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Constipation induced gut microbiota dysbiosis exacerbates experimental autoimmune encephalomyelitis in C57BL/6 mice. 2021

Xiuli Lin, and Yingying Liu, and Lili Ma, and Xiaomeng Ma, and Liping Shen, and Xueying Ma, and Zhaoyu Chen, and Hao Chen, and Donghong Li, and Zhumin Su, and Xiaohong Chen
Department of Neurology and Multiple Sclerosis Research Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.

Constipation is a common gastrointestinal dysfunction which has a potential impact on people's immune state and their quality of life. Here we investigated the effects of constipation on experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Constipation was induced by loperamide in female C57BL/6 mice. The alternations of gut microbiota, permeability of intestinal barrier and blood-brain barrier, and histopathology of colon were assessed after constipation induction. EAE was induced in the constipation mice. Fecal microbiota transplantation (FMT) was performed from constipation mice into microbiota-depleted mice. Clinical scores, histopathology of inflammation and demyelination, Treg/Th17 and Treg17/Teff17 imbalance both in the peripheral lymphatic organs and central nervous system, cytokines include TGF-β, GM-CSF, IL-10, IL-17A, IL-17F, IL-21, IL-22, and IL-23 in serum were assessed in different groups. Compared with the vehicle group, the constipation mice showed gut microbiota dysbiosis, colon inflammation and injury, and increased permeability of intestinal barrier and blood-brain barrier. We found that the clinical and pathological scores of the constipation EAE mice were severer than that of the EAE mice. Compared with the EAE mice, the constipation EAE mice showed reduced percentage of Treg and Treg17 cells, increased percentage of Th17 and Teff17 cells, and decreased ratio of Treg/Th17 and Treg17/Teff17 in the spleen, inguinal lymph nodes, brain, and spinal cord. Moreover, the serum levels of TGF-β, IL-10, and IL-21 were decreased while the GM-CSF, IL-17A, IL-17F, IL-22, and IL-23 were increased in the constipation EAE mice. In addition, these pathological processes could be transferred via their gut microbiota. Our results verified that constipation induced gut microbiota dysbiosis exacerbated EAE via aggravating Treg/Th17 and Treg17/Teff17 imbalance and cytokines disturbance in C57BL/6 mice.

UI MeSH Term Description Entries
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D011788 Quality of Life A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral, social environment as well as health and disease. HRQOL,Health-Related Quality Of Life,Life Quality,Health Related Quality Of Life
D003248 Constipation Infrequent or difficult evacuation of FECES. These symptoms are associated with a variety of causes, including low DIETARY FIBER intake, emotional or nervous disturbances, systemic and structural disorders, drug-induced aggravation, and infections. Colonic Inertia,Dyschezia
D004681 Encephalomyelitis, Autoimmune, Experimental An experimental animal model for central nervous system demyelinating disease. Inoculation with a white matter emulsion combined with FREUND'S ADJUVANT, myelin basic protein, or purified central myelin triggers a T cell-mediated immune response directed towards central myelin. The pathologic features are similar to MULTIPLE SCLEROSIS, including perivascular and periventricular foci of inflammation and demyelination. Subpial demyelination underlying meningeal infiltrations also occurs, which is also a feature of ENCEPHALOMYELITIS, ACUTE DISSEMINATED. Passive immunization with T-cells from an afflicted animal to a normal animal also induces this condition. (From Immunol Res 1998;17(1-2):217-27; Raine CS, Textbook of Neuropathology, 2nd ed, p604-5) Autoimmune Encephalomyelitis, Experimental,Encephalomyelitis, Allergic,Encephalomyelitis, Experimental Autoimmune,Allergic Encephalomyelitis,Allergic Encephalomyelitis, Experimental,Autoimmune Experimental Encephalomyelitis,Experimental Allergic Encephalomyelitis,Experimental Autoimmune Encephalomyelitis,Encephalomyelitis, Autoimmune Experimental,Encephalomyelitis, Experimental Allergic,Experimental Allergic Encephalomyelitides,Experimental Encephalomyelitis, Autoimmune
D005260 Female Females
D000069196 Gastrointestinal Microbiome All of the microbial organisms that naturally exist within the GASTROINTESTINAL TRACT. Enteric Bacteria,Gastric Microbiome,Gastrointestinal Flora,Gastrointestinal Microbial Community,Gastrointestinal Microbiota,Gastrointestinal Microflora,Gut Flora,Gut Microbiome,Gut Microbiota,Gut Microflora,Intestinal Flora,Intestinal Microbiome,Intestinal Microbiota,Intestinal Microflora,Bacteria, Enteric,Flora, Gastrointestinal,Flora, Gut,Flora, Intestinal,Gastric Microbiomes,Gastrointestinal Microbial Communities,Gastrointestinal Microbiomes,Gastrointestinal Microbiotas,Gut Microbiomes,Gut Microbiotas,Intestinal Microbiomes,Intestinal Microbiotas,Microbial Community, Gastrointestinal,Microbiome, Gastric,Microbiome, Gastrointestinal,Microbiome, Gut,Microbiome, Intestinal,Microbiota, Gastrointestinal,Microbiota, Gut,Microbiota, Intestinal,Microflora, Gastrointestinal,Microflora, Gut,Microflora, Intestinal
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D016207 Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Cytokine
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D058504 Th17 Cells A subset of helper-effector T-lymphocytes which synthesize and secrete INTERLEUKINS IL-17; IL-17F; and IL-22. These cytokines are involved in host defenses and tissue inflammation in autoimmune diseases. T Helper 17 Cell,TH-17 Cell,Th17 Cell,Type 17 Helper T Cell,T Helper 17 Cells,TH-17 Cells,Type 17 Helper T Cells,Cell, TH-17,Cell, Th17,Cells, TH-17,Cells, Th17,TH 17 Cell,TH 17 Cells

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