Table 1. Gut microbiota-derived metabolites found at abnormal levels and correlations between metabolites and gut bacteria in obesity.

References	Participants	Biofluid	Platform	Fecal microbiota analysis method	Correlations between metabolites and gut bacteria	Differences in metabolites and gut microbiota between obese and control
Calvani et al. (2010) [25]	15 morbidly obese insulin-resistant male patients and 10 age-matched controls	Urine samples	Untargeted: high-resolution proton NMR (1H NMR) spectroscopy for gut microbiome-derived metabolites	-	- Correlation between 2-hydroxyisobutyrate and Faecalibacterium prausnitzii	↑2-hydroxyisobutyrate in obese ↓ hippuric acid, trigonelline and xanthine in obese
Tiihonen et al. (2010) [21]	20 obese subjects and 20 normal weight subjects	Fecal samples	Targeted: GC–MS for phenolic and acidic compounds, GC for protein and fat and high pH ion exchange chromatography (HPLC) and a pulsed electrochemical detector for soluble and insoluble carbohydrates	Quantitative real-time PCR	-	↑ Branched-chain fatty acids, phenolic acids, lactic acid, 2-methylbutyric acid, valeric acid, isovaleric acid, 3-OH-benzenepropanoic acid, di- and hydroxy acids in obese subjects ↑sulphate-reducing bacteria and Bacteroides in normal weight subjects
Payne et al. (2011) [23]	15 obese and 15 normal-weight Swiss children	Fecal samples	Targeted: high pressure liquid chromatog­raphy (HPLC) for SCFA, branched chain fatty acids and intermediate metabolites	qPCR and temperature gradient gel electrophoresis (TGGE)	- Correlations between lactate and butyrate and lactate-utilizing butyrate-producing species including clostridial cluster XIVa species Eubacterium hallii and Anaerostipes caccae in obese children. - Correlations between propionate and Gram-negative Bacteroides–Prevotella group and Gram-positive species of clostridial cluster IX.	↑ isobutyrate, formate, butyrate and propionate in obese ↑ lactate and valerate in normal-weight subjects
Raman et al. (2013) [26]	30 obese NAFLD patients and 30 healthy controls	Fecal samples	Targeted: gas chromatography–mass spectrometry for volatile organic compounds	Multitag pyrosequencing	-	↑ Lactobacillus species and phylum Firmicutes (Lachnospiraceae; genera, Dorea, Robinsoniella, and Roseburia) in obese ↓ Ruminococcaceae; genus, Oscillibacter in obese ↑ Fecal ester compounds including aliphatic esters of ethanoic, propanoic, butanoic and pentanoic acids in obese
Bondia-Pons et al. (2014) [19]	16 Finnish monozygotic twin pairs discordant for weight and 9 concordant pairs	Plasma	Untargeted: Two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC_GC-TOFMS) for polar metabolites and ultraperformance liquid chromatography coupled to quadrupole-TOFMS (UPLC-QTOFMS) for molecular lipids Targeted: UPLC coupled to triple-quadrupole MS (UPLC-QqQMS) for bile acids (BAs)	Denaturing gradient gel electrophoresis (DGGE)	- Negative correlations between bifidobacterial diversity and clusters of carbohydrates and amino acids and long-chain TGs. - Positive correlations between Lachnospiraceae diversity and clusters of amino acids and TCA cycle metabolites. - Positive correlations between Bacteroides diversity and clusters of BA lithocholic acid (LCA) and phosphatidyl ethanolamines. - Positive correlations between Ruminococcaceae diversity and clusters of long-chain polyunsaturated fatty acid (PUFA)-containing TGs.	-
Druart et al. (2014) [29]	Obese women	Serum	Targeted: gas–liquid chromatography for PUFA-derived bacterial metabolites	phylogenetic microarray and qPCR analysis of 16S rDNA	- Positive correlations between CLnA cis-9,trans-11,cis-15-18:3 and bifidobacteria, E. ventriosum and lactobacilli. - Positive correlations between CLA cis-9,cis-11-18:2 and bifidobacteria and Eubacterium ventriosum. - Positive correlations between CLA trans-9,trans-11-18:2 and E. ventriosum.	-
Ahmad et al. (2016) [28]	50 participants with normal BMI (18.5 to <25 kg/m2) and 50 obese (BMI > 30 kg/m2)	Fasting plasma and serum samples and urine specimens	Untargeted: NMR-based metabolic profiling	_	-	↑urinary excretion of hippurate, phenylacetylglutamine, 4-cresyl sulfate and formate in the lean group ↑urinary excretion of metabolites associated with bacterial degradation of choline such as TMA and DMA in the obese group ↓urinary excretion of indoxyl sulfate in the obese group
