Effect of High-Fat Diet and <i>Lactiplantibacillus plantarum</i> 299v on the Gut Microbiome of Adolescent and Adult Rats

Childhood and adolescent obesity and its associated morbidities are increasing in part due to the ingestion of diets high in fat (HFD). Changes in the gastrointestinal microbiome have been associated with these morbidities, including insulin resistance, cardiovascular disease, and inflammatory states. The use of dietary probiotics may mitigate these microbiome-associated morbidities and improve health during maturation. Using our established model of obesity in rats consuming an HFD from weaning, we examined the gut microbiome with a single-strain probiotic in the drinking water [<i>Lactiplantibacillus plantarum</i> 299v (Lp299v, LP299V^®)] of adolescent and adult rats. Our main finding was a differential effect of HFD and probiotic on the gut microbiome that was associated with maturation (adolescence vs. adulthood). Specifically, probiotic treatment of adolescent rats on an HFD led to alterations in the enrichment of the gut microbiome, which were associated with the morbidities of obesity, while adult rats under the same conditions exhibited minimal changes, demonstrating differences in plasticity associated with maturation. Of particular relevance in this regard is the fact that <i>Oscillospiraceae</i> and <i>Lachnospiraceae,</i> associated with beneficial short-chain fatty acid production, were enriched in adolescent rats on an HFD and treated with Lp299v. Our data suggest that the use of probiotics in childhood and adolescence may improve health in adulthood by potentially affecting the developing gastrointestinal microbiome.