Aims: This study aimed to investigate the protective effect of Bifidobacterium animalis subsp. lactis A6 on dextran sodium sulphate (DSS)-induced colitis in C57BL/6J mice. Methods and Results: Mice were randomly divided into three groups (n = 8 per group). Each group was administered with PBS (Control and DSS group) or B. lactis A6 with a dosage of ~4.0 × 10 9 CFU day −1 (DSS + A6 group) for 21 consecutive days. The DSS and DSS + A6 group mice were ad libitum drinking 2.5% DSS water during day 15-21, while the Control group mice were given normal water. The administration of B. lactis A6 significantly inhibited DSS-induced bodyweight loss and colon shortening (p < 0.001), but showed no significant influence on the spleen enlargement (p > 0.05). The intestinal barrier integrity was improved by reducing colonic damage, recovering mucus layer loss and enhancing tight junction expression including ZO-1, occludin and claudin-1. In addition, B. lactis A6 attenuated the oxidative stress by decreasing MDA and increasing SOD and GSH levels in colon tissues. Moreover, B. lactis A6 suppressed DSS-induced inflammatory responses via downregulating TNF-α, IL-1β and IL-6 levels and upregulating IL-10 level in colon tissues. Conclusion: B. lactis A6 effectively alleviated DSS-induced colitis by maintaining intestinal barrier integrity, reducing oxidative stress and inhibiting inflammatory responses. Significance and Impact of the Study: This study suggests that B. lactis A6 could act as a candidate probiotic for UC treatment.

Background The physiology and application characteristics of probiotics are closely associated with the growth phase. Bifidobacterium animalis subsp. lactis A6 is a promising probiotic strain isolated from the feces of a healthy centenarian in China. In this study, RNA-seq was carried out to investigate the metabolic mechanism between the exponential and the stationary phase in B. lactis A6. Results Differential expression analysis showed that a total of 815 genes were significantly changed in the stationary phase compared to the exponential phase, which consisted of 399 up-regulated and 416 down-regulated genes. The results showed that the transport and metabolism of cellobiose, xylooligosaccharides and raffinose were enhanced at the stationary phase, which expanded carbon source utilizing profile to confront with glucose consumption. Meanwhile, genes involved in cysteine-cystathionine-cycle (CCC) pathway, glutamate dehydrogenase, branched-chain amino acids (BCAAs) biosynthesis, and Clp protease were all up-regulated in the stationary phase, which may enhance the acid tolerance of B. lactis A6 during stationary phase. Acid tolerance assay indicated that the survival rate of stationary phase cells was 51.07% after treatment by pH 3.0 for 2h, which was 730-fold higher than that of 0.07% with log phase cells. In addition, peptidoglycan biosynthesis was significantly repressed, which is comparable with the decreased growth rate during the stationary phase. Remarkably, a putative gene cluster encoding Tad pili was up-regulated by 6.5 to 12.1-fold, which is consistent with the significantly increased adhesion rate to mucin from 2.38% to 4.90% during the transition from the exponential phase to the stationary phase. Conclusions This study reported growth phase-associated changes of B. lactis A6 during fermentation, including expanded carbon source utilizing profile, enhanced acid tolerance, and up-regulated Tad pili gene cluster responsible for bacterial adhesion in the stationary phase. These findings provide a novel insight into the growth phase associated characteristics in B. lactis A6 and provide valuable information for further application in the food industry.