Aim: The gut microbiota is a contributing factor in overall health throughout the human lifecycle. Probiotics are natural, safe, and beneficial modulators of gut microbiota. However, the relationship between probiotics and gut microbiota in aging is unclear. Recently, we reported that the human origin strain Lactobacillus acidophilus DDS-1 demonstrated superior probiotic traits in an in vitro setting. 1 Taking this further, we evaluated the changes in microbial ecology, and immune and metabolite status in young and aging mice using DDS-1. Methods: A total of 32 C57BL/6 J mice were used in this study, which were divided into four groups based on age and treatments: young control and treatment, and aging control and treatment groups. Each group had eight mice. Each mouse was caged individually and supplemented with probiotic DDS-1 in the normal chow for 4 weeks. We sequenced bacterial 16S rRNA genes V1-V3 region of fecal, cecal, and mucosal samples. Cytokine analysis was performed on colonic and blood samples. All clinical parameters, such as body weights, colon length, and colon and spleen weights, were recorded. Colonic sections were routinely stained with hematoxylin and eosin. Metabolic and short-chain fatty acid profiling was performed to understand the metabolic status of the mice. Results: Supplementation with DDS-1 modulated the microbiota community and promoted the abundance of beneficial bacteria, such as Akkermansia and S-24-7. At phylum level, Bacteroidetes levels were increased from 63 ± 0.30 to 69 ± 0.75, and for Firmicutes from 28 ± 0.44 to 30 ± 0.28 after DDS-1 treatment. Interestingly, Verrucomicrobia levels were increased from 3 ± 0.48% to 4.0 ± 26% at phylum level, and the only identifiable species under Verrucomicrobia was Akkermansia municiphilia. There were no significant differences in clinical parameters. Although there was no change in overall colonic anatomy, the goblet cells were more in number in probiotic-treated groups. DDS-1 was able to reduce proinflammatory cytokines IL-1, 2, 5, IL-1β, and MIP 1α and increase anti-inflammatory IL-10 levels in the serum samples. At the tissue level, IL-1, IL-1β, and IL-12 levels were downregulated in treated groups. Metabolomics analysis correlated well with the microbiota findings. Conclusion: DDS-1 supplementation promoted the growth of beneficial composition of gut microbiota. These results show the potential of probiotics for gut health in the elderly human population. Reference 1 Vemuri R, Shinde T, Shastri MD et al. A human origin strain Lactobacillus acidophilus DDS-1 exhibits superior in vitro probiotic efficacy in comparison to plant or dairy origin probiotics. Int. J. Med. Sci. 2018; 15(9): 840-8.