Variation in Microbiome LPS Immunogenicity Contributes to Autoimmunity in Humans

Vatanen, Tommi; Kostić, Aleksandar; d’Hennezel, Eva; Siljander, Heli; Franzosa, Eric A.; Yassour, Moran; Kolde, Raivo; Vlamakis, Hera; Arthur, Timothy D.; Hämäläinen, Anu‐Maaria; Peet, Aleksandr; Tillmann, Vallo; Uibo, Raivo; Mokurov, Sergei; Доршакова, Н. В.; Ilonen, Jorma; Virtanen, Suvi Μ.; Szabo, Susanne J.; Porter, Jeffrey A.; Lähdesmäki, Harri; Huttenhower, Curtis; Gevers, Dirk; Cullen, Thomas W.; Knip, Mikael; Xavier, Ramnik J.

doi:10.1016/j.cell.2016.05.056

Cited by 275 publications

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“…Bacteria in the Bacteroides genus, particularly the B. fragilis group, which includes B. fragilis, B. ovatus, and B. vulgatus, were found to enhance bacterial translocation (54). Bacteroides lipopolysaccharide (LPS) is structurally distinct from Escherichia coli LPS and inhibits innate immune signaling and endotoxin tolerance, suggesting that it may preclude immune development in early infancy (9). Notably, some of the diseasediscriminative bacteriophage contigs detected were related to prophages in Bacteroides.…”

Section: Discussionmentioning

confidence: 99%

“…Changes in intestinal bacteria have been linked to the development of T1D in some studies (5,6). Some common observations include increased abundance of the Bacteroides genus (7)(8)(9) and reduced abundance of butyrateproducing bacteria (7,10). In a study that included 11 seropositive children from Finland and Estonia, of whom 4 progressed to T1D, Kostic et al demonstrated a reduction in bacterial diversity among the cases (11).…”

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confidence: 99%

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Intestinal virome changes precede autoimmunity in type I diabetes-susceptible children

Zhao

Vatanen

Droit

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Viruses have long been considered potential triggers of autoimmune diseases. Here we defined the intestinal virome from birth to the development of autoimmunity in children at risk for type 1 diabetes (T1D). A total of 220 virus-enriched preparations from serially collected fecal samples from 11 children (cases) who developed serum autoantibodies associated with T1D (of whom five developed clinical T1D) were compared with samples from controls. Intestinal viromes of case subjects were less diverse than those of controls. Among eukaryotic viruses, we identified significant enrichment ofCircoviridae-related sequences in samples from controls in comparison with cases. Enterovirus, kobuvirus, parechovirus, parvovirus, and rotavirus sequences were frequently detected but were not associated with autoimmunity. For bacteriophages, we found higher Shannon diversity and richness in controls compared with cases and observed that changes in the intestinal virome over time differed between cases and controls. Using Random Forests analysis, we identified disease-associated viral bacteriophage contigs after subtraction of age-associated contigs. These disease-associated contigs were statistically linked to specific components of the bacterial microbiome. Thus, changes in the intestinal virome preceded autoimmunity in this cohort. Specific components of the virome were both directly and inversely associated with the development of human autoimmune disease.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Intestinal virome changes precede autoimmunity in type I diabetes-susceptible children

Zhao

Vatanen

Droit

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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250

240

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“…The outer membranes of both types of bacteria contain large molecules called lipopolysaccharides, or LPS, but, whereas E. coli LPS activates a potent response from the human immune system, Bacteroides LPS actually inhibits the immune system. So, compared with that of Russian infants, the gut immune system in Finnish and Estonian infants is silent, potentially making these children prone to strong, unregulated immune reactions and disorders like T1D, the authors suggest (13).…”

Section: Impoverished Gutmentioning

confidence: 99%

Cleaning up the hygiene hypothesis

Scudellari¹

2017

Proc. Natl. Acad. Sci. U.S.A.

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“…The importance of extensive and well documented metadata should be underscored for any future microbiome analysis to remove the possibility of confounding data. Additionally, Vatenan et al proposed a role for differences in lipopolysaccharide (LPS) contribution based on differentially abundant bacteria in the DIABIMMUNE study, however the analysis on LPS structure was done on isolates not associated with disease and with isolates not collected from subjects in the DIABIMMUNE study [18]. Thus, further work is necessary.…”

Section: Pathogenesis Of Type 1 Diabetes-testing the Hygiene Hypothesmentioning

confidence: 99%

“…This was observed in DIPP where B. dorei had a higher relative and absolute abundance of this species approximately 8 months prior to seroconversion [13] and in BABYDIET in those children provided a complex diet early in life [20]. In DIABIMMUNE, an intriguing hypothesis was raised that the LPS structure of B. dorei may prevent immunotolerance in the gut thereby leading to autoimmunity [18]. However, this idea requires more testing with the appropriate genetic constructs of B. dorei.…”

Section: Comparing the Cohortsmentioning

confidence: 99%

Contrasting Efforts: The Microbiome and Type 1 Diabetes

Russell¹,

Triplett²

2017

Diabetes Case Rep

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In the search for environmental triggers of type 1 diabetes (T1D), disease associations with the human gut microbiome are of great interest. Three studies of children at high genetic risk for T1D have examined associations between microbial taxa and the development of T1D autoimmunity: DIPP (Diabetes Prediction and Prevention), BABYDIET (Primary Prevention of Type 1 Diabetes in Relatives at Increased Genetic Risk), and DIABIMMUNE (Pathogenesis of Type 1 Diabetes-Testing the Hygiene Hypothesis). These studies are herein examined for their findings, including areas for improvement and means to go beyond preliminary taxonomic associations for predicting functional influences by microbes. These studies serve as useful tools for guiding future research and deserve careful consideration.

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Variation in Microbiome LPS Immunogenicity Contributes to Autoimmunity in Humans

Cited by 275 publications

References 0 publications

Intestinal virome changes precede autoimmunity in type I diabetes-susceptible children

Intestinal virome changes precede autoimmunity in type I diabetes-susceptible children

Cleaning up the hygiene hypothesis

Contrasting Efforts: The Microbiome and Type 1 Diabetes

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