Fig. 4: Microbiota effect on large intestinal metabolism.
a, Abundance fold changes of 31 metabolites with higher large intestine than small intestine concentrations, thus hypothesized to be of microbial origin (significantly changing metabolites from differential analysis; Fig. 2a,b). The log2-transformed fold changes for luminal content (left) and mucus (right) were calculated from averaged concentrations for the four large intestinal sampling sites of five male SPF mice versus five male germ-free mice. Boxplots are thus based on 20 data points, the median log2(fold change) is indicated in red, boxes contain the 25th to 75th percentiles, and the whiskers extend to the most extreme data points not considered outliers. The grey area marks absolute log2(fold change) ≤ 2. Symbols on the left indicate previous evidence: (
) common knowledge about certain metabolites, for example see Koh et al. and de Aguiar Vallim et al.29,66; (Δ) evidence from Han et al.19 using the comparison of Swiss-Webster germ-free versus conventional mice to identify differential metabolite abundances; (□) evidence from Matsumoto et al.33 using germ-free and ‘ex-germ-free’ mice that were inoculated in the stomach with faecal suspension from SPF BALB/c mice to classify metabolites as mouse- or microorganism-derived; (
) evidence from Marcobal et al.30 who used germ-free and conventional Swiss-Webster mice to compare metabolite levels; (
) evidence from Sridharan et al.32 using reaction network models to predict microbiota-dependent metabolic products. All data used from published work including explanations can be found in Supplementary Table 7. In addition, (◯) denotes metabolites detected exclusively in male SPF mice. For the SPF exclusive metabolites, fold changes cannot be calculated, as indicated by ∞. b,c, Large intestinal concentration of 2-oxoglutarate (b) and hydrocinnamate (c) in SPF and germ-free luminal content and mucus. Solid bars show the mean concentration of measurements from five male mice, averaged over the four large intestinal sites. The 20 corresponding data points are displayed as circles. Abbreviations: FC, fold change; cont, luminal content; GF, germ-free; muc, mucus.
