# Mechanisms of action of bile acids in pediatric gastroesophageal reflux: Exploration through non-targeted and targeted metabolomics methods

**Authors:** Linqian Zhang, Kang Wang, Qianwen Shi, Panjian Lai, Haiying Fang, Yuhe Chen, Xiaobing Li

PMC · DOI: 10.1371/journal.pone.0343229 · PLOS One · 2026-03-13

## TL;DR

This study explores how bile acids contribute to pediatric bile reflux gastritis using metabolomics to identify key differences in bile acid levels and related metabolic pathways.

## Contribution

The study introduces novel insights into the mechanisms of pediatric bile reflux gastritis through combined non-targeted and targeted metabolomics analyses.

## Key findings

- Ten differential metabolites were identified in gastric juice of BRG patients, including fatty acids and phospholipids.
- Key metabolic pathways like glycerophospholipid metabolism and Th17 cell differentiation were highlighted as relevant to BRG.
- Aberrant TBA levels in gastric juice and peripheral blood suggest potential diagnostic value for BRG.

## Abstract

To investigate the pathogenesis of pediatric bile reflux gastritis (BRG) using non-targeted and targeted metabolomics analyses of the changes and content differences of bile acids (BAs) in gastric juice.

Data from 25 pediatric BRG patients treated at Jinhua Maternal and Child Health Care Hospital between May 2022 and August 2023 were retrospectively analyzed. Twenty-five patients with gastritis without bile reflux and 25 healthy controls were selected for the comparison of total bile acids (TBA) levels of gastric juice and peripheral blood and the identification of differential metabolites. The correlations of gastric juice and peripheral blood TBA levels with the clinical characteristics of the pediatric BRG patients were analyzed. ROC curves were constructed to evaluate the diagnostic performance of TBA in identifying BRG, as indicated by the area under the curve (AUC), sensitivity, and specificity.

Identification and quantitative metabolomics Studies have identified the top 10 differential metabolites in gastric juice between the BRG and healthy control groups, which include fatty acids, phospholipids, 23-carbon compounds, amines, vitamins, steroids, peptide hormones, monosaccharides, polyketides, and non-ribosomal peptides. This indicated that glycerophospholipid metabolism, prodigiosin biosynthesis, lysine degradation, glycerolipid metabolism, and primary BA biosynthesis were the most relevant pathways. Differential metabolites were primarily concentrated in the T helper 17 (Th17) cell differentiation pathway (P < 0.05, effect value>0.1).

The metabolites and metabolic pathways identified in different groups will aid in elucidating the pathogenic mechanisms underlying pediatric BRG. Gastric juice and peripheral blood TBA levels showed a trend of aberrant expression in pediatric BRG patients, potentially guiding clinical diagnosis.

## Linked entities

- **Chemicals:** fatty acids (PubChem CID 264), steroids (PubChem CID 139082353)
- **Diseases:** gastritis (MONDO:0004966)

## Full-text entities

- **Genes:** IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, PDCD1 (programmed cell death 1) [NCBI Gene 5133] {aka ADMIO4, AIMTBS, CD279, PD-1, PD1, SLEB2}, AR (androgen receptor) [NCBI Gene 367] {aka AIS, AR8, DHTR, HPCX3, HUMARA, HYSP1}, NR1H4 (nuclear receptor subfamily 1 group H member 4) [NCBI Gene 9971] {aka BAR, FXR, HRR-1, HRR1, PFIC5, RIP14}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, VIP (vasoactive intestinal peptide) [NCBI Gene 7432] {aka PHM27}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}
- **Diseases:** bilious vomiting (MESH:D014839), (LES) (MESH:D004941), inflammation (MESH:D007249), anxiety (MESH:D001007), BR (MESH:D001655), CAG (MESH:D005757), carcinogenic (MESH:D011230), fatigue (MESH:D005221), H. pylori-infected (MESH:D016481), mucosal injury (MESH:D052016), immune dysregulation (OMIM:614878), gastric mucosal lesions (MESH:D013272), cancer (MESH:D009369), emotional disorders (MESH:D009358), intestinal polyps (MESH:D007417), chronic gastritis (MESH:D005756), GC (MESH:D013274), cytotoxicity (MESH:D064420), pain (MESH:D010146), depression (MESH:D003866), IM (MESH:D007410), Barrett's esophagus (MESH:D001471), abdominal pain (MESH:D015746), RE (MESH:D005764), Helicobacterpylori infection (MESH:D007239), esophageal adenocarcinoma (MESH:D000230)
- **Chemicals:** glycerophospholipid (MESH:D020404), amines (MESH:D000588), steroids (MESH:D013256), hydrotalcite (MESH:C010467), LPS (MESH:D008070), GCDCA (MESH:D005999), BA (MESH:D001647), TDCA (MESH:D013657), GCA (MESH:D006000), phospholipids (MESH:D010743), Lysine (MESH:D008239), GUDCA (MESH:C024033), lipid (MESH:D008055), prodiginine (MESH:C010307), Prodigiosin (MESH:D011353), GDCA (MESH:D006002), monosaccharides (MESH:D009005), TCA (MESH:D013656), UDCA (MESH:D014580), TCDCA (MESH:D013655), TUDCA (MESH:C031655), GLCA (MESH:C027746), polyketides (MESH:D061065), Fatty acids (MESH:D005227), TLCA (MESH:D013658), 3-oxo-Delta4,6-LCA (-), H+ (MESH:D006859), deoxycholic acid (MESH:D003840)
- **Species:** Serratia marcescens (species) [taxon 615], Helicobacter pylori (species) [taxon 210], Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]

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## References

26 references — full list in the complete paper: https://tomesphere.com/paper/PMC12987485/full.md

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Source: https://tomesphere.com/paper/PMC12987485