. 2020 Jul 2;15(7):e0235480. doi: 10.1371/journal.pone.0235480

Table 4. Relative plasma metabolite concentrations for antioxidants, markers of oxidation and inflammation, methylated metabolites, TCA cycle, and urea cycle intermediates in healthy cats (H cats) and chronic kidney disease (CKD) cats at baseline (after feeding pretrial food¹ for 14 days) and after feeding Food A² (containing scFOS) or Food B³ (containing apple pomace) as fiber sources for 4 weeks each.

	Mean Values^*						Group Effect^‡
	H Cats			CKD Cats			Overall Effect of Health	Overall Effect of Both Treatments	H Cats: Treatment with Food B versus Food A^¥	CKD Cats: Treatment with Food B versus Food A^¥	Overall Effect of Interaction
Metabolites	BSL	Food A	Food B	BSL	Food A	Food B	P-value	P-value	P-value	P-value	P-value
Tocopherol Metabolism
α-tocopherol	0.99	0.97	1.05^§	0.90	0.91	0.95	0.08	0.04	0.01	0.62	0.28
α-CEHC sulfate	0.95	0.93	1.13	1.63	3.12^§	2.48	0.78	0.36	0.46	0.43	0.08
γ-tocopherol/β-tocopherol	1.75^#	0.84^§	1.49	1.18^#	0.79^§	1.15	0.03	0.000	0.002	0.08	0.43
Glutathione Metabolism
oxidized glutathione (GSSG)	0.83	1.34^§	1.03	1.20	0.97	1.58	0.41	0.26	0.21	0.03	0.02
Cysteine-glutathione disulfide	0.88	1.12^§	0.97	0.99	0.99	1.23^§	0.31	0.01	0.04	0.012	0.005
cysteinylglycine	0.68	1.41^§	1.09^§	1.15	1.33	1.84	0.32	0.03	0.74	0.34	0.42
cysteinylglycine disulfide	0.72	1.06^§	1.01^§	0.85	1.10^§	1.22^§	0.12	0.000	0.58	0.15	0.27
5-oxoproline	0.93	0.98	0.92	1.11	1.13	1.10	0.03	0.38	0.13	0.77	0.44
2-aminobutyrate	0.77	1.12^§	1.28^§	0.73	1.00^§	1.06^§	0.49	0.000	0.16	0.53	0.40
2-hydroxybutyrate/2-hydroxyisobutyrate	0.89	1.40^§	1.39^§	1.44	1.76^§	1.72^§	0.45	0.000	0.76	0.91	0.13
Ophthalmate	0.27	0.96^§	0.93^§	0.93	2.07^§	1.17^§	0.12	0.000	0.52	0.17	0.72
Sphingolipid Metabolism
Sphinganine	0.81	2.55^§	1.02	1.10	1.30	2.65^§	0.28	0.004	0.003	0.012	0.001
sphinganine-1-phosphate	0.93	2.66^§	0.95	1.08	1.28	3.24^§	0.58	0.01	0.002	0.019	0.001
Sphingosine	0.80	2.92^§	0.99	1.01	1.21	2.84^§	0.20	0.005	0.004	0.008	0.001
sphingosine 1-phosphate	0.89	1.71^§	0.95	0.93	1.03	1.84^§	0.63	0.01	0.007	0.009	0.001
sphingadienine	0.93	2.20^§	0.91	0.99	1.10	2.12^§	0.56	0.03	0.001	0.005	0.000
Glycine, Serine, & Threonine Metabolism
Glycine	0.94^#	1.00^§	0.98	1.13^#	1.10	1.12	0.049	0.43	0.53	0.31	0.14
Sarcosine	1.44	0.79^§	0.95^§	1.49	0.83^§	0.88^§	0.94	<0.001	0.038	0.74	0.35
dimethylglycine	0.80	1.31^§	1.43^§	0.86	1.13^§	1.10^§	0.23	<0.001	0.16	0.62	0.03
Betaine	0.46	1.15^§	1.30^§	0.54	1.19^§	1.37^§	0.17	<0.001	0.09	0.15	0.43
S-adenosylhomocysteine (SAH)	0.75^#	1.03	0.65	1.52^#	1.12^§	0.98^§	0.005	0.0387	0.020	0.46	0.02
TCA Cycle
Citrate	0.96	0.98	1.05^§	1.11	1.09	1.02^§	0.36	0.81	0.046	0.18	0.01
aconitate [cis or trans]	0.82^#	1.18^§	0.95^§	1.12^#	1.10	1.23^§	0.09	0.000	0.000	0.004	0.000
alpha-ketoglutarate	1.11	1.11	1.35^§	0.94	0.99	0.91	0.20	0.49	0.004	0.13	0.01
succinylcarnitine	1.03	0.97	1.01	1.38	1.35	1.25	0.13	0.56	0.40	0.55	0.74
Succinate	1.12^#	1.28	1.07	0.90^#	0.91	1.18^§	0.08	0.53	0.12	0.012	0.008
Malate	1.33	1.46	1.43	0.96	0.88	0.98	0.03	0.61	0.64	0.36	0.76
Urea Cycle
Arginine	1.05	1.03	1.00	1.05	1.02	1.03	0.85	0.73	0.58	0.99	0.88
argininosuccinate	0.76	0.88	0.92	1.11	1.02	0.72^§	0.59	0.39	0.63	0.10	0.03
Urea	0.87^#	0.93^§	0.91	1.48^#	1.31^§	1.24	0.03	0.99	0.66	0.55	0.01
Ornithine	0.94	0.98	1.02	1.05	1.02	1.13	0.20	0.08	0.43	0.08	0.41
Citrulline	0.95^#	0.88	0.85	1.30^#	1.19	1.08^§	0.01	0.01	0.76	0.23	0.70
Arginine and Proline Metabolism
2-oxoarginine	0.97	1.08	1.00	0.78	0.90	0.87	0.20	0.10	0.42	0.58	0.61
Homoarginine	1.40	1.52	1.70	1.08	1.34	1.23	0.57	0.33	0.29	0.79	0.65
Homocitrulline	0.65	1.11^§	1.08^§	1.22	1.89^§	1.44^§	0.07	0.000	0.83	0.26	0.39
Proline	0.95	1.01	1.02	0.99	0.94	1.08	0.79	0.08	0.92	0.026	0.18
dimethylarginine (SDMA + ADMA)	0.88^#	0.91	0.93	1.20^#	1.21	1.14	0.002	0.77	0.56	0.82	0.52
N-acetylarginine	0.87^#	0.94^§	0.94^§	1.17^#	1.16	1.11	0.01	0.14	0.93	0.71	0.01
N-delta-acetylornithine	0.98	0.93	1.00	1.22	1.17	1.18	0.34	0.70	0.52	0.79	0.96
trans-4-hydroxyproline	1.12	0.93^§	0.91	1.23	1.08	1.08	0.25	0.03	0.81	0.99	0.93
pro-hydroxy-pro	1.44	0.85^§	0.92^§	1.20	0.95^§	0.92^§	0.73	0.000	0.25	0.88	0.03
N-methylproline	1.04	1.10	0.92	1.30	1.29	1.10	0.36	0.12	0.016	0.74	0.30
N-monomethylarginine	1.00	0.94	0.92	1.13	1.04	1.07	0.09	0.11	0.60	0.43	0.64
Argininate	1.12	1.71^§	1.59^§	1.30	1.64^§	1.27^§	0.30	0.000	0.49	0.81	0.95

^{1–3, ‡, ¥, #} See Table 3.

*For each metabolite, mean value is the group mean of re-scaled data to have median equal to 1.

^§The mixed model was used to test whether the difference of two paired observations from a single cat at baseline and the end of the 4 week feeding period was different than zero.

Significance was established when P ≤ 0.05 (for type 1 error) and q ≤ 0.1 (q-values were used to estimate false discovery rate in multiple comparisons).