Leuconostoc citreum enhances the colonization ability of Lactiplantibacillus plantarum in the gut by synergistically modifying the intestinal niche.

Lactiplantibacillus plantarum HNU082 (Lp082) underwent rapid mutation after a second intervention, with more mutations observed in the human gut than in mice.

• An intermittent intervention trial was conducted in both mice and humans
• After two interventions, Lp082 strain rapidly mutated after the second intervention
• A greater number of mutations were observed in the human gut compared to the mouse gut
• The mutation pattern was identified through analysis of the abundance of Lp082 and fluctuations of gut microbiota

Leuconostoc citreum was identified as the most positively correlated microbial species with Lp082 colonization.

• Key microbial factors promoting Lp082 colonization were identified by analyzing abundance changes and correlation analysis
• L. citreum was identified through examination of abundance changes and correlation analysis among gut microbiota fluctuations
• The synergistic effect of L. citreum on Lp082 colonization was subsequently verified in vivo

Coadministration of L. citreum more than doubled Lp082 abundance in the gut.

• The synergistic effect was verified in vivo through coadministration experiments
• Coadministration of L. citreum resulted in more than a doubling of Lp082 abundance
• The enhanced colonization was achieved through regulation of other bacterial species in the gut

Coadministration of L. citreum with Lp082 reduced the number of bacterial species competing with Lp082 in the gut.

• L. citreum synergistically modified the intestinal niche to favor Lp082 colonization
• The mechanism involved reducing the number of species competing with Lp082
• This competitive reduction was part of a synergistic modulation of the intestinal environment

Coadministration of L. citreum increased beneficial fecal metabolite levels in the host intestine.

• Beyond microbial competition effects, L. citreum coadministration also modulated the metabolic environment
• Beneficial fecal metabolite levels were increased in the host intestine following coadministration
• These metabolite changes represent part of the synergistic intestinal niche modification attributed to L. citreum

Limited colonization ability of Lp082 in the intestines has hindered its long-term health-modulating effects.

• Lp082 exhibits a wide range of health-modulating effects
• Its limited ability to colonize the intestines has been identified as a barrier to long-term efficacy
• The intermittent intervention trial design in mice and humans was motivated by the need to overcome this colonization limitation