Low-dose penicillin exposure in early life decreases Th17 and the susceptibility to DSS colitis in mice through gut microbiota modification

Jin, Shuang; Zhao, Di; Cai, Chenwen; Song, Dongjuan; Shen, Jun; Xu, Antao; Qiao, Yongxia; Ran, Zhihua; Zheng, Qing

doi:10.1038/srep43662

Cited by 58 publications

(51 citation statements)

References 62 publications

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“…This phenomenon was consistent with findings in a previous study, which demonstrated distinct expansion in the abundance of SFB in the small intestines of mice lacking activation-induced cytidine deaminase and immunoglobulin A (7,58). In addition, treatment with antibiotics inhibited colo-nization by SFB (59). These results hint that loss of selective stressors, including immune pressure or antibiotics, may enable overcolonization of SFB in the intestine.…”

supporting

confidence: 92%

Impaired Autophagy in Intestinal Epithelial Cells Alters Gut Microbiota and Host Immune Responses

Yang

Liu

Zhao

et al. 2018

Appl Environ Microbiol

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Establishing and maintaining beneficial interactions between the host and associated gut microbiota are pivotal requirements for host health. Autophagy is an important catabolic recycling pathway that degrades long-lived proteins and some organelles by lysosome to maintain cellular homeostasis. Although impaired autophagy is thought to be closely correlated with Crohn's disease (CD), the functional role of autophagy in the maintenance of gut microbiota is poorly understood. As autophagy-related 5 () is a key gene associated with the extension of the phagophoric membrane in autophagic vesicles, we established a gut-specific knockout mouse model, and we found that the disruption of autophagic flux in the intenstinal epithelium cells dramatically altered the composition of the gut microbiota and reduced alpha diversity. Microbial function prediction indicated that the pathway allocated for infectious diseases was enriched in mice. " Arthromitus" and the family were increased in mice, whereas and the family were reduced. Transcriptome analysis revealed that two key inflammatory bowel disease (IBD)-related transcription factors, RORC and TBX21, of host cells were upregulated in mice, thus elevating the Muc2-related immunological response. The findings suggest that intestinal autophagy plays a vital role in modulating the diversity and composition of gut microbiota. The homeostasis of host-microbiota interactions is of great importance to host health. Previous studies demonstrated that disruption of autophagy was linked to inflammatory bowel disease. However, the interaction mechanism of gut microbiota regulated by autophagy was obscure. In an intestinal epithelium-specific autophagy-related 5 () knockout mouse model, we observed a significant alteration and decreased diversity in the gut microbiota of -deficient mice compared with that of wild-type mice. Although the numbers of some organisms (e.g., and members of the family) associated with the control of inflammation decreased, those of proinflammationory bacteria (e.g., " Arthromitus") and potential pathogens (the family) increased in mice. Differential gene expression analysis revealed that two key genes, and, involved in inflammatory bowel disease were upregulated in mice. Our study suggests that deficiency results in an imbalance of the host-microbe interaction and deterioration of the gut microenvironment.

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supporting

confidence: 92%

Impaired Autophagy in Intestinal Epithelial Cells Alters Gut Microbiota and Host Immune Responses

Yang

Liu

Zhao

et al. 2018

Appl Environ Microbiol

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“…Prior work has shown that SFB colonization can be modulated by diet, (138,139) probiotics, (140) and antibiotics. (141)(142)(143) This highlights the potential for the development of noninvasive clinical interventions in the pediatric gut microbiome, which could be utilized to support postpubertal skeletal growth and maturation. Although SFB colonizes humans and upregulates T H 17 pathway genes, (24,31) it is important to note other commensals have been shown to clinically induce T H 17/IL17A-mediated immunity.…”

