# The Gut Microbiota–Tryptophan–Brain Axis in Autism Spectrum Disorder: A New Frontier for Probiotic Intervention

**Authors:** Yi Cheng, Liangyu Zhang, Yalin Li, Chunru Zheng, Teng Ma, Zhihong Sun

PMC · DOI: 10.3390/microorganisms14020312 · Microorganisms · 2026-01-29

## TL;DR

This paper explores how gut microbiota and tryptophan metabolism affect autism and how probiotics might help.

## Contribution

The paper highlights the gut microbiota–tryptophan–brain axis as a new target for probiotic treatment in autism.

## Key findings

- ASD patients show disrupted tryptophan metabolism and gut microbiota dysbiosis.
- Probiotics like Lactobacillus and Bifidobacterium may improve ASD symptoms by regulating this metabolic axis.
- Current probiotic interventions need more safety studies and clearer molecular mechanisms.

## Abstract

Tryptophan (Trp) metabolism is involved in regulating various physiological and pathological processes, including neurological function, immune response, and gut homeostasis. This article focuses on autism spectrum disorder (ASD) and explores its relationship with abnormalities in the gut microbiota–Trp–brain axis. Studies have shown that ASD patients exhibit Trp metabolism disorders, with gut microbiota dysbiosis inducing systemic inflammation, activating indoleamine 2,3-dioxygenase 1 (IDO1), and promoting increased Trp entry into the kynurenine pathway (KP). This leads to a series of pathological changes, including the production of neurotoxic substances, serotonin system disorders, and impaired intestinal barrier function, which in turn exacerbate ASD symptoms through the gut–brain axis. Furthermore, based on preclinical and clinical studies, we have summarized that specific probiotic strains (such as Lactobacillus and Bifidobacterium) can alleviate the clinical manifestations of ASD by regulating the gut microbiota–Trp metabolic axis, improving immune responses, and enhancing intestinal barrier function. We emphasize that current probiotic interventions still face challenges such as insufficient long-term safety assessments and unclear molecular mechanisms. Future research should combine multi-omics technologies and multi-modal approaches to promote the development of personalized and precise intervention strategies. In summary, this review highlights the crucial role of tryptophan metabolism in ASD and the potential of probiotics as a novel adjunctive therapy targeting this metabolic pathway.

## Linked entities

- **Genes:** IDO1 (indoleamine 2,3-dioxygenase 1) [NCBI Gene 3620]
- **Chemicals:** tryptophan (PubChem CID 1148), kynurenine (PubChem CID 846)
- **Diseases:** autism spectrum disorder (MONDO:0005258)

