Human-derived Lactobacillus Strains Interact With Bifidobacteria Strain By Metabolites And Alleviate Lipid Metabolism Of ApoE^-/- Mice On The Western Diet

Gut microbiota is a complicated micro-ecosystem,which is tightly linked with the host health.Different microorganisms interact with each other and maintain the balance of gut micro-ecosystem together.And those gut microorganisms positively correlated with host healthy condition can be developed as candidate probiotics for treating specific diseases.In our previous clinical study,we used a high-fiber dietary formula to modulate the gut microbiota which contributed to alleviation of obesity in one genetic obese child.Bifidobacteria and Lactobacillus were positively correlated with each other,and were dramatically increased in the post-intervention gut of the obese child.We obtained Bifidobacterium pseudocatenulatum C95 as the representative of Bifidobacteria spp.,as well as Lactobacillus mucosae A1 and Lactobacillus crispatus B4 as the representatives of Lactobacillus spp..In addition,L.mucosae A1 was positively associated with the amelioration of host hyperlipidemia.In this study,we predicted the metabolic complementarity between B.pseudocatenulatum C95 and Lactobacillus strains using genome data.Further,based on the phenomenon that Apo E deficiency can lead to the aggravation of blood lipid accumulation in host,we used a western diet-fed Apo E^-/-mouse model to validate the effect of L.mucosae A1 on treating hyperlipidemia.Firstly,the genome of two Lactobacillus strains showed that both of two Lactobacillus strains harbored abundant carbohydrate utilization genes as well as genes for acetate production,bacteriocin production,exopolysaccharide（EPS）biosynthesis and S-layer protein production.The function of B.pseudocatenulatum C95 for alleviating obesity and gut microbiota has been verified by genome analysis and animal experiments.Then,we used metabolic network of the three strains and Netcooperate method to obtain the results that B.pseudocatenulatum C95 can provide 36%metabolic substrates for L.mucosae A1,L.mucosae A1 can provide 38%metabolic substrates for B.pseudocatenulatum C95,and B.pseudocatenulatum C95 can provide 57%metabolic substrates for L.crispatus B4.Thus,through the supply of metabolic substrates between different bacteria,the three strains may grow better in the gut.These interaction relationships provided a clue for the co-abundance relationship between Bifidobacteria and Lactobacillus in the post-intervention gut.In addition,the animal experiment showed that L.mucosae A1 decreased the weight of adipose tissue,attenuated the severe triglycerides accumulation in serum and liver,and alleviated atherosclerosis of Apo E^-/-mice on the western diet,while it also reduced the serum lipopolysaccharide-binding protein（LBP）content of mice.L.mucosae A1 shifted the gut microbiota structure of Apo E^-/-mice on the western diet,especially recovering 29members of gut microbiota enhanced by the western diet.26 of the 29 members were positively associated with host parameters related to lipid accumulation and atherosclerosis of Apo E^-/-mice.Thus,L.mucosae A1 can be a new candidate of probiotics to alleviate hyperlipidemia and atherosclerosis.In summary,based on genome data,the study elucidated the metabolic interaction between two Lactobacillus strains and B.pseudocatenulatum C95,providing the positive relationship between Bifidobacteria and Lactobacillus found by microbial co-abundance mathematical model a biological sense.The study also showed that L.mucosae A1 can alleviate severe lipid accumulation and shift the gut microbiota structure of Apo E^-/-mice on a Western diet.These effects of L.mucosae A1 not only provided a rationale for the clinical development of the strain to prevent or treat dyslipidemia and atherosclerosis,but also highlights the advantage of such function-based rather than taxonomy-based strategies for the selection of probiotics.