Gut Microbiota Interventions With Clostridium butyricum and Norfloxacin Modulate Immune Response in Experimental Autoimmune Encephalomyelitis Mice

Abstract

Gut microbiota has been proposed as an important environmental factor which can intervene and modulate central nervous system autoimmunity. Here, we altered the composition of gut flora with Clostridium butyricum and norfloxacin in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. We found that appropriate C. butyricum (5.0 × 10 6 CFU/mL intragastrically daily, staring at weaning period of age) and norfloxacin (5 mg/kg intragastrically daily, 1 week prior to EAE induction) treatment could both ameliorate EAE although there are obvious differences in gut microbiota composition between these two interventions. C. butyricum increased while norfloxacin decreased the abundance and diversity of the gut microbiota in EAE mice, and both of the treatments decreased firmicutes / bacteroidetes ratio. In the genus level, C. butyricum treatment increased the abundance of Prevotella while Akkermansia and Allobaculum increased in norfloxacin treatment. Moreover, both interventions reduced Desulfovibroneceae and Ruminococcus species. Although there was discrepancy in the gut microbiota composition with the two interventions, C. butyricum and norfloxacin treatment both reduced Th17 response and increased Treg response in the gastrointestinal tract and extra-gastrointestinal organ systems in EAE mice. And the reduced activity of p38 mitogen-activated kinase and c-Jun N-terminal kinase signaling in spinal cord could be observed in the two interventions. The results suggested that manipulation of gut microbiota interventions should take factors such as timing, duration, and dosage into consideration. The discrepancy in the gut microbiota composition and the similar protective T cells response of C. butyricum and norfloxacin implies that achieving intestinal microecology balance by promoting and/or inhibiting the gut microbiota contribute to the well-being of immune response in EAE mice.

Association of Probiotic Clostridium butyricum Therapy with Survival and Response to Immune Checkpoint Blockade in Patients with Lung Cancer

“…In subgroup analysis of patients with or without antibiotic therapy prior to initiation of ICB, the impact of probiotic CBT on patients' survival were more significant in cancer patients who receiving antibiotic therapy than those who did not receiving antibiotic therapy , suggesting that a clinical setting of probiotic CBT under the condition of antibiotic use may be necessary to maximize the benefit from probiotic CBT and detect a beneficial effect of probiotic CBT. Probiotic CBT improve dysbiosis under the condition of antibiotic therapies (8)(9)(10)(11)(13)(14)(15). Bifidobacterium, which promotes antitumor immunity and facilitates efficacy of ICB, is significantly increased in combination with probiotic CBT and clindamycin when compared with only probiotic CBT (13,15), suggesting that a combination therapy of probiotic CBT with antibiotics to deplete microbial communities could potentially improve responses to ICB therapy (20).…”

Clinical Features and Gut Microbial Alterations in Anti-leucine-rich Glioma-Inactivated 1 Encephalitis—A Pilot Study

“…The protocol of 16S rRNA sequencing was based on our previous studies (17). The QIAamp DNA Stool Mini Kit (Qiagen, Germany) was applied to extract the bacterial DNA from stool samples.…”

Probiotics in Treatment of Viral Respiratory Infections and Neuroinflammatory Disorders

“…The abundance and diversity of the gut microbiota were increased in C. butyricum-treated EAE mice while decreased in norfloxacin group; although both interventions reduced the firmicutes/bacteroidetes ratio. In both groups, a decrease in Th17 response and an increase in Tregs response were observed [139].…”

“…Interestingly, L. reuteri intake modified the relative frequency of these taxa [138]. Chen et al (2019) examined the effect of treatment of mice with either probiotic Clostridium butyricum (C. butyricum), a butyric acid-producing bacterium, (3 weeks before EAE induction) or antibiotic norfloxacin (one week before EAE induction) on gut microbiota and immune response in EAE mice [139]. Despite differences in gut microbiota composition between groups, both treatments alleviated EAE.…”