Peripartum Antibiotics Promote Gut Dysbiosis, Loss of Immune Tolerance, and Inflammatory Bowel Disease in Genetically Prone Offspring

Publication date: 11 July 2017
Source:Cell Reports, Volume 20, Issue 2
Author(s): Jun Miyoshi, Alexandria M. Bobe, Sawako Miyoshi, Yong Huang, Nathaniel Hubert, Tom O. Delmont, A. Murat Eren, Vanessa Leone, Eugene B. Chang
Factors affecting the developing neonatal gut microbiome and immune networks may increase the risk of developing complex immune disorders such as inflammatory bowel diseases (IBD). In particular, peripartum antibiotics have been suggested as risk factors for human IBD, although direct evidence is lacking. Therefore, we examined the temporal impact of the commonly used antibiotic cefoperazone on both maternal and offspring microbiota when administered to dams during the peripartum period in the IL-10-deficient murine colitis model. By rigorously controlling for cage, gender, generational, and murine pathobiont confounders, we observed that offspring from cefoperazone-exposed dams develop a persistent gut dysbiosis into adulthood associated with skewing of the host immune system and increased susceptibility to spontaneous and chemically dextran sodium sulfate (DSS)-induced colitis. Thus, early life exposure to antibiotic-induced maternal dysbiosis during a critical developmental window for gut microbial assemblage and immune programming elicits a lasting impact of increased IBD risk on genetically susceptible offspring.

Graphical abstract

Teaser

Miyoshi et al. show that maternal and neonatal exposure to antibiotics can cause enduring changes in the gut microbiome that adversely affect the development of the immune system. In genetically susceptible individuals, the persistence of intestinal dysbiosis and immune imbalance may increase risk for immune disorders like inflammatory bowel diseases.


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