Antibiotic-induced acceleration of type 1 diabetes alters maturation of innate intestinal immunity

Zhang, Xue Song; Li, Jackie; Krautkramer, Kimberly A.; Badri, Michelle; Battaglia, Thomas; Borbet, Timothy C.; Koh, Hyunwook; Ng, Sandy; Sibley, Rachel A; Li, Yuanyuan; Pathmasiri, Wimal; Sk, Jindal; Shields-Cutler, Robin R.; Hillmann, Ben; Al‐Ghalith, Gabriel A.; Ruiz, Victoria; Livanos, Alexandra E.; Wout, Angélique B. van‘t; Nagalingam, Nabeetha A.; Rogers, Arlin B.; Sumner, Susan; Knights, Dan; Denu, John M.; Li, Huilin; Ruggles, Kelly V.; Bonneau, Richard; Williamson, R. Anthony; Rauch, Marcus; Blaser, Martin J.

doi:10.7554/elife.37816

Cited by 75 publications

(91 citation statements)

References 143 publications

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“…We aimed to determine whether exposure to a single antibiotic course early-in-life would increase the severity of the experimental colitis induced in mice by DSS challenge. Nursing dams were given a pulsed antibiotic treatment (PAT) using therapeutic doses of the macrolide antibiotic, tylosin, in their drinking water from day 5 to 10 of life of their pups, as we have described [16,32,33]. The pups were exposed to the antibiotic in the milk ingested from their mother.…”

Section: Effects Of a Single Early-life Antibiotic Course On The Sevementioning

confidence: 99%

A single early-in-life antibiotic course increases susceptibility to DSS-induced colitis

et al. 2020

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Background: There is increasing evidence that the intestinal microbiota plays a crucial role in the maturation of the immune system and the prevention of diseases during childhood. Early-life short-course antibiotic use may affect the progression of subsequent disease conditions by changing both host microbiota and immunologic development. Epidemiologic studies provide evidence that early-life antibiotic exposures predispose to inflammatory bowel disease (IBD). Methods: By using a murine model of dextran sodium sulfate (DSS)-induced colitis, we evaluated the effect on disease outcomes of early-life pulsed antibiotic treatment (PAT) using tylosin, a macrolide and amoxicillin, a beta-lactam. We evaluated microbiota effects at the 16S rRNA gene level, and intestinal T cells by flow cytometry. Antibiotic-perturbed or control microbiota were transferred to pups that then were challenged with DSS. Results: A single PAT course early-in-life exacerbated later DSS-induced colitis by both perturbing the microbial community and altering mucosal immune cell composition. By conventionalizing germ-free mice with either antibiotic-perturbed or control microbiota obtained 40 days after the challenge ended, we showed the transferrable and direct effect of the stillperturbed microbiota on colitis severity in the DSS model. Conclusions: The findings in this experimental model provide evidence that early-life microbiota perturbation may increase risk of colitis later in life.

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Section: Effects Of a Single Early-life Antibiotic Course On The Sevementioning

confidence: 99%

A single early-in-life antibiotic course increases susceptibility to DSS-induced colitis

et al. 2020

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“…FFAR2 and FFAR3 are found to be expressed in various immune cells [52], plausibly because the number of SCFAs-producing microbes in the gut is dominated [52]. These SCFAs interact with the intestinal epithelial cells and are associated with an altered intestinal gene expression and its normal maturation by post-translational histone modifications [53]. FFAR2 and FFAR3 are G-protein coupled receptors (GPCRs) expressed on intestinal epithelial cells [19].…”

Section: Role Of the Gut Microbiota-immune Axis In T1dmentioning

confidence: 99%

Probiotics and Prebiotics for the Amelioration of Type 1 Diabetes: Present and Future Perspectives

et al. 2019

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Type 1-diabetes (T1D) is an autoimmune disease characterized by immune-mediated destruction of pancreatic beta (β)-cells. Genetic and environmental interactions play an important role in immune system malfunction by priming an aggressive adaptive immune response against β-cells. The microbes inhabiting the human intestine closely interact with the enteric mucosal immune system. Gut microbiota colonization and immune system maturation occur in parallel during early years of life; hence, perturbations in the gut microbiota can impair the functions of immune cells and vice-versa. Abnormal gut microbiota perturbations (dysbiosis) are often detected in T1D subjects, particularly those diagnosed as multiple-autoantibody-positive as a result of an aggressive and adverse immunoresponse. The pathogenesis of T1D involves activation of self-reactive T-cells, resulting in the destruction of β-cells by CD8+ T-lymphocytes. It is also becoming clear that gut microbes interact closely with T-cells. The amelioration of gut dysbiosis using specific probiotics and prebiotics has been found to be associated with decline in the autoimmune response (with diminished inflammation) and gut integrity (through increased expression of tight-junction proteins in the intestinal epithelium). This review discusses the potential interactions between gut microbiota and immune mechanisms that are involved in the progression of T1D and contemplates the potential effects and prospects of gut microbiota modulators, including probiotic and prebiotic interventions, in the amelioration of T1D pathology, in both human and animal models.

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“…One study uses a multivariate linear model to fit the microbiome and host transcriptome data after unsupervised dimensionality reduction in a stepwise way (de Steenhuijsen Piters et al 2016). Additionally, sparse and compositionally robust partial least squares regression (CompPLS) has been also used for simultaneous variable selection and multi-omics data integration (Table 1) (Ramanan et al 2016;Zhang et al 2018). By adding sparsity into the loading vectors of the projection of the highdimensional data, CompPLS manages to produce easily interpretable results in a computationally efficient way (Chun and Keleş 2010).…”

Section: Integrating the Metagenome And Host Transcriptomementioning

confidence: 99%

Host and microbiome multi-omics integration: applications and methodologies

Wang

et al. 2019

Biophys Rev

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The study of the microbial community-the microbiome-associated with a human host is a maturing research field. It is increasingly clear that the composition of the human's microbiome is associated with various diseases such as gastrointestinal diseases, liver diseases and metabolic diseases. Using high-throughput technologies such as next-generation sequencing and mass spectrometry-based metabolomics, we are able to comprehensively sequence the microbiome-the metagenome-and associate these data with the genomic, epigenomics, transcriptomic and metabolic profile of the host. Our review summarises the application of integrating host omics with microbiome as well as the analytical methods and related tools applied in these studies. In addition, potential future directions are discussed.

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Antibiotic-induced acceleration of type 1 diabetes alters maturation of innate intestinal immunity

Cited by 75 publications

References 143 publications

A single early-in-life antibiotic course increases susceptibility to DSS-induced colitis

A single early-in-life antibiotic course increases susceptibility to DSS-induced colitis

Probiotics and Prebiotics for the Amelioration of Type 1 Diabetes: Present and Future Perspectives

Host and microbiome multi-omics integration: applications and methodologies

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