- gadB-mediated GABA biosynthesis confers oxidative stress tolerance in Lactiplantibacillus plantarum SAL, a cross-protective function distinct from classical acid resistance.
- 1.5% L-Glu supplementation synergistically enhances SAL antioxidative capacity, preserving ~10^8 CFU/mL under 8 mM H2O2 versus ~10^7 without.
- SAL exhibits superior probiotic traits and antitumour effects and, with L-Glu, restores colon barrier integrity, increases goblet cells, and normalises MDA and GSSG.
Front Nutr. 2026 Sep 21;13:1909350. doi: 10.3389/fnut.2026.1909350. eCollection 2026.
ABSTRACT
INTRODUCTION: The therapeutic efficacy of probiotics is often limited by poor survival under gastrointestinal oxidative stress; however, stress adaptation mechanisms in Lactiplantibacillus remain poorly understood. This study evaluated the probiotic properties of a host-derived strain, Lactiplantibacillus plantarum SAL, elucidated the molecular basis of its oxidative stress tolerance, and assessed whether L-glutamate (L-Glu) supplementation synergistically enhances its protective effects on intestinal barrier integrity.
METHODS: Probiotic traits (gastrointestinal tolerance, antibacterial activity) and antitumor efficacy (CT26 colon cancer xenograft model in nude mice) of L. plantarum SAL were assessed. Transcriptome profiling of H2O2-challenged SAL identified key stress-responsive genes. The effects of L-Glu supplementation on oxidative stress resistance and antibacterial activity were evaluated in vitro. A D-galactose (D-gal)-induced oxidative injury mouse model was used to investigate the restorative effects of the L. plantarum SAL + L-Glu synbiotic on intestinal barrier function.
RESULTS: Compared with the reference strain L. plantarum WCFS1, SAL possessed superior probiotic traits, with significantly higher viability at 6% NaCl (p < 0.01) and in simulated gastric fluid at pH 1.5 after 2 h (p < 0.001). SAL administration markedly suppressed tumor growth and attenuated splenomegaly in the colon cancer model, with inhibition rates of 21.26% by tumor weight and 32.51% by tumor volume. Transcriptomic profiling identified 313 differentially expressed genes (149 upregulated, 164 downregulated), revealing glutamate decarboxylase (gadB) as a key oxidative stress tolerance gene. Heterologous expression of recombinant GadB confirmed its enzymatic activity (14.06 U/mg), mediating resistance via γ-aminobutyric acid (GABA) biosynthesis. Supplementation with 1.5% L-Glu significantly increased the antioxidative capacity of L. plantarum SAL, maintaining viable counts at ~108 CFU/mL under 8 mM H2O2 versus ~107 CFU/mL without supplementation. In the D-gal-induced oxidative damage model, the L. plantarum SAL + L-Glu synbiotic restored colon barrier integrity, increased goblet cell numbers, reduced inflammatory infiltration, and decreased plasma levels of malondialdehyde (MDA) and oxidized glutathione (GSSG) to levels comparable to those of normal controls (p > 0.05). Mechanistically, GadB-mediated GABA biosynthesis conferred cross-protection against oxidative stress, a function distinct from its canonical acid resistance role and previously unrecognized in Lactiplantibacillus.
CONCLUSION: Augmentation of the gadB pathway by exogenous L-Glu enhances the probiotic efficacy of L. plantarum SAL by synergistically boosting oxidative stress tolerance and reinforcing intestinal barrier repair. These findings establish gadB-mediated GABA biosynthesis as a previously unrecognized cross-protective mechanism against oxidative stress, thereby extending the classical acid-resistance paradigm of the GAD system. This targeted metabolic modulation thus offers a promising synbiotic strategy for counteracting oxidative stress-linked gut disorders. Although Nrf2 activation is a plausible mediator, direct confirmation in intestinal tissues and dose optimization are still required.
PMID:42890181 | PMC:PMC13671104 | DOI:10.3389/fnut.2026.1909350
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