Maternal obesogenic diet attenuates microbiome dependent offspring weaning reaction with worsening of steatotic liver disease

Am J Pathol. 2023 Nov 27:S0002-9440(23)00445-5. doi: 10.1016/j.ajpath.2023.11.006. Online ahead of print.ABSTRACTThe mechanisms by which maternal obesity increases the susceptibility to steatotic liver disease (SLD) in offspring are incompletely understood and models using different maternal obesogenic diets (MODEs) display phenotypic variability, likely reflecting the influence of timing and diet composition. Here we compare three maternal obesogenic diets using standardized exposure times to identify differences in offspring disease progression. We found that the severity of hepatic inflammation and fibrosis in offspring depends on the composition of maternal obesogenic diet. Offspring cecal microbiome composition was shifted in all MODE groups relative to control. Decreased alpha-diversity in some MODE offspring with shifts in abundance of multiple genera suggestive of delayed maturation of the microbiome. Next we demonstrated that the weaning reaction typically characterized by a spike in intestinal expression of Tnfa and Ifng is attenuated in MODE offspring in an early microbiome dependent manner shown using cross-fostering. Cross-fostering also switched the severity of disease progression in offspring dependent on the diet of the fostering dam. These results identify maternal diet composition and timing of exposure as modifiers in mediating transmissible changes in the microbiome. These changes in the early microbiome alter a critical window during weaning that drives s...
Source: Am J Pathol - Category: Pathology Authors: Source Type: research