Unravelling the Link between the Gut Microbiome and Autoimmune Kidney Diseases: A Potential New Therapeutic Approach

Int J Mol Sci. 2024 Apr 28;25(9):4817. doi: 10.3390/ijms25094817.

Abstract

The gut microbiota and short chain fatty acids (SCFA) have been associated with immune regulation and autoimmune diseases. Autoimmune kidney diseases arise from a loss of tolerance to antigens, often with unclear triggers. In this review, we explore the role of the gut microbiome and how disease, diet, and therapy can alter the gut microbiota consortium. Perturbations in the gut microbiota may systemically induce the translocation of microbiota-derived inflammatory molecules such as liposaccharide (LPS) and other toxins by penetrating the gut epithelial barrier. Once in the blood stream, these pro-inflammatory mediators activate immune cells, which release pro-inflammatory molecules, many of which are antigens in autoimmune diseases. The ratio of gut bacteria Bacteroidetes/Firmicutes is associated with worse outcomes in multiple autoimmune kidney diseases including lupus nephritis, MPO-ANCA vasculitis, and Goodpasture's syndrome. Therapies that enhance SCFA-producing bacteria in the gut have powerful therapeutic potential. Dietary fiber is fermented by gut bacteria which in turn release SCFAs that protect the gut barrier, as well as modulating immune responses towards a tolerogenic anti-inflammatory state. Herein, we describe where the current field of research is and the strategies to harness the gut microbiome as potential therapy.

Keywords: ANCA; SCFA; autoimmunity; diet therapy; glomerulonephritis; gut microbiota; immune responses; kidney disease; vasculitis.

Publication types

  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases* / immunology
  • Autoimmune Diseases* / microbiology
  • Autoimmune Diseases* / therapy
  • Fatty Acids, Volatile / metabolism
  • Gastrointestinal Microbiome* / immunology
  • Humans
  • Kidney Diseases / immunology
  • Kidney Diseases / microbiology
  • Kidney Diseases / therapy

Substances

  • Fatty Acids, Volatile

Grants and funding

Kim Maree O’Sullivan is funded by the Australian National Health and Medical Research Council ID 2001325.