TABLE 1.
Meta-omic studies reporting statistically significant changes in the GI microbiome in CRC or IBD. Abbreviations: healthy controls (HC); irritable bowel syndrome (IBS); high-resolution magic angle spinning nuclear magnetic resonance (HR-MAS NMR); gas chromatography (GC); capillary electrophoresis (CE); ion cyclotron resonance Fourier transform mass spectrometry (ICR-FT/MS); time-of-flight mass spectrometry (ToFMS); liquid chromatography (LC); high performance LC (HPLC); ultra-performance LC (UPLC); medium-chain fatty acids (MCFA); long-chain fatty acids (LCFA).
| Cohort type (N) | Sample type(s) | Method | Increased in disease | Decreased in disease | References |
|---|---|---|---|---|---|
| CRC | |||||
| CRC (31): Colorectal tumour biopsy vs. normal tissue | Mucosal biopsy | Metabolomics: HR-MAS NMR and GC/MS | Choline-containing compounds, taurine, scyllo-inositol, lactate, phosphocholine, phosphate, L-glycine, 2-hydroxy-3-methyl valerate, L-proline, L-phenylalanine, palmitic acid, margaric acid, oleic acid, stearic acid, uridine, 11-eicosenoic acid, propyl octadecanoate, cholesterol | Lipids, polyethylene glycol, glucose, fumarate, malate, mannose, galactose, 1-hexadecanol, arachidonic acid | Chan et al. (2009) |
| CRC (11) vs. HC (10) | Stool, mucosal biopsy | Metabolomics: GC/ToFMS | Uracil, uridine, proline | Fructose, linoleic acid, nicotinic acid, glucose, galactose, 3-phosphoglycerate, citric acid, inosine, creatine | Phua et al. (2014) |
| Meta-analysis of CRC (386) vs. tumor-free controls (392) | Stool | Metagenomics: WGS | Metabolic modules: amino acid degradation, organic acid metabolism, glycoprotein degradation, bile acid conversion | Metabolic modules: carbohydrate degradation | Wirbel et al. (2019) |
| CRC stage 0 (73); stage I/II (111); stage III/IV (68); multiple polypoid adenomas (MP, 67); vs. HC (251); normal with history of surgery (HS, 34) | Stool | Metagenomics: WGS, Metabolomics: CE/ToFMS | Taxonomy: sulfide-producing species – Desulfovibrio vietnamensis, D. longreachensis, Bilophilia wadsworthia Metabolites: deoxycholate (MP vs. HC); glychocholate, and taurocholate, branched-chain amino acids, phenylalanine, tyrosine and glycine (S0 vs. HC); serine (SIII/IV vs. HC), Pathway gene abundance: amino acid metabolism, sulfide production, phenylalanine and tyrosine biosynthesis (all CRCs vs. HC); sulfate reductase (dsrA), cofactor and vitamin biosynthesis, lysine biosynthesis and degradation, methane metabolism (SIII/IV vs. HC) | Taxonomy: butyrate-producing species - Lachnospira multipara, Eubacterium eligens, Pathway gene abundance: tryptophan biosynthesis (SIII/IV vs. HC) | Yachida et al. (2019) |
| Healthy Alaskan Natives (high-risk group for CRC) (32) vs. Healthy Rural Africans (low risk for CRC) (21) | Stool, urine | Metataxonomics: 16S rRNA sequencing, Metabolomics: 1H-NMR spectroscopy, GC, HPLC-MS | Enriched in high-risk population: Actinobacteria, Verrumicrobia, Lachnospiraceae, Bifidobacterium spp., Escherichia-Shigella spp., choline, formate, cholate, chenodeoxycholate, deoxycholate, conjugated bile acids, nicotinamide/niacin metabolites | Enriched in low-risk population: Ruminococcaeceae, Prevotellaceae, Prevotella 9, Ruminococcaceae, Succinivibrio, Eubacterium coprostanoligenes, amino acids, purines a , pyrimidines a , butyrate, propionate, nicotinate | Ocvirk et al. (2020) |
| CRC (14) vs. HC (14) | Stool | Metaproteomics: LC-MS/MS | Desulfobacterales, Methanobacteriaceae, Sporolactobacillaceae, Bacteroides fragilis, Peptostreptococcus anaerobius, DNA replication, recombination, and repair proteins, iron intake and transport proteins, superoxide dismutases | Sutterellaceae, Epulopiscium, Gordonibacter, NADH:flavin oxidoreductases/NADH oxidases, energy production and conversion proteins, amino acid transport and metabolism, coenzyme transport and metabolism, lipid transport and metabolism, translation machinery, cell wall, membrane, and envelope biogenesis, cell motility, post-translational modification, protein turnover, and chaperones, inorganic ion transport and metabolism | Long et al. (2020) |
| IBD | |||||
| Identical twin pairs (N = 17 pairs): discordant colonic CD*(4p); discordant ileal CD*(2p); concordant ICD*(2p); concordant CCD*(2p) vs. HC (7 pairs), *in remission | Stool | Metabolomics: ICR-FT/MS | Bile acid metabolism b (glycocholate, glycochenodeoxycholate taurocholate, Trihydroxy-6β-cholanate), amino acid metabolism b , tyrosine b , tryptophan (ICD only), phenylalanine (ICD only), fatty acid biosynthesis (ICD only; oleic acid, stearic acid, palmitic acid, linoleic acid, arachidonic acid), Urea cycle a , b , vitamin B6 metabolism b | Arachidonic acid metabolism/prostaglandins a , b (PGs; PGF2a) | Jansson et al. (2009) |