Liu et al. (2017) [9]	257 young Chinese obese individuals and lean controls	Serum	Untargeted: high performance liquid chromatograph (HPLC)-MS Targeted: ultra-high performance liquid chromatog­raphy (UHPLC) coupled to a Shimadzu 8050 Triple Quad mass spectrometry for amino acids	shotgun sequencing	- Negative correlations between phenylalanine, tyrosine, leucine, isoleucine and valine and Bacteroides species including B. thetaiotaomicron, B. intestina­lis, B. ovatus and B. uniformis - Negative correlations between glutamate and B. thetaiotaomicron - Positive correlations between glutamate and Ruminococcus sp., D. longicatena, C. comes	↑Phenylalanine, tyrosine, leucine, isoleucine, valine and glutamate in obese
Org et al. (2017) [20]	531 middle-aged Finnish men	Serum and plasma	Targeted: nuclear magnetic resonance (NMR) spectroscopy platform for lipids, lipoproteins, fatty acids, amino acids, ketone bodies and glycolysis precursor molecules and liquid chromatography with on-line tandem mass spectrometry (LC-MS/MS) for TMAO, choline, betaine, and carnitine	16S ribosomal RNA gene sequencing	- correlation between acetate and microbial diversity - Positive correlation between glutamine, glycated hemoglobin and acetate and microbial richness - Positive correlations between acetate and phylum Tenericutes, family Christensenellaceae, unclassified Clostridales, Peptococcaceae, and several members of family Clostridiaceae - Negative correlations between acetate and Blautia and Oscillospira - Positive correlations between Blautia and saturated, monounsaturated fatty acids, pyruvate and glycerol, isoleucine and valine - Negative correlations between Blautia and polyunsaturated fatty acids, including omega-3, 22:6 docosahexaenoic acid, omega-6, and 18:22 linoleic acids - Positive correlation between glutamine and Clostridales - Negative correlations between isoleucine and valine and Christensenellaceae - Positive correlation between TMAO and Peptococcaceae and Prevotella - Negative correlation between TMAO and Faecalibacterium prausnitzii	↑ Collinsella with higher levels of glycerol and phenylalanine in obese subjects ↑ phylum Tenericutes and family Christensenellaceae with higher levels of acetate in normal-weight subjects ↑ Blautia with higher levels of BCAA (isoleucine and leucine), alanine, glycerol, and pyruvate in obese subjects ↓Methanobacteriaceae with higher levels of glycerol and total and monounsaturated fatty acid in obese subjects
Houttu et al. (2017) [22]	52 overweight and 47 obese pregnant women in early pregnancy	Serum	Untargeted: high-throughput proton NMR metabolomics platform for lipids, amino acids and GlycA	16S ribosomal RNA gene sequencing	- Correlations between Prevotella copri and branched chain amino acids	↑several VLDL subclasses and isoleucine, leucine, valine, phenylalanine and GlycA in obese pregnant women. ↓ lipids in certain HDL subclasses and omega-6 fatty acid, 18:2 linoleic acid in obese pregnant women ↑bacterial family Prevotellaceae, genus Prevotella and species copri in obese pregnant women ↓ Prevotella uniformis in obese pregnant women
López-Contreras et al. (2017) [27]	67 normal-weight and 71 obese children aged 6–12 years	Serum	Targeted: mass spectrometry for amino acids	16S rRNA sequencing	- Negative correlation between Bacteroides eggerthii and citrulline - Negative correlation between Bacteroides plebeius and unclassified Christensenellaceae and phenylalanine - Negative correlation between unclassified Christensenellaceae and arginine, methionine and ornithine	↑ BCAA, leucine and valine, aromatic amino acids, phenylalanine and tyrosine in obese children ↑B. plebeius and unclassified Christensenellaceae in normal-weight children
Piening et al. (2018) [24]	23 healthy participants with BMI 25–35 kg/m2 No control group	Plasma	Untargeted: LC-MS	16S ribosomal RNA gene sequencing and whole genome metagenomic shotgun sequencing	- Correlation between Bacteroides vulgatus and BCAA metabolism - Positive correlation between antioxidant 3-indolepropionic acid and Proteobacteria in the insulin resistant subjects - Positive correlation between N6-trimethyllysine and phylum Proteobacteria in the insulin sensitive subjects	-