Effects of Lactobacillus helveticus KLDS 1.1105 Postbiotics and Their Exopolysaccharides on Immune Function and Gut Microbiota in Immunosuppressed Mice.

High-dose postbiotics and EPS significantly restored immune organ indexes in cyclophosphamide-induced immunosuppressed mice.

• A cyclophosphamide (CTX)-induced immunosuppression mouse model was established to evaluate immune effects.
• High-dose postbiotics were administered at 1200 mg/kg and EPS at 200 mg/kg.
• Both treatments restored thymus and spleen organ indexes that were reduced by CTX-induced immunosuppression.
• Lower doses of postbiotics showed comparatively lesser effects than the high-dose formulation.

Both LHPs and EPS increased activities of splenic lymphocytes and natural killer (NK) cells in immunosuppressed mice.

• Splenic lymphocyte proliferation activity was significantly increased following high-dose postbiotic (1200 mg/kg) and EPS (200 mg/kg) treatment.
• NK cell activity was restored in both LHP and EPS treatment groups compared to CTX-only controls.
• These effects indicate restoration of cellular immune function suppressed by cyclophosphamide.

LHPs and EPS improved intestinal barrier integrity in immunosuppressed mice.

• High-dose postbiotics (1200 mg/kg) and EPS (200 mg/kg) were associated with improved intestinal barrier function.
• Restoration of intestinal barrier integrity was observed as part of the immunomodulatory effects of both treatments.
• Intestinal barrier compromise is a known consequence of CTX-induced immunosuppression in this model.

Both postbiotics and EPS restored the Th17/Treg balance and activated the TLR4/NF-κB signaling pathway.

• CTX-induced immunosuppression disrupted the Th17/Treg balance, which was restored by LHP and EPS treatment.
• The TLR4/NF-κB signaling pathway was activated following treatment with both postbiotics and EPS.
• Restoration of Th17/Treg balance is a key indicator of immunomodulatory activity.
• These molecular pathway effects suggest a mechanistic basis for the observed immune restoration.

Treatment with LHPs and EPS restored gut microbiota balance and promoted short-chain fatty acid (SCFA) production.

• Both high-dose postbiotics (1200 mg/kg) and EPS (200 mg/kg) restored the balance of gut microbiota disrupted by CTX.
• Restoration of gut microbiota composition was associated with promotion of short-chain fatty acid (SCFA) production.
• SCFAs are known to play important roles in immune regulation and intestinal health.
• The gut microbiota-regulating function was identified alongside immunomodulatory effects as a key outcome.

Comparative analysis indicated that EPS is a key bioactive component responsible for the immunoregulatory activity of the postbiotic formulation.

• EPS was administered at 200 mg/kg and produced effects comparable to high-dose postbiotics at 1200 mg/kg across multiple immune parameters.
• Overall effects of postbiotics and EPS alone were systematically compared across immune organ indexes, lymphocyte activity, NK cell activity, intestinal barrier integrity, Th17/Treg balance, TLR4/NF-κB activation, gut microbiota composition, and SCFA production.
• The comparative analysis suggested EPS accounts for a substantial portion of the immunomodulatory activity observed in the full postbiotic formulation.
• Postbiotics are defined in this study as inactive probiotics and their metabolites, with EPS representing one key metabolite fraction.