Table 1.
Overview of currently known bacterial metabolites, their effect on gastrointestinal motility, and experimental models used for the assessment of gut motility
| Bacterial metabolite | Effect on gut motility | Methods used | Model organism and effect size (N) | Reference |
|---|---|---|---|---|
| Lipopolysaccharides | -Regulation of BMP2 (growth factor produced by macrophages, which regulate peristaltic activity of the colon) and CSF-1 expression (a growth factor secreted by enteric nervous system) |
-Ex vivo organ bath model (colonic contractility measurements) Bead expulsion test (colonic transit analysis) -GI transit assay using carmine red in vivo (gut motility measurements) -Rhodamine B dextran fluorescence detection (gastric emptying and small intestinal transit) |
Mice (N = NS*) | 40 |
| -Signaling via TLR4 receptor leads to delayed gastrointestinal motility | -Fecal pellets collection (stool frequency) Bead expulsion test (colonic transit analysis) -Isometric muscle recordings of colonic longitudinal muscle strips |
Mice (N = 5-10) | 36 | |
| -Signaling through TLR4 activates ICCs to produce nitric oxide and inhibits the pacemaker currents of the gut contractility | -Whole-cell patch clamp (cultured ICCs measurements of membrane currents and potentials) -RT-PCR in cultured ICCs from small intestine |
Mice (N = 6-11) | 67 | |
| Lipopeptides and peptidoglycan | -Signaling via TLR2 receptor resulted in inhibition of neurogenesis leading to significant dysmotility and loss of colonic myenteric neurons | -GI transit assay using carmine red in vivo (gut motility measurements) -Bead latency test (distal colonic transit time) -Detection of fluorescein isothiocyanate-dextran (determination of colonic geometric center) |
Mice (N = NS) | 44 |
| Salmonella typhimurium-derived enterotoxin | -Causing dramatic changes in intestinal myoelectric activity and substantial fluid production | -Ex vivo organ bath (measurement of myoelectric activities in ileal loops) | Rabbits (N = 8) | 49 |
| Short-chain fatty acids | -Stimulation of PYY production in human enteroendocrine cells | -ELISA (PYY quantification) | NA | 76 |
| -Modulation of 5-HT release from model of enterochromaffin cells (butyrate, propionate) | -RIN14B cell line in vitro (5-HT release measurements) | NA | 90 | |
| -Increase of the proportion of cholinergic neurons translating to increased gut motility |
-Ex vivo organ bath model (colonic contractility measurements) -Bead expulsion test (colonic transit analysis) |
Rats (N = 5-6) | 41 | |
| -Stimulation of increase/decrease in colonic motility (butyrate, propionate, acetate) | -Ex vivo organ bath model (colonic contractility measurements) | Guinea pigs and rats (N = 4-9 and N = 4-6) | 93,94 | |
| -Stimulation of GLP-1 production (butyrate, propionate, acetate) |
-Ex vivo organ bath model (colonic contractility measurements) -Evans Blue dye detection (small intestinal transit) |
Mice (N = 4-7) | 95 | |
| -Modulation of ghrelin signaling (acetate, propionate and butyrate) | -Cell culture (activation of G protein coupled receptors using β-arrestin assay) | NA | 71 | |
| Tryptophan metabolites | -Acceleration of gastrointestinal transit by activation of epithelial 5-HT4 receptor in the proximal colon (tryptamine) | -Ussing Chamber (assessment of epithelial ionic flux) -GI transit assay using carmine red in vivo (gut motility measurements) |
Mice (N = 4-6) | 5 |
| -Modulation of secretion of GLP-1 (indole) | -Total GLP-1 assay (GLP-1 quantification) | NA | 96 | |
| -AhR signaling in the colonic neurons alters gut motility (indole-3-carbinol) | -GI transit assay using carmine red in vivo (gut motility measurements) -Live video imaging and spatiotemporal mapping of colonic motility |
Mice (N = 8-18) | 39 | |
| -Enhancement of the epithelial barrier functions by increasing of expression of genes involved in maintenance of epithelial cell structure and function (indole) | -Microarrays | NA | 97 | |
