Abstract
BackgroundConstipation 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).MethodsConstipation 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.ResultsCompared 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.ConclusionsOur 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.
Highlights
Constipation is a common gastrointestinal dysfunction which has a potential impact on people’s immune state and their quality of life
We observed that the Prevotella, Ruminococcus, and Turicibacter were increased while the Lactobacillus was decreased in constipation mice (Fig. 1f )
The linear discriminant analysis (LDA) score showed that constipation greatly increased the levels of Turicibacter and Ruminococcus while decreased the levels of Lactobacillus compared to vehicle mice
Summary
Constipation is a common gastrointestinal dysfunction which has a potential impact on people’s immune state and their quality of life. Constipation is a common clinical symptom of gastrointestinal dysfunction worldwide. It is characterized by difficult or infrequent passage of stool, hardness of stool, and/or a feeling of incomplete evacuation [1, 2]. Due. Lin et al J Transl Med (2021) 19:317 to the stressful lifestyle, the prevalence of constipation is estimated to be as high as 20% in some populations including Asia [3,4,5]. Lin et al J Transl Med (2021) 19:317 to the stressful lifestyle, the prevalence of constipation is estimated to be as high as 20% in some populations including Asia [3,4,5] It affects the quality of people’s life among all ages and genders [3,4,5]. The alterations in gut microbiota have been implicated in the pathogenesis of both intestinal and non-intestinal autoimmune diseases such as ulcerative colitis and Crohn’s disease, rheumatoid arthritis and multiple sclerosis (MS) [6,7,8]
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