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. 2022 Jan 11;71(12):2463–2480. doi: 10.1136/gutjnl-2021-325753

Figure 4 .

Figure 4

HFD-induced obesity in mice leads to depletion of biotin serum levels together with depletion of bacterial biotin production lineages. (A) Plasma biotin concentration of age-matched Chow-fed and HFD-fed C57BL6/J mice after 4 (left panel) and 13 weeks (right panel) (**P value<0.01; Chow n=7 for day 35 and day 90, HFD n=5 for d35 and n=8 for d90, Wilcoxon rank-sum test) (B) Relative abundance profiles of biotin producers (bacteria with all biotin biosynthesis genes from pimelate and no biotin transport gene), biotin transporters (bacteria with no gene involved in biotin biosynthesis) and biotin producers+transporters (bacteria harboring biotin biosynthesis and transport genes) in these same mice at baseline (day 1), day 35 and day 90 (*P value and FDR<0.05 pairwise Wilcoxon rank-sum test). (C) Serum biotin concentration of germ-free (GF) and conventionally raised (CONV-R) C57BL6/J mice (*P value<0.05, C57BL6/J GF n=7 and CONV-R n=5; Wilcoxon rank-sum tests). (D) Plasma biotin concentration and (E) total bacterial 16S rRNA gene load measured by qPCR in chow-fed mice with (n=7) and without (n=8) large spectrum antibiotics (100mg/kg of vancomycin and 200 mg/kg of ampicillin, neomycin and metronidazole) diluted in water for 14 days (*P value<0.05; Wilcoxon rank-sum test). (F) Beta-coefficients obtained with multivariate linear regression models between diet, phenotype and the abundances of biotin production and transport inferred from 16S data and serum biotin in a same global model with all covariates (*P value<0.05) from fecal transfer experiments in mice from panels g and h. (G) Serum biotin levels of Swiss Webster mice colonized with faecal slurries of 4 subjects from the MetaCardis subcohort (2 NOB; 2 SOB). Mice were colonized for 28 days and were fed either chow (NOB, n=16; SOB, n=12) or western diet (NOB, n=17; SOB, n=17) (*P value and FDR<0.05; ***P value<0.001 and FDR<0.05; Wilcoxon rank-sum test). (h) Abundance of biotin production module inferred from PICRUSt functional profiles of 16S rRNA gene amplicon data of mice from panel F (**P value<0.05; Wilcoxon rank-sum test). CONV-R, conventionally raised; GF, germ-free; HFD, high-fat diet; ns, not significant; WD, Western diet.