Section: Discussionmentioning

confidence: 99%

Specific Commensal Bacterium Critically Regulates Gut Microbiota Osteoimmunomodulatory Actions During Normal Postpubertal Skeletal Growth and Maturation

et al. 2020

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The commensal gut microbiota critically regulates immunomodulatory processes that influence normal skeletal growth and maturation. However, the influence of specific microbes on commensal gut microbiota osteoimmunoregulatory actions is unknown. We have shown previously that the commensal gut microbiota enhances TH17/IL17A immune response effects in marrow and liver that have procatabolic/antianabolic actions in the skeleton. Segmented filamentous bacteria (SFB), a specific commensal gut bacterium within phylum Firmicutes, potently induces TH17/IL17A‐mediated immunity. The study purpose was to delineate the influence of SFB on commensal gut microbiota immunomodulatory actions regulating normal postpubertal skeletal development. Two murine models were utilized: SFB‐monoassociated mice versus germ‐free (GF) mice and specific‐pathogen‐free (SPF) mice +/− SFB. SFB colonization was validated by 16S rDNA analysis, and SFB‐induced TH17/IL17A immunity was confirmed by upregulation of Il17a in ileum and IL17A in serum. SFB‐colonized mice had an osteopenic trabecular bone phenotype, which was attributed to SFB actions suppressing osteoblastogenesis and enhancing osteoclastogenesis. Intriguingly, SFB‐colonized mice had increased expression of proinflammatory chemokines and acute‐phase reactants in the liver. Lipocalin‐2 (LCN2), an acute‐phase reactant and antimicrobial peptide, was substantially elevated in the liver and serum of SFB‐colonized mice, which supports the notion that SFB regulation of commensal gut microbiota osteoimmunomodulatory actions are mediated in part through a gut–liver–bone axis. Proinflammatory TH17 and TH1 cells were increased in liver‐draining lymph nodes of SFB‐colonized mice, which further substantiates that SFB osteoimmune‐response effects may be mediated through the liver. SFB‐induction of Il17a in the gut and Lcn2 in the liver resulted in increased circulating levels of IL17A and LCN2. Recognizing that IL17A and LCN2 support osteoclastogenesis/suppress osteoblastogenesis, SFB actions impairing postpubertal skeletal development appear to be mediated through immunomodulatory effects in both the gut and liver. This research reveals that specific microbes critically impact commensal gut microbiota immunomodulatory actions regulating normal postpubertal skeletal growth and maturation. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

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“…45,46 Some case reports provide evidence that SFB could be detected at certain inflammatory sites both in ulcerative colitis (UC) and Chrons disease (CD) patients, while depletion of SFB by penicillin decreased Th17 and susceptibility to Dextran Sodium Sulfate (DSS)-induced colitis in mice. 47 On the other hand, SFB colonization could be important for the defense against bacterial pathogens, for instance, antibiotic use reduced SFB and Th17 cell numbers, decreasing resistance against intestinal pathogen Citrobacter rodentium (C. rodentium) infection. In contrast, colonization of mice with SFB conferred higher resistance to C. rodentium and was correlated with increased expression of genes associated with inflammation and antimicrobial defenses.…”

Section: Microbiota Shapes the Development Of The Immune System And Hmentioning

confidence: 99%

Intestinal barrier and gut microbiota: Shaping our immune responses throughout life

2017

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The gastrointestinal (GI) tract is considered the largest immunological organ in the body having a central role in regulating immune homeostasis. Contrary to earlier belief, the intestinal epithelial barrier is not a static physical barrier but rather strongly interacts with the gut microbiome and cells of the immune system. This intense communication between epithelial cells, immune cells and microbiome will shape specific immune responses to antigens, balancing tolerance and effector immune functions. Recent studies indicate that composition of the gut microbiome affects immune system development and modulates immune mediators, which in turn affect the intestinal barrier. Moreover, dysbiosis may favor intestinal barrier disruption and could be related to increased susceptibility to certain diseases. This review will be focused on the development of the intestinal barrier and its function in host immune defense and how gut microbiome composition throughout life can affect this role.

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Low-dose penicillin exposure in early life decreases Th17 and the susceptibility to DSS colitis in mice through gut microbiota modification

Cited by 58 publications

References 62 publications

Impaired Autophagy in Intestinal Epithelial Cells Alters Gut Microbiota and Host Immune Responses

Impaired Autophagy in Intestinal Epithelial Cells Alters Gut Microbiota and Host Immune Responses

Specific Commensal Bacterium Critically Regulates Gut Microbiota Osteoimmunomodulatory Actions During Normal Postpubertal Skeletal Growth and Maturation

Intestinal barrier and gut microbiota: Shaping our immune responses throughout life

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