Supplementary Figure 1

Transcription

1 Supplementary Figure 1. (A C) Comparison of Shannon evenness between children who became anti islet autoantibody positive (anti islet aab+) and children who remained autoantibody negative (anti islet aab ) for three age classes. (D F) Comparison of Chao richness between children who became anti islet aab+ and children who remained anti islet aab for three age classes. P values were obtained by Wilcoxon Mann Whitney tests.

2 Supplementary Figure 2. Eigenvector centrality of genera for bacterial interaction networks for children who became anti islet autoantibody positive (anti islet aab+) and children who remained autoantibody negative (anti islet aab ) for age 0.5±0.25 years (A), age 1±0.25 years (B) and age 2±0.5 years (C). The rows of each plot are ordered by decreasing eigenvector centrality values of bacterial networks of children who became anti islet aab+. Vertical lines indicate eigenvector centrality values of 0.05 and 0.5, respectively.

3 Supplementary Figure 3. Node degree of genera for bacterial interaction networks for children who became anti islet autoantibody positive (anti islet aab+) and children who remained autoantibody negative (antiislet aab ) for age 0.5±0.25 years (A), age 1±0.25 years (B) and age 2±0.5 years (C). The rows of each plot are ordered by increasing node degree values of children who became anti islet aab+. Vertical lines indicate a node degree of 1.

4 Supplementary Table 1. Descriptive summary of the cohort for anti islet autoantibody positive (anti islet aab+) and negative children (anti islet aab ). became anti islet aab+ (N=22) remained anti islet aab (N=22) P Value (*) Median number stool samples per child (range) 7 (2 11) 7 (3 10) Median age at antiislet aab seroconversion 1.54 ( ) in years (range) Number of children delivered via Caesarean section Median duration of breast feeding in months 7.1 (0 16.4) 7.6 (0 18.7) 0.73 (range) Median age of introduction in months 5.16 ( ) 5.76 ( ) 0.69 (range) Median age of first exposure in months (range) 11.0 ( ) 9.1 ( ) 0.9 (*) For binary variables P values were obtained by Fisher s Exact tests and for continuous variables P values were obtained by Wilcoxon Mann Whitney tests Supplementary Table 2. Community composition compared by multivariable npmanova. The table shows the p values of multivariable npmanova analyses for three different age intervals. Significant results are labelled with asterisks and bold font. Age C section (yes/no) Breast feeding at sampling time (yes/no) Duration since introduction Duration since introduction Anti islet autoantibody status (positive/negative) 0.5±0.25 years ** 0.001** ±0.25 years * ±0.5 years

5 Supplementary Table 3. Comparsion of the abundances of genera between children who became anti islet autoantibody positive and children who remained anti islet autoantibody negative for age 0.5 years. Percentages represent the fraction of the total number of reads of each genus in the particular anti islet autoantibody group. Associated covariates were detected via stepwise AIC multiple regression models. Wilcoxon Mann Whitney or Brunner Munzel test P values were obtained by testing for differences in the abundances of genera between children who became anti islet aab+ and children who remained anti islet aab. developed antiislet autoantibodies (%) remained antiislet autoantibody negative (%) Covariate adjusted P Value Associated Bacterial genera P Value covariates (*) Dorea food Barnesiella none Haemophilus none Bacteroides feeding; age Sporobacterium none Veillonella age Anaeroglobus food Citrobacter breast feeding Enterococcus age; Blautia ; age Terrahaemophilus none Butyricicoccus E none Slackia Clostridium C section Granulicatella C section; age Anaerostipes Erwinia none Lactococcus none Gemella age Enterobacter none Turicibacter Neisseria C section Sutterella none Gemmiger feeding Roseburia ; Sarcina none Bilophila feeding; Eubacterium none Dysgonomonas C section; age Pantoea breast feeding Corynebacterium Salmonella breast feeding Candidatus_Nardonella Klebsiella none Dialister none Ruminococcus ; age Lactobacillus none Prevotella none Robinsoniella none Bacillus C section; age Subdoligranulum none Streptococcus none Rothia Alistipes

6 Faecalibacterium Coprococcus none Cronobacter Anaerotruncus C section Nocardioides none Kluyvera Abiotrophia age Pseudomonas Coriobacterium Akkermansia C section; Coprobacillus none Actinomyces age Butyrivibrio none Lachnospira ; Pectobacterium Holdemania age Eggerthella breast feeding Shigella Odoribacter breast feeding Parabacteroides breast feeding Collinsella Porphyromonas none Gordonibacter Brenneria Phascolarctobacterium feeding; Serratia Escherichia Fusobacterium none Staphylococcus none Bifidobacterium none Megasphaera none (*) : duration since first introduction : duration since first introducton breast: breast feeding at sampling time (yes, no) age: age of the children

