1. Volume 92, Issue 3, Pages 634-645 (September 2017)
Evaluation of the impact of gut microbiota on uremic solute accumulation by a CE- TOFMS–based metabolomics approach 
Eikan Mishima, Shinji Fukuda, Chikahisa Mukawa, Akinori Yuri, Yoshitomi Kanemitsu, Yotaro Matsumoto, Yasutoshi Akiyama, Noriko N. Fukuda, Hiroki Tsukamoto, Kei Asaji, Hisato Shima, Koichi Kikuchi, Chitose Suzuki, Takehiro Suzuki, Yoshihisa Tomioka, Tomoyoshi Soga, Sadayoshi Ito, Takaaki Abe 
Kidney International 
Volume 92, Issue 3, Pages (September 2017)
DOI: /j.kint
Copyright © 2017 International Society of Nephrology Terms and Conditions

2. Figure 1
Adenine-induced renal failure mice under specific pathogen–free (SPF) and germ-free (GF) conditions. (a) Changes in body weight after feeding the mice an adenine-containing or a normal diet. (b) Images of the entire kidney and weights of the right kidney. Bar = 1 cm. (c) Histologic images of kidney sections with Masson’s trichrome (MT) and Sirius Red staining. Bar = 200 μm. (d) Quantitative analysis of the remaining tubular areas in cortex and fibrosis area indicated by MT staining and Sirius Red–positive staining, respectively. (e) Blood urea nitrogen (BUN) and plasma creatinine levels. *P < 0.05, **P < 0.01, ***P < compared between indicated groups (analysis of variance). N = 4 in SPF control (SPF-C) and GF control (GF-C), and N = 6 in SPF renal failure (SPF-RF) and GF renal failure (GF-RF) mice. To optimize viewing of this image, please see the online version of this article at
Kidney International  , DOI: ( /j.kint )
Copyright © 2017 International Society of Nephrology Terms and Conditions

3. Figure 2
Plasma metabolome profiles of specific pathogen–free (SPF) and germ-free (GF) mice. (a) Principal component analysis derived from the profiles of measured plasma metabolites. The scores for the first principal component (PC1) versus the second principal component (PC2) are presented. (b) Venn diagram of measured plasma metabolites. GF-C, germ-free control; GF-RF, germ-free renal failure; SPF-C, specific pathogen–free control; SPF-RF, specific pathogen–free renal failure.
Kidney International  , DOI: ( /j.kint )
Copyright © 2017 International Society of Nephrology Terms and Conditions

4. Figure 3
Profiles of Group 1 microbiota-derived uremic solutes (M-USs). Plasma (μM), fecal, and urinary levels of Group 1 M-USs. Fecal and urinary levels were corrected for fecal weight (nmol/g) and urinary creatinine (μmol/mg urinary creatinine), respectively. An example pattern of Group 1 M-USs in the plasma is shown in the left diagram. The levels of p-cresyl sulfate and phenyl sulfate are not each concentration but show relative intensities estimated from the peak areas. *P < 0.05, ***P < compared between indicated groups (analysis of variance). GF-C, germ-free control; GF-RF, germ-free renal failure; N.D., not detected; SPF-C, specific pathogen–free control; SPF-RF, specific pathogen–free renal failure.
Kidney International  , DOI: ( /j.kint )
Copyright © 2017 International Society of Nephrology Terms and Conditions

5. Figure 4
Profiles of Group 2 microbiota-derived uremic solutes (M-USs). Plasma (μM), fecal (nmol/g), and urinary (μmol/mg urinary creatinine) levels of Group 2 M-USs. *P < 0.05, ***P < compared between indicated groups (analysis of variance). GF-C, germ-free control; GF-RF, germ-free renal failure; N.D., not detected; SPF-C, specific pathogen–free control; SPF-RF, specific pathogen–free renal failure.
Kidney International  , DOI: ( /j.kint )
Copyright © 2017 International Society of Nephrology Terms and Conditions

6. Figure 5
Profiles of Group 3 microbiota-derived uremic solutes (M-USs). Plasma (μM), fecal (nmol/g), and urinary (μmol/mg urinary creatinine) levels of Group 3 M-USs. *P < 0.05, **P < 0.01, and ***P < compared between indicated groups (analysis of variance). GF-C, germ-free control; GF-RF, germ-free renal failure; N.D., not detected; SPF-C, specific pathogen–free control; SPF-RF, specific pathogen–free renal failure; TMAO, trimethylamine-N-oxide.
Kidney International  , DOI: ( /j.kint )
Copyright © 2017 International Society of Nephrology Terms and Conditions

7. Figure 6
Profiles of guanidine uremic toxins, urea, and short-chain fatty acids (SCFAs). The levels of (a) guanidine uremic toxins, (b) urea, and (c) SCFAs in the plasma (μmol), feces (nmol/g), and urine (μmol/mg urinary creatinine). *P < 0.05, **P < 0.01, ***P < between indicated groups (analysis of variance). #P < 0.05 between indicated groups (Wilcoxon). ADMA, asymmetric dimethylarginine; GF-C, germ-free control; GF-RF, germ-free renal failure; GSA, guanidinosuccinate; N.D., not detected; SDMA, symmetrical dimethylarginine; SPF-C, specific pathogen–free control; SPF-RF, specific pathogen–free renal failure.
Kidney International  , DOI: ( /j.kint )
Copyright © 2017 International Society of Nephrology Terms and Conditions

8. Figure 7
Amino acid profiles. The levels of amino acids in the plasma (μmol), feces (nmol/g), and urine (μmol/mg urinary creatinine) are shown. Cysteine was not detected in any samples in the present study. *P < 0.05, **P < 0.01, ***P < between indicated groups (analysis of variance). Ala, alanine; Arg, arginine; Asn, asparagine; Asp, aspartate; GF-C, germ-free control; GF-RF, germ-free renal failure; Gln, glutamine; Glu, glutamate; Gly, glycine; His, histidine; Ile, isoleucine; Leu, leucine; Lys, lysine; Met, methionine; Phe, phenylalanine; Pro, proline; Ser, serine; SPF-C, specific pathogen–free control; SPF-RF, specific pathogen–free renal failure; Thr, threonine; Trp, tryptophan; Tyr, tyrosine; Val, valine.
Kidney International  , DOI: ( /j.kint )
Copyright © 2017 International Society of Nephrology Terms and Conditions