| CD (83); UC (68); pouchitis (13) vs. HC (40) | Stool | Metabolomics: GC-MS | Styrene c | MCFAs, hexanoate b , protein fermentation metabolites | De Preter et al. (2015) |
| Paediatric IBD in remission -CD (26); UC(10) vs. healthy 1st-degree relatives (54) | Stool | Metataxonomics: 16S rRNA sequencing, Metabolomics: UPLC/ToFMS | Enterobacteriaceae, cholate b , conjugated and sulphated bile acids b , taurine b , tryptophan b , adrenate b | Stercobilin b , acetyl-glutamic acid b , boldione b , estradiol b , androstenedione b , azelaic acid b | Jacobs et al. (2016) |
| Paediatric IBD (newly diagnosed, treatment naive)-CD (36); UC (20); IBD-U (13) vs. endoscopic non-IBD controls (29) | Stool, blood | Metabolomics: UPLC-MS/MS | Folate and pterine biosynthesis, purine metabolism b , amino acid metabolism, nicotinate and nicotinamide metabolism b , urea cycle, protein biosynthesis, bile acid biosynthesis c , sphingolipid metabolism c , ammonia recycling c , taurine metabolism c , oxidation of branched-chain FAs c , phospholipid metabolism c , glycerolipid metabolism c | L-tryptophan, kynurenic acid, aspartate, threonine, asparagine, cytosine, histidine b , taurine b | Kolho et al. (2017) |
| CD (208); UC (126); IBD-U (21); IBS (412) vs. HC (1,025) | Stool | Metagenomics: WGS | Sugar a degradation, succinate fermentation, Aspartate and asparagine biosynthesis, arginine biosynthesis, lysine biosynthesis b , proline biosynthesis c , aromatic compounds degradation, saturated FA elongation b , specific fatty acid and lipid biosynthesis b , thiamin salvage c , Bacteroides spp., Enterobacteriaceae b , Bacteroidaceae | Pyruvate and mixed acid fermentation b , general amino acid biosynthesis (see exceptions in previous column), tryptophan degradation b , valine degradation b , coenzyme A biosynthesis b , coenzyme B biosynthesis, specific fatty acid and lipid biosynthesis b , nucleotides and nucleosides biosynthesis, phosphopantothenate biosynthesis b , Faecalibacterium prausnitzii b , Bifidobacterium longum b , Roseburia hominis, Actinobacteria, Rikenellaceae, Akkermansiaceae, Firmicutes | Vich Vila et al. (2018) |
| Pediatric IBD (treatment naïve): CD (25); UC (22) vs. non-IBD (24) | Mucosal-luminal interface (MLI) biopsy | Metaproteomics: MS | DNA replication, recombination, and repair proteins, defence mechanism proteins (CRISPR/Cas), cell wall, membrane and envelope biogenesis proteins, amino acid transport and metabolism, mobilome, cysteine degradation, Proteobacteria, Verrucomicrobia, Ascomycota, Spirochetes, F. prausnitzii strain L2-6 | Cysteine biosynthesis, Bacteroides | Zhang et al. (2019) |
| CD (68); UC (53) vs. non-IBD (34) | Stool | Metagenomics: WGS, Metabolomics: LC-MS | Sphingolipids, carboximic acids a , bile acids (cholate, chenodeoxycholate) a , organonitrogen compounds, cholesteryl esters, phenylacetamides b , phosphatidylcholines, α-amino acids, lactate | LCFAs, butyrate d , propionate d , secondary bile acids (lithocholate, deoxycholate) d , flavonoids, indoles a , b , cinnamic acids a , triacylglycerols, tetrapyrroles a , b , triterpenoids, alkyl-phenylketones, brassinolides a , b , ergosterols a , quinolines a , b , vitamin D a , stigmastanes a , lactones, β-diketones b , cholesterols a , phenylbenzodioxanes, pantothenate (vitamin B5) | Franzosa et al. (2019) |
| CD (67); UC (38) vs. non-IBD (27) | Stool, colon biopsy, blood | Metagenomics: WGS, Metatranscriptomics, Metabolomics: LC-MS | Cholate b , chenodeoxycholate b , taurochenodeoxycholate b , C8 carnitine b , anti-ompc b , calprotectin c , adrenate, arachidonate, putrescine, taurine, Escherichia coli, Klebsiella pneumoniae, Roseburia gnavus b | Deoxycholate, lithocholate, propionate, C16:0 LPE, adipate, C20:4 carnitine, 3'-O-methyladenosine, suberate, nicotinate (B3), pantothenate (B5), F. prausnitzii, Alistipes finegoldii, Alistipes shahii, Alistipes putredinis, Subdoligranulum unclassified | Lloyd-Price et al. (2019) |
| Treatment-naive UC (18) vs. HC (14) | Mucosal biopsy | Metabolomics: GC-ToFMS, UPLC-MS | Lysophospholipids c , acyl carnitines c , arachidonate c , asparagine c , citrulline c , dimethylarginine c , glutamyl-L-amino acids c , glutamate c , kynurenine c , L-valine c , L-isoleucine c , nicotinamide c | beta-alanine c , creatine c , eicosapentaenoate c , fructose c , glutaryl-carnitine c , glycerol-3-phosphate c , guanosine c , leucylglycine c , linoleate c , L-glutamine c , methylmalonyl carnitine c | Diab et al. (2019) |
a
Includes derivatives of the molecule class.
b
Significantly different in CD only.
c
Significantly different in UC only.
d
Difference not statistically significant in this cohort.