Table 2.
Metabolites Relevant for Human Health and Disease, and Associated References
| Metabolite | Health Implications | References | HMDB ID | Recon2 ID | |
|---|---|---|---|---|---|
| Short‐chain fatty acids produced by gut microbiota | Acetate | Serves as carbon source in the liver, affects immune system by binding GPR receptors, may have a role in adipogenesis, and stimulates colonic function. | 10, 119 | HMDB00042 | ac |
| Propionate | Serves as carbon source in the liver, has anti‐inflammatory properties, lowers blood cholesterol, stimulates satiety, and alters brain function in rats. | 10, 119 | HMDB00237 | ppa | |
| Butyrate | Serves as the main energy source for colonocytes, has anti‐inflammatory properties, prevents oxidative stress, and may protect against colonic cancer. | 119, 120 | HMDB00039 | but | |
| Microbial fermentation products | Lactate | Certain circumstances in the gut may lead to toxic levels of d‐lactate in blood, causing d‐lactic acidosis. Positively correlated with Faecalibacterium prausnitzii. | 69, 119 | HMDB01311 | lac_D |
| HMDB00190 | lac_L | ||||
| Formate | Decreased levels were found in urine of IBD patients. Formate is associated with blood pressure. | 121, 122 | HMDB00142 | for | |
| Ethanol | Produced by many gut bacteria, disrupts the intestinal epithelial barrier. Ethanol consumption can promote intestinal overgrowth. | 123, 124 | HMDB00108 | etoh | |
| Acetaldehyde | Produced from ethanol by gut microbiota, toxic and carcinogenic. Disrupts the intestinal epithelial barrier. | 24, 123 | HMDB00990 | acald | |
| Succinate | Decreased levels were found in urine of IBD patients and in a rat model after bariatric surgery. | 32, 121 | HMDB00254 | succ | |
| Lipid metabolism | Choline | Choline deficiency and disrupted choline metabolism are associated with NAFLD. Choline has also been linked to CVD risk. | 25, 26, 125 | HMDB00097 | chol |
| Betaine | Phosphatidylcholine‐derived betaine has been linked to CVD risk. | 26 | HMDB00043 | glyb | |
| Ethanolamine | Host‐derived ethanolamine can be exploited as a carbon source by pathogenic Salmonella typhimurium during inflammation. | 126 | HMDB00149 | etha | |
| Phosphatidylcholine | Biomarker of disrupted fatty acid metabolism, related to obesity and resistance to insulin. Phosphatidylcholine metabolites are linked to CVD. | 26, 57 | pchol_hs | ||
| Phosphatidyl‐ethanolamine | Altered in plasma of individuals with type 2 diabetes. | 127 | HMDB60501 | pe_hs | |
| l‐Carnitine | Higher l‐carnitine levels were found in obese subjects. Dietary l‐carnitine is converted to TMA by gut microbiota, linking it to CVD risk. | 128, 129 | HMDB00062 | crn | |
| Acylcarnitines | Biomarkers of disrupted fatty acid metabolism after high‐fat feeding. Acylcarnitine pools are altered in obese subjects. | 57, 128 | e.g., acrn, c4crn, and c8crn | ||
| Dimethylamine | Increased urinary levels in NAFLD. Negatively correlated with F. prausnitzii. | 69, 125 | HMDB00087 | ||
| Trimethylamine (TMA) | It is formed from choline and l‐carnitine by gut bacteria, and has been linked to CVD. Increased urinary levels in NAFLD. | 26, 125, 129 | HMDB00906 | ||
| Bile acids | Cholate | Gut microbes transform bile acids to secondary bile acids, permitting their reabsorption via the colonic epithelium. The gut microbiota may contribute to obesity, type 2 diabetes, inflammation, and cancer by controlling bile acid pools. | 10, 124, 130 | HMDB00619 | cholate |
| Lithocholate | HMDB00761 | C03990 | |||
| Glycocholate | HMDB00138 | gchola | |||
| Taurocholate | HMDB00036 | tchola | |||
| Deoxycholate | HMDB00626 | C04483 | |||
| Glycochenodeoxycholate | HMDB00637 | dgchol | |||
| Taurochenodeoxycholate | HMDB00951 | tdchola | |||
| Amino acids | Branched‐chain amino acids | High levels of leucine, isoleucine, and valine are associated with obesity and type 2 diabetes. | 128, 131, 132, 133 | HMDB00172 | ile_L |
| HMDB00687 | leu_L | ||||
| HMDB00883 | val_L | ||||
| Aromatic amino acids | High levels of tyrosine, phenylalanine, and tryptophan are associated with type 2 diabetes. | 128, 132, 133 | HMDB00159 | phe_L | |
| HMDB00158 | tyr_L | ||||
| HMDB00929 | trp_L | ||||
| Glutamine and glutamate | High glutamate/glutamine ratio is associated with type 2 diabetes. | 132 | HMDB00641 | gln_L | |
| HMDB00148 | glu_L | ||||
| Taurine | Elevated levels were found in fecal samples of UC patients. Associated with certain gut bacterial species. | 69, 134 | HMDB00251 | taur | |
| Phenolic compounds | Phenylacetate | Increased production by gut bacteria on a high‐protein diet, may give rise to toxic products. Elevated in colorectal cancer. | 25, 135 | HMDB00209 | pac |
