Background <p>Paraprobiotics, the non-viable microbial cells with health benefits, have gained interest as candidates for preventing food allergies owing to their safety and stability. Heat-killed <i>Lactiplantibacillus plantarum</i> FM8 (FM8) has been reported to induce interleukin (IL)-10 production in dendritic cells in vitro; however, its in vivo efficacy as a standalone intervention remains unexplored. We investigated the preventive effect of heat-killed FM8 in a murine model of ovalbumin (OVA)-induced food allergy.</p> Methods <p>BALB/c mice were assigned to control, OVA-induced allergy, or three FM8 treatment groups receiving FM8 at low (2 × 10⁹ CFU/day), medium (1 × 10¹⁰ CFU/day), or high (5 × 10¹⁰ CFU/day) doses. Food allergy was induced by repeated OVA sensitization and challenge. Allergy symptoms, OVA-specific immunoglobulin E (IgE), and IL-10 levels were measured. Tight junction gene expression, mucin production, gut microbiota composition, and short-chain fatty acids (SCFAs) were also analyzed.</p> Results <p>FM8 supplementation attenuated allergic responses in a dose-dependent manner. Allergy symptom scores were reduced in the High group, and the rectal temperature decline following OVA challenge was ameliorated in both the Med and High groups. The sensitization-induced increase in OVA-specific IgE was also attenuated in these groups. <i>IL-4</i> expression in Peyer’s patches was reduced, whereas colonic <i>IL-10</i> expression and serum IL-10 levels were increased in the High group. FM8 supplementation was further associated with increased ileal expression of tight junction-related genes (<i>Occludin</i>,<i> Claudin-1</i> and <i>Zo-1</i>) and <i>Muc2</i>, along with a trend toward increased fecal mucin levels; however, no comparable changes in tight junction-related gene expression were observed in the colon. Although taxa with reported SCFA-producing potential were enriched in the High group, cecal acetate and propionate levels remained unchanged, while butyrate levels were decreased.</p> Conclusions <p>FM8 may prevent food allergy by promoting IL-10-associated immunoregulation and enhancing gut barrier-related responses, without a corresponding increase in cecal SCFA concentrations. The contribution of SCFA-related mechanisms remains to be clarified, and further studies are needed to determine clinically feasible dosing and efficacy in humans.</p> Graphical abstract <p></p>

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Preventive effect of heat-killed Lactiplantibacillus plantarum FM8 in an ovalbumin-induced food allergy murine model

  • Hideaki Takahashi,
  • Tadashi Fujii,
  • Chikako Yamada,
  • Kotoyo Fujiki,
  • Kento Kuramitsu,
  • Shoei Okuda,
  • Mamoru Tanaka,
  • Takayuki Asahina,
  • Kohei Funasaka,
  • Eizaburo Ohno,
  • Yoshiki Hirooka,
  • Takumi Tochio

摘要

Background

Paraprobiotics, the non-viable microbial cells with health benefits, have gained interest as candidates for preventing food allergies owing to their safety and stability. Heat-killed Lactiplantibacillus plantarum FM8 (FM8) has been reported to induce interleukin (IL)-10 production in dendritic cells in vitro; however, its in vivo efficacy as a standalone intervention remains unexplored. We investigated the preventive effect of heat-killed FM8 in a murine model of ovalbumin (OVA)-induced food allergy.

Methods

BALB/c mice were assigned to control, OVA-induced allergy, or three FM8 treatment groups receiving FM8 at low (2 × 10⁹ CFU/day), medium (1 × 10¹⁰ CFU/day), or high (5 × 10¹⁰ CFU/day) doses. Food allergy was induced by repeated OVA sensitization and challenge. Allergy symptoms, OVA-specific immunoglobulin E (IgE), and IL-10 levels were measured. Tight junction gene expression, mucin production, gut microbiota composition, and short-chain fatty acids (SCFAs) were also analyzed.

Results

FM8 supplementation attenuated allergic responses in a dose-dependent manner. Allergy symptom scores were reduced in the High group, and the rectal temperature decline following OVA challenge was ameliorated in both the Med and High groups. The sensitization-induced increase in OVA-specific IgE was also attenuated in these groups. IL-4 expression in Peyer’s patches was reduced, whereas colonic IL-10 expression and serum IL-10 levels were increased in the High group. FM8 supplementation was further associated with increased ileal expression of tight junction-related genes (Occludin, Claudin-1 and Zo-1) and Muc2, along with a trend toward increased fecal mucin levels; however, no comparable changes in tight junction-related gene expression were observed in the colon. Although taxa with reported SCFA-producing potential were enriched in the High group, cecal acetate and propionate levels remained unchanged, while butyrate levels were decreased.

Conclusions

FM8 may prevent food allergy by promoting IL-10-associated immunoregulation and enhancing gut barrier-related responses, without a corresponding increase in cecal SCFA concentrations. The contribution of SCFA-related mechanisms remains to be clarified, and further studies are needed to determine clinically feasible dosing and efficacy in humans.

Graphical abstract