# Multi-Omics Profiling of mTBI-Induced Gut–Brain Axis Disruption: A Preliminary Study for Biomarker Screening and Mechanistic Exploration

**Authors:** Xianqi Zhang, Tingting Wang, Yishu Liu, Shilin Miao, Pei Liu, Yadong Guo, Jifeng Cai, Changquan Zhang

PMC · DOI: 10.3390/biomedicines14020311 · Biomedicines · 2026-01-30

## TL;DR

This study explores how mild traumatic brain injury affects the gut-brain connection, identifying potential biomarkers and metabolic changes in rats.

## Contribution

The study introduces a multi-omics approach to identify gut microbiota and brain metabolite changes linked to mTBI.

## Key findings

- Key gut bacteria like Staphylococcus and Streptococcus were altered after mTBI.
- Brain metabolites such as C24:1 Sphingomyelin showed significant changes.
- Disruptions in fatty acid and phospholipid metabolism were linked to inflammation.

## Abstract

Background/Objectives: Mild Traumatic Brain Injury (mTBI) is a prevalent form of cranial trauma that can elicit a range of acute and chronic neuropsychiatric symptoms, and may increase the risk of neurodegenerative diseases. Its accurate identification remains a significant challenge in the field of forensic medicine. This study aimed to identify differential gut microbiota as potential biomarkers following mTBI and to preliminarily explore the association between alterations in gut microbiota and brain metabolites. Methods: An animal model was used to induce mTBI in male Sprague-Dawley (SD) rats. Dynamic changes in the gut microbiota and brain metabolites were analyzed via 16S rRNA sequencing and untargeted metabolomics. Results: Key discriminative taxa included Staphylococcus, Streptococcus, and Aeromonadaceae. Concurrently, brain metabolites, such as C24:1 Sphingomyelin and Thioetheramide PC, exhibited significant alterations. Multi-omics integration revealed that these changes were strongly correlated; in addition, a pathway analysis implicated disruptions in short-chain fatty acid and glycerophospholipid metabolism, which were linked to the regulation of inflammatory factors. Conclusions: This study demonstrates that mTBI induces distinct, time-dependent alterations in both the gut microbiota and brain metabolome, thereby providing a novel direction for research into the forensic diagnosis and mechanistic investigation of mTBI. Future studies are warranted to validate these potential biomarkers in human cohorts and to further elucidate the causal mechanisms underlying gut–brain axis interactions.

## Linked entities

- **Chemicals:** C24:1 Sphingomyelin (PubChem CID 44260126), Thioetheramide PC (PubChem CID 10259406)