| Phenylpropionate | Can be converted to benzoic acid by gut bacteria and give rise to hippurate, which is implicated in a variety of disease states. | 136 | HMDB11743 | ||
| 3‐Hydroxyphenylpropionate (3‐HPPA) | Can be converted to benzoic acid by gut bacteria and give rise to hippurate, which is implicated in a variety of disease states. | 136 | HMDB00375 | 3hhpa1 | |
| Phenylacetylglutamine | Decreased excretion in autism. Lower levels in obese subjects. Positively associated with age in humans. Associated with certain gut bacterial species. | 31, 69, 128, 137 | HMDB06344 | pheacgln | |
| Benzoic acid | Converted into hippurate by the host, which is implicated in a variety of disease states. | 136 | HMDB01870 | bz | |
| 4‐Hydroxyphenylacetate | Elevated in colorectal cancer. Negatively correlated with Subdoligranulum variable. | 25, 69 | HMDB00020 | 4hphac | |
| Hippurate (N‐benzoylglycinate) | Related to a variety of health and disease states. Hippurate levels in urine are decreased in CD patients due to altered gut microbiota. Diminished excretion was also found in obese individuals as well as patients with schizophrenia and autism. Associated with certain gut bacterial species. | 31, 69, 136, 138, 139 | HMDB00714 | bgly | |
| p‐Cresol | Produced by gut bacteria. May be a significant factor in autism, is elevated in colorectal cancer, and has been linked to inflammatory bowel disease. Also linked to cardiovascular disease in chronic kidney disease patients. Interferes with the sulfonation of acetaminophen (paracetamol). | 25, 31, 140, 141 | HMDB01858 | pcresol1 | |
| p‐Cresyl sulfate | Formed from gut bacteria‐derived p‐cresol, and is directly linked to progression of chronic kidney disease. Elevated in the urine of children with autism. Positively associated with age in humans. Associated with certain gut bacterial species. | 25, 69, 137, 142 | HMDB11635 | pcs1 | |
| Indolic compounds | Indole | Produced by gut bacteria, converted to uremic toxin indoxyl sulfate by the host. | 143 | HMDB00738 | indole1 |
| Indoxyl sulfate | Formed from bacteria‐derived indole, and is directly linked to progression of chronic kidney disease. | 142 | HMDB00682 | inds1 | |
| Polyamines | Cadaverine | Produced by gut bacteria. Increased levels were found in fecal samples of UC patients. | 134 | HMDB02322 | |
| Putrescine | Produced by gut bacteria and in human tissues. Polyamines are toxic at high concentrations and associated with cancer. Increased fecal putrescine was found in a rat model after bariatric surgery. | 24, 32 | HMDB01414 | ptrc | |
| Spermine | HMDB01256 | sprm | |||
| Spermidine | HMDB01257 | spmd | |||
| Hormones/Precursors | GABA (γ‐aminobutyric acid) | Directly produced by gut bacteria with implications for the gut–brain axis. Increased urinary levels were found in a rat model after bariatric surgery. | 29, 32 | HMDB00112 | 4abut |
| Dopamine | Directly produced by gut bacteria with implications for the gut–brain axis. | 29 | HMDB00073 | dopa | |
| Norepinephrine | Directly produced by gut bacteria with implications for the gut–brain axis. | 29 | HMDB00216 | nrpphr | |
| Serotonin | Directly produced by gut bacteria. The microbiota also regulates tryptophan availability, affecting serotonin biosynthesis in the CNS and thus brain and behavior. | 29 | HMDB00259 | srtn | |
| Histamine | Histamine and N‐methylhistamine levels are increased in IBD patients. Histamine is also directly produced by gut bacteria. | 29, 144 | HMDB00870 | hista | |
| N‐Methylhistamine | HMDB00898 | mhista | |||
| l‐Dopa | l‐Dopa is dehydroxylated by the gut microbiota. Manipulating the microbiota has been proposed as an approach to control l‐Dopa bioavailability in PD treatment. | 29, 145, 146 | HMDB00181 | 34dhphe | |
| Other | Ammonia | Produced by many gut bacteria. Inhibits the mitochondrial oxygen condition and short‐chain fatty acid oxidation in colonocytes. | 147 | HMDB00051 | nh4 |
| Hydrogen sulfide | Produced by some gut bacteria, e.g., Escherichia coli. Toxic to colonocytes, disturbs their metabolism. Found to be increased in stool samples of colonic cancer patients. Implicated in IBD. | 24, 147, 148 | HMDB00598 | ||
| Glutathione | Glutathione levels in the liver were lower in mice colonized with human baby flora than in conventional mice. Increased glutathione synthesis as stress response was also found in NAFLD. | 60, 149 | HMDB00125 | gthrd |
CD, Crohn's disease; CNS, central nervous system; CVD, cardiovascular disease; IBD, inflammatory bowel disease; NAFLD, nonalcoholic fatty liver disease; PD, Parkinson's disease; UC, ulcerative colitis.
If available, HMDB150 (http://www.hmdb.ca/) and Recon2118 (http://humanmetabolism.org) IDs are shown.
1
Will be included in subsequent releases of Recon2.