Table 2. Differences in cerebrospinal fluid metabolite concentrations between patients with an infectious disease (Hisotoplasma, Lyme, rabies, West Nile virus) and non-infectious conditions (multiple sclerosis, controls)^a.

Metabolite	Potential Pathway(s) Involved	Effect Sizeb	P-valuec
Betaine	1-carbon metabolism/ cell volume/choline oxidation	0.58	0.0022
Formated	1-carbon metabolism/acetate synthesis	0.68	<0.0001
Glycinee	1-carbon metabolism/glutathione synthesis/excitotoxicity	0.62	0.0011
Cholinee	1-carbon metabolism/lipid turnover	0.45	0.0166
Serine	1-carbon metabolism/protein catabolism	-0.52	0.0059
Pyroglutamatee	Amino acid/glutathione metabolism	0.80	<0.0001
N-Acetylneuraminate	Amino sugar metabolism/innate immunity	-0.48	0.0117
Fructose	Carbohydrate	-0.52	0.0059
Acetatee	Carbohydrate and fatty acid metabolism	-0.44	0.0182
2-Oxoglutarate	Cell volume/TCA cycle/amino acid metabolism	0.39	0.0387
N-Acetylaspartate	Cell volume/TCA cycle/myelin synthesis	0.37	0.0499
Glutamate	Cell volume/TCA cycle/neurotransmitter	0.82	<0.0001
Methanolf	Drug metabolite; microbial metabolism	-0.46	0.0140
Pyruvated	Energy metabolism	0.55	0.0007
Lactatee	Energy metabolism	0.21	0.0059
Carnitined	Fatty acid catabolism	0.54	0.0009
2-Hydroxybutyratee	Glutathione synthesis/energy metabolism	0.65	0.0007
Acetonee	Ketone bodies	0.70	0.0002
3-Hydroxybutyratee	Ketone bodies	0.59	0.0022
Acetoacetatee	Ketone bodies	0.51	0.0070
Isobutyrate	Microbial metabolism	-0.41	0.0292
Isopropanol	Microbial/ketone metabolism	0.76	0.0001
2-Oxoisocaproated	Organic acid	0.39	0.0170
Urea	Protein catabolism	0.38	0.0444
Phenylalanine	Protein catabolism	0.37	0.0494
Quinolinated	Tryptophan metabolism/excitotoxicity	0.51	0.0016
Ornithined	Urea cycle	0.36	0.0258
3-Hydroxyisobutyrated	Valine metabolism	0.40	0.0150

^aMetabolites identified by factor analysis using z-score normalization are shown in bold. ^bCliff’s Delta d statistic. Positive values indicate increased concentrations in patients with an infection compared to no infectious disease.

^cResult of Mann-Whitney U test.

^dDifference in median concentrations confirmed after log transformation of the data improved homoscedasticity. P-value reported corresponds to test performed on log-transformed data.

^eAssumption of equal variances not met. P-value reported corresponds to test performed on log-transformed data.

^fTentatively assigned.