi and microbial ligands, revealing the abnormal cytokine response pattern of pbmcs to pathogen stimulation in patients with schizophrenia.
The study found that after stimulation by ten pathogens or microbial ligands, cytokines induced by the same type of stimulant had a more pronounced correlation. In addition, monocyte-derived and t-cell-derived cytokines form two relatively independent clusters in healthy controls; in patients with schizophrenia, the distinction between these two clusters is significantly reduced, and many of the correlations between cytokines weaken or even disappear.
It is worth noting that the cytokine levels produced by pbmcs in patients with schizophrenia after stimulation of the microbial product cell wall acyldipeptide (mdp) are significantly lower than those of healthy controls, in addition to the results of elevated levels of mdp in the serum of patients and positive correlation with the course of the disease, indicating that the immune response weakens as the bacterial translocation increases in patients as the disease progresses. This also suggests that MDP may be one of the upstream mediators of immune activation in patients with schizophrenia, and that low levels of inflammation caused by MDP can lead to altered intestinal barrier permeability and the entry of microbial products into the peripheral circulation and potential interactions.
The study simultaneously sequenced single-cell transcriptomes of pre- and post-mdp-stimulating patients with schizophrenia and control group pbmcs cells, and found that antiviral and inflammatory programs were generally suppressed and the chemokine/cytokine-receptor interaction network was impaired in various immune cell subsets of mdp-stimulated patients with schizophrenia.
In short, the study depicts the molecular and cellular basis of impaired immune function in patients with schizophrenia, and proposes the interaction between congenital immune damage, decreased pathogen clearance, increased translocation of bacterial metabolites and passivation of innate immune response in the development of schizophrenia, which provides a new perspective and theoretical basis for the pathological mechanisms of systemic immune activation, neuroinflammation and brain abnormalities in patients with schizophrenia.
Dr. Gao Yuan and Dr. Fan Yajuan of the Class of 2018 of our university are the first authors of the paper, Professor Zhu Feng and Professor Ma Xiancang are the corresponding authors of the paper, and the First Affiliated Hospital of Xi'an Jiaotong University is the only signatory unit. Molecular Psychiatry (Molecular Psychiatry) is nature's top international journal in the field of mental illness, with a latest impact factor of 15.992. In recent years, professor Ma Xiancang and Professor Zhu Feng's team have focused on the field of genetic variation of psychiatric diseases on the international frontier scientific issues - enterobacteria - immunity - brain axis research, which is the latest research results published around the intestinal brain axis after molecular psychiatry in 2019 and nature communication in 2020. The team continues to conduct more in-depth research around the relationship between gut microbiome-mediated immune alterations and schizophrenia.
The second from the left is Professor Ma Xiancang, the third from the left is Professor Zhu Feng, the first from the right is Dr. Gao Yuan, and the third from the right is Dr. Fan Yajuan
The research has been funded by the National Natural Science Foundation of China, the Outstanding Youth Science Foundation project, and the Shaanxi Provincial Natural Science Foundation Key Project.
Zhu Feng, MD, Professor, Doctoral Supervisor, Deputy Director of the Department of Psychiatry and Psychology of the First Affiliated Hospital of Xi'an Jiaotong University, Winner of the National Natural Science Foundation of China Outstanding Youth Fund, Young Top Talent of Xi'an Jiaotong University, Visiting Scholar of Massachusetts General Hospital, Project Leader of Shaanxi Psychiatry Research Center. He is currently a youth member of the Basic and Clinical Branch of Psychiatry of the Chinese Society of Neuroscience. His main research interests are hereditary-enterobacterial-immune-brain axis of mental illness.
Ma Xiancang, Chief Physician of the Department of Psychiatry of the First Affiliated Hospital of Xi'an Jiaotong University, Doctoral Supervisor, is currently a member of the Standing Committee of the Psychiatric Branch of the Chinese Medical Association, a member of the Standing Committee of the Psychiatrist Branch of the Chinese Medical Doctor Association, a vice chairman of the Psychology and Psychiatry Professional Committee of the Chinese Research Hospital Association, a vice president of the Spirit and Psychology Branch of the Chinese Geriatric Association, a vice chairman of the Shaanxi Mental Health Association, and a chairman of the Psychiatrist Branch of the Shaanxi Medical Doctor Association. The main research direction is the genetics of mental diseases - enterobacteria - immunity - brain axis.
Article links:
https://www.nature.com/articles/s41380-021-01362-0
Source: The First Affiliated Hospital of Xi'an Jiaotong University