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Gut microbiome metagenomics analysis suggests a functional model for the development of autoimmunity for type 1 diabetes.
PLoS One 2011; 6(10):e25792Plos

Abstract

Recent studies have suggested a bacterial role in the development of autoimmune disorders including type 1 diabetes (T1D). Over 30 billion nucleotide bases of Illumina shotgun metagenomic data were analyzed from stool samples collected from four pairs of matched T1D case-control subjects collected at the time of the development of T1D associated autoimmunity (i.e., autoantibodies). From these, approximately one million open reading frames were predicted and compared to the SEED protein database. Of the 3,849 functions identified in these samples, 144 and 797 were statistically more prevalent in cases and controls, respectively. Genes involved in carbohydrate metabolism, adhesions, motility, phages, prophages, sulfur metabolism, and stress responses were more abundant in cases while genes with roles in DNA and protein metabolism, aerobic respiration, and amino acid synthesis were more common in controls. These data suggest that increased adhesion and flagella synthesis in autoimmune subjects may be involved in triggering a T1D associated autoimmune response. Extensive differences in metabolic potential indicate that autoimmune subjects have a functionally aberrant microbiome. Mining 16S rRNA data from these datasets showed a higher proportion of butyrate-producing and mucin-degrading bacteria in controls compared to cases, while those bacteria that produce short chain fatty acids other than butyrate were higher in cases. Thus, a key rate-limiting step in butyrate synthesis is more abundant in controls. These data suggest that a consortium of lactate- and butyrate-producing bacteria in a healthy gut induce a sufficient amount of mucin synthesis to maintain gut integrity. In contrast, non-butyrate-producing lactate-utilizing bacteria prevent optimal mucin synthesis, as identified in autoimmune subjects.

Authors+Show Affiliations

Department of Microbiology and Cell Science, University of Florida, Gainesville, Florida, United States of America.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22043294

Citation

Brown, Christopher T., et al. "Gut Microbiome Metagenomics Analysis Suggests a Functional Model for the Development of Autoimmunity for Type 1 Diabetes." PloS One, vol. 6, no. 10, 2011, pp. e25792.
Brown CT, Davis-Richardson AG, Giongo A, et al. Gut microbiome metagenomics analysis suggests a functional model for the development of autoimmunity for type 1 diabetes. PLoS ONE. 2011;6(10):e25792.
Brown, C. T., Davis-Richardson, A. G., Giongo, A., Gano, K. A., Crabb, D. B., Mukherjee, N., ... Triplett, E. W. (2011). Gut microbiome metagenomics analysis suggests a functional model for the development of autoimmunity for type 1 diabetes. PloS One, 6(10), pp. e25792. doi:10.1371/journal.pone.0025792.
Brown CT, et al. Gut Microbiome Metagenomics Analysis Suggests a Functional Model for the Development of Autoimmunity for Type 1 Diabetes. PLoS ONE. 2011;6(10):e25792. PubMed PMID: 22043294.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Gut microbiome metagenomics analysis suggests a functional model for the development of autoimmunity for type 1 diabetes. AU - Brown,Christopher T, AU - Davis-Richardson,Austin G, AU - Giongo,Adriana, AU - Gano,Kelsey A, AU - Crabb,David B, AU - Mukherjee,Nabanita, AU - Casella,George, AU - Drew,Jennifer C, AU - Ilonen,Jorma, AU - Knip,Mikael, AU - Hyöty,Heikki, AU - Veijola,Riitta, AU - Simell,Tuula, AU - Simell,Olli, AU - Neu,Josef, AU - Wasserfall,Clive H, AU - Schatz,Desmond, AU - Atkinson,Mark A, AU - Triplett,Eric W, Y1 - 2011/10/17/ PY - 2011/07/15/received PY - 2011/09/11/accepted PY - 2011/11/2/entrez PY - 2011/11/2/pubmed PY - 2012/4/7/medline SP - e25792 EP - e25792 JF - PloS one JO - PLoS ONE VL - 6 IS - 10 N2 - Recent studies have suggested a bacterial role in the development of autoimmune disorders including type 1 diabetes (T1D). Over 30 billion nucleotide bases of Illumina shotgun metagenomic data were analyzed from stool samples collected from four pairs of matched T1D case-control subjects collected at the time of the development of T1D associated autoimmunity (i.e., autoantibodies). From these, approximately one million open reading frames were predicted and compared to the SEED protein database. Of the 3,849 functions identified in these samples, 144 and 797 were statistically more prevalent in cases and controls, respectively. Genes involved in carbohydrate metabolism, adhesions, motility, phages, prophages, sulfur metabolism, and stress responses were more abundant in cases while genes with roles in DNA and protein metabolism, aerobic respiration, and amino acid synthesis were more common in controls. These data suggest that increased adhesion and flagella synthesis in autoimmune subjects may be involved in triggering a T1D associated autoimmune response. Extensive differences in metabolic potential indicate that autoimmune subjects have a functionally aberrant microbiome. Mining 16S rRNA data from these datasets showed a higher proportion of butyrate-producing and mucin-degrading bacteria in controls compared to cases, while those bacteria that produce short chain fatty acids other than butyrate were higher in cases. Thus, a key rate-limiting step in butyrate synthesis is more abundant in controls. These data suggest that a consortium of lactate- and butyrate-producing bacteria in a healthy gut induce a sufficient amount of mucin synthesis to maintain gut integrity. In contrast, non-butyrate-producing lactate-utilizing bacteria prevent optimal mucin synthesis, as identified in autoimmune subjects. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/22043294/Gut_microbiome_metagenomics_analysis_suggests_a_functional_model_for_the_development_of_autoimmunity_for_type_1_diabetes_ L2 - http://dx.plos.org/10.1371/journal.pone.0025792 DB - PRIME DP - Unbound Medicine ER -