Prenatal Stressor Induced Alterations to Microflora Development

To determine the impact of a prenatal stressor on microflora development, an acoustical startle stressor (i.e., 3 random 110 dB beeps over a 10 min period occurring 5 days per week) was used to evoke a stress response from pregnant rhesus monkeys either early (days 50-92) or late (days 105-147) in the 169 day gesta-tional period. These periods represent crucial time periods in nervous system and GI system development, thus making it likely that disruption of physiological homeostasis at these time points affects fetal development. This stressor resulted in a significant increase in cortisol in the pregnant mothers, but did not appear to significantly affect the number of miscarriages, gestational length, or birth weight (Bailey et al. 2004b). The stressor did, however, significantly affect the development of the intestinal microflora.

Control Early Stress Late Stress

Published in the Journal of Pediatric Gastroenterology and Nutrition, ©Lippincott, Williams & Wilkins, 2004

Control Early Stress Late Stress

Published in the Journal of Pediatric Gastroenterology and Nutrition, ©Lippincott, Williams & Wilkins, 2004

Fig. 11.3 Anaerobically grown Lactobacillus spp. during the first 24 weeks of life. Data are the mean (SE) of log(10) transformed number of colony forming units per gram of fecal matter (CFU/g). Concentrations on day 2 of life were not significantly different between pregnancy conditions. * Both Early Stress and Late Stress infants had significantly fewer anaerobic lactobacilli than did control infants across the first 24 weeks of life (p < 0.05). In addition, there was a developmental trend for increasing titers across the 24 week period in both control and prenatally stressed infants (p < 0.05). Reproduced from Journal of Pediatric Gastroenterology and Nutrition, 2004, with permission from Lipincott, Williams, & Wilkins

During the first 6 months of life, lactobacilli levels in the monkeys born from mothers exposed to the stressor during gestation were significantly lower than levels found in infants from non-stressed control mothers, with the biggest differences in mean levels found at 2 weeks of age (Fig. 11.3). As successful nursing progressed, bifidobacteria began to predominate in the intestines. And, as with the lactobacilli, bifidobacteria levels were significantly lower in the intestines of infant monkeys from mothers that were exposed to the acoustical startle stressor during gestation. This effect, however, was only evident in the offspring from mothers exposed to the stressor late in gestation (Fig. 11.3) (Bailey et al. 2004b). As with the previous study involving maternal separation, none of the monkeys in this study were intentionally infected with enteric pathogens. However, approximately 43% of the infants from mothers stressed early in gestation and 12% of infants from mothers stressed late in gestation became subclinically colonized with Shigella flexneri, an endemic pathogen in the monkey colony. Importantly, Shigella were not detected in any of the infants born from the non-stressed control condition (Bailey et al. 2004b), suggesting that prenatal stress, particularly late in gestation, disrupted the development of natural resistance to the enteric pathogen, S. flexneri.

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