Early‐Life Sickness May Predispose Individuals to Behavioral Changes Following Gut Dysbiosis in Adulthood

Abstract

Although it is well‐established that the immune system plays an important role in the development of physiology and behavior, the gut microbiome has recently become of interest in the study of developmental origins of behavior. Some studies suggest that the effects of early‐life immune activation may not occur until a secondary stressor is introduced, though the precise nature and timing of the stressor may be critical in the response. In order to test the hypothesis that early‐life immune stress makes an individual more vulnerable to future insults, we mimicked an early‐life infection by injecting pups at postnatal day 3 and 5 with lipopolysaccharide (LPS; cell wall component of gram‐negative bacteria) or saline, and subsequently exposed the same animals to antibiotic treatment (known to influence microbial community composition ad behavior) or water in adulthood. We tracked physiology across development, and paired males and females with a novel individual of the same sex in adulthood to score behavior before antibiotic treatment, immediately following treatment, and after recovery from antibiotics. LPS‐treated females exhibited impaired reproductive physiology and function in adulthood (e.g., smaller ovaries and abnormal estrous cycles), and female and male gut microbial communities were strongly affected by antibiotic treatment in adulthood, but only slightly affected by postnatal LPS alone. Interestingly, LPS‐treated males exhibited more robust changes in their behavioral response following adult antibiotic treatment, including decreased investigation and increased grooming. These data suggest that males may be more vulnerable than females to behavioral abnormalities after being predisposed to an immune challenge early in life. Collectively, these results provide evidence that some of the sex‐specific behavioral consequences of a stressor may not transpire until an individual is faced with a secondary stressor, and the context in which an individual is exposed can greatly influence the response.Support or Funding InformationNational Institute of Child Health and Human Development (T32HD49336); National Science Foundation, Division of Integrative Organismal Systems (1656414); and Indiana UniversityThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.