From genes to environment: A life-course approach to prevent pediatric autoimmune diseases

Table 4 Candidate next-generation probiotics and their potential role in autoimmune disease prevention

Candidate NGP	Key mechanism(s)	Relevance to autoimmune diseases
Akkermansia muciniphila	Enhances gut barrier integrity, increases mucin production, modulates Treg/Th17 balance	Associated with reduced inflammation; protective role in type 1 diabetes and multiple sclerosis models
Faecalibacterium prausnitzii	Produces butyrate (short-chain fatty acid), exerts anti-inflammatory effects via IL-10 induction and NF-κB inhibition	Lower abundance linked with IBD and rheumatoid arthritis; supplementation may restore tolerance
Bacteroides fragilis (polysaccharide A strain)	Promotes Treg differentiation and reduces pro-inflammatory cytokines	Shown to prevent colitis and experimental autoimmune encephalomyelitis in animal models
Roseburia species	Butyrate production strengthens the epithelial barrier and suppresses pro-inflammatory pathways	Reduced levels observed in IBD and type 1 diabetes; potential for restoring immune tolerance
Clostridium clusters IV and XIVa	Induce colonic Treg expansion, short-chain fatty acids production	Protective in colitis and systemic autoimmune models; contributes to mucosal immune balance
Prevotella histicola	Modulates dendritic cells and T cell responses, decreasing pro-inflammatory Th1/Th17 cells	Demonstrated efficacy in reducing MS-like symptoms in experimental models
Escherichia coli Nissle 1917 (engineered forms)	Enhances epithelial barrier, modulates innate immunity, and can be engineered for anti-inflammatory metabolite production	Shown protective effects in IBD; engineered strains under study for systemic autoimmunity

The table presents emerging next-generation probiotics with potential roles in the prevention or modulation of autoimmune diseases. These candidate microbes - identified through human and preclinical studies - exert immunoregulatory effects through mechanisms such as strengthening epithelial barrier integrity, producing short-chain fatty acids, inducing regulatory T cells, and suppressing pro-inflammatory pathways including nuclear factor kappa-light-chain-enhancer of activated B cells, Th1, and T helper 17 cell signaling. Alterations in the abundance of these organisms have been associated with autoimmune conditions such as type 1 diabetes, multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease. The table highlights key mechanisms of action and summarizes evidence supporting their relevance in restoring immune tolerance and reducing chronic inflammation. These next-generation probiotics represent promising therapeutic and preventive strategies, although most remain in early stages of investigation and require validation in pediatric populations. Treg: Regulatory T cell; Th17: T helper 17 cell; IL-10: Interleukin-10; NF-κB: Nuclear factor kappa-light-chain-enhancer of activated B cells; IBD: Inflammatory bowel disease; MS: Multiple sclerosis.