Bifidobacterium breve207-1 protects against later-life colitis following early-life antibiotic exposure by enhancing intestinal barrier and immune homeostasis.

BACKGROUND

The early colonization of bacteria has a significant impact on immune system development. The disruption of gut microbiota by antibiotics in early life is a major risk factor for pediatric inflammatory bowel disease. This study explores how Bifidobacterium breve 207-1 modulates gut microbiota and immune responses after early antibiotic exposure, and whether such intervention mitigates DSS-induced colitis later in life.

METHODS

Newborn mice were administered with normal saline, ceftriaxone, or B. breve 207-1 from birth to day 21. The Ceftri + 207-1 + DSS group continued to receive B. breve 207-1 thereafter. Starting at day 42, all "-DSS" groups received 3% DSS drinking water to induce colitis.

RESULTS

DSS increased inflammation scores versus the NS-Water group. The scores of the Ceftri + 207-1-DSS and Ceftri + 207-1-207-1 + DSS (the group receiving B. breve 207-1 continuously from birth to day 46) groups were lower than the Ceftri-DSS group (P < 0.0001). Gut microbiota analysis showed the relative abundance of Actinobacteria and Firmicutes was significantly higher in the Ceftri + 207-1-DSS group (P < 0.05). Long-term use of B. breve 207-1 from early life enhanced the relative abundance of beneficial gut bacteria, such as Bifidobacterium and Lactobacillus spp. (P < 0.05). Compared to the NS-DSS group, the Ceftri + 207-1-DSS group exhibited significantly higher concentrations of butyric and valeric acids (P < 0.05). Treatment with B. breve 207-1 during early life and its long-term usage resulted in increased levels of SCFAs (P < 0.05). Furthermore, these treatments enhanced the indices related to changes in the mucosal barrier (including mRNA for KI67 and MUC2) and colonic mechanical barrier (including mRNA for Claudin-1, ZO-1, and Occludin). With regards to systemic immune changes induced by B. breve 207-1 administration during early life, the anti-inflammatory cytokines (particularly IL-10 and TGF-β) were elevated (P < 0.05), while the pro-inflammatory cytokines (mainly IL-6 and TNF-α) were reduced (P < 0.05).

CONCLUSIONS

B. breve 207-1 enhances immune development after antibiotic exposure, mitigates the severity of DSS-induced colitis later in life, likely through early remodeling of the gut microbiota and enhancement of intestinal barrier function. Our results suggest that the early postnatal period represents a strategic opportunity for probiotic intervention to confer protection against later-life colitis in the context of early antibiotic exposure. Notably, B. breve 207-1 may influence the composition of early-stage gut microbiota and subsequently affect local and systemic immune development.