Screening and Genetic Analysis of Bifidobacterium longum subsp. Longum dipro-X for IBD Alleviation.

Abstract

Given the limitations of current IBD treatments, this study conducted an in-depth investigation of 17 human-derived Bifidobacterium longum subsp. longum strains. Primary screening using a lipopolysaccharide (LPS)-induced RAW264.7 macrophage inflammation model identified strain F05-044-CM-09 as exhibiting significantly stronger inhibition of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-α) production compared to other strains. To explore the genetic basis of its anti-inflammatory effect, strain-specific gene analysis revealed that F05-044-CM-09 harbors a gene encoding the CHAP domain, suggesting that anti-inflammatory efficacy may involve immunomodulation through dendritic cell activation and interleukin-2 (IL-2) production. A safety assessment performed prior to animal experiments confirmed the absence of virulence genes and genes encoding D-lactate production. In a dextran sulfate sodium (DSS)-induced murine colitis model, F05-044-CM-09 intervention significantly ameliorated disease phenotypes by mitigating body weight loss and colon shortening, restoring colonic gland architecture, and reducing inflammatory cell infiltration. Analysis of serum biomarkers showed that F05-044-CM-09 significantly reduced LPS levels, whereas serum TNF-α levels showed a decreasing trend that was not statistically significant. However, colonic TNF-α concentrations were significantly reduced following F05-044-CM-09 intervention. In summary, F05-044-CM-09 has the potential to alleviate enteritis and a good safety profile. It is a promising candidate for the development of anti-inflammatory probiotics and offers new possibilities for IBD treatment.