## Full-text entities

- **Genes:** Uchl1 (ubiquitin C-terminal hydrolase L1) [NCBI Gene 29545], Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, Il2 (interleukin 2) [NCBI Gene 16183] {aka Il-2}, App (amyloid beta precursor protein) [NCBI Gene 54226] {aka Abeta}, Nsmaf (neutral sphingomyelinase activation associated factor) [NCBI Gene 353233] {aka FAN}, Nefl (neurofilament light chain) [NCBI Gene 83613] {aka NF-L, NF68, Nfl}, Vip (vasoactive intestinal peptide) [NCBI Gene 117064] {aka vip/phi27}, Il10 (interleukin 10) [NCBI Gene 25325] {aka IL10X, If2a}, Il10 (interleukin 10) [NCBI Gene 16153] {aka CSIF, If2a, Il-10}, Cldn1 (claudin 1) [NCBI Gene 65129], Cxcl1 (C-X-C motif chemokine ligand 1) [NCBI Gene 81503] {aka CINC-1, Gro1}, Ocln (occludin) [NCBI Gene 83497], Csf3 (colony stimulating factor 3 (granulocyte)) [NCBI Gene 12985] {aka Csfg, G-CSF, MGI-IG}, Il1b (interleukin 1 beta) [NCBI Gene 24494] {aka IL-1F2}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, Pla2g2a (phospholipase A2 group IIA) [NCBI Gene 29692] {aka sPLA2}, Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, Gfap (glial fibrillary acidic protein) [NCBI Gene 24387], Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, Tjp1 (tight junction protein 1) [NCBI Gene 292994] {aka ZO-1}
- **Diseases:** neurological impairments (MESH:D009422), dementia (MESH:D003704), neuronal loss (MESH:D009410), depression (MESH:D003866), TBI (MESH:D000070642), CNS diseases (MESH:D002493), edema (MESH:D004487), neuroinflammation (MESH:D000090862), dizziness (MESH:D004244), concussion (MESH:D001924), atrophy (MESH:D001284), anxiety (MESH:D001007), AD (MESH:D000544), loss of consciousness (MESH:D014474), neuropsychiatric symptoms (MESH:D001523), cranial trauma (MESH:D020197), neural damage (MESH:D015441), attentional deficits (MESH:D001289), brain injury (MESH:D001930), head injuries (MESH:D006259), myelin disruption (MESH:D003711), PD (MESH:D010300), injury (MESH:D014947), neurodegenerative diseases (MESH:D019636), headache (MESH:D006261), Inflammatory (MESH:D007249)
- **Chemicals:** ethanol (MESH:D000431), Thioetheramide PC (MESH:C081346), flavonoids (MESH:D005419), DAPI (MESH:C007293), SCFAs (MESH:D005232), glycolipids (MESH:D006017), coumarins (MESH:D003374), sphingolipids (MESH:D013107), alcohols (MESH:D000438), Liothyronine (MESH:D014284), alkaloids (MESH:D000470), heterocyclic compounds (MESH:D006571), Colfosceril Palmitate (MESH:C081581), paraformaldehyde (MESH:C003043), arachidonic acid (MESH:D016718), nucleotides (MESH:D009711), lipid (MESH:D008055), isoflurane (MESH:D007530), phenolic acids (MESH:C017616), endocannabinoid (MESH:D063388), agarose (MESH:D012685), terpenoids (MESH:D013729), benzene (MESH:D001554), phospholipid (MESH:D010743), citrate (MESH:D019343), alpha-Linolenic acid (MESH:D017962), steroids (MESH:D013256), amines (MESH:D000588), PC (MESH:C053518), phosphatidylcholine (MESH:D010713), carbohydrates (MESH:D002241), butyrate (MESH:D002087), xylene (MESH:D014992), lignans (MESH:D017705), cholines (MESH:D002794), amino acids (MESH:D000596), nitrogen (MESH:D009584), glycerophospholipid (MESH:D020404), tryptamines (MESH:D014363), AraS (-), paraffin (MESH:D010232), linoleic acid (MESH:D019787), methanol (MESH:D000432), Sphingomyelin (MESH:D013109), H&amp;E (MESH:D006371), PA (MESH:D011478), 2-AG (MESH:C094503), bile acids (MESH:D001647)
- **Species:** Ruminococcus (genus) [taxon 1263], gut metagenome (species) [taxon 749906], Agromyces (genus) [taxon 33877], Bacilli (class) [taxon 91061], Clostridia (class) [taxon 186801], Actinomycetota (actinobacteria, phylum) [taxon 201174], Allobaculum (genus) [taxon 174708], Agathobacter rectalis (species) [taxon 39491], Sutterella (genus) [taxon 40544], Sphingomonas (genus) [taxon 13687], Pseudomonadota (proteobacteria, phylum) [taxon 1224], Shigella (genus) [taxon 620], Bacillota (clostridial firmicutes, phylum) [taxon 1239], Mycoplasma (genus) [taxon 2093], Turicibacter (genus) [taxon 191303], Helicobacter (genus) [taxon 209], Lactobacillus (genus) [taxon 1578], Bifidobacterium (genus) [taxon 1678], Spirochaetia (class) [taxon 203692], Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116], Prevotella (genus) [taxon 838], Staphylococcus (genus) [taxon 1279], Bacteroides (genus) [taxon 816], Mus musculus (house mouse, species) [taxon 10090], Aerococcus (genus) [taxon 1375], Escherichia coli (E. coli, species) [taxon 562], Lactobacillaceae (family) [taxon 33958], Corynebacterium (genus) [taxon 1716], Streptococcus (genus) [taxon 1301]

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12938811/full.md

## References

47 references — full list in the complete paper: https://tomesphere.com/paper/PMC12938811/full.md

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Source: https://tomesphere.com/paper/PMC12938811