Bacterial Polysaccharides and Host Immune Modulation

Bacterial polysaccharides, complex carbohydrates displayed on microbial surfaces or secreted into the host environment, serve as critical mediators of host–microbe communication. By interacting with innate immune receptors and shaping adaptive lymphocyte populations, these molecules can either trigger pro-inflammatory responses or promote immune tolerance. Capsular polysaccharides from commensal species often induce regulatory pathways that prevent excessive inflammation, whereas structural polysaccharides such as lipopolysaccharide can evoke strong innate defence mechanisms. Understanding the structural diversity, receptor specificity and downstream signalling cascades of these polysaccharides offers new avenues for vaccine design, microbiome-based therapies and modulation of inflammatory diseases across the gut, central nervous system and peripheral organs.

Research from Nature Portfolio

Recent investigations have established the capsular polysaccharide A (PSA) of a gut commensal as a potent immunomodulator in viral encephalitis; PSA engages B cells to induce IL-10-producing CD4+ and CD8+ regulatory T cells, thereby curbing innate inflammation and improving survival in a herpes simplex model. Complementing this, studies of live bacterial therapy in renal fibrosis demonstrate that reduction of lipopolysaccharide levels—a key anionic polysaccharide of Gram-negative bacteria—leads to enhanced systemic concentrations of the host metabolite 1,5-anhydroglucitol, which activates TGR5-mediated anti-inflammatory signalling and attenuates tissue scarring. Together, these works highlight the versatility of microbial polysaccharides in orchestrating protective immune programmes across distinct tissues.

Bacterial Polysaccharides and Host Immune Modulation publication trend

The graph below shows the total number of articles in bacterial polysaccharides and host immune modulation across all publications each year (not limited to Nature Index journals).

Technical terms

Polysaccharide A (PSA): A capsular carbohydrate of Bacteroides fragilis that induces regulatory T and B cell responses through IL-10 secretion.

Lipopolysaccharide (LPS): An anionic polysaccharide component of Gram-negative bacterial outer membranes that can trigger innate immune responses.

Phase variation: A reversible genetic mechanism altering bacterial surface structures, such as polysaccharide promoters, affecting immune recognition.

Regulatory T cells (Tregs): A subset of T lymphocytes that maintain immune homeostasis by suppressing excessive inflammatory responses.

Toll-like receptor 2 (TLR2): A pattern recognition receptor that recognises microbial lipoproteins and polysaccharides, initiating anti-inflammatory signalling.

References

1. Inflammation and bacteriophages affect DNA inversion states and functionality of the gut microbiota. Cell Host & Microbe (2024).
2. Bacteroides fragilis polysaccharide A induces IL-10 secreting B and T cells that prevent viral encephalitis. Nature Communications (2019).
3. The Protective Role of Bacteroides fragilis in a Murine Model of Colitis-Associated Colorectal Cancer. mSphere (2018).
4. Bacteroides fragilis Prevents Clostridium difficile Infection in a Mouse Model by Restoring Gut Barrier and Microbiome Regulation. Frontiers in Microbiology (2018).
5. The gut microbe Bacteroides fragilis ameliorates renal fibrosis in mice. Nature Communications (2022).