Skip to main content

Table 2 Microbial metabolites: their synthesis, mechanisms of action, and effects on health and disease

From: Microbial metabolism of dietary components to bioactive metabolites: opportunities for new therapeutic interventions

(Co-) Metabolites Microbial phyla/species Molecular targets Effects on health & disease
Butyrate

Synthesized predominantly via butyryl-CoA:acetate CoA transferase pathway [37]
Bacteriodes
Ruminococcaceae
Lachnospiraceae
Energy source for colonocytes
Inhibits HDAC [43, 53, 54, 102]
Activates GPR41 and GPR43 [38, 39]
Activates GPR109A [40]
Suppresses nuclear NF-kB activation [40, 46, 47]
Modulates PPAR-γ [59, 102]
Increased intestinal barrier function [52, 59]
Anti-inflammatory [44, 46, 62, 103]
Anti-lipogenic [41]
Improves insulin sensitivity [41, 102, 103]
Increases energy expenditure [41, 102]
Anti-cancer [51, 61]
Propionate

Synthesized predominantly via succinate pathway [36]
Propionibacterium
Bacteroides
Negativicutes,
Selenomonas ruminantium,
Roseburia inulinivorans
Escherichia coli
Activates GPR41 [89] and GPR43 [38, 39]
Upregulates GLP-1, PYY, leptin [34]
Increases oxidative stress, alters phospholipid composition, induces inflammation in the brain [179]
Anti-inflammatory [56]
Anti-cancer
Anti-lipogenic [41]
Improves insulin sensitivity [41]
Increases energy expenditure [41]
Increases satiety [104]
Associated with autistic spectrum disorder [179]
Acetate

Synthesized directly from acetyl-CoA or from CO2 via the Wood-Ljungdahl pathway [34]
Most anaerobic gut bacteria studied produce acetate Energy substrate
Activates GPR43 [57, 58] and GPR41 [38, 39]
Activates AMPK pathway [34]
Anti-inflammatory [57, 58]
Anti-lipogenic [41]
Improves insulin sensitivity [41]
Increases energy expenditure [41]
Reduces glycemia in diabetic rodent models [34]
Protects against asthma [90]
TMA

Cleavage from choline via CutC & CutD [108] and from L-carnitine via YeaW & YeaX or CntA & CntB [111]
Desulfovibrio
Proteus mirabilis
Ruminococcus
Akkermansia muciniphilia
TAAR5 [118]
Potentially others
Excessive levels lead to fish malodor syndrome
TMAO

Oxidized from TMA by FMO3 in liver [120]
Osmolyte [116]
Mechanisms remains unknown
Accelerates atherosclerosis [15, 112, 115]
Contributes to kidney dysfunction and chronic kidney disease [116]
Indole

Synthesized from tryptophan via tryptophanase
Lactobacillus
Bifidobacterium longum
Bacteroides fragilis,
Parabacteroides distasonis
Clostridium bartlettii
E. hallii
Activates AhR [125]
Modulates GLP-1 secretion [131]
Maintains host-microbe homeostasis at mucosal surface [125127]
Signals with intestinal L cells to influence host metabolism [131]
Indole sulfate

Hepatic sulfonation from indole
Cytotoxic
Produces free radicals [142]
Stimulates endothelial release of microparticles [140]
Enhances monocyte adhesion to vascular endothelium [141]
Induces renal and vascular dysfunction [139141]
Associated with chronic kidney disease [138]
Associated with cardiovascular disease [141]
Indole-3-aldehyde

Synthesized from tryptophan via unidentified enzymes
Lactobacillus Activates AhR resulting in IL-22 production [125] Maintains host-microbe homeostasis at mucosal surface [125]
IPA

Synthesized from tryptophan
Clostridium sporogenes Activates PXR [132]
Scavenges hydroxyl radicals [134]
Reduces DNA damage and lipid peroxidation in neurons [135]
Inhibits beta-amyloid fibril formation [134]
Maintains intestinal barrier function and mucosal homeostasis [132]
Anti-oxidant [134, 135, 137]
Protects against ischemia-induced neuronal damage [134]
Potential therapy for Alzheimer’s disease [134]
PCS

Hepatic sulfination of p-cresol, which is synthesized from tyrosine by hydroxyphenylacete decarboxylase [144]
Clostridium difficile Damages cell membranes [154]
Induces apoptosis [155]
Activates NADPH oxidase [156]
Activates JNK and p38-MAPK [157]
Activates Rho-K [158]
Activate EGF receptor [159]
Accumulates in and predicts chronic kidney disease [146149]
EPS

Hepatic sulfination of 4-ethylphenol, potentially from paracoumaric acid via decarboxylase and vinyl phenol reductase or from genistein
Produced by unknown commensal bacteria No specific molecular targets identified but assumed to be similar to para-cresol sulfate Associated with autistic spectrum disorder [28]
Potential uremic toxin [153]
HYA

Derived from linoleic acid via linoleate isomerase activity [169]
Lactobacillus plantarum Activates GPR40 [176]
Activates Nrf2 [175]
Maintains intestinal barrier [176]
Anti-inflammatory [175]
CLA

CLnA

Derived from linoleic acid via linoleate isomerase activity [169]
Lachnospiraceae
Lactobacillus
Bifidobacteria
Faecalibacterium prausnitzii
Propionibacterium
Modulates PPARγ [171]
Activates PPARα [172]
Inhibits cyclooxygenase and lipoxygenase [173, 174]
Modulates cytokine production and T-cell responses [180]
Reduces adiposity [170]
Improves insulin sensitivity [170]
Anti-cancer [170]
Reduces atherosclerosis [170]
Anti-inflammatory [170]
  1. AhR aryl hydrocarbon receptor, AMPK AMP kinase, CLA conjugated linoleic acid, CLnA conjugated linolenic acid, CoA coenzyme A, EGF epidermal growth factor, EPS 4‐ethylphenylsulfate, GLP glucagon-like peptide, GPR G-protein coupled receptor, HDAC histone deacetylase, HYA 10‐hydroxy‐cis‐12‐ octadecenoate, IL interleukin, IPA indole-3-propionate, JNK c-Jun N-terminal protein kinase, MAPK mitogen-activated protein kinase, Nrf2 nuclear factor (erythroid-derived 2)-like 2, PCS para‐cresyl sulfate, PPAR peroxisome proliferator-activated receptor, PXR pregnane X receptor, PYY Peptide YY, Rho-K rho-kinase, TMA trimethylamine, TMAO trimethylamine N‐oxide