TABLE 1.
Targeting the gut microbiota: a potential approach to balance tryptophan metabolism
| Microbial manipulation | Influenced tryptophan metabolism | Model | Design | Findings | Reference |
|---|---|---|---|---|---|
| Antibiotics | Serotonin synthesis | C57BL/B6 mice | Mice were orally treated with an antibiotic mix (ampicillin, neomycin, metronidazole, and vancomycin), whereas the control group received water for 4 weeks | Colonic motility ↓Colonic TPH1 ↓Colonic motility ↓ | Ge et al., 2017 (38) |
| Kynurenine pathway | NIH Swiss mice | Mice were orally treated or were not treated with an antibiotic cocktail (ampicillin, vancomycin, neomycin, metronidazol, and amphotericin-B) for 2 months | Circulating tryptophan ↑Peripheral kynurenine ↓ | Desbonnet et al., 2015 (51) | |
| Preterm piglets | Piglets were orally administered or were not administered with an antibiotic cocktail (ampicillin, gentamycin, and metronidazole) for 4 days | Circulating tryptophan ↑Peripheral kynurenine ↓ | Jiang et al., 2017 (55) | ||
| Microbial degradation | Piglets | Piglets were orally administered or were not administered with an antibiotic cocktail (olaquindox, oxytetracycline calcium, and kitasamycin) for 35 days | Circulating tryptophan ↑Jejunal tryptophan ↓Colonic tryptamine ↑ | Mu et al., 2017 (18) | |
| Colonic tryptamine ↑ | |||||
| Piglets | Piglets were orally administered or were not administered with an antibiotic cocktail (ampicillin, gentamycin, and metronidazole) for 13 days | Fecal indole ↑Fecal indolic compounds ↑ | Gao et al., 2018 (54) | ||
| Pigs | Pigs were orally administered or were not administered with an antibiotic cocktail (olaquindox, oxytetracycline calcium, and kitasamycin) for 35 days | Colonic indole ↑ | Zhang et al., 2017 (56) | ||
| Distal ileal cannulated piglets | Piglets were distal ileal infused with an antibiotic cocktail (ampicillin, gentamycin, and metronidazole), whereas the control group received saline for 25 days | Circulating tryptophan ↓Fecal indolic compounds ↑ | Gao et al., 2018 (12) | ||
| Probiotics | Serotonin synthesis | BALB/C mice | Mice were orally administered or were not administered with Lactobacillus casei 327 | Colonic serotonin ↑Colonic TPH1 ↑Colonic transit ↑ | Hara et al., 2018 (57) |
| Kynurenine pathway | BioBreeding rats | Rats were orally administered or were not administered with Lactobacillus johnsonii cell-free supernatant | Circulating kynurenine ↓Intestinal IDO activity ↓ | Valladares et al., 2013 (58) | |
| Healthy adults | Healthy adults were orally administered or were not administered with Lactobacillus johnsonii for 8 weeks | Circulating tryptophan ↑Circulating kynurenine ↓ | Marcial et al., 2017 (59) | ||
| Sprague-Dawley rats | Rats were orally administered or were not administered with probiotic Bifidobacteria infantis for 14 days | Circulating tryptophan ↑Circulating kynurenine/tryptophan ratio ↓ | Desbonnet et al., 2008 (60) | ||
| Microbial degradation | C57BL mice | Mice were orally administered or were not administered with Lactobacillus reuteri | Circulating tryptophan ↓Peripheral tryptophan metabolites (eg., IAld, IAA, ILA) ↑ | Cervantes-Barragan et al., 2017 (44) | |
| Card9 (-/-) mice | Card9 (-/-) mice were orally administered or were not administered with 3 tryptophan-metabolizing Lactobacillus strains (L. murinus, L. reuteri, and L. taiwanensis) | Intestinal tryptophan metabolite IAA ↓ | Lamas et al., 2016 (62) | ||
| Nutrients | Serotonin synthesis | Piglets | Piglets were fed with sow, formula, or milk for 19 days | Formula vs. sowColonic ECs number ↓Colonic serotonin ↓ | Saraf et al., 2017 (66) |
| GF mice | GF mice colonizing with human gut microbiota and GF mice were fed with polysaccharide-rich diet | Colonic transit ↑Colonic serotonin ↑ | Kashyap et al., 2013 (63) | ||
| GF mice | GF mice colonizing with human gut microbiota compared with GF mice | Colonic serotonin ↑Colonic TPH1↑Colonic transit ↑ | Reigstad et al., 2015 (70) | ||
| Kynurenine pathway | Human primary IEC & IEC cell line | IEC cells were treated or were not treated with commensal bacteria and butyrate | IEC IDO1 expression ↓ | Martin-Gallausiaux et al., 2018 (53) | |
| Microbial degradation | C57BL/6J mice | Mice were fed with high-fat diet, whereas the control group were fed with low-fat diet | Cecal IAA ↓Cecal tryptamine ↓ | Krishnan et al., 2019 (64) | |
| Piglets | Piglets were fed with sow, formula, or milk for 19 days | Formula vs. sow: colonic tryptamine ↑ | Saraf et al., 2017 (66) | ||
| In vitro culture | A tryptophan-utilizing strain isolated from piglet feces was in vitro cultured using glucose or FOS as substrate | FOS: indole ↑ | Wang et al., 2011 (67) | ||
| In vitro culture | A mix of microbial population from pig feces was in vitro cultured in 4 types of carbohydrate sources (sugar beet pulp, rye grass hay, alfalfa hay, and FOS) | FOS: indolic compounds ↓ | Li et al., 2009 (68) | ||
| Pigs | Pigs were fed or were not fed with RS for 100 days | Colonic indolic compounds ↓Colonic tryptamine ↓ | Zhou et al., 2017 (69) | ||
| Cecal cannulated piglets | Cecal cannulated piglets were infused with corn starch, whereas the control group received saline for 19 days | Fecal tryptophan ↑Fecal indolic compounds ↑ | Gao et al., 2019 (10) | ||
| BALB/C & C57BL/6 mice | Mice fed with tryptophan or sugar as an energy source | Colonic IAld ↑ | Zelante et al., 2013 (61) |
BALB/C, albino, laboratory-bred strain; EC, enterochromaffin cell; FOS, fructooligosaccharides; GF, germ-free; IAA, indole-3-acetic-acid; IAld, indole-3-aldehyde; IDO, indoleamine 2,3-dioxygenase; IEC, intestinal epithelial cell; ILA, indole-3-lactic acid; RS, resistant starch; TPH1, tryptophan hydroxylase 1.