Oral fermented rice bran supplementation suppresses viral replication and stimulates immune functions in immunocompetent and immunocompromised mice infected with influenza virus.

backgroundThe number of immunosuppressed elderly persons, who are at a higher risk of developing influenza infection-related complications, has been increasing. Fermented rice bran (FRB) is used as a dietary supplement, exhibits a variety of biological activities, and may exhibit anti-influenza virus activity. However, the effect of FRB supplements on influenza A virus (IFV) infection remains unknown. We aimed to investigate the effects of FRB on influenza prevention by oral administration to IFV-infected mice in an immunocompetent or immunocompromised state.

methodsFRB was produced by fermentation of rice bran with a mixture of Bacillus spp, Lactobacillus sp, Bifidobacterium sp, and Aspergillus sp. BALB/c mice orally received FRB (20 mg/day) for 1 or 2 months prior to intranasal IFV inoculation or immediately after IFV infection until 14 days post-inoculation. Weight changes, virus production, levels of neutralizing antibodies, immunoglobulin A (IgA) and interferon-γ (IFN-γ), and histological changes of the intestine were analyzed in FRB-administered mice.

resultsFRB-administered immunocompetent mice without 5-fluorouracil (5-FU) treatment showed suppressed body weight loss caused by IFV-infection and rapid weight recovery. The virus yields in the lungs of FRB groups were reduced 3 days post-infection. Neutralizing antibody titers in the blood and respiratory tract and IgA levels in the lung and intestine were increased in FRB groups after 14 days of infection. An elevation in IFN-γ levels was observed in the blood of FRB-treated mice on days 3 and 14 after virus inoculation. In immunocompromised mice treated with 5-FU, oral FRB administration beginning 1 month prior to IFV inoculation resulted in significant suppression of body weight loss, reduced viral titers in the lung, elevated systemic and local neutralizing antibody titers, and preservation of normal colonic morphology compared with the control group. In contrast, when FRB was administered 1 h after viral inoculation, these protective effects were present but notably less pronounced than those observed with supplementation pre-inoculation.

conclusionsFRB stimulates local and systemic adaptive immune functions, favors early recovery from influenza, and prolongs protective effects against IFV infection in both immunocompetent and immunocompromised mice.