(a,b) Spearman correlation of A. muciniphila percent abundance with fasting glucose (a) and HbA1c (b) in participants in the Advento Study (n=94) (c) A. muciniphila percent abundance in normal (n=58), pre-diabetic (n=31) and type 2 diabetic subjects (n=11). Bar plot represents mean and 95% confidence interval. Significance assessed by one-tailed Mann–Whitney test. (d) Heat map of Pearson correlation coefficients between each individual IFNγ-dependent gene and abundance of A. muciniphila of duodenal biopsies in three groups of samples. Individual P value<0.2, combined FDR<0.1 for 59 out of 69 genes (Supplementary Data 6); genes ranked by strength of correlation according to Fisher’s combined probability test. Grey colour indicates that a gene was below the level of detection. *P<0.05, **P<0.01, ***P<0.001. (e) Graphical model for regulation of glucose metabolism by IFNγ through the microbiota. IFNγ regulates expression of genes such as Irgm1 and Gbp4, which in turn, contribute to regulation of A. muciniphila levels in the gut. Differences in A. muciniphila abundance ultimately result in differences in systemic glucose tolerance in the host, with higher abundance of A. muciniphila inducing improvement of tolerance. CVID, Common Variable Immunodeficiency; CVID-GI, CVID with gastrointestinal symptoms; HV, healthy volunteer.