## Full-text entities

- **Genes:** BDNF (brain derived neurotrophic factor) [NCBI Gene 627] {aka ANON2, BULN2}, IDO1 (indoleamine 2,3-dioxygenase 1) [NCBI Gene 3620] {aka IDO, IDO-1, INDO}, Htr2a (5-hydroxytryptamine (serotonin) receptor 2A) [NCBI Gene 15558] {aka 5-HT-2, 5-HT-2A, E030013E04, Htr-2, Htr2}, Tph1 (tryptophan hydroxylase 1) [NCBI Gene 21990] {aka Tph}, Kmo (kynurenine 3-monooxygenase) [NCBI Gene 98256], Grin1 (glutamate receptor, ionotropic, NMDA1 (zeta 1)) [NCBI Gene 14810] {aka GluN1, GluRdelta1, GluRzeta1, M100174, NMD-R1, NMDAR1}, Haao (3-hydroxyanthranilate 3,4-dioxygenase) [NCBI Gene 107766] {aka 0610007K21Rik, 0610012J07Rik, 3-HAO, 3-HAOxase, 3HAO}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, Trpc1 (transient receptor potential cation channel, subfamily C, member 1) [NCBI Gene 22063] {aka Mtrp1, Trp1, Trrp1}, IDO2 (indoleamine 2,3-dioxygenase 2) [NCBI Gene 169355] {aka INDOL1}, TDO2 (tryptophan 2,3-dioxygenase) [NCBI Gene 6999] {aka HYPTRP, TDO, TO, TPH2, TRPO}, IL22 (interleukin 22) [NCBI Gene 50616] {aka IL-21, IL-22, IL-D110, IL-TIF, ILTIF, TIFIL-23}, Aadat (aminoadipate aminotransferase) [NCBI Gene 23923] {aka Aadt, KATII, Kat2, Kyat2, mKat-2}, AHR (aryl hydrocarbon receptor) [NCBI Gene 196] {aka FVH3, RP85, bHLHe76}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, HTR1A (5-hydroxytryptamine receptor 1A) [NCBI Gene 3350] {aka 5-HT-1A, 5-HT1A, 5HT1a, ADRB2RL1, ADRBRL1, G-21}, TPH2 (tryptophan hydroxylase 2) [NCBI Gene 121278] {aka ADHD7, NTPH}, SLC6A4 (solute carrier family 6 member 4) [NCBI Gene 6532] {aka 5-HTT, 5-HTTLPR, 5HTT, HTT, OCD1, SERT}, IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}, IL5 (interleukin 5) [NCBI Gene 3567] {aka EDF, IL-5, TRF}, EIF2AK4 (eukaryotic translation initiation factor 2 alpha kinase 4) [NCBI Gene 440275] {aka GCN2, PVOD2}, NADSYN1 (NAD synthetase 1) [NCBI Gene 55191] {aka VCRL3}, Htr7 (5-hydroxytryptamine (serotonin) receptor 7) [NCBI Gene 15566] {aka 5-HT-X, 5-HT7}, Ahr (aryl-hydrocarbon receptor) [NCBI Gene 11622] {aka Ah, Ahh, Ahre, In, bHLHe76}, IL4 (interleukin 4) [NCBI Gene 3565] {aka BCGF-1, BCGF1, BSF-1, BSF1, IL-4}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, Ido1 (indoleamine 2,3-dioxygenase 1) [NCBI Gene 15930] {aka Ido, Indo}, IL17A (interleukin 17A) [NCBI Gene 3605] {aka CTLA-8, CTLA8, IL-17, IL-17A, IL17, ILA17}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, TPH1 (tryptophan hydroxylase 1) [NCBI Gene 7166] {aka TPRH, TRPH}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, Il22 (interleukin 22) [NCBI Gene 50929] {aka IL-22, IL-22a, ILTIFa, If2b1, Iltif}
- **Diseases:** diarrhea (MESH:D003967), autoimmune diseases (MESH:D001327), pervasive developmental disorders (MESH:D002659), anxiety disorders (MESH:D001008), CRS (MESH:D013313), Dysregulation (MESH:D021081), neurological dysfunction (MESH:D009461), metabolic diseases (MESH:D008659), ASD (MESH:D000067877), Asperger's disorder (MESH:D020817), serotonin dysfunction (MESH:D020230), injury to (MESH:D014947), neurodegenerative diseases (MESH:D019636), inflammation (MESH:D007249), GI symptom (MESH:D012817), anxiety (MESH:D001007), neuroinflammation (MESH:D000090862), schizophrenia (MESH:D012559), abdominal pain (MESH:D015746), Autism (MESH:D001321), dysbiosis (MESH:D064806), tumors (MESH:D009369), Mental Disorders (MESH:D001523), Alzheimer's disease (MESH:D000544), neurotoxic (MESH:D020258), constipation (MESH:D003248), depression (MESH:D003866), obsessive compulsive symptoms (MESH:D009771), neuronal damage (MESH:D009410), cognitive decline (MESH:D003072), restricted interests (MESH:D002313), neurodevelopmental disorders (MESH:D002658), immune dysregulation (OMIM:614878), depressive and anxious behaviors (MESH:D011596), abnormal brain function (MESH:D001927), symptoms (MESH:D012816), childhood disintegrative disorder (MESH:D020964), GI (MESH:D005767), neurodevelopmental dysfunction (MESH:D065886), infection (MESH:D007239)
- **Chemicals:** propionic acid (MESH:C029658), indole compounds (MESH:D007211), iron (MESH:D007501), I3M (MESH:C016517), risperidone (MESH:D018967), Valerate (MESH:D014631), QA (MESH:D017378), Kyn (MESH:D007737), glutamate (MESH:D018698), norepinephrine (MESH:D009638), GABA (MESH:D005680), aromatic amino acid (MESH:D024322), indoleacrylic acid (MESH:C001446), fructo-oligosaccharide (MESH:C116580), corticosterone (MESH:D003345), indole propionate (MESH:C015292), aripiprazole (MESH:D000068180), KA (MESH:D007736), lactic acid (MESH:D019344), LPS (MESH:D008070), lipid (MESH:D008055), prebiotic (MESH:D056692), DSS (MESH:D016264), ATP (MESH:D000255), SCFAs (MESH:D005232), M8 (MESH:C017233), 3-methylindole (MESH:D012862), 5-HT (MESH:D012701), Indole (MESH:C030374), ondansetron (MESH:D017294), Trp (MESH:D014364), IAA (MESH:C030737), NAD+ (MESH:D009243), DA (MESH:D004298), ILA (MESH:C024139), indole-3-carboxylic acid (MESH:C012382), 5-HIAA (MESH:D006897), NO (MESH:D009614), bile acids (MESH:D001647), oxytocin (MESH:D010121), CCFM1077 (-), 5-HTs (MESH:C055058), fatty acids (MESH:D005227), carbohydrate (MESH:D002241), amino acid (MESH:D000596)
- **Species:** Lactococcus lactis subsp. lactis (subspecies) [taxon 1360], Veillonella (genus) [taxon 29465], Lactobacillus acidophilus (species) [taxon 1579], Lactococcus lactis (species) [taxon 1358], Escherichia coli (E. coli, species) [taxon 562], Faecalibacterium (genus) [taxon 216851], Bifidobacterium longum (species) [taxon 216816], Lactobacillus (genus) [taxon 1578], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Lacticaseibacillus rhamnosus (species) [taxon 47715], Saccharomyces boulardii [taxon 252598], Mus musculus (house mouse, species) [taxon 10090], Prevotella (genus) [taxon 838], Akkermansia (genus) [taxon 239934], Romboutsia timonensis (species) [taxon 1776391], Bacillota (clostridial firmicutes, phylum) [taxon 1239], Parasutterella (genus) [taxon 577310], Bacteroidia (class) [taxon 200643], gut metagenome (species) [taxon 749906], Limosilactobacillus reuteri (species) [taxon 1598], Paraprevotella (genus) [taxon 577309], Streptococcus thermophilus (species) [taxon 1308], Gallus gallus (bantam, species) [taxon 9031], Roseburia intestinalis (species) [taxon 166486], Corynebacterium (genus) [taxon 1716], Bifidobacterium (genus) [taxon 1678], Homo sapiens (human, species) [taxon 9606], Clostridium (genus) [taxon 1485], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], Bacteroides (genus) [taxon 816], Fusobacterium (genus) [taxon 848], Rattus norvegicus (brown rat, species) [taxon 10116]
- **Cell lines:** T-Helper 17 — Cairina moschata (Muscovy duck), Telomerase immortalized cell line (CVCL_JF18)

## Full text

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## Figures

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## References

114 references — full list in the complete paper: https://tomesphere.com/paper/PMC12943225/full.md

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Source: https://tomesphere.com/paper/PMC12943225