7 Supplementary Table 4. Comparsion of the abundances of genera between children who became anti islet autoantibody positive and children who remained anti islet autoantibody negative for age 1 years. Percentages represent the fraction of the total number of reads of each genus in the particular anti islet autoantibody group. Associated covariates were detected via stepwise AIC multiple regression models. Wilcoxon Mann Whitney or Brunner Munzel test P values were obtained by testing for differences in the abundances of genera between children who became anti islet aab+ and children who remained anti islet aab. Bacterial genera developed antiislet autoantibodies (%) remained antiislet autoantibody negative (%) P Value Covariate adjusted P Value Associated covariates (*) Candidatus_Nardonella Holdemania ; age; Salmonella none Faecalibacterium age Terrahaemophilus Pantoea none Rothia Bacillus none Brenneria Megasphaera none Clostridium Shigella Klebsiella breast feeding Escherichia Dysgonomonas none Gemmiger none Collinsella none Robinsoniella age Anaerotruncus Haemophilus food Lactobacillus ; age Turicibacter none Bacteroides none Parabacteroides C section Cronobacter Serratia Blautia feeding; Slackia food; Enterobacter none Odoribacter Enterococcus none Pseudomonas Bifidobacterium none Granulicatella none Pectobacterium Bilophila C section; Citrobacter breast feeding Gemella none Lactococcus food; age Lachnospira Streptococcus C section Dialister none Kluyvera Ruminococcus Sutterella Anaeroglobus age; Dorea food Fusobacterium none

8 Neisseria none Coriobacterium none Anaerostipes Porphyromonas none Erwinia none Staphylococcus Eggerthella none Eubacterium none Akkermansia none Roseburia none Nocardioides none Coprobacillus none Abiotrophia age Corynebacterium C section; age Barnesiella Gordonibacter Prevotella none Alistipes age Sporobacterium none Subdoligranulum none Butyricicoccus none Butyrivibrio Veillonella feeding; Actinomyces none Sarcina C section Coprococcus Phascolarctobacterium feeding; (*) : duration since first introduction : duration since first introducton breast: breast feeding at sampling time (yes. no) age: age of the children

9 Supplementary Table 5. Comparsion of the abundances of genera between children who became anti islet autoantibody positive and children who remained anti islet autoantibody negative for age 2 years. Percentages represent the fraction of the total number of reads of each genus in the particular anti islet autoantibody group. Associated covariates were detected via stepwise AIC multiple regression models. Wilcoxon Mann Whitney or Brunner Munzel test P values were obtained by testing for differences in the abundances of genera between children who became anti islet aab+ and children who remained anti islet aab. developed antiislet autoantibodies (%) remained antiislet autoantibody negative (%) Covariate adjusted P Value Associated covariates (*) Bacterial genera P Value Erwinia none Enterobacter Abiotrophia age Blautia none Staphylococcus none Bacillus none Bifidobacterium C section Corynebacterium none Ruminococcus none Granulicatella none Haemophilus food Turicibacter Lactobacillus Lachnospira none Prevotella none Streptococcus none Enterococcus Klebsiella none Pantoea Anaerotruncus none Kluyvera none Holdemania C section Nocardioides 2.00E none Akkermansia none Megasphaera none Alistipes none Subdoligranulum C section Dorea ; age Eubacterium ; age Neisseria none Coprococcus none Dysgonomonas none Porphyromonas C section Slackia ; age Candidatus_Nardonella C section; age; Pseudomonas C section Veillonella Faecalibacterium age Brenneria C section Sarcina Bacteroides none Terrahaemophilus Anaeroglobus ; Robinsoniella C section Gordonibacter Serratia C section Lactococcus none Barnesiella none Phascolarctobacterium none Gemmiger none ; age; Coprobacillus

10 Butyricicoccus Pectobacterium C section Anaerostipes age; Parabacteroides none Dialister C section; age; Rothia age Bilophila ; Roseburia age Sutterella ; age Citrobacter C section; Coriobacterium age Gemella none Escherichia C section Cronobacter C section Salmonella C section; Collinsella age Actinomyces none Odoribacter none Butyrivibrio none Eggerthella age Shigella C section Fusobacterium none Clostridium none Sporobacterium (*) : duration since first introduction : duration since first introducton breast: breast feeding at sampling time (yes, no) age: age of the children