Intergenerational transfer of antibiotic-perturbed microbiota enhances colitis in susceptible mice

Abstract

Antibiotic exposure in children has been associated with the risk of Inflammatory Bowel Disease (IBD). Since antibiotic use in children or in their pregnant mother can affect how the intestinal microbiome develops, we asked whether the transfer of an antibiotic-perturbed microbiota from mothers to their children could affect their risk of developing IBD. Here we demonstrate that germ-free adult pregnant mice inoculated with a gut microbial community shaped by antibiotic exposure transmitted their perturbed microbiota to their offspring with high fidelity. Without any direct or continued exposure to antibiotics, this dysbiotic microbiota in the offspring remained distinct from controls for at least 21 weeks. By using both IL-10-deficient and wild type mothers, we showed that both inoculum and genotype shape the microbiota populations in the offspring. Since IL10−/− mice are genetically susceptible to colitis, we could assess the risk due to maternal transmission of an antibiotic-perturbed microbiota. We found that the IL10−/− offspring that had received the perturbed gut microbiota developed markedly increased colitis. Taken together, our findings indicate that antibiotic exposure shaping the maternal gut microbiota has effects that extend to their offspring with both ecological and long-term disease consequences.

US Immigration Westernizes the Human Gut Microbiome

“…Previous studies have demonstrated intergenerational effects of microbiome perturbations in animal models. These include loss of microbiota carbohydrate degradation function following removal of dietary fiber (Sonnenburg et al, 2016) and intergenerational loss of diversity following antibiotic perturbation (Schulfer et al, 2018). The data presented here extend these findings to humans by providing evidence that compounded intergenerational loss of taxonomic and functional diversity is occurring in U.S. immigrant populations, supporting the model of disappearing human microbiota proposed by Blaser and Falkow (Blaser and Falkow, 2009).…”

Influence of Early Life, Diet, and the Environment on the Microbiome

“…34 In animal models, peri-partum antibiotic exposure in the mother can lead to persistent gut dysbiosis in the offspring and colitis in susceptible individuals. 47,48 Although these studies do not provide an exact mechanistic explanation of the effect of antibiotic use on microbiome development or on disease susceptibility, they do highlight that early antibiotic exposure is linked in some way to the normal development of microbial community and to disease development.…”

Probiotic Lactobacillus reuteri Prevents Postantibiotic Bone Loss by Reducing Intestinal Dysbiosis and Preventing Barrier Disruption

“…Antibiotic‐treated and posttreated mice serve as additional models for investigating the roles of a depleted microbiome and dysbiosis, respectively, on organ health . Only a few studies to date have examined the effect of antibiotic treatment on bone health; most have focused on the impact of chronic treatment.…”

“…Antibiotic-treated and posttreated mice serve as additional models for investigating the roles of a depleted microbiome and dysbiosis, respectively, on organ health. (36)(37)(38)(39) Only a few studies to date have examined the effect of antibiotic treatment on bone health; most have focused on the impact of chronic treatment. The results have been inconsistent, likely because of different treatment lengths, differences in age at the initiation of treatment, and possibly differences in starting microbiome composition.…”