| -Regulation of intestinal barrier function in vivo by acting as a ligand for xenobiotic sensor, pregnane X receptor (IPA) | -Fluorescein isothiocyanate-dextran detection in serum (intestinal permeability assay in vivo) | Mice (N = 3-6) | 98 | |
| -Reduction of intestinal permeability in mice fed a high fat diet | -Fluorescein isothiocyanate-dextran detection in plasma (intestinal permeability assay in vivo) -TEER (colonic intestinal permeability assay in vitro) |
Mice (N = 7-9) | 99 | |
| Bile acids | -Modulation of 5-HT release from model of enterochromaffin cells (cholate, deoxycholate) | -RIN14B cell line in vitro (5-HT release measurements) | NA | 90 |
| -Bacterial bile salt hydrolase activity is associated with faster gastrointestinal transit in gnotobiotic mouse model | -GI transit assay using carmine red in vivo (gut motility measurements) | Mice (N = 5-6) | 100 | |
| -Promote gastrointestinal motility by activation TGR5 receptors located on enterochromaffin cells |
-Ex vivo organ bath model (colonic contractility measurements) -Evans Blue dye detection (gastrointestinal transit) -Bead expulsion test (colonic transit analysis) -Fecal pellets collection (stool frequency) |
Mice (N = NS) | 101 | |
| 5-hydroxyindole | -Modulation of gut motility via L-type voltage-dependent Ca2+ channels located on the colonic smooth muscle cells -Control of serotonin release from model of enterochromaffin cells |
-RIN14B cell line in vitro (5-HT release measurements) -GI transit assay using carmine red in vivo (gut motility measurements) -Ex vivo organ bath model (colonic contractility measurements) |
Rats (N = 6-10) | 4 |
| Protein P9 | -Production of protein P9 signals to L cells to produce GLP-1 | -ELISA (GLP-1 quantification) | NA | 72 |
| Indole and indole-3-carboxaldehyde | -Activation of TRPA1 in EECs, leads to production of 5-HT from enterochromaffin cells and thus modulate gut motility | -Real-time measurements of EECs in vivo in zebrafish (activation of TRPA1 and gut motility) -Amperometry (5-HT release) |
Zebrafish (N = 117-213) | 102 |
| Quercetin | -Improvement of the symptoms of constipation in rat loperamide-induced constipation model | -Charcoal propulsion test (gut motility) | Rats (N = 3) | 103 |
| Heptadecanoic and stearic acid (saturated long-chain fatty acids) | -Enhancement of colonic contractility ex vivo and stool frequency in vivo |
-Ex vivo organ bath model (colonic contractility measurements) -Fecal pellets collection (stool frequency) |
Rats (N = 6-8) | 104 |
| Isovaleric acid (branched-chain fatty acids) | -Causes contractile relaxation of colonic smooth muscles via cAMP/PKA pathway |
-Ex vivo organ bath model (colonic contractility measurements) -Isolated muscle cells culture (direct activation of PKA activity) |
Mice (N = 4-7) | 8 |
| Polyamines (spermidine, putrescine, spermine) and trace amines (isoamylamine, cadaverine) | -Modulation of intestinal peristalsis | -Ex vivo organ bath model (ileal and colonic contractility measurements) | Mice (N = 7) | 105 |
| Ferulic acid | -Acceleration of gastrointestinal transit and gastric emptying | -Charcoal propulsion test (gut transit) -Phenol red detection (gastric emptying) |
Rats (N = 8) | 106 |
| Histamine | -Promotion of colonic motility via activation of histamine receptors in the gut | -Fecal output assay | Mice (N = 3-5) | 107 |
| 3-(3,4-dihydroxyphenyl)propionic acid (DHPPA) | -Potent stimulation of ileal motility ex vivo | -Ex vivo organ bath model (ileal contractility measurements) | Mice (N = 4-6) | 108 |
| Dopamine | -Inhibition of longitudinal muscle contractility | -Ex vivo organ bath model (longitudinal ileal muscle contractility measurements) | Guinea pigs (N = 10) | 109 |
| -Decreased the duration of the MMCs in the small intestine (duodenum and jejunum) | -Implanted Ni/Cr electrodes | Dogs (N = 4) | 110 | |
| -Induced phase-III like MMCs in the duodenum | -Intestinal radiopaque tube | Humans, healthy (N = 14) | 111 |
*NS = not specified
**NA = not applicable.