Figure 7: An unexpected impact of Cs on aromatic amino acid metabolism.

(A) Schematic of the experiment. Germ-free C57BL/6 mice (n=3 per group) were colonized with hCom1a or its single-strain dropout variant (ΔCs and ΔCh) and housed for 3 weeks before sacrifice. Fecal pellets, cecal contents, and urine samples were subjected to targeted metabolite profiling. (B) Certain gut bacteria can reduce phenylalanine (Phe) to phenylpropionic acid (PPA), which is converted to hippuric acid and cinnamoylglycine by the host. Other gut bacteria oxidize Phe to phenylacetic acid (PA), which is metabolized in the liver to phenylacetylglycine (PAGly). (C) ΔCs differs markedly from hCom1a and ΔCh in terms of AAA metabolite output. hCom1a and ΔCh convert phenylalanine almost exclusively to PA (from which the host generates PAGly); hippurate is nearly undetectable in the urine and serum (Figure S3). In contrast, ΔCs converts Phe predominantly to phenylpropionic acid (which the host metabolizes to hippurate); PAGly levels are very low in the urine and serum (Figure S3). (D) C. sporogenes, which is undetectable in hCom1a- and ΔCh-colonized mice, rises to a relative abundance of 10⁻⁵-10⁻⁴ in ΔCs-colonized mice. The relative abundance of Cspo in cecal contents from hCom1a-, ΔCs-, and ΔCh-colonized mice is shown. Statistical significance was assessed using a Student’s two tailed t-test (*: p<0.05; **: p<0.01; ***: p<0.001; ****: p<0.0001, n.s: no significance). See also Figure S2, S3, and S5, and Table S4.