Administration of Non-Absorbable Antibiotics to Pregnant Mice to Perturb the Maternal Gut Microbiota Is Associated with Alterations in Offspring Behavior

Abstract

There is increasing evidence that the gut microbiota plays a major role in host health and disease. In this study, we examined whether perturbation of the maternal gut microbiota during pregnancy, induced by administration of non-absorbable antibiotics to pregnant dams, influences the behavior of offspring. Terminal restriction fragment length polymorphism analyses of fecal bacterial composition showed that the relative abundance of the bacterial order Lactobacillales was lower in offspring born from antibiotic-treated dams (20.7±3.4%) than in control offspring (42.1±6.2%) at P24, while the relative abundance of the bacterial family Clostridium subcluster XIVa was higher in offspring born from antibiotic-treated dams (34.2±5.0%) than in control offspring (16.4±3.3%). Offspring born from antibiotic-treated dams exhibited low locomotor activity in both familiar and novel environments, and preferred to explore in the peripheral area of an unfamiliar field at postnatal week 4. At postnatal weeks 7–8, no difference was observed in the level of locomotor activity between control offspring and offspring from antibiotic-treated dams, while the tendency for the offspring from antibiotic-treated dams to be less engaged in exploring the inside area was still observed. The behavioral phenotypes of the offspring from antibiotic-treated dams at postnatal week 4 could be rescued to a considerable extent through fostering of these offspring by normal dams from postnatal day 1. Although the detailed underlying mechanisms are not fully elucidated, the present results suggest that administration of non-absorbable antibiotics to pregnant dams to perturb the maternal gut microbiota during pregnancy leads to alterations in the behavior of their offspring.

The Central Nervous System and the Gut Microbiome

“…Perinatal administration of antibiotics can affect offspring health and immune status in both humans and mouse models (Russell et al, 2013; Stensballe et al, 2013). Administration of nonabsorbable antibiotics to rodent dams resulted in shifts of both the maternal and offspring gut microbiomes and induced hypoactivity compared to controls (Degroote et al, 2016; Tochitani et al, 2016). Moreover, offspring exhibited anxiety-like behavior and deficits in locomotion (Tochitani et al, 2016).…”

“…Administration of nonabsorbable antibiotics to rodent dams resulted in shifts of both the maternal and offspring gut microbiomes and induced hypoactivity compared to controls (Degroote et al, 2016; Tochitani et al, 2016). Moreover, offspring exhibited anxiety-like behavior and deficits in locomotion (Tochitani et al, 2016). Similarly, offspring Wistar rats exhibited reduced social behavior and increased anxiety as a result of nonabsorbable antibiotics administration to dams early in gestation (Degroote et al, 2016).…”

Intestinal Dysbiosis Secondary to Proton-Pump Inhibitor Use

“…Intestinal dysbiosis has been demonstrated to be associated with inflammatory bowel disease (IBD) [3,4], irritable bowel syndrome [5], and nonsteroidal anti-inflammatory drugs-induced enteropathy [6]. Moreover, gut dysbiosis has been reported in patients with types 1 and 2 diabetes [7,8], multiple sclerosis [9], autism [10], and rheumatoid arthritis [11]. …”

Microbiota and Neurodevelopmental Trajectories: Role of Maternal and Early-Life Nutrition

“…Administration of antibiotics to pregnant rats caused impairments in social behaviour and pre-pulse inhibition of the offspring [68]. In mice, administration of non-absorbable antibiotics during pregnancy reduced the exploratory behaviour in the offspring [69]. These results warrant further research on the effect of microbiota.…”