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Background: Probiotics are a potentially effective therapy for inflammatory bowel disease (IBD); IBD is linked to impaired gut microbiota and intestinal immunity. However, the utilization of an antibiotic cocktail (Abx) prior to the probiotic intervention remains controversial. This study aims to identify the effect of Abx pretreatment from dextran sulfate sodium (DSS)-induced colitis and to evaluate whether Abx pretreatment has an enhanced effect on the protection of Clostridium butyricum Miyairi588 (CBM) from colitis. Results: The inflammation, dysbiosis, and dysfunction of gut microbiota as well as T cell response were both enhanced by Abx pretreatment. Additionally, CBM significantly alleviated the DSS-induced colitis and impaired gut epithelial barrier, and Abx pretreatment could enhance these protective effects. Furthermore, CBM increased the benefit bacteria abundance and short-chain fatty acids (SCFAs) level with Abx pretreatment. CBM intervention after Abx pretreatment regulated the imbalance of cytokines and transcription factors, which corresponded to lower infiltration of Th1 and Th17 cells, and increased Th2 cells. Conclusions: Abx pretreatment reinforced the function of CBM in ameliorating inflammation and barrier damage by increasing beneficial taxa, eliminating pathogens, and inducing a protective Th2 cell response. This study reveals a link between Abx pretreatment, microbiota, and immune response changes in colitis, which provides a reference for the further application of Abx pretreatment before microbiota-based intervention. [ABSTRACT FROM AUTHOR]

Background and Aim: Autophagy and gut microbiota correlates closely with the inflammatory bowel disease. Herein, we aimed to study the roles of rapamycin on the gut microbiota in inflammatory bowel disease. Methods: Acute colitis was induced with dextran sodium sulfate (DSS) and 2,4,6‐trinitrobenzenesulfonic acid solution in mice. Mice were administered with rapamycin or hydroxychloroquine. Weight loss, disease activity index scores, histopathological score, serum inflammatory cytokines, intestinal permeability, and colonic autophagy‐related proteins were detected. Cecal content was also preserved in liquid nitrogen and subsequently analyzed following the 16S DNA sequencing. The antibiotic cocktail‐induced microbiome depletion was performed to further investigate the relationship between autophagy activation and gut microbiota. Results: Compared with the control group, the colonic autophagy‐related proteins of P62, mTOR, and p‐mTOR increased significantly, while the levels of LC3B and ATG16L1 decreased (all P < 0.05) in the model group. After rapamycin intervention, the colonic pathology of mice improved, while the disease activity index score decreased substantially; the colon length increased, and the expression of IL‐6 and TNF‐α decreased. Following hydroxychloroquine treatment, some indicators suggested aggravation of colitis. Principal coordinates analysis showed that the DSS group was located on a separate branch from the rapamycin group but was closer to the hydroxychloroquine group. Compared with the DSS group, the rapamycin group was associated with higher abundances of f_Lactobacillaceae (P = 0.0151), f_Deferribacteraceae (P = 0.0290), g_Lactobacillus (P = 0.0151), g_Mucispirillum (P = 0.0137), s_Lactobacillus_reuteri (P = 0.0028), and s_Clostridium sp Culture_Jar‐13 (P = 0.0082) and a lower abundance of s_Bacteroides_sartorii (P = 0.0180). Linear discriminant analysis effect size showed that rapamycin increased the abundances of Lactobacillus‐reuteri, Prevotellaceae, Paraprevotella, Christensenella and Streptococcus and decreased those of Peptostreptococcaceae and Romboutsia Bacteroides‐sartorii. Besides, the improvement effect of autophagy activation on colitis disappears following gut microbiome depletion. Conclusion: The therapeutic effects of rapamycin on extenuating experimental colitis may be related to the gut microbiota. [ABSTRACT FROM AUTHOR]