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De-feng Li,1,* Mei-feng Yang,2,* Jing Xu,3 Hao-ming Xu,3 Min-zheng Zhu,3 Yu-jie Liang,4 Yuan Zhang,5 Cheng-mei Tian,6 Yu-qiang Nie,3 Rui-yue Shi,1 Li-sheng Wang,1 Jun Yao1 1Department of Gastroenterology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, People’s Republic of China; 2Department of Hematology, Yantian District People’s Hospital, Shenzhen, People’s Republic of China; 3Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People’s Hospital (School of Medicine of South China University of Technology), Guangzhou, People’s Republic of China; 4Department of Child and Adolescent Psychiatry, Shenzhen Kangning Hospital, Shenzhen, People’s Republic of China; 5Department of Medical Administration, Huizhou Institute of Occupational Diseases Control and Prevention, Huizhou, People’s Republic of China; 6Department of Emergency, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li-sheng Wang; Jun Yao, Department of Gastroenterology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), No. 1017, Dongmen North Road, Luohu District, Shenzhen, 518020, People’s Republic of China, Tel +86 755 25533018, Email wanglsszrmyy@163.com; yao.jun@szhospital.comAbstract: The recent rapid development in the field of extracellular vesicles (EVs) based nanotechnology has provided unprecedented opportunities for nanomedicine platforms. As natural nanocarriers, EVs such as exosomes, exosome-like nanoparticles and outer membrane vesicles (OMVs), have unique structure/composition/morphology characteristics, and show excellent physical and chemical/biochemical properties, making them a new generation of theranostic nanomedicine. Here, we reviewed the characteristics of EVs from the perspective of their formation and biological function in inflammatory bowel disease (IBD). Moreover, EVs can crucially participate in the interaction and communication of intestinal epithelial cells (IECs)-immune cells-gut microbiota to regulate immune response, intestinal inflammation and intestinal homeostasis. Interestingly, based on current representative examples in the field of exosomes and exosome-like nanoparticles for IBD treatment, it is shown that plant, milk, and cells-derived exosomes and exosome-like nanoparticles can exert a therapeutic effect through their components, such as proteins, nucleic acid, and lipids. Moreover, several drug loading methods and target modification of exosomes are used to improve their therapeutic capability. We also discussed the application of exosomes and exosome-like nanoparticles in the treatment of IBD. In this review, we aim to better and more clearly clarify the underlying mechanisms of the EVs in the pathogenesis of IBD, and provide directions of exosomes and exosome-like nanoparticles mediated for IBD treatment.Keywords: extracellular vesicles, exosome, exosome-like nanoparticles, inflammatory bowel disease, theranostic

Asperger syndrome (AS) is a chronic neurodevelopmental disorder. Although all of the clinically diagnosed cases display normal intelligence and speech functions, barriers in social interaction and communication seriously affect mental health and psychological function. In addition to traditional psychological/behavioral training and symptomatic medication, in-depth studies of intestinal microbiota and mental health have indicated that probiotics (e.g., Lactobacillus rhamnosus) can effectively reduce the occurrence of AS. Fecal microbiota transplantation (FMT) is a type of biological therapy that involves the transplant of intestinal microbiota from healthy donors into the patient's gastrointestinal tract to improve the gut microenvironment. In this case report, we describe the first case of adult AS treated with FMT. The patient suffered from diarrhea-predominant irritable bowel syndrome for 6 years with symptoms of diarrhea and abdominal pain. After three rounds of FMT, the diarrhea and abdominal pain were significantly improved. Moreover, the symptoms of AS were also significantly ameliorated. We found that FMT changed the structure of the intestinal microbiota as well as the patient's serum metabolites, and these changes were consistent with the patient's symptoms. The metabolites may affect signaling pathways, as revealed by Kyoto Encyclopedia of Genes and Genomes enrichment analysis. The changes in microbial metabolites following FMT may affect other regions (e.g., the nervous system) via the circulatory system, such that the bacteria-gut-blood-brain axis may be the means through which FMT mitigates AS.

Quan Lu,1,2,* Mei-feng Yang,3,* Yu-jie Liang,4,* Jing Xu,5 Hao-ming Xu,5 Yu-qiang Nie,5 Li-sheng Wang,1,2 Jun Yao,1,2 De-feng Li1,2 1Department of Gastroenterology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University), Shenzhen, Guangdong, People’s Republic of China; 2Department of Gastroenterology, Shenzhen People’s Hospital (The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, People’s Republic of China; 3Department of Hematology, Yantian District People’s Hospital, Shenzhen, Guangdong, People’s Republic of China; 4Department of Child and Adolescent Psychiatry, Shenzhen Kangning Hospital, Shenzhen, Guangdong, People’s Republic of China; 5Department of Gastroenterology and Hepatology, Guangzhou First People’s Hospital (School of Medicine of South China University of Technology), Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun Yao; De-feng Li, Department of Gastroenterology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University), No. 1017, Dongmen North Road, Luohu District, Shenzhen, 518020, People’s Republic of China, Tel +86 755 25533018, Email yao.jun@szhospital.com; ldf830712@163.comAbstract: As a main digestive organ and an important immune organ, the intestine plays a vital role in resisting the invasion of potential pathogens into the body. Intestinal immune dysfunction remains important pathogenesis of inflammatory bowel disease (IBD). In this review, we explained the interactions among symbiotic flora, intestinal epithelial cells, and the immune system, clarified the operating mechanism of the intestinal immune system, and highlighted the immunological pathogenesis of IBD, with a focus on the development of immunotherapy for IBD. In addition, intestinal fibrosis is a significant complication in patients with long-term IBD, and we reviewed the immunological pathogenesis involved in the development of intestinal fibrogenesis and provided novel antifibrotic immunotherapies for IBD.Keywords: inflammatory bowel disease, immune system, immunological pathogenesis, immunotherapy

Additional file 3: Table S1. The demographic and clinical characteristics of 15 UC patients.

Additional file 1: Figure S1. DSS alters β-diversity (PCA & PCoA) of gut microbiota in mice models of colitis. (A) PCA (Principal Component Analysis). The PC1 coordinate indicates the primary principal component while its contribution value to sample variability is depicted in percentage in brackets. The PC2 coordinate represents the second principal component while its contribution value to sample variability is depicted in percentage in brackets. Samples are represented by colored dots in the panel. Sample compositions which are similar are located more closely together on the PCA diagram. Samples of various different environments signify their respective aggregation distribution. (B) PCoA (Principal Co-ordinate Analysis). PCoA is a dimension reduction analysis based on the distance matrix, and the percentage (the number in brackets of the axis title) is used to evaluate the explanation degree of each coordinate axis to the overall difference of microbial structure. Generally, it is better that the sum of PCoA1 and PCoA2 is more than 50%. Table S1. Alterations of microbial structure at different levels in acute / chronic colitis mice.

Gut dysbacteriosis is closely related to various intestinal and extraintestinal diseases. Fecal microbiota transplantation (FMT) is a biological therapy that entails transferring the gut microbiota from healthy individuals to patients in order to reconstruct the intestinal microflora in the latter. It has been proved to be an effective treatment for recurrent Clostridium difficile infection. Studies show that the gut microbiota plays an important role in the pathophysiology of neurological and psychiatric disorders through the microbiota-gut-brain axis. Therefore, reconstruction of the healthy gut microbiota is a promising new strategy for treating cerebral diseases. We have reviewed the latest research on the role of gut microbiota in different nervous system diseases as well as FMT in the context of its application in neurological, psychiatric, and other nervous system-related diseases (Parkinson’s disease, Alzheimer’s disease, multiple sclerosis, epilepsy, autism spectrum disorder, bipolar disorder, hepatic encephalopathy, neuropathic pain, etc.).