Table 2. Metabolites differing at some stage between neuter groups.

Ranking	Subpathway	Metabolite	19 Weeks	21 Weeks	25 weeks	31 weeks	33 weeks	37 weeks	43 weeks	52 weeks
1	Dipeptide	felinylglycine *	0.92	1.68	$3.52$	$8.08$	$4.56$	$2.31$	1.42	1.11
2	Feline metabolism	gamma-glutamylfelinylglycine *	0.91	1.47	$2.94$	$7.24$	$4.04$	$2.1$	1.4	1.06
3	Feline metabolism	felinine *	0.84	1.35	$2.1$	$4.48$	$2.89$	1.78	1.35	0.97
4	Tryptophan metabolisma	kynurenine	0.98	1.06	$0.74$	$0.58$	$0.71$	0.86	0.96	0.93
5	Fatty acid, dihydroxy	2-hydroxydecanoic acid	0.91	0.89	$0.65$	$0.52$	$0.63$	1.02	1.16	1.47
6	Feline metabolism	N-acetylfelinine *	0.93	1.3	1.77	$4.64$	$2.92$	1.91	1.22	0.98
7	Endocannabinoid a	N-stearoyl taurine	1.03	1.09	2.02	$3.7$	$4.27$	$3.17$	2.01	2.13
8	Tryptophan metabolisma	tryptophan	1.08	1.12	0.97	$0.74$	0.85	0.94	1.05	1.03
9	Fatty acid, dicarboxylatea	eicosanodioate	1.16	1.17	0.91	$0.61$	$0.72$	0.96	1.05	1
10	Lysolipida	1-docosahexaenoylglycerophosphocholine*	1.05	0.78	0.78	$0.59$	0.83	0.96	0.95	1.14
11	Cysteine, methionine, SAM, taurine metabolism	N-acetylmethionine	1	0.92	0.7	$0.58$	$0.64$	0.76	0.91	0.86
12	Pyrimidine metabolism, thymine containing	thymidine	0.85	0.92	1.63	$3.24$	1.65	1.07	1.17	1.18
13	Tocopherol metabolism	alpha-tocopherol	1.08	1.21	1.24	$1.5$	1.12	1.04	1.18	1.09
14	Sphingolipid	palmitoyl sphingomyelin	1.08	1.31	$1.43$	$1.49$	0.95	0.95	1.06	1.02
15	Histidine metabolism	histidine	0.98	0.93	0.89	$0.83$	0.97	0.96	0.99	1.04
16	Lysolipida	1-palmitoylglycerophosphoethanolamine	0.95	0.89	0.66	$0.59$	$0.67$	1.13	1.03	0.76
17	Sterol	cholesterol	1.09	1.29	$1.33$	$1.37$	1.01	1.04	1.13	1.08
18	Dipeptide derivative	anserine	1.02	0.96	1.14	$1.41$	1.3	1.15	1.01	0.93
19	Lysolipida	1-docosapentaenoylglycerophosphocholine*	1.32	0.79	0.79	$0.56$	0.96	0.96	1.24	1.09
20	Dipeptide derivative	carnosine	0.95	0.89	0.86	$0.77$	1.06	1.01	0.96	0.89
21	Valine, leucine and isoleucine metabolism	2-methylbutyrylcarnitine (C5)	0.97	1.11	0.86	$0.62$	0.81	0.98	1.08	1.11
22	Lysolipida	1-oleoylglycerophosphoethanolamine	0.87	1.23	1.11	$2.48$	0.8	1.28	1.5	0.81
23	Alanine and aspartate metabolism	N-acetylaspartate (NAA)	2.02	1.22	1.71	$3.57$	1.85	1.13	1.03	1.63
24	Chemicala	2-ethylhexanoate	1.03	1.53	1.57	$1.87$	0.91	1.26	1.14	1.1
25	Glycerolipid metabolism	glycerophosphorylcholine (GPC)	1.02	1.14	1.1	$1.36$	0.93	0.92	1.05	0.89
26	Long chain fatty acida	cis-vaccenate (18:1n7)	1.02	1.18	1.21	$1.44$	1.09	1.06	1.22	1.21
27	Urea cycle; arginine-, proline-, metabolisma	citrulline	1.04	1.07	0.77	$0.66$	0.78	0.92	0.88	1.05
28	Essential fatty acida	eicosapentaenoate (EPA; 20:5n3)	1.04	0.92	0.88	$0.69$	0.8	1.04	1.01	1.32
29	Pyrimidine metabolism, cytidine containing	5-methylcytidine	1	1.02	0.9	$0.71$	$0.68$	0.82	0.98	0.79
30	Benzoate metabolisma	2-aminobutyrate	1.11	1.06	0.95	$0.73$	0.83	1.06	1.11	0.82
31	Benzoate metabolisma	4-vinylphenol sulfate	0.62	0.83	1.13	$2.2$	0.85	0.67	0.9	1.02
32	Glutathione metabolisma	5-oxoproline	1.02	1.04	1.01	$0.83$	0.88	0.93	1.02	1.02
33	Tryptophan metabolisma	indolepropionate	0.8	1.05	0.77	$0.51$	$0.5$	0.65	0.98	1.02
34	Essential fatty acida	docosahexaenoate (DHA) 22.6n3.	0.94	0.96	0.96	0.79	$0.76$	0.98	0.85	0.98
35	Fructose, mannose, galactose, starch, and sucrose metabolisma	mannose	1.04	1.18	$1.39$	1.24	1.01	1.13	1.14	1.07
36	Pyrimidine metabolism, cytidine containing	2'-deoxycytidine	1	0.99	1.02	0.84	$0.74$	0.83	0.99	0.94
37	Creatine metabolism	creatine	1.27	1.25	1.23	1.58	$2.45$	1.54	1.55	1.3
38	Glycine, serine and threonine metabolism	N-acetylthreonine	0.9	1.08	0.92	0.97	0.89	0.89	0.96	$0.67$
39	Glutathione metabolisma	glutathione, oxidized (GSSG)	0.88	0.9	0.96	0.79	$1.77$	1.34	0.9	1.06
40	Fatty acid, monohydroxy	2-hydroxypalmitate	1.08	0.96	1.06	0.87	$0.73$	0.82	0.77	1.1
41	Urea cycle; arginine-, proline-, metabolisma	trans-4-hydroxyproline	0.91	1.13	1.02	1.07	$0.67$	0.82	0.88	0.78
42	Vitamin A metabolism	retinoate	1.08	0.68	0.88	1.07	$1.88$	1.49	1.26	1.2
43	Food component/Plant	thymol sulfate	1.05	1.19	1.07	0.95	0.87	1.08	$1.59$	1.13
44	Purine metabolism, adenine containinga	N1-methyladenosine	1.07	1.07	0.88	0.89	0.92	0.89	$1.36$	0.92
45	Glycine, serine and threonine metabolism	serine	1.05	1.14	1.21	0.97	0.76	$0.68$	0.89	0.94

Fold-change values of the 45 named metabolites identified as significantly different (FDR corrected p<0.05) at some stage between the two neuter groups (highlighted in red, up in CN; highlighted in green, down in CN). A further 16 unknown metabolites also met this significance cut-off, with all differences between 25–37 weeks and 11 significantly different at week 31. The list is sorted by decreasing significance values at week 31, the time point with the largest number of significant differences.

Metabolites in bold belong to metabolic subpathways found to have more significant metabolite groups than would be expected by chance between the two neuter groups at some time point (see text).

^a indicates subpathways that contained more significant metabolites than would be expected by chance within at least one of the neuter groups between timepoints.

*Putative identification: no standard metabolite tested.