Bifidobacterium ameliorates lupus nephritis and modulates aberrant differentiation of lymphocyte subsets.

Abstract

The gut microbiota is crucial in the progression of lupus nephritis (LN), and probiotics have emerged as a potential therapeutic approach. This study investigates the role of Bifidobacterium in LN pathogenesis and its effects on immune cell populations. Clinical samples were collected from 61 systemic lupus erythematosus (SLE) patients, and flow cytometry was used to analyse changes in CD4+ T- and B-cell subsets. ELISA quantified cytokine secretion and autoantibodies in both human and murine models. Additionally, 16S rRNA sequencing identified variations in gut microbiota abundance among patients and helped screen for potential probiotics. Histopathological examination and immunofluorescence staining assessed kidney injury improvements in MRL/lpr mice treated with Bifidobacterium, its total metabolites and short-chain fatty acids (SCFAs). SLE patients showed decreased gut microbiota abundance and diversity, particularly a reduction in Bifidobacterium. Clinical data revealed lower proportions of memory B cells, central memory T cells, Treg cells and IL-2, alongside increased effector memory T cells, Th1 and Th17 cells, IL-10 and IFN-γ in LN patients. Supplementation with Bifidobacterium, its metabolites and SCFAs corrected the imbalances in CD4+ T- and B-cell subsets and cytokine levels, reduced autoantibody levels in mice and alleviated kidney damage. Bifidobacterium is significantly diminished in SLE patients, influencing kidney injury and immune cell balance in LN. Moreover, Bifidobacterium, its total metabolites and SCFAs' supplementation in MRL/lpr mice notably improved kidney damage and restored immune cell equilibrium in MRL/lpr mice.