TY - JOUR
T1 - Maternal Obesogenic Diet Attenuates Microbiome-Dependent Offspring Weaning Reaction with Worsening of Steatotic Liver Disease
AU - Lian, Vung
AU - Hinrichs, Holly
AU - Young, Monica
AU - Faerber, Austin
AU - Özler, Oğuz
AU - Xie, Yan
AU - Ballentine, Samuel J.
AU - Tarr, Phillip I.
AU - Davidson, Nicholas O.
AU - Thompson, Michael D.
N1 - Publisher Copyright:
© 2024 American Society for Investigative Pathology
PY - 2024/2
Y1 - 2024/2
N2 - The mechanisms by which maternal obesity increases the susceptibility to steatotic liver disease in offspring are incompletely understood. Models using different maternal obesogenic diets (MODEs) display phenotypic variability, likely reflecting the influence of timing and diet composition. This study compared three maternal obesogenic diets using standardized exposure times to identify differences in offspring disease progression. This study found that the severity of hepatic inflammation and fibrosis in the offspring depends on the composition of the maternal obesogenic diet. Offspring cecal microbiome composition was shifted in all MODE groups relative to control. Decreased α-diversity in some MODE offspring with shifts in abundance of multiple genera were suggestive of delayed maturation of the microbiome. The weaning reaction typically characterized by a spike in intestinal expression of Tnfa and Ifng was attenuated in MODE offspring in an early microbiome-dependent manner 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 susceptibility to progressive liver disease in the offspring.
AB - The mechanisms by which maternal obesity increases the susceptibility to steatotic liver disease in offspring are incompletely understood. Models using different maternal obesogenic diets (MODEs) display phenotypic variability, likely reflecting the influence of timing and diet composition. This study compared three maternal obesogenic diets using standardized exposure times to identify differences in offspring disease progression. This study found that the severity of hepatic inflammation and fibrosis in the offspring depends on the composition of the maternal obesogenic diet. Offspring cecal microbiome composition was shifted in all MODE groups relative to control. Decreased α-diversity in some MODE offspring with shifts in abundance of multiple genera were suggestive of delayed maturation of the microbiome. The weaning reaction typically characterized by a spike in intestinal expression of Tnfa and Ifng was attenuated in MODE offspring in an early microbiome-dependent manner 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 susceptibility to progressive liver disease in the offspring.
UR - http://www.scopus.com/inward/record.url?scp=85182914416&partnerID=8YFLogxK
U2 - 10.1016/j.ajpath.2023.11.006
DO - 10.1016/j.ajpath.2023.11.006
M3 - Article
C2 - 38029921
AN - SCOPUS:85182914416
SN - 0002-9440
VL - 194
SP - 209
EP - 224
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